leuprolide and Endometriosis

Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective antiestrogen that induces endometrial atrophy and/or amenorrhea. The purpose of this systematic review is to provide an evaluation of safety and effectiveness of gestrinone for the treatment of endometriosis.. We performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science and Scopus. Our selected primary outcomes were the changes in dysmenorrhea, pain relief including pelvic pain and dyspareunia. The secondary outcomes embrace hormones parameters, pregnancy rate and adverse events.. Of 3269 references screened, 16 studies were included involving 1286 women. All studies compared gestrinone with other drugs treatments (placebo, Danazol, Mifepristone tablets, Leuprolide acetate, Quyu Jiedu Recipe) during 6 months. When compared with other drugs treatments, gestrinone relieved dysmenorrhea, pelvic pain, and morphologic response in the ovary. There was an increase on the pregnancy rate. Regarding the side effects observed, gestrinone showed the same adverse events and increased the risk of acne and seborrhea when compared to other treatments. Even if there was any difference in efficacy between gestrinone, danazol, leuprolide acetate, or Quyu Jiedu Recipe Chinese Medicine, it remains unclear due to insufficient data.. Based limited evidence available suggests that gestrinone appeared to be safe and may have some efficacy advantages over danazol, as well as other therapeutic interventions for treating endometriosis. However, this conclusion should be interpreted with caution, due the quality of the evidence provided is generally very low or unclear.. CRD42021284148.

Topics: Danazol; Dysmenorrhea; Endometriosis; Female; Gestrinone; Humans; Leuprolide; Pelvic Pain; Pregnancy

Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.. We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.. Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.. For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.

Topics: Danazol; Endometriosis; Female; Gestrinone; Humans; Leuprolide; Levonorgestrel; Mifepristone; Network Meta-Analysis

We aimed to examine how leuprorelin has been studied for the treatment of women with endometriosis in Asia. We conducted a literature search of PubMed, the Cochrane Library and ClinicalTrials.gov. This review includes randomised trials of women with endometriosis treated with leuprorelin in Asia. Phase I-IV clinical trials published between January 1 2000 and December 31 2016 and written in English were included. Four studies were identified, showing that leuprorelin significantly improves pain and quality of life. The oestrone and oestradiol levels are decreased by leuprorelin but can be increased using an 'add-back' therapy with conjugated equine oestrogen and methoxyprogesterone. Menopause is more common in women treated with leuprorelin. The bone mineral density is reduced in women treated with leuprorelin. There are limited studies investigating the use of leuprorelin for the treatment of endometriosis in Asian populations. However, the research that has been conducted supports the use of leuprorelin in an Asian population.

Topics: Asian People; Endometriosis; Female; Gonadotropins; Humans; Leuprolide; Pain

The most common location of extragenital endometriosis is the bowel. Medical treatment may not provide long-term improvement in patients who are symptomatic, and consequently most of these patients may require surgical intervention. Over the past century, surgeons have continued to debate the optimal surgical approach to treating bowel endometriosis, weighing the risks against the benefits. In this expert review we will describe how the recommended surgical approach depends largely on the location of disease, in addition to size and depth of the lesion. For lesions approximately 5-8 cm from the anal verge, we encourage conservative surgical management over resection to decrease the risk of short- and long-term complications.

Topics: Anal Canal; Conservative Treatment; Contraceptives, Oral, Combined; Danazol; Digestive System Surgical Procedures; Endometriosis; Endosonography; Estrogen Antagonists; Female; Humans; Intestinal Diseases; Laparoscopy; Leuprolide; Magnetic Resonance Imaging; Ovulation Inhibition; Pelvic Pain; Postoperative Complications; Progestins; Rectal Diseases; Ultrasonography

Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.. To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.. We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.. We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.. We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.. We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR. Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.

Topics: Danazol; Dysmenorrhea; Dyspareunia; Endometriosis; Estrenes; Female; Gestrinone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Mifepristone; Norpregnadienes; Oximes; Prevalence; Randomized Controlled Trials as Topic; Receptors, Progesterone

To evaluate the role and efficacy of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues (GnRH-a) combined with add-back therapy.. Prospective, randomized controlled studies of the use of GnRHa with add-back therapy in treatment of endometriosis were enrolled in this study from Medline, Embase, Cochrane library, China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM) and Data Base of Wanfang.After quality assessment and data extraction, meta-analysis were conducted in the change of BMD, reproductive hormone (E2) and visual pain score(VAS) by Stata 11.0 software.. A total of 785 patients from 13 randomized controlled trail (RCT) studies enrolled in this study after exclude no following up, poor quality and repeat published studies.377 patients were in group of GnRH-a with add-back treatment and 408 patients were in group of GnRna alone.The findinds were showed in meta-analysis: (1) there was a significant difference in percentage change of bone mineral density (BMD) between two groups, the add-back therapy was more effective in prevention of bone loss which was (SMD = 0.223, 95%CI:0.003 to 0.443, P = 0.047). (2) There was no significant difference in the level of reproductive hormone between two groups (SMD = -0.053, 95% CI:-0.479 to 0.373, P = 0.807). (3) There was also no significant difference in the visual pain score between the two groups (SMD = -0.157, 95% CI: -0.474 to 0.160, P = 0.332).. GnRH-a with add-back therapy have been shown to be more effective in preventing loss of BMD than GnRH-a treatment alone.However, the long term effect of preventing BMD should be studied.

Topics: Bone Density; Drug Administration Schedule; Drug Therapy, Combination; Endometriosis; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lumbar Vertebrae; Pain Measurement; Pelvic Pain; Randomized Controlled Trials as Topic

Thanks to recent advances in biotechnology, the use of peptides and proteins as drugs has become a concrete clinical reality, and consequently an interesting challenge has emerged for non-parenteral drug delivery. Leuprolide is a synthetic nonapeptide agonist to the luteinizing hormone-releasing hormone (LH-RH) receptor with principal clinical applications for prostate cancer. Although a large number of formulations available, they mainly consist in depot subcutaneous injections or implantable devices. Both of these routes of administration present multiple limitations considering the large clinical applications of this active substance.. The objective of this review is to critically discuss the formulations currently available on the market for leuprolide optimization and to consider how drug delivery plays an important role in improving the bioavailability of this compound.. Due to its physicochemical properties and its economical market, leuprolide is an interesting candidate for drug delivery to improve the efficacy of existing treatments, dose adjustments, and patient compliance and safety.

Topics: Administration, Cutaneous; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Amino Acid Sequence; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemistry, Pharmaceutical; Endometriosis; Female; Genital Diseases, Female; Gonadotropin-Releasing Hormone; Humans; Infusions, Parenteral; Injections, Subcutaneous; Leuprolide; Male; Prostatic Neoplasms; Puberty, Precocious; Receptors, LHRH

Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices.. To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis.. We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011.. We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis.. We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself.. The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).. There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.

Topics: Danazol; Dydrogesterone; Endometriosis; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Medroxyprogesterone Acetate; Pelvic Pain; Progesterone Congeners; Progestins

Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG) versus gonadotropin-releasing hormone (GnRH) analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology.

Topics: Asian People; Buserelin; Endometriosis; Europe; Female; Hormone Antagonists; Humans; Japan; Leuprolide; Nandrolone; Treatment Outcome; White People

Thoracic endometriosis is a rare disease, which presents in women at a mean age of 35 years, later than for pelvic endometriosis. There are no known predisposing factors for the condition and its pathogenesis is not yet clearly established. The symptoms always appear in connection with the periods of the person affected by the condition, occurring within 24-48 h after the start of menstruation. Catamenial pneumothorax is the most common clinical entity. It is associated with pelvic endometriosis in 30-50% of cases. Thoracoscopy, preferably performed during menstruation, allows full inspection of the diaphragm and the pleural cavity for defects in the diaphragm, endometrial nodules and bullae. The level of CA 125 is often elevated but this is not a reliable or specific marker. Medical treatment is aimed at blocking the action of estrogen on the endometrium and ectopic endometrial implants. GnRH analogues or danazol are the preferred treatments. Surgery to repair and strengthen the diaphragm and/or resect nodules or bullae also has a role, supplemented by pleurodesis to prevent further pneumothorax or effusions. The main risk is recurrence, and thus the current usual practice is to combine surgery, immediately followed by hormone therapy focusing on GnRH analogues.

Topics: Adult; alpha 1-Antitrypsin Deficiency; Biomarkers; CA-125 Antigen; Combined Modality Therapy; Danazol; Diagnosis, Differential; Endometriosis; Estrogen Receptor Modulators; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Pneumothorax; Pulmonary Emphysema; Recurrence; Thoracic Diseases; Thoracic Surgery, Video-Assisted; Thoracoscopy

It has been postulated that gonadotropin-releasing hormone (GnRH) analogues may act directly on endometrial cells and inhibit their growth and proliferation by regulation of apoptotic and angiogenic mechanisms. Eutopic endometrial cells from patients with endometriosis show an increased proliferation rate and are less susceptible to cell death by apoptosis than those from subjects without the disease. Notably, the GnRH analogue, leuprorelin, inhibits cell proliferation and increases the apoptotic rate in eutopic endometrial cell cultures, an effect that appears to be mediated by an increase in the expression of the pro-apoptotic proteins Bax and FasL and a decrease in the expression of the anti-apoptotic protein Bcl-2. Angiogenesis is an important process in the development of endometrial tissue, and it is regulated by vascular endothelial growth factors (VEGFs) and angiopoietins. VEGF levels are elevated in peritoneal fluid and endometriotic tissue from patients with endometriosis. In addition, it has been demonstrated that the expression of VEGF is potentiated by a variety of cytokines, including IL-1beta. Recent studies show that leuprorelin reduces the production of VEGF-A and IL-1beta in eutopic endometrial cell cultures, suggesting a mechanism by which it could inhibit the development of endometriosis. Thus, GnRH analogues appear to be effective in reducing the growth of endometrial cells, not only due to their classical pituitary endocrine effects, but also via a direct effect on the endometrial cells themselves.

Topics: Apoptosis; Cell Proliferation; Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Neovascularization, Pathologic; Stromal Cells

Leuprolide acetate is a synthetic nonapeptide that is a potent gonadotropin-releasing hormone receptor (GnRHR) agonist used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. As its basic mechanism of action, leuprolide acetate suppresses gonadotrope secretion of luteinizing hormone and follicle-stimulating hormone that subsequently suppresses gonadal sex steroid production. In addition, leuprolide acetate is presently being tested for the treatment of Alzheimer's disease, polycystic ovary syndrome, functional bowel disease, short stature, premenstrual syndrome and even as an alternative for contraception. Mounting evidence suggests that GnRH agonist suppression of serum gonadotropins may also be important in many of the clinical applications described above. Moreover, the presence of GnRHR in a multitude of non-reproductive tissues including the recent discovery of GnRHR expression in the hippocampi and cortex of the human brain indicates that GnRH analogs such as leuprolide acetate may also act directly via tissue GnRHRs to modulate (brain) function. Thus, the molecular mechanisms underlying the therapeutic effect of GnRH analogs in the treatment of these diseases may be more complex than originally thought. These observations also suggest that the potential uses of GnRH analogs in the modulation of GnRH signaling and treatment of disease has yet to be fully realized.

Topics: Animals; Endometriosis; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Male; Prostatic Neoplasms; Puberty, Precocious; Receptors, LHRH

Endometriosis is an enigmatic, debilitating disease that affects up to 15% of all women of reproductive age. It is characterised by pelvic pain and infertility. Current treatment regimens control the disease by inducing a hypoestrogenic state. Although the absence of circulating oestrogen levels leads to a regression of the disease, this hypoestrogenism also induces many unpleasant side effects. As such, these and other shortcomings of current drug therapies emphasise their limitations and the necessity for the development of novel endometriosis treatments. In this review, current therapies for medical management of endometriosis are discussed, as are their shortcomings. Potential target areas that may be attractive alternatives to current therapies are also reviewed. Emphasis is placed upon the emerging research using TNF inhibitors, their potential benefits over current treatment regimens and the development of future potential therapeutic targets.

Topics: Adolescent; Adult; Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal; Aromatase Inhibitors; Ascitic Fluid; Cell Adhesion Molecules; Cytokines; Drug Design; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Goserelin; Hormone Antagonists; Humans; Hypothalamo-Hypophyseal System; Infertility, Female; Leuprolide; Matrix Metalloproteinases; Middle Aged; Protease Inhibitors; Tumor Necrosis Factor-alpha

Topics: Delayed-Action Preparations; Drug Administration Schedule; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Middle Aged

Endometriosis is a common condition for which a number of treatments have been proposed. Medical treatments are based on the hormonal responsiveness of endometriosis implants. These therapies include progestins (with or without estrogens), androgens, and gonadotropin-releasing hormone (GnRH) analogs. Surgical treatments may include hysterectomy with oophorectomy or organ-sparing surgery involving ablation or resection of visible lesions of endometriosis and restoration of pelvic anatomy. There are no studies that directly compare the effectiveness or adverse effects of medical therapy and surgical therapy. Studies on medical therapy compare different treatments with placebo or with other active treatments. Hormone-based therapies for endometriosis show 80%-100% effectiveness in relief of pelvic pain over a 6-month course of therapy. Serious adverse outcomes after medical therapy are unusual. Studies on surgical therapy are largely anecdotal, with noncomparative reports on a variety of surgical methods. A few comparative surgical studies have been reported. Because of the noncomparative nature of many of the surgical studies, the use of combinations of surgical procedures and techniques in the reported studies, and the reporting of results from surgeons with an unusually high level of technical skill, the gynecological practitioner has little basis in the literature for assessing the optimum surgical approach. Surgical complications are believed to be underreported and may be related to how aggressive a surgical procedure is undertaken.

Topics: Androgens; Contraceptives, Oral; Danazol; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Hysterectomy; Laparoscopy; Leuprolide; Nafarelin; Ovariectomy; Pain; Pain Measurement; Progestins; Recurrence; Research Design; Treatment Outcome

Topics: Buserelin; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Nafarelin; Osteoporosis

The gonadotropin-releasing hormone (GnRH) agonists are a relatively new class of drugs that are potentially effective in treating disorders that are aggravated either by estrogen or testosterone. GnRH agonists are effective in the treatment of endometriosis, as well as other disorders, such as advanced prostrate cancer, precocious puberty and uterine leiomyomata. While the GnRH agonists reduce the extent of the endometrial lesions and the occurrence of pelvic pain associated with endometriosis, these agents are associated with physical and psychiatric side effects. The adverse effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. Preliminary results of a prospective, double-blind placebo-controlled study and an open label trial indicates that depressive mood symptoms increase in women treated with GnRH agonist therapy for endometriosis. Additional evidence suggest that sertraline effectively manages depressive mood symptoms associated with GnRH agonist therapy. The reason for the decline in mood on GnRH agonists is postulated to be associated with the decline in estrogen levels. Effective treatment strategies for depressive mood symptoms in women on GnRH agonists therapy may offer insight into the mechanisms of action of estrogen on mood.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nafarelin; Randomized Controlled Trials as Topic; Sertraline

Chronic pelvic pain is a condition that affects one in seven women of reproductive age in the United States. Direct and indirect medical costs associated with this condition are estimated to be more than $3 billion annually before factoring in the costs of diagnostic testing. At many medical centers, endometriosis is the most common single cause of chronic pelvic pain; other causes include intra-abdominal adhesions, chronic pelvic inflammatory disease, ovarian cysts, and adenomyosis. The current approach to diagnosis and treatment of chronic pelvic pain is a two-step approach, with medical history, physical examination, laboratory testing, and empiric therapy (nonsteroidal anti-inflammatory drugs, oral contraceptives, and/or antibiotics) comprising Step 1 and surgical diagnosis with laparoscopy as Step 2. At many centers, the most common diagnosis at the time of laparoscopy for chronic pelvic pain is endometriosis, typically minimal to mild disease that can be effectively treated with hormonal therapy. Therefore, a rational alternative approach is a 3-month empiric course of therapy with a gonadotropin-releasing hormone agonist before laparoscopy. The advantages of this approach are the high rate of pain relief in women, the possibility of avoiding an invasive procedure (laparoscopy), the ability to extend therapy, if pain is relieved, to the full 6-month therapeutic course of endometriosis, and a potentially lower cost relative to laparoscopy.

Topics: Chronic Disease; Cost of Illness; Endometriosis; Female; Hormone Antagonists; Humans; Laparoscopy; Leuprolide; Managed Care Programs; Pelvic Pain; United States

Leuprorelin (leuprolide acetate) is a gonadotrophin-releasing hormone (GnRH) analogue used to treat a wide range of sex hormone-related disorders including advanced prostatic cancer, endometriosis and precocious puberty. It acts primarily on the anterior pituitary, inducing a transient early rise in gonadotrophin release. With continued use, leuprorelin causes pituitary desensitisation and/or down-regulation, leading to suppressed circulating levels of gonadotrophins and sex hormones. Clinical trials in men with advanced prostatic cancer demonstrate that leuprorelin (usually monthly depot injections of 3.75 or 7.5 mg) is less likely to cause serious adverse cardiovascular effects than diethylstilbestrol, and has comparable efficacy to bilateral orchiectomy or other GnRH analogues. Therefore, the choice between leuprorelin and orchiectomy may be made on the basis of the patient's treatment preference, along with specific patient characteristics and cost implications. Monthly intramuscular or subcutaneous administration of depot leuprorelin 3.75 mg was superior to placebo, and comparable to oral danazol 800 mg/day or intranasal buserelin 900 micrograms/day, in achieving objective and subjective responses in women with endometriosis. Thus, leuprorelin is an effective alternative to other treatments for women with endometriosis, but the recommended duration of its use in this clinical setting is limited to 6 months because it reduces bone mineral density. In children with central precocious puberty, leuprorelin (usually monthly intramuscular or subcutaneous injections of depot leuprorelin 3.75 to 15mg) decreases mean growth velocity and signs of sexual maturation and increases predicted adult height compared with baseline measurements. Although effects on final adult height are predicted from available data and require confirmation in long term follow-up studies, the absence of effective alternatives to GnRH analogues makes leuprorelin a first-line therapy for children with this rare disease. In women with uterine leiomyomata, monthly intramuscular administration of depot leuprorelin 3.75 mg for 6 months markedly reduces uterine volume and fibroid-related symptoms, but, as with other GnRH analogues, these effects dissipate following discontinuation of the drug. As adjuvant therapy in women undergoing in vitro fertilisation or gamete intrafallopian transfer, leuprorelin (usually 0.5 to 1 mg/day subcutaneously) reduces the risk of cancelled cycles for oocyte re

Topics: Amino Acid Sequence; Androgen Antagonists; Animals; Antineoplastic Combined Chemotherapy Protocols; Controlled Clinical Trials as Topic; Endometriosis; Female; Fertility; Gonadal Steroid Hormones; Half-Life; Humans; Leiomyoma; Leuprolide; Male; Metabolic Clearance Rate; Molecular Sequence Data; Prostatic Neoplasms; Puberty, Precocious; Uterine Neoplasms

This review addresses the question of whether the different gonadotropin releasing hormone (GnRH) agonists in clinical use might have different impacts, related to their chemical structure, delivery system and dose. Impact was investigated in benign gynecological disorders, i.e. endometriosis and leiomyoma. Arguments are presented indicating that a difference in impact of different analogs can be expected. All currently used intranasal, daily subcutaneous and depot preparations finally give rise to low levels of serum estradiol. The number of days before the first ovulatory menstruation after discontinuation of GnRH agonist treatment is remarkably constant. Four weeks after the last impact of the agonist, there is resumption of follicle growth. This phenomenon is independent of chemical structure, delivery system and dose. One should realize, however, that it generally takes about 30 days before the impact of a depot preparation disappears. Consequently, the impact of a depot preparation lasts 4 weeks longer than that of an otherwise applied agonist. Thus resumption of pituitary activity after discontinuation of a depot formulation takes 4 weeks longer than after discontinuation of non-depot formulations. All agonists have an impressive effect on endometriosis, independent of their chemical structure and delivery system. However, there are no studies comparing different agonists with the same delivery system in comparable endometriosis groups. Similarly, all agonists considerably reduce myoma volume, independently of their chemical structure and delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Buserelin; Dose-Response Relationship, Drug; Drug Delivery Systems; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Leuprolide; Menstrual Cycle; Nafarelin; Structure-Activity Relationship; Triptorelin Pamoate

Leuprorelin (leuprolide, D-Leu6-(des-Gly10-NH2)-LH-RH ethylamide) acetate is a super-active agonist of luteinizing hormone-releasing hormone (LH-RH). We developed once-a-month injectable microcapsules of this agonist by our novel in-water drying method. This depot formulation can release the drug at an apparent zero-order rate over one month with bioerosion of copoly (lactic/glycolic acid) utilized as a wall material of the polycore microcapsules. A dramatic prolonged depression of pituitary-gonadal axis, chemical castration, was achieved by the once-a-month injection in experimental animals; it expects a reliable efficacy for treating hormone-dependent prostatic, breast cancers and endometriosis. Studies on the dosage design of this new delivery system of leuprorelin are summarized.

Topics: Amino Acid Sequence; Animals; Breast Neoplasms; Capsules; Delayed-Action Preparations; Drug Delivery Systems; Endometriosis; Glycolates; Humans; Injections; Lactates; Lactic Acid; Leuprolide; Male; Molecular Sequence Data; Polymers; Prostatic Neoplasms

To evaluate the efficacy and safety of 40-mg relugolix (REL) compared with those of leuprorelin (LEU) in women with endometriosis-associated pain.. Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled study in Japanese patients.. Hospitals and clinics.. Women aged ≥20 years with regular menstrual cycles (25-38 days) experiencing endometriosis or ovarian endometrioma and reporting pelvic pain.. In the REL group, 40 mg of REL was orally administered once a day for 24 weeks. In the LEU group, 3.75 or 1.88 mg of LEU was subcutaneously injected every 4 weeks for 24 weeks.. The primary endpoint was the change in the maximum visual analog scale score for pelvic pain from baseline until 28 days before the end of treatment.. Changes in the maximum visual analog scale score were -52.6 ± 1.3 for REL and -57.5 ± 1.4 for LEU. Ovarian endometrioma decreased by 12.26 ± 17.52 cm. Relugolix was noninferior to LEU for treating endometriosis-associated pelvic pain. Safety profiles of both medications were comparable, although menses returned earlier in patients taking REL, a huge benefit for women who plan to conceive after treatment.. ClinicalTrials.gov: NCT03931915.

Topics: Administration, Oral; Adult; Double-Blind Method; Endometriosis; Female; Fertility Agents, Female; Follow-Up Studies; Hormone Antagonists; Humans; Japan; Leuprolide; Pain Measurement; Pelvic Pain; Phenylurea Compounds; Pyrimidinones; Receptors, LHRH

Endometriosis is an invasive but benign disease of women that develops in endometrial glands outside the endometrium and uterine muscle. It affects about 15-20% of women of childbearing age. One effective way to treat endometriosis is to use GnRH agonists, which inhibit estrogen production. However, one of the possible side effects of this treatment is obesity and BMI increasing, which is a concern for some patients. This study investigated the role of leuprolide acetate in treating overweight patients (BMI≥30) and their comparison with non-overweight patients (BMI<30) for six months. Also, the effect of this medicine was evaluated on the expression of the MIF gene, which is an effective gene in obesity. For this purpose, a clinical trial was performed on 75 women with endometriosis aged 18 to 35 years. These patients were divided into two groups. The first group consisted of 38 patients with BMI<30. The second group consisted of 37 patients with BMI≥30. Both groups were treated with leuprolide acetate at a dose of 3.75 mg/month (intramuscularly) for six months. In addition to clinical evaluations, the expression of the MIF gene was assessed by the real-time PCR technique. The results showed that treatment with leuprolide acetate during six months in both groups reduced dysmenorrhea, dyspareunia, and chronic pelvic pain (P<0.05). Although this decrease was greater in the BMI <30 group, the difference was not significant. Also, after collecting the side effects of the medication, it was found that hypoestrogenism, such as cramps and spotting, was more in the first group; Endogenous complications such as oily skin, acne, and hirsutism were also more common in the second group. The results of MIF gene expression showed that the expression level before and after the start of the experiment in the second group (BMI≥ 30) is higher than the first group (BMI <30). The results also showed that the two groups increased the expression of the MIF gene after treatment with leuprolide acetate. This increase was statistically significant in the second group (P = 0.042). Generally, it was found that this medication causes more weight gain in obese people and increases the risk of obesity-related diseases among these patients. Therefore, it is recommended that this treatment be used with caution in obese patients with endometriosis.

Topics: Adolescent; Adult; Endometriosis; Female; Humans; Intramolecular Oxidoreductases; Leuprolide; Macrophage Migration-Inhibitory Factors; Obesity; Treatment Outcome; Young Adult

Endometriosis affects the responsiveness to ovarian stimulation. This study aimed to assess the role of Dienogest pretreatment for endometriosis suppression as compared to Gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis pursuing IVF treatment.. In this randomized controlled trial, 134 women with endometriosis-related infertility were randomly allocated to group A (n = 67) who had monthly depot GnRHa for 3 months before ovarian stimulation in IVF treatment (Ultra-long protocol), and Group B (n = 67) who had daily oral Dienogest 2 mg/d for 3 months before starting standard long protocol for IVF. The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures included the number of mature oocytes, fertilization rate, quality of life assessed by FertiQoL scores, cost of treatment, and pregnancy outcomes.. Although there was no statistically significant difference between both groups regarding ovarian stimulation, response parameters, and pregnancy outcomes, the Dienogest group had a lower cost of treatment (2773 vs. 3664 EGP, P < 0.001), lower side effects (29.9% vs. 59.7%, P < 0.001), higher FertiQoL treatment scores (33.2 vs. 25.1, P < 0.001) and higher tolerability scores (14.1 vs. 9.4, P < 0.001 < 0.001).. Our study indicates that Dienogest is a suitable and safe substitute for GnRHa pretreatment in endometriosis patients.. NCT04500743 "Retrospectively registered on August 5, 2020".

Topics: Adult; Embryo Transfer; Endometriosis; Female; Humans; Infertility, Female; Leuprolide; Nandrolone; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Progestins; Treatment Outcome

The recurrence of deep infiltrating endometriosis (DIE) after its surgical excision is a big problem: postoperative treatment is crucial.. To compare two postoperative treatments: Dienogest and GnRH agonists.. Prospective Randomized Controlled Trial (RCT).. 146 women submitted to laparoscopic eradication of DIE with bowel and parametrial surgery.. The primary outcome was to demonstrate the non-inferiority of Dienogest about the reduction in pain recurrence. Secondary outcomes were differences in terms of treatment tolerability, side effects, imaging relapse rate, and pregnancy rate.. Both Dienogest and GnRH agonists were associated with a highly significant reduction of pain at 6 and 30 months, without any significant difference (. Dienogest has proven to be as effective as GnRH agonists in preventing recurrence of DIE and associated pelvic pain after surgery. Also, it is better tolerated by patients.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Intestines; Laparoscopy; Leuprolide; Nandrolone; Pelvic Pain; Peritoneum; Postoperative Care; Pregnancy; Recurrence; Reoperation; Secondary Prevention; Treatment Outcome; Triptorelin Pamoate

Relugolix is a once-daily, oral, nonpeptide, gonadotropin-releasing hormone receptor antagonist. The aim of this study was to evaluate safety of relugolix over 24 weeks in women with endometriosis-associated pain.. This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan. Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks. Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks. The primary outcome was safety, including bone mineral density (BMD) and treatment-emergent adverse events (TEAEs). Secondary endpoints included visual analog scale (VAS) scores for endometriosis-associated pain. Analysis sets were defined as all patients who were administered the study drug.. Of 487 randomized patients in the preceding study, 397 enrolled in this extension study and continued to receive placebo (n = 77), relugolix 10 mg (n = 84), relugolix 20 mg (n = 78), relugolix 40 mg (n = 89), or leuprorelin (n = 69). Baseline characteristics were similar between extension study patients and patients in the preceding study. Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups. Mean (SD) change in BMD from baseline at Week 24 was - 0.2 (1.99)% for placebo;  - 1.6 (2.34)%,  - 2.6 (2.94)%, and  - 4.9 (2.91)% for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 4.4 (2.16)% for leuprorelin. Mean ± SD change from baseline in mean VAS score (mm) for pelvic pain at end of treatment was - 3.2 ± 12.16 for placebo; - 6.8 ± 10.56, - 9.0 ± 11.84, and - 11.9 ± 11.26 for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 12.7 ± 12.57 for leuprorelin. Estradiol levels decreased with increasing relugolix dose and remained below postmenopausal levels throughout the 24-week relugolix 40-mg treatment period.. Treatment with relugolix for 24 weeks was generally well tolerated and demonstrated similar pain reduction to leuprorelin in women with endometriosis. The dose-dependent loss in BMD observed with relugolix treatment was expected due to an induced hypoestrogenic state. Relugolix demonstrated a similar benefit/risk profile to injectable therapy in this phase 2 study. Trial registration NCT01452685 (ClinicalTrials.gov, registered 17/10/2011).

Topics: Double-Blind Method; Endometriosis; Female; Humans; Japan; Leuprolide; Pelvic Pain; Phenylurea Compounds; Pyrimidinones; Treatment Outcome

To evaluate the effects of gonadotropin-releasing hormone agonists (GnRH-a) on fertility in women with mild endometriosis who are undergoing in vitro fertilization and embryo transfer (IVF-ET) procedures.. Prospective, randomized, controlled trial.. Three tertiary university hospitals.. Four hundred infertile women with mild endometriosis, documented with laparoscopy, undergoing IVF and 200 women with tubal factor infertility.. Administration of GnRH-a for 3 months before an IVF attempt (group A, n = 200) or IVF without GnRH-a (group B, n = 200).. Follicular fluid (FF) levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and IL-1 receptor antagonist; fertilization rate (FR), implantation rate (IR), quality of embryos, and clinical pregnancy rate (PR).. Women who received GnRH-a had a statistically significantly reduced concentration of FF cytokines compared with women who did not receive this regimen. Women in group B had a reduced FR (61.7; 95% CI, 59.20-64.20) compared with the women in group A (72.7; 95% CI, 70.50-74.90) and compared with the women with tubal factor infertility (74.7; 95% CI, 72.00-77.24). The embryo quality, IR, and clinical PR showed no statistically significant improvement in the women of group A compared with group B.. Women who received GnRH-a for 3 months had a lower concentration of FF cytokines. These women had also a higher FR than the women who did not receive GnRH-a. However, the IR, embryo quality, and clinical PR showed no statistically significant difference when comparing the two groups. CLINICALTRIALS.. NCT01269125.

Topics: Adult; Delayed-Action Preparations; Drug Administration Schedule; Endometriosis; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pregnancy; Pregnancy Rate; Prospective Studies; Time Factors

To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain.. A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature.. Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive.. Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Topics: Adolescent; Adult; Cost-Benefit Analysis; Endometriosis; Female; Fertility Agents, Female; Humans; Hydrocarbons, Fluorinated; Leuprolide; Markov Chains; Middle Aged; Models, Economic; Pain; Pyrimidines; Severity of Illness Index; United States; Young Adult

Does the GnRH antagonist, ASP1707, reduce endometriosis-associated pelvic pain?. ASP1707 significantly reduced endometriosis-associated pelvic pain in a dose-related manner.. GnRH agonists are an effective therapeutic option for endometriosis that is refractory to non-steroidal anti-inflammatory drugs, oral contraceptives, and progestins. However, GnRH agonists cause complete suppression of estradiol (E2), resulting in hypoestrogenic side-effects such as bone loss that may increase the future risk of osteoporotic fractures.. This was a Phase II, multicenter, double-blind, randomized, parallel-group, placebo-controlled study conducted in 540 women from 04 December 2012 to 30 July 2015 in Europe and Japan. A sample size of 504 (84 subjects per group) was calculated to provide ≥80% power to detect a dose-related treatment effect among placebo and ASP1707 doses in change from baseline in pelvic pain, assuming different dose-response curves after 12 weeks of treatment.. Of 912 women with endometriosis-associated pelvic pain screened, 540 were enrolled, and 532 received ≥1 dose of study drug (placebo, n = 88; ASP1707 3 mg, n = 86; ASP1707 5 mg, n = 91; ASP1707 10 mg, n = 90; ASP1707 15 mg, n = 88; leuprorelin, n = 89) for 24 weeks.. After 12 weeks of treatment with ASP1707, the mean (95% CI) changes in numeric rating score (NRS) for overall pelvic pain (OPP) were -1.56 (-1.91, -1.21), -1.63 (-1.99, -1.27), -1.93 (-2.27, -1.60), -2.29 (-2.64, -1.94), and -2.13 (-2.47, -1.79) for placebo, ASP1707 3 mg, ASP1707 5 mg, ASP1707 10 mg, and ASP1707 15 mg, respectively. Mean (95% CI) changes in NRS for dysmenorrhea were -1.50 (-2.00, -1.00), -2.72 (-3.22, -2.21), -2.85 (-3.33, -2.38), -3.97 (-4.46, -3.48), and -4.18 (-4.66, -3.70), respectively. Mean (95% CI) changes in NRS for non-menstrual pelvic pain (NMPP) were -1.53 (-1.88, -1.19), -1.51 (-1.87, -1.16), -1.80 (-2.14, -1.47), -2.03 (-2.37, -1.68), and -1.86 (-2.20, -1.52), respectively. Statistically significant dose-related treatment effects in reduction in NRS for OPP (P = 0.001), dysmenorrhea (P < 0.001), and NMPP (P = 0.029) were observed after 12 weeks among ASP1707 doses and were maintained through 24 weeks. Serum estradiol and bone mineral density decreased dose dependently with ASP1707 through 24 weeks, however, to a lesser extent than with leuprorelin.. This study was not powered for pairwise comparison of each ASP1707 group versus placebo.. All doses of ASP1707 reduced serum E2 levels to within the target range and to a lesser extent than leuprorelin. ASP1707 is a potential alternative treatment to leuprorelin for endometriosis-associated pelvic pain with lower impact on bone health.. This study was funded by Astellas Pharma Inc. T.D'.H is Vice President and Head of Global Medical Affairs Fertility at Merck, Darmstadt, Germany since October 1, 2015. At the time that the TERRA study was conducted, he served as Principal Investigator in his role as Coordinator of the Leuven University Fertility Center. Since October 2015, T.D'.H has left Leuven University Hospital Gasthuisberg, but continues to serve as Professor in Reproductive Medicine and Biology at KU Leuven (University of Leuven) Belgium and at the Dept of Obstetrics, Gynecology and Reproduction at Yale University, New Haven, USA. T. Fukaya and Y. Osuga report personal consulting fees from Astellas Pharma Inc. during the conduct of the study and outside the submitted work. G.M. Holtkamp, and L. Skillern are employed by Astellas Pharma Europe B.V.; K. Miyazaki is employed by Astellas Pharma Inc.; B. López, was a biostatistician for Astellas Pharma Europe B.V. during conduct of the study; R. Besuyen was a contract Associate Director of Medical Science for Astellas during conduct of the study.. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01767090. EudraCT number 2012-002791-14.. 18 December 2012.. One subject signed informed consent on 04 December 2012; the first subject was randomized on 16 April 2013.

Topics: Administration, Oral; Adolescent; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Endometriosis; Female; Hormone Antagonists; Humans; Imidazoles; Leuprolide; Middle Aged; Pain Measurement; Pelvic Pain; Receptors, LHRH; Sulfones; Treatment Outcome; Young Adult

To explore the potential occurrence of long-term side effects and tolerability of gonadotropin-releasing hormone agonist (GnRHa) plus 2 different add-back regimens in adolescent patients with endometriosis.. Follow-up questionnaire sent in 2016 to patients who participated in a drug trial between 2008 and 2012.. Tertiary care center in Boston, Massachusetts.. Female adolescents with surgically confirmed endometriosis (n = 51) who enrolled in a GnRHa plus add-back trial as adolescents.. Leuprolide depot 11.25 mg intramuscular injection every 3 months, plus oral norethindrone acetate 5 mg daily or oral norethindrone acetate 5 mg daily and oral conjugated equine estrogens 0.625 mg daily.. Side effects during and after treatment, irreversible side effects, changes in pain, overall satisfaction.. The response rate was 61% (25 of 41; 10 subjects could not be located). Almost all (24 of 25) reported side effects during treatment; 80% (16 of 21) reported side effects lasting longer than 6 months after stopping treatment. Almost half (9 of 20) reported side effects they considered irreversible, including memory loss, insomnia, and hot flashes. Despite side effects, participants rated GnRHa plus add-back as the most effective hormonal medication for treating endometriosis pain; two-thirds (16 of 25) would recommend it to others. More participants who received a modified 2-drug add-back regimen vs standard 1-drug add-back would recommend GnRHa and believed it was the most effective hormonal medication.. Subjects believed that GnRHa used with add-back was effective and would recommend it to others, despite significant side effects. Those who received 2-drug add-back reported more success than those who received standard add-back. A subset of patients reported side effects they consider to be irreversible.

Topics: Adolescent; Boston; Endometriosis; Estrogens, Conjugated (USP); Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Longitudinal Studies; Norethindrone; Surveys and Questionnaires; Young Adult

Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. "Add-back therapy," the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis.. Twelve-month double-blind, placebo-controlled trial.. Pediatric Gynecology clinic in Boston, Massachusetts.. Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa.. Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months.. The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals.. At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (P. Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL.

Topics: Adolescent; Boston; Contraceptives, Oral, Synthetic; Double-Blind Method; Drug Therapy, Combination; Endometriosis; Estrogens; Estrogens, Conjugated (USP); Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Norethindrone; Norethindrone Acetate; Pain; Quality of Life; Treatment Outcome; Young Adult

Low-dose add-back therapy during postoperative GnRH agonist treatment could lower the risk of add-back-induced endometriosis recurrence and reduce treatment dropout compared with a regular dose. However, the effect of low-dose add-back therapy is still unknown. The aim of this study was to determine whether low-dose add-back therapy can also effectively relieve the hypoestrogenic side effects and simultaneously maintain a therapeutic response of GnRH agonist treatment.. This analysis was a prospective cohort study. During postoperative GnRH agonist treatment, a total of 107 women were prescribed add-back therapy [oral combination tablet; estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg)] (Indivina; Orion, Espoo, Finland) for 20 weeks. Patients in the low dose add-back therapy group were prescribed the tablet once a day, and patients in the regular dose group were given the tablet twice a day. Hypoestrogenic side effects, such as hot flashes and insomnia, were recorded. Patients were also questioned regarding their pelvic symptoms and pain to evaluate the possibility of endometriosis recurrence. Lumbar spine (L2-L4) bone mineral density was measured using dual X-ray absorptiometry. The dropout rates in both groups were also evaluated.. The incidence of hypoestrogenic side effects was lower in the low dose group compared with the regular dose group, including hot flashes (19.2% vs. 21.8%, p = 0.741) and insomnia (15.4% vs. 18.2%, p = 0.699), although there were no significant difference between the groups. In addition, a higher number of patients in the regular dose group dropped out of treatment compared to the low dose group (14.5% and 9.6%, respectively, p = 0.435). The patients in both groups had a significant loss of mean bone mineral density during therapy (p < 0.001 and p = 0.018 for the low dose and regular dose groups, respectively).. Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Topics: Adult; Bone Density; Drug Combinations; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Hormone Replacement Therapy; Hot Flashes; Humans; Leuprolide; Medroxyprogesterone Acetate; Patient Dropouts; Prospective Studies; Sleep Initiation and Maintenance Disorders

To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis.. From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient's subjective symptoms during non-menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed.. After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P = 0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5% (48/101) in the test group, 44.0% (44/100) in the control group, P = 0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33±38) pmol/L in the test group, (38±40) pmol/L in the control group, P = 0.414; the serum level of FSH, was (5.1±2.8) U/L in the test group, (5.3±2.3) U/L in the control group, P = 0.666; the serum level of LH, was (0.6±0.8) U/L in the test group, (0.6±0.9) U/L in the control group, P = 0.907], had no statistically significant difference between the two groups (all P > 0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9% (34/46), 15.2% (7/46) respectively in the test group, 72.3% (34/47), 2.1% (1/47) respectively in the control group, had statistically significant difference between the two groups (P = 0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6% (38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P = 0.082).. Leuprolide acetate is effective and safe in the treatment of endometriosis.

Topics: Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Double-Blind Method; Endometrial Neoplasms; Endometriosis; Estradiol; Female; Hormones; Humans; Leuprolide; Treatment Outcome

The hemostatic and inflammatory systems may activate each other. Endometriosis is a chronic inflammatory disease affecting 10% of women. The objective of this study was to compare the hemostatic effects of two treatments widely prescribed to women with endometriosis: the levonorgestrel intrauterine system (LNG-IUS) and the gonadotropin-releasing hormone analog (GnRHa) leuprolide acetate.. In this randomized open-label controlled trial, 44 women with endometriosis were randomly allocated to one of two groups: 22 women were assigned to use LNG-IUS and 22 to use GnRHa. The assessed variables were D-dimers, fibrinogen, prothrombin time, activated partial thromboplastin time, coagulation factors (F) II, V, VII, VIII, IX, X, and XI, antithrombin (AT), protein C, free protein S, tissue plasminogen activator (t-PA), α2-antiplasmin, thrombin-antithrombin complex, and prothrombin fragment 1+2. All variables were assessed before treatment and six months after treatment onset.. In the LNG-IUS group, FVIII decreased 10% after six months of use. In the GnRHa group, there was a 6% increase in AT, 29% reduction in D-dimers, and 19% increase in t-PA. The LNG-IUS users exhibited a significantly greater reduction of FVIII than the GnRHa users (LNG-IUS: -6.4 ± 14.3% vs. GnRHa: 4.2 ± 12.3%, p=0.02). The women in the GnRHa group exhibited a greater increase of AT than the LNG-IUS users (LNG-IUS: -0.7 ± 9.5% vs. GnRHa: 6.5 ± 10.1%, p=0.02).. Both hormonal treatments for endometriosis exhibited no association with a procoagulant profile.

Topics: Adolescent; Adult; Blood Coagulation; Contraceptive Agents, Female; Delayed-Action Preparations; Endometriosis; Female; Fertility Agents, Female; Hemostasis; Hemostatics; Humans; Leuprolide; Levonorgestrel; Treatment Outcome; Young Adult

Different gonadotropin-releasing-hormone agonist (GnRH-a) formulations with different potency and associated side effects, therefore, different compliance and persistence of therapy. This study was to evaluate the difference of hormonal profile and side effects due to hypoestrogenic status after treatment of leuprorelin and triptorelin in Chinese women with ovarian endometrioma after conservative surgical treatment.. A total of 302 women underwent laparoscopic excision of ovarian endometriomas with rASRM III and IV were enrolled in the study.Subjects were randomized into two groups with use of a random table. Twenty two patients dropped out during the study. Thus 142 patients had three doses of i.m. leuprorelin (group A) and 138 patients had three doses of i.m. triptorelin(group B) at 4 weeks intervals after surgical treatment. Menopausal symptoms were evalutaed using a questionnaire and serum sex hormonal levels were also measured during the follow-up.. At week 4 after the treatment, most of the patients in leuprorelin group have no obvious side effects. After 9 weeks, bone pain, hot flashes and sweating, and irregular bleeding were the main side effects and showed no difference between the groups. Anxiety, depression, vaginal dryness, headache, and acne rates were all significantly higher in triptorelin group than in leuprorelin group. A significant difference in FSH (p=0.003), LH (p=0.026) and E2 (p=0.002) levels between the groups were observed after 21 days of the GnRHa treatment. The FSH (p=0.021) and E2 (p=0.033) levels remained higher in the leuprorelin group than the triptorelin group after six weeks of treatment, but the difference of LH(p=0.917) level was no longer discernible.. Leuprorelin in down-regulating the pituitary-ovarian function was more moderate, and the hormonal levels decrease progressively and gradually, therefore, with lower rate of menopausal symptoms. Leuprorelin acetate maybe better tolerated than triptorelin.

Topics: Adolescent; Adult; Biomarkers; Chemotherapy, Adjuvant; China; Drug Administration Schedule; Endometriosis; Female; Follow-Up Studies; Hormone Antagonists; Hormones; Humans; Laparoscopy; Leuprolide; Middle Aged; Ovarian Diseases; Single-Blind Method; Treatment Outcome; Triptorelin Pamoate; Young Adult

To study the effectiveness and safety of combined laparoscopy and gonadotropin-releasing hormone agonist (GnRH-a) in the treatment of endometriosis (EM).. From January to December 2010, 198 patients with EM undergoing treatment in Department of Obstetrics and Gynecology, Beijing Anzhen Hospital were randomly divided into three groups, which include 52 cases treated by only laparoscopy in laparoscopy group; 76 cases treated by laparoscopy combined with domestic Leuprolide acetate with dose of 3.75 mg every 28 days in Leuprolide acetate group; 70 cases treated by laparoscopy combined with imported Goserelin acetate with dose of 3.6 mg every 28 days in Goserelin acetate group. The efficacy, pregnancy rate and adverse reactions were compared among the three groups.. Thirteen cases lost following up, including 3 cases in laparoscopy group, 6 cases in Leuprolide acetate group and 4 cases in Goserelin acetate group. (1) Effective rates: effective rates were 47% (23/49) in laparoscopy group, 77% (54/70) in Leuprolide acetate group and 74% (49/66) in Goserelin acetate group. Compared with laparoscopy group, the effective rate of Leuprolide acetate group and Goserelin acetate group was significantly elevated (P < 0.05). There was no statistically significant difference between Leuprolide acetate group and Goserelin acetate group (P > 0.05).(2) Recurrence rate: recurrence rate were 33% (16/49) in laparoscopy group, 13% (9/70) in Leuprolide acetate group and 12% (8/66) in Goserelin acetate group. Compared with laparoscopy group, the recurrence rate of Leuprolide acetate group and Goserelin acetate group was significantly declined (P < 0.05). There was no statistically significant difference between Leuprolide acetate group and Goserelin acetate group (P > 0.05). (3) Pregnancy rate: the number of patients require fertility were 28 cases in laparoscopy group, 39 cases in Leuprolide acetate group and 35 cases in Goserelin acetate group. After 2 years follow up, pregnancy rate of 62% (24/39) in Leuprolide acetate group and 60% (21/35) in Goserelin acetate group were high than 39% (11/28) in laparoscopy group significantly, which did not reached significant difference (P > 0.05). (4) Adverse drug reaction:rates of a adverse reactions were 21% (15/70) in Leuprolide acetate group and 20% (13/66) in Goserelin acetate group, including irregular vaginal bleeding associated with low estrogen level. There was no significant difference in adverse reactions (P > 0.05).. Compared with laparoscopy alone, laparoscopy combined with GnRH-a is more effective in treatment of, which exhibit lower recurrence rate, higher pregnancy rate and fewer adverse reactions. Domestic Leuprolide acetate have similar safety and efficacy compared with imported GnRH-a.

Topics: Adult; Electrocoagulation; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Subcutaneous; Laparoscopy; Leuprolide; Metrorrhagia; Pregnancy; Pregnancy Rate; Treatment Outcome; Young Adult

To explore the effects of progressive muscle relaxation (PMR) training on anxiety, depression and quality of life (QOL) of endometriosis patients under gonadotrophin-releasing hormone (GnRH) agonist therapy.. This was a controlled, randomized, open-label study. One hundred consecutive Han Chinese endometriosis patients, aged 18-48 years, were randomly assigned to a PMR group (n=50) and a control group (n=50). In a study of 12 weeks' duration, both groups received one dose of depot leuprolide, 11.25mg IM. In addition to the GnRH agonist therapy, the PMR group received 12 weeks of PMR training. Anxiety level was measured using the state-trait anxiety inventory (STAI). Depression was assessed using subscale D of the hospital anxiety and depression scale (HADS-D). Health-related QOL was measured with SF-36 instrument. The patients were evaluated with STAI, HADS-D and SF-36 before and after the PMR intervention.. The control group and the PMR group were comparable at baseline. After 12 weeks of intervention, both groups showed significant improvement in overall QOL (P<0.05). The PMR group, but not the control group, showed significant improvement in state anxiety, trait anxiety and depression after intervention (P<0.05). Moreover, the PMR group showed significant improvement in all QOL domains after intervention; by contrast, the control group showed significant improvement in all physical health domains and only two mental health domains after intervention. Between-group comparisons of the improvement in scores after intervention showed that the PMR group had significantly better improvement in the scores of anxiety, depression and overall/domain QOL than the control group (P<0.05). Repeated measures ANOVA revealed that both PMR intervention and time had significant individual as well as interactive effects on state anxiety, trait anxiety depression and overall QOL (P<0.05).. This study suggests that PMR training is effective in improving anxiety, depression and QOL of endometriosis patients under GnRH agonist therapy. This is the first study to explore the effects of psychosomatic therapy on emotional status and QOL of endometriosis patients, and may serve as an important reference for future psychosomatic interventions on endometriosis.

Topics: Adolescent; Adult; Anxiety; Depression; Endometriosis; Exercise Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Muscle Relaxation; Quality of Life; Young Adult

To analyze the secondary efficacy and safety outcomes from a recent trial comparing dienogest (DNG) with leuprolide acetate (LA) in women with endometriosis.. A 24-week, open-label, randomized, multicenter study of DNG versus LA in women with endometriosis-related pain was assessed for outcomes such as responder rates (using predefined thresholds of pain relief), changes in single symptoms/signs and sum scores from the Biberoglu and Behrman (B&B) scale, clinical laboratory parameters, and measures of quality of life.. Dienogest was non-inferior to LA for treatment response using all predefined thresholds of pain relief and provided equivalent improvements in B&B symptoms and signs. No clinically relevant changes in laboratory parameters were observed during DNG treatment, whereas estrogen levels decreased in the LA group. Compared with LA, DNG was associated with pronounced improvements in specific quality-of-life measures.. The analyses provide supportive evidence that the efficacy of DNG is equivalent to that of LA for treating endometriosis symptoms, with specific quality-of-life benefits and a favorable safety profile.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Dysmenorrhea; Endometriosis; Estrogens; Female; Humans; Leuprolide; Middle Aged; Nandrolone; Pelvic Pain; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Young Adult

To compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis-associated pain.. Prospective, randomized, double-blind controlled trial.. Academic medical centers in Rochester, New York, and Boston, Massachusetts.. Forty-seven women with endometriosis-associated pelvic pain.. Forty-eight weeks of either depot leuprolide, 11.25 mg IM every 12 weeks with hormonal add-back using norethindrone acetate 5 mg orally, daily; or a generic monophasic oral contraceptive (1 mg norethindrone + 35 mg ethinyl estradiol) given daily.. Biberoglu and Behrman (B&B) pain scores, numerical rating scores (NRS), Beck Depression Inventory (BDI), and Index of Sexual Satisfaction (ISS).. Based on enrollment of 47 women randomized to continuous oral contraceptives and to leuprolide, there were statistically significant declines in B&B, NRS, and BDI scores from baseline in both groups. There were no significant differences, however, in the extent of reduction in these measures between the groups.. Leuprolide and continuous oral contraceptives appear to be equally effective in the treatment of endometriosis-associated pelvic pain.

Topics: Adult; Contraceptives, Oral, Hormonal; Double-Blind Method; Endometriosis; Female; Fertility Agents, Female; Humans; Leuprolide; Patient Satisfaction; Pelvic Pain; Peritoneal Diseases; Quality of Life; Sexuality; Young Adult

Dienogest is a selective progestin that has been investigated in a clinical trial programme for the treatment of endometriosis. The current non-inferiority trial compared the efficacy and safety of dienogest against leuprolide acetate (LA) for treating the pain associated with endometriosis.. Patients with confirmed endometriosis were randomized to treatment with dienogest (2 mg/day, orally) or LA (3.75 mg, depot i.m. injection, every 4 weeks) for 24 weeks. The primary efficacy variable was absolute change in pelvic pain from baseline to end of treatment, assessed by visual analogue scale (VAS). Safety variables included adverse event profile, laboratory parameters, bone mineral density (BMD), bone markers and bleeding patterns.. A total of 252 women were randomized to treatment with dienogest (n = 124) or LA (n = 128); 87.9 and 93.8% of the respective groups completed the trial. Absolute reductions in VAS score from baseline to Week 24 were 47.5 mm with dienogest and 46.0 mm with LA, demonstrating the equivalence of dienogest relative to LA. Hypoestrogenic effects (e.g. hot flushes) were reported less frequently in the dienogest group. As expected, bleeding episodes were suppressed less with dienogest than with LA. Changes in mean lumbar BMD between screening and final visit were +0.25% with dienogest and -4.04% with LA subgroups (P = 0.0003). Markers of bone resorption increased with LA but not dienogest.. Dienogest 2 mg/day orally demonstrated equivalent efficacy to depot LA at standard dose in relieving the pain associated with endometriosis, although offering advantages in safety and tolerability.

Topics: Adult; Bone Density; Endometriosis; Female; Humans; Leuprolide; Nandrolone; Pelvic Pain; Progestins; Quality of Life

The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-IUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment.. This was a randomized, prospective, open clinical study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion, and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index; systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment.. After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean+/-SD) of VCAM (92.8+/-4.2 to 91.2+/-2.7 ng/mL, p=.04), CRP (0.38+/-0.30 to 0.28+/-0.21 mg/dL, p=.03), total cholesterol (247.0+/-85.0 to 180.0+/-31.0 mg/dL, p=.0002), triglycerides (118.0+/- 76.0 to 86.5+/-41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5+/-66.0 to 114.5+/-25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0+/-20.5 to 48.5+/-10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5+/-2.9 to 13.0+/-2.7 mumol/L, p=.04) and a reduction in IL-6 levels (4.3+/-3.9 to 2.3+/-0.8 pg/mL, p=.005), VCAM (94.0+/-3.8 to 92.0+/-1.6 ng/mL, p=.03) and total leukocytes (7330+/-2554 to 6350+/-1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference.. This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment.

Topics: Adult; Biomarkers; Cardiovascular System; Contraceptive Agents, Female; Endometriosis; Female; Homocysteine; Humans; Interleukin-6; Intrauterine Devices, Medicated; Leuprolide; Levonorgestrel; Pain; Pain Measurement; Prospective Studies; Treatment Outcome; Tumor Necrosis Factor-alpha

This was a preliminary study to determine the effect of aromatase inhibitors in preventing the flare induced by GnRH agonist (GnRH-a) in women with endometriosis (n = 9) or leiomyomata (n = 4) who were given letrozole on the first 5 days of the GnRH-a therapy. Serum LH and FSH levels showed the typical flare 1 day after the injection of the GnRH-a; however, E(2) declined immediately after letrozole administration and was notably suppressed at 1, 2, and 4 days after GnRH-a. No patients complained of clinical symptoms typical of the GnRH-a flare phenomenon.

Topics: Adult; Aromatase Inhibitors; Endometriosis; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Letrozole; Leuprolide; Luteinizing Hormone; Nitriles; Progesterone; Triazoles

To assess the recurrence rate of endometrioma after laparoscopic cystectomy plus hormonal suppression treatment or plus dietary therapy compared to post-operative placebo.. A randomized comparative trial was conducted on 259 consecutive women who underwent laparoscopic unilateral/bilateral cystectomy for endometrioma. Seven days after surgery, the patients were randomly allocated on the basis of a computer-generated randomization sequence, to one of four post-operative management arms as follows: placebo (n=65) or gonadotrophin-releasing hormone analogue (tryptorelin or leuprorelin, 3.75 mg every 28 days) (n=65) or continuous low-dose monophasic oral contraceptives (ethynilestradiol, 0.03 mg plus gestoden, 0.75 mg) (n=64) or dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n=65) for 6 months. At 18 months' follow-up after surgery, all patients were monitored with a clinical gynecologic examination, and a transvaginal ultrasonography for possible evidence of endometrioma recurrence.. At 18 months' transvaginal ultrasonographic follow-up after surgery, no significant recurrence rate of endometrioma was detected in women who received a postoperative course of hormonal suppression treatment or dietary therapy when compared with placebo (placebo vs. GnRH-a P=0.316, placebo vs. estroprogestin P=0.803, placebo vs. dietary therapy P=0.544). Second-look laparoscopy was performed on a clinical basis and confirmed the ultrasonographic suspicion of recurrence of endometrioma in all cases: 10 (16.6%) in the post-operative placebo group vs. 6 (10.3%) in the post-operative GnRH-a group vs. 9 (15.0%) in the post-operative continuous estroprogestin group vs. 11 (17.8%) in the post-operative dietary therapy group. Of 36 patients with recurrent ovarian endometriosis, 8 had recurrence on the treated ovary, 20 on the contralateral ovary that appeared to be normal at the time of the first-line surgery, and 8 on both the treated and untreated ovaries. Endometrioma recurrences were associated with moderate-to-severe painful symptoms in 14/36 patients (38.8%), while the remaining 22 (61.1%) patients were asymptomatic.. A 6-month course of hormonal suppression treatment or dietary therapy after laparoscopic cystectomy had no significant effect on the recurrence rate of ovarian endometriosis when compared with surgery plus placebo. So, treatment of endometrioma can be carried out exclusively by laparoscopic cystectomy without post-operative therapy, if a complete excision of ovarian endometriosis has been assured.

Topics: Adult; Combined Modality Therapy; Contraceptives, Oral, Combined; Diet Therapy; Dietary Supplements; Endometriosis; Endometrium; Ethinyl Estradiol; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Gynecologic Surgical Procedures; Humans; Laparoscopy; Leuprolide; Minerals; Norpregnenes; Secondary Prevention; Treatment Outcome; Ultrasonography; Uterine Diseases; Vitamins

We compared the effects of levonorgestrel-releasing intrauterine devices (LNG-IUD) and a gonadotropin-releasing hormone agonist (GnRHa) on uterine volume, uterine arteries pulsatility index (PI) and endometrial thickness before and after six months of endometriosis treatment. Sixty women aged 18-40 y were allocated randomly to one of two groups: LNG-IUDs were inserted in 30 women, and GnRHa monthly injections were performed on the other 30. All 60 women were submitted to transvaginal 2-D ultrasound scans on the day that the treatment started and then six months later. Measurements of uterine arteries PI, uterine volume and endometrial thickness were performed at both evaluations. The use of LNG-IUDs significantly decreased endometrial thickness (pre = 6.08 +/- 3.00 mm, post = 2.7 +/- 0.98 mm; mean +/- SD), as did the use of GnRHa (pre = 6.96 +/- 3.82 mm, post = 3.23 +/- 2.32 mm). The uterine volume decreased in the GnRHa group (pre = 86.67 +/- 28.38 cm(3), post = 55.27 +/- 25.52 cm(3)), but not in the LNG-IUD group (pre = 75.77 +/- 20.88 cm(3), post = 75.97 +/- 26.62 cm(3)). Uterine arteries PI increased for both groups; however, the increase was higher in the GnRHa group (0.99 +/- 0.84 vs. 0.38 +/- 0.84, p = 0.007; PI increase in GnRHa and in LNG-IUD groups, respectively). In conclusion, levonorgestrel released directly onto the endometrium by the LNG-IUD induced smaller uterine changes than did the hypoestrogenism induced by GnRHa. Nevertheless, both promoted similar effects on endometrial thickness.

Topics: Adolescent; Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices, Medicated; Leuprolide; Levonorgestrel; Pulsatile Flow; Ultrasonography; Uterine Diseases; Uterus; Young Adult

Health status instruments, which measure the subjective functioning and well-being of respondents, are increasingly being used in international, multi-centre trials of new treatments. If the results of such trials in different countries are to be pooled, it is vitally important for researchers to know how comparable the instruments are across cultures. In this study, we evaluated the response rate, data quality, score reliability and scaling assumptions of the 30-item Endometriosis Health Profile (EHP-30) in the USA.. Data were obtained from a multi-centre study which recruited 225 patients from 43 clinic sites in the United States of America. It was a randomised, evaluator-blinded, Phase III study. In the evaluation of the EHP-30 reported here, the two groups (Depot Medroxyprogesterone Acetate [DMPA] and Leuprolide Acetate [LA]) are combined, and analyses are based on the data gained at baseline. Questionnaires were self-completed by patients when they visited the clinics.. Data completeness was very high, with 97.33% of respondents completing all of the items on the EHP-30. Furthermore, there were no more than a maximum of two missing responses for any given item. No floor and ceiling effects were found for any of the dimensions of the questionnaire. Internal consistency reliability was high for all dimensions (alpha ranged from 0.84 to 0.91). The psychometric properties of the instrument, outlined in the development of the UK version, are supported in the American context.. The data presented here suggest that the EHP-30 is a valid and reliable measure that can be appropriately and meaningfully used in studies that include respondents from the USA.

Topics: Adult; Antineoplastic Agents, Hormonal; Endometriosis; Female; Health Status; Humans; Leuprolide; Medroxyprogesterone Acetate; Psychometrics; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; United States

To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy.. Randomized comparative trial.. University hospital.. Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV (r-AFS).. Six months of placebo (n = 110) versus GnRH-a (tryptorelin or leuprorelin, 3.75 mg every 28 days) (n = 39) or continuous estroprogestin (ethynilestradiol, 0.03 mg plus gestoden, 0.75 mg) (n = 38) versus dietary therapy (vitamins, minerals salts, lactic ferments, fish oil) (n = 35).. Painful symptoms (visual analogue scale score) and quality-of-life endometriosis-related symptoms (SF-36 score) at 12 months' follow-up.. Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups. Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain. Surgery plus placebo showed significative decrease in dyspareunia scores. Postoperative medical and dietary therapy allowed a better quality of life than placebo.. Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life.

Topics: Adult; Combined Modality Therapy; Contraceptives, Oral, Hormonal; Drug Combinations; Dysmenorrhea; Dyspareunia; Endometriosis; Ethinyl Estradiol; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Norpregnenes; Ovulation Inhibition; Pain, Postoperative; Placebos

A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain.. This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months.. DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months.. DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Topics: Administration, Cutaneous; Adult; Antineoplastic Agents, Hormonal; Bone Density; Contraceptive Agents, Female; Endometriosis; Female; Fertility Agents, Female; Hip; Humans; Leuprolide; Lumbar Vertebrae; Medroxyprogesterone Acetate; Pelvic Pain; Quality of Life; Radiography; Treatment Outcome; Uterine Diseases

The objective was to evaluate the duration of pituitary desensitization after the administration of 3.5 mg of triptorelin (T) and leuprolin (L) depot preparations in patients with endometriosis.. Two groups of 30 patients received, on 21st day of the cycle, 3.75 mg i.m. of triptorelin (T group), and of leuprolin acetate (L group). From the first to the eighth week following gonadotrophin-releasing hormone agonists (GnRH-a) administration both groups underwent pelvic ultrasound and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) evaluation. Statistical analysis was performed using the ANOVA test and the median test. A p-value < 0.05 was considered significant.. Pituitary suppression was achieved from two to six and from two to seven weeks after the administration of 3.75 mg of leuprolin and triptorelin, respectively. FSH and LH serum levels were significantly higher in the L group than in the T group after the fourth week.. Leuprolin and triptorelin depots (3.75 mg) promote satisfactory ovarian suppression lasting for six and seven weeks, respectively, after administration, with significantly different ambient levels of endogenous LH.

Topics: Analysis of Variance; Delayed-Action Preparations; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Ovulation Inhibition; Pituitary Gland; Triptorelin Pamoate

To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA-SC 104) with that of leuprolide acetate in treatment of endometriosis.. Phase 3, multicenter, randomized, evaluator-blinded, comparator-controlled trial.. Clinical trial sites in Canada and United States.. Two hundred seventy-four women with surgically diagnosed endometriosis.. Intramuscular injections of DMPA-SC (104 mg) or leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months of posttreatment follow-up.. Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density (BMD), hypoestrogenic symptoms, bleeding, and weight.. The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (month 6) and in reducing all five symptoms after 12 months' follow-up (month 18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6, with scores returning to baseline at 12 months' follow-up. No statistically significant differences in median weight changes were observed between groups. Compared with leuprolide, DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding.. Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding.

Topics: Adult; Bone Density; Delayed-Action Preparations; Endometriosis; Estrogens; Female; Flushing; Humans; Injections, Subcutaneous; Leuprolide; Medroxyprogesterone Acetate; Pain; Palliative Care; Quality of Life; Single-Blind Method; Treatment Outcome; Uterine Hemorrhage

This pilot study examined the effect of a low-dose E and pulsed progestogen hormone therapy (HT) regimen for add-back during long-term GnRH-agonist therapy on bone mineral density (BMD) in five patients with stage IV endometriosis. Bone mineral density was stable after initiation of HT for the entire follow-up period (up to 10 years). One patient stopped her treatment on two occasions to conceive and was successful each time with delivery of a normal baby. No patient had return of pelvic pain after HT add-back.

Topics: Adult; Bone Demineralization, Pathologic; Bone Density; Chronic Disease; Drug Combinations; Endometriosis; Estradiol; Female; Fertility Agents, Female; Hormone Replacement Therapy; Humans; Leuprolide; Pelvic Pain; Pilot Projects; Progestins; Treatment Outcome

The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months.. Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period.. CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life.. Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.

Topics: Adolescent; Adult; Delayed-Action Preparations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices, Medicated; Leuprolide; Levonorgestrel; Pelvic Pain

To evaluate the influence of two medical treatments for endometriosis on insulin sensitivity.. After surgery, 26 women with endometriosis were randomly allocated to a 6-month treatment with a GnRH agonist (Leuprorelin 3.75 mg/28 days) or a subdermal progestin implant (etonogestrel 68 mg). Insulin sensitivity (SI) and glucose utilization independent of insulin (Sg) were investigated at baseline and after 6 months by a frequently sampled intravenous glucose tolerance test (FSIGT) associated with the minimal model method.. Both therapies tended to decrease SI, but the effect did not reach statistical significance in the GnRH agonist group (5.43+/-1.29 vs. 3.99+/-0.8) and was significant in the etonogestrel group (5.74+/-1.12 vs. 3.95+/-0,78; p=.046). Sg, fasting glucose, insulin, C-peptide and C-peptide/insulin were not modified by either treatment.. The modifications of glucose-insulin metabolism induced by the GnRH agonist are of no relevance for the short-term use of this molecule. Even if the modification induced by the etonogestrel implant is subtle and of no major impact, it should be taken into consideration for the long-term treatment of individuals with abnormalities of glucose-insulin metabolism.

Topics: Blood Glucose; C-Peptide; Desogestrel; Drug Implants; Endometriosis; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leuprolide

It has been proposed that hormonal supplementation during prolonged GnRH agonist therapy prevents hypoestrogenic side effects, including bone loss. The optimal combination for long-term treatments with safe metabolic profile remains questionable. A norprogesterone derivative, promegestone, was assessed for the first time in a double-blind trial.. Seventy-eight patients with endometriosis with rAFS (Revised American Society for Reproductive Medicine) scores of III-IV were randomly assigned to monthly leuprorelin 3.75 mg (1 year) which, after the third injection was used in combination with promegestone 0.5 mg (P) plus either estradiol placebo (PL) or estradiol 2 mg (E) per day. Bone mineral density (BMD) was determined at baseline, 6 and 12 months, and biological and clinical quarterly assessments were performed. Analysis was by the intention to treat method.. At month 12, BMD changes from baseline were -6.1 +/- 3.7 and -4.9 +/- 4.0% in the PL-P group, at the spine and hip, respectively. This bone loss was prevented in the E-P group: -1.9 +/- 3.1 and -1.4 +/- 2.3%, respectively (P < 0.0001 inter-group comparisons). The BMD decrease in the E-P group was explained by the changes occurring during the first 6 months of treatment. There was no deleterious change in lipid parameters. Clinical improvement was observed without an inter-group difference.. Estradiol 2 mg and promegestone 0.5 mg per day is an effective and safe add-back therapy, which can be proposed for prolonged leuprorelin treatment over 6 months in severe endometriosis.

Topics: Absorptiometry, Photon; Adult; Bone Density; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Humans; Leuprolide; Lumbar Vertebrae; Promegestone; Treatment Outcome

To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.. Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).. Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).. Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery.

Topics: Adult; Danazol; Endometriosis; Female; Fertility Agents, Female; Humans; Leuprolide; Ovulation Induction; Postoperative Period; Pregnancy; Pregnancy Rate; Preoperative Care; Prospective Studies

Endometriosis is a common gynecologic syndrome of unknown etiology and pathogenesis. Growth factors and inflammatory mediators produced by peritoneal leukocytes have recently been postulated to participate in the pathogenesis of endometriosis. Angiogenic factors released from peritoneal macrophages may also play a role in the development of this disease. In the present study, we investigate the soluble levels of vascular endothelial growth factor (VEGF), epidermal growth factor-receptor (EGF-R), granulocyte/macrophage-colony stimulating factor (GM-CSF), Insulin-like growth factor-1 (IGF-1) and interferon-gamma (IFN-gamma) in the serum of 28 women with and 20 without endometriosis. We also compared these levels before, during and after treatment with danazol and leuprorelin acetate depot, the two therapeutic regiments of choice concerning this disease. We found that only sVEGF levels were higher in women with endometriosis in comparison to controls (P < 0.001) while sEGF-R is not present. GM-CSF, IGF-1 and IFN-gamma soluble levels are not affected in either healthy or endometriotic subjects. The 6-month treatment with danazol decreased sVEGF levels (P < 0.02) and increased sEGF-R levels (P < 0.001). These observations support the view that VEGF may be associated with the disease process and that danazol may bring sVEGF levels to a normal threshold. However, future studies will be focused on the anti-angiogenic control of the action of VEGF in patients with endometriosis.

Topics: Adult; Danazol; Delayed-Action Preparations; Endometriosis; Endothelial Growth Factors; ErbB Receptors; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Leuprolide; Lymphokines; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism.. Prospective, randomized, double-blind, placebo-controlled, crossover trial.. Clinical research center, university hospital.. Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy.. Collection of serum and urine samples and measurement of bone density. Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks.. In both protocol A and B, LH and E(2) levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). CONCLUSION (S): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.

Topics: Adult; Bone Density; Calcium; Cross-Over Studies; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Homeostasis; Humans; Leiomyomatosis; Leuprolide; Medroxyprogesterone Acetate; Placebos; Uterine Neoplasms

To determine if there is an age-related effect on bone mineral density (BMD) loss with GnRH agonist treatment of endometriosis and, in particular, whether the impact of this therapy in terms of BMD loss is different if it is used at an age prior to attainment of peak BMD than after attaining it.. Data from a randomized, double-placebo-controlled clinical trial comparing efficacy and safety of two GnRH agonists, without add-back, for the treatment of endometriosis, were analyzed.. No significant age-related effect was detected for either GnRH agonist on absolute BMD loss with a single, six-month course. However, in women at an age prior to peak BMD, prevention of the natural increase in BMD with these drugs may prevent women from attaining their peak BMD and thus increase their risk of osteoporosis in later life.. GnRH agonists should be used with caution and perhaps only with strategies designed to minimize the impact on BMD in women prior to attainment of peak BMD.

Topics: Absorptiometry, Photon; Adolescent; Adult; Age Factors; Aged; Bone Density; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Nafarelin; Osteoporosis; Randomized Controlled Trials as Topic

To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis.. Prospective, randomized trial.. Three tertiary care assisted reproductive technology programs.. IVF-ET candidates with surgically confirmed endometriosis.. Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens.. Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure.. The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%).. Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed.

Topics: Adult; Embryo Implantation; Embryo Transfer; Endometriosis; Female; Fertilization in Vitro; Humans; Infertility, Female; Leuprolide; Ovulation Induction; Pregnancy; Prospective Studies; Treatment Outcome

Endometriosis is a common finding in women with infertility, but the mechanism by which it renders a woman infertile remains unclear. The medical treatment of pelvic endometriosis includes hormonal therapy that directly attacks endometriosis lesions or indirectly by inhibiting endometrial proliferation through estrogenic deprivation. The aim of this study was to compare the efficacy and safety of leuprorelin acetate depot and danazol for endometriosis in infertile women.. This randomized trial involved 81 women 19-41 years old with regular menses and known pelvic endometriosis who were recruited from the Fertility Center of the Second University of Naples between 1992 and 1999. Fifty-four women were given 3.75 mg of leuprolide acetate depot every 28 days for 24 weeks and the remaining 27 took 200 mg of danazol three times daily for 24 weeks. Efficacy assessments were based on pre-admission and end-of-treatment laparoscopic scores and subjective symptoms scores at 4-week intervals during and after treatment. Safety was evaluated by adverse events and clinical laboratory tests.. In each group, endometriosis growth and symptoms significantly improved during treatment (p < 0.001). Significantly fewer patients randomized to leuprorelin acetate (5.5%) withdrew during treatment compared with 18.5% randomized to danazol (p < 0.05). After treatment symptoms returned in each group, but severity was less than at admission at all time points (p < 0.02). Hypoestrogenic side-effects were more common in those receiving leuprorelin, particularly hot flushes, but anabolic/androgenic side-effects of weight gain and acne were more common in those receiving danazol.. Both leuprorelin acetate depot and danazol are effective in the treatment of endometriosis in infertile patients. The hypoestrogenic side-effects of leuprorelin may be better tolerated than the androgenic, anabolic effects of danazol.

Topics: Administration, Oral; Adult; Antineoplastic Agents, Hormonal; Danazol; Delayed-Action Preparations; Endometriosis; Estrogen Antagonists; Female; Humans; Infertility, Female; Leuprolide; Severity of Illness Index; Treatment Outcome

To assess post-treatment effects in endometriosis patients of a 12-month course of GnRH agonist alone or with one of three "add-back" regimens.. This is a post-treatment follow-up analysis of a randomized, double-masked, placebo-controlled 52-week trial. All patients had received monthly leuprolide acetate and were randomized to one of four groups: A-daily placebo; B-daily norethindrone acetate 5 mg; C-daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg; and D-daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial trial, 123 completed at least 280 days of therapy and entered the follow-up period. Physical findings and symptoms were quantified, and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post-therapy.. Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups (P <.05). Findings were not affected by endometriosis scores noted on screening laparoscopy. Mean bone mineral density values remained at or above baseline in all add-back groups. The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow-up visit (P <.001).. GnRH agonist and norethindrone acetate alone or combined with low-dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy.

Topics: Adult; Bone Density; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Endometriosis; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Norethindrone; Norethindrone Acetate; Patient Dropouts; Prospective Studies

Adhesion molecules regulate the interaction of cells with the extracellular matrix and/or other cells. The intercellular adhesion molecule-1 (ICAM-1; CD54) is a member of the immunoglobulin superfamily and expressed by several cell types, including leukocytes and endothelial cells. A circulating form of the usually membrane-bound molecule was identified and characterized in normal human serum and in sera from patients with endometriosis. In the present study, we established the serum-soluble ICAM-1 (sICAM-1) levels in patients with endometriosis. We also studied the effect of danazol and leuprorelin acetate depot on the levels of sICAM-1. Thirty-eight women, 18-45 years of age, with regular menses and documented pelvic endometriosis were recruited from a University Hospital setting. Twenty-two women with endometriosis were randomly divided into two groups. Danazol (600 mg) were given every day for 6 months, and 3.75 mg of leuprorelin acetate depot every 28 days for 6 months. Serum sICAM-1 concentrations were measured before, during and after treatment, and its quantitative determination was performed by an ELISA technique using a specific immunoassay. We found that (1) sICAM-1 levels were higher in women with endometriosis in comparison to healthy subjects; (2) the 6 month treatment with danazol or leuprorelin acetate depot increased sICAM-1 levels (P<0.001); (3) 3 months after termination of both treatments, sICAM-1 levels were unchanged. Although the mechanism leading to the increase of sICAM-1 needs to be further clarified, any benefits of medical treatment of endometriosis such as danazol or leuprorelin appear to be independent of changes in ICAM-1 serum levels.

Topics: Adolescent; Adult; Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Intercellular Adhesion Molecule-1; Leuprolide; Middle Aged

Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12% of women during their reproductive life. For the past ten years the gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and safe drugs in the treatment of endometriosis. Nevertheless, gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease. The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone-Gyn) 3.75 mg subcutaneously per month with that of the gestagen lynestrenol (LYN) (Orgametril) 5 mg orally twice per day in women with severe endometriosis, in terms of postoperative revised American Fertility Society (r-AFS) scores I-IV at first-look laparoscopy (score after removal of endometriotic lesions or adhesions) to the r-AFS score after six months' treatment. Secondary objectives were the improvement of clinical symptoms and the side-effect profile. Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospective randomized study between 1996 and 1998. All the participants underwent a first-look laparoscopy with resection of endometriotic lesions and six months' therapy with one of the above mentioned drugs, and a further second-look laparoscopy. The six months' treatment with LAD or LYN led to a significant reduction of the r-AFS score points in both groups. The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After the medical treatment a mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group. This difference was statistically significant (p = 0.000014, Wilcoxon test). The improvement in the symptoms of dysmenorrhea, chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group. LAD was more effective than LYN in the suppression of circulating serum 17 beta-estradiol levels after 6 months of treatment (mean 27.7 +/- 9.3 pg/ml versus 42.6 +/- 59.3 pg/ml). All the observed side-effects were deemed tolerable by the women who participated in this study. As the reduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group, GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis. Due to the limited treatment of 6 months' duration of GnRH-agonists, gestagens might be used as

Topics: Adult; Delayed-Action Preparations; Dysmenorrhea; Dyspareunia; Endometriosis; Estradiol; Female; Fertility; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leuprolide; Lynestrenol; Pelvic Pain; Progesterone; Progesterone Congeners; Prospective Studies; Second-Look Surgery

In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory.. A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence.. During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography.. This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV.

Topics: Adult; Delayed-Action Preparations; Dysmenorrhea; Dyspareunia; Endometriosis; Female; Humans; Leuprolide; Pelvic Pain; Postoperative Care; Pregnancy; Recurrence; Reoperation

We performed a randomized controlled study to determine the efficacy of add-backed therapy by every-other-day administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) on GnRH agonists (GnRH-a) treatment in Japanese women with symptomatic endometriosis. At the end of treatment, serum estrone and estradiol levels in the add-back group (n = 11) were significantly higher than those in the control group (n = 10). The assessment of Beecham classification by bimanual examination, serum CA-125 levels, and the frequency of genital bleeding revealed no significant differences between the two groups. The add-back group showed reduced Kupperman indices relative to those of the control group, and could prevent the loss of bone density. These findings led to a conclusion that GnRH-a therapy added back by every-other-day administration of 0.625 mg CEE and 2.5 mg MPA was a safe and effective treatment for Japanese women with endometriosis.

Topics: Adult; Animals; Bone Density; Bone Remodeling; CA-125 Antigen; Endometriosis; Estradiol; Estrogens, Conjugated (USP); Estrone; Female; Gonadotropin-Releasing Hormone; Horses; Humans; Leuprolide; Medroxyprogesterone Acetate; Middle Aged; Uterine Hemorrhage

To determine the effects of treatment with danazol and leuprolide acetate depot on serum-soluble CD23 concentrations in women with endometriosis.. This randomized trial involved 20 women 18-42 years old with regular menses and known pelvic endometriosis who were recruited from a university hospital between 1993 and 1998. Ten women took 200 mg of danazol three times daily for 6 months, and the remaining ten were given 3.75 mg of leuprolide acetate depot every 28 days for 6 months. Blood-soluble CD23 levels were measured before treatment, during the last 15 days of the 6-month treatment course, and 3 months after treatment. Only one blood sample was taken from ten women without endometriosis, between the 5th and 7th days of their menstrual cycles. For statistical analysis, we used independent and paired t tests with the Pearson correlation coefficient.. Soluble CD23 levels were significantly higher in women with endometriosis before treatment than in ten normal controls. Levels decreased significantly during treatment with either danazol or leuprolide acetate. Three months after treatment, soluble CD23 values remained lower than before treatment. There was no correlation between soluble CD23 concentrations and severity of endometriosis.. Our findings suggest that endometriosis increases soluble CD23 levels, which can be suppressed with either danazol or leuprolide acetate injection.

Topics: Adolescent; Adult; Danazol; Double-Blind Method; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Leuprolide; Receptors, IgE

The purpose of this study was a quantification of changes in endometriosis-associated pain and quality of life during the stimulatory phase of gonadotropin-releasing hormone agonist therapy.. One hundred twenty women with significant endometriosis-associated pain participated in a 1-month double-blind, randomized, placebo-controlled trial. Pain was measured at baseline and at 2 and 4 weeks with visual analog scales and the Endometriosis Symptom Severity score. Quality of life was measured with the SF-36 instrument. Group means and SEMs were calculated. Paired t tests were used after determination of data normality.. Compared with placebo-treated control subjects women treated with gonadotropin-releasing hormone agonist had a statistically (P <. 0001) and clinically significant temporary increase in pain and a concomitant decrease in quality of life.. The stimulatory phase of gonadotropin-releasing hormone agonist therapy is associated with an increase in endometriosis-associated pain and a decrease in quality of life.

Topics: Adolescent; Adult; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pain; Prospective Studies; Quality of Life

This study was undertaken to evaluate serum leptin concentrations in women with endometriosis during treatment with danazol and with leuprolide depot.. Twenty patients aged 18 to 42 years with regular menses and documented pelvic endometriosis were recruited from a university hospital setting. Treatment was 200 mg danazol 3 times daily for 6 months or 3.75 mg leuprolide depot every 28 days for 6 months. Serum leptin concentrations were measured before, during, and after treatment. A single blood sample was taken from each of 10 control women without endometriosis for comparison. Serum leptin level was measured with a radioimmunoassay kit with human leptin, and analysis of variance and paired t tests were used for statistical analysis.. Serum leptin levels were almost the same among women with endometriosis as in the control group. Leptin levels were higher among women with endometriosis during treatment with danazol and leuprolide(P <.001). Three months after treatment, leptin values remained moderately higher than before treatment.. Danazol and leuprolide increased serum leptin levels. The mechanism of leptin increase is unclear. Further studies are needed to determine whether an adipogonadal axis exists.

Topics: Adolescent; Adult; Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Infertility, Female; Leptin; Leuprolide

To compare the potency, side effects, and duration of action of triptorelin and leuprorelin acetate after i.m. injections.. Prospective, double-blind crossover clinical study.. A teaching hospital.. Fifty-four patients with pelvic endometriosis.. Twenty-seven patients had three doses of i.m. triptorelin (3.75 mg) followed by three doses of i.m. leuprorelin acetate at 4-week intervals. Twenty-one patients had three doses of i.m. leuprorelin acetate (3.75 mg) followed by three doses of i.m. triptorelin, also at 4-week intervals.. Menopausal symptoms, time taken for menstruation to return, serum E(2), FSH, LH levels, lipid profiles, and liver function tests.. The potencies of triptorelin and leuprorelin acetate in lowering the serum E(2), FSH, and LH levels were comparable. The severity of menopausal symptoms, changes in the lipid profile and liver function parameters were similar after triptorelin and leuprorelin acetate. The resurgence of ovarian activities and the spontaneous return of menstruation occurred significantly earlier after leuprorelin acetate than triptorelin.. Both drugs are equally potent in down-regulating the pituitary-ovarian function, and their side effects are similar. Triptorelin has a longer duration of drug action and can be administered over a longer interval period.

Topics: Adult; Double-Blind Method; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Liver; Luteinizing Hormone; Menopause; Menstruation; Prospective Studies; Triptorelin Pamoate

In order to assess the endocrinological changes associated with 2 types of low-dose GnRH agonists depot as well as their clinical efficacy, we performed a randomized prospective comparison study of patients having uterine leiomyomas or endometriosis.. A prospective randomized study involving 67 patients with uterine leiomyomas or endometriosis was carried out. These patients were randomly administered either buserelin MP 1.8 mg (Group B, n = 34) or leuprolide 1.88 mg (Group L, n = 33). In each group we evaluated the symptoms of genital bleeding and hot flashes during GnRHa treatment, as well as the levels of serum LH, FSH, and estradiol 8 weeks after the start of treatment. In addition, the endometrial thickness was measured by transvaginal ultrasonography, and changes in the volume of the uterine leiomyoma or endometrial cyst at the end of treatment. The GnRHa depot was administered from 3 to 8 times, 28 days apart, in both groups.. The incidence of menstruation-like genital bleeding 8 weeks after treatment was significantly (p < 0.01) higher in Group B. However this difference disappeared by 12 weeks after treatment. The climacteric symptom of hot flashes was found to be significantly (p < 0.01) more severe in Group L, and this tendency continued until 20 weeks after treatment. The 2 groups did not differ significantly with regard to the levels of the serum LH, FSH, and estradiol at 8 weeks after treatment or in the endometrial thickness at the end of the GnRHa treatment. In both groups, the volumes of the uterine leiomyomas were significantly (p < 0.01) lower after the treatment. In contrast, the volumes of the endometrial cysts did not decrease after administration of GnRHa in both groups.. Leuprolide 1.88 induced pituitary down regulation more rapidly than buserelin MP. However the hypoestrogenic symptoms such as hot flashes were more severe in cases treated with leuprolide 1.88 than in those treated with buserelin MP. Our data confirm that the therapeutic efficacy of buserelin MP and leuprolide 1.88 are similar, with both being sufficient to treat uterine leiomyomas and endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Buserelin; Endometriosis; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Leiomyoma; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Ovarian Diseases; Prospective Studies; Treatment Outcome; Ultrasonography; Uterine Diseases; Uterine Hemorrhage

Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRHa) is limited to 6 months because of possible adverse effects on bone metabolism. We designed a randomized, double-blind, placebo-controlled, prospective study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 microg of ethinyl estradiol with 0.15 mg desogestrel) designed to suppress the adverse effects of hypoestrogenism while preserving the efficacy of GnRHa. Both regimens showed significant improvements in endometriosis, dysmenorrhea, and pelvic pain; effects were significantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher loss of lumbar spine bone mineral density (BMD). Urinary levels of pyridinium crosslinks increased significantly in the GnRHa + placebo group, and declined to normal in the GnRHa + add-back group. The add-back therapy protects women taking GnRHas from severe loss of BMD and accelerated bone collagen resorption, but reduces the efficacy of the GnRHa.

Topics: Amino Acids; Bone Density; Calcium; Desogestrel; Double-Blind Method; Endometriosis; Ethinyl Estradiol; Female; Humans; Leuprolide; Pelvic Pain; Placebos; Prospective Studies

Our purpose was to assess the changes in uterine volume and uterine artery pulsatility index in response to gonadotropin-releasing hormone agonist treatment in women undergoing hysterectomy for nonfibroid-related uterine bleeding.. A double-blind, placebo-controlled randomized trial of 51 women awaiting hysterectomy in a gynecology outpatient clinic was conducted. The women were treated for 8 weeks with either leuprolide acetate depot or placebo. Vaginal ultrasonographic examinations were performed before and after treatment. The paired t test was used for statistical analysis.. In those allocated to therapy with gonadotropin-releasing hormone agonist the mean uterine volume decreased by 34% and the uterine artery pulsatility index increased from 2.25 to 2.7. No significant changes were seen in the placebo group. The intersonographer variability was low and there was a high correlation between uterine size as measured by ultrasonography before hysterectomy and that measured postoperatively.. Treatment with gonadotropin-releasing hormone agonists leads to uterine shrinkage and an increase in the uterine artery pulsatility index even in the absence of uterine fibroids.

Topics: Adult; Arteries; Double-Blind Method; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leuprolide; Middle Aged; Postoperative Period; Preoperative Care; Pulse; Ultrasonography; Uterine Hemorrhage; Uterus

To evaluate and compare the safety and efficacy of leuprolide versus placebo in managing chronic pelvic pain in women with clinically suspected endometriosis.. Women 18-45 years of age with moderate to severe pelvic pain of at least 6 months' duration underwent extensive, noninvasive diagnostic testing and laboratory evaluation, including pelvic ultrasound, complete blood count, determination of erythrocyte sedimentation rate, and endocervical cultures. Those with clinically suspected endometriosis were randomized to double-blind treatment for 3 months with depot leuprolide (3.75 mg/mo) or placebo. The accuracy of the clinical diagnosis of endometriosis was evaluated by posttreatment laparoscopy.. Of 100 women randomized, 95 completed the study: 49 in the leuprolide group and 46 in the placebo group. Women in the leuprolide group had clinically and statistically significant (P < or = .001) mean improvements from baseline after 12 weeks of therapy in all pain measures. These mean improvements were significantly greater (P < or = .001) than those in the placebo group. At 12 weeks, mean decreases in physician-rated scores for dysmenorrhea, pelvic pain, and pelvic tenderness were 1.7, 1.0, and 0.8 points greater, respectively, in the leuprolide group than in the placebo group (on a four-point scale). Thirty-eight (78%) of 49 and 40 (87%) of 46 patients in the leuprolide and placebo groups, respectively, had laparoscopically confirmed endometriosis after 12 weeks of treatment. No women withdrew from the study because of adverse events.. Depot leuprolide was effective and safe for treating patients with chronic pelvic pain and clinically suspected endometriosis, confirming the potential of its empiric use in these patients.

Topics: Adolescent; Adult; Algorithms; Chronic Disease; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Female; Humans; Laparoscopy; Leuprolide; Middle Aged; Pelvic Pain

To examine the impact of treating endometriosis with nafarelin or leuprolide acetate depot on patient quality of life (QOL) and subjective clinical measures.. A randomized, multicenter study was conducted on 192 women with endometriosis. Patients received nafarelin or leuprolide for six months and were followed for up to six months after treatment. QOL was defined by seven items, including symptom severity, daily activities, pain medication use and need for bed rest.. No significant differences were found at baseline between treatments for patients with mild, moderate or no endometriosis symptoms. Those with severe symptoms of endometriosis at baseline and taking nafarelin had a significantly greater improvement in QOL at the last posttreatment visit than those receiving leuprolide (P < .01). Nafarelin was associated with significantly fewer days with moderate or severe hot flashes than leuprolide during treatment (P < .05) and with significantly fewer moderate or severe hypoestrogenic symptoms overall at three months of treatment (P < .05). Additionally, poorer QOL was significantly associated with hypoestrogenic and endometriosis symptoms.. Treatment of endometriosis with nafarelin was associated with fewer days of moderate or severe hot flashes as compared to leuprolide and with greater improvement in QOL after treatment in patients with severe symptoms at baseline.

Topics: Adult; Analgesics; Bed Rest; Endometriosis; Female; Fertility Agents, Female; Hormones; Hot Flashes; Humans; Leuprolide; Middle Aged; Nafarelin; Pain; Quality of Life; Severity of Illness Index; Treatment Outcome

To evaluate the efficacy and safety of a GnRH agonist, leuprolide acetate depot, alone and in combination with three hormonal add-back regimens in the management of endometriosis-associated pelvic pain.. Two hundred and one patients were enrolled in this multicenter, randomized, double-blind, 1-year trial. All patients were given an intramuscular injection of leuprolide acetate depot 3.75 mg every 4 weeks. Patients were assigned to one of four treatment groups: Group A received placebos for progestin and estrogen, group B received norethindrone acetate 5 mg daily and placebo for estrogen, group C received norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg daily, and group D received norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg daily. Pelvic pain scores were assessed monthly, and bone density was measured after 24 and 52 weeks.. By week 8, all four groups showed significant improvement in pelvic pain scores compared with baseline levels. A higher proportion of group D patients terminated the study prematurely due to a lack of improvement in symptoms. Group A experienced a 6.3 +/- 2.3% (P < or = .001) loss in bone density after 52 weeks of treatment, whereas bone density was preserved in all three add-back groups.. The use of leuprolide acetate depot in combination with norethindrone acetate 5 mg alone, or with norethindrone acetate and conjugated equine estrogens 0.625 mg, provides effective suppression of pelvic pain symptoms associated with endometriosis while protecting against bone loss.

Topics: Adult; Bone Density; Cohort Studies; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Endometriosis; Equilin; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Leuprolide; Lipid Metabolism; Lipids; Lumbar Vertebrae; Norethindrone; Pain Measurement; Patient Dropouts; Pelvic Pain; Progesterone Congeners; Vasomotor System

Endometriosis is thought to affect 5-10% of reproductive age women in the general population and is commonly treated with gonadotropin-releasing hormone (GnRH) agonists. Recent studies suggest depressive symptoms are associated with women treated with GnRH agonist for endometriosis.. A retrospective pilot study of 42 female patients, 22 in the treatment group (sertraline) and 20 in the control group (no sertraline), was conducted. All subjects had laproscopically diagnosed endometriosis and were treated with 24 weeks of GnRH agonist therapy. Assessment instruments included the Hamilton Depression Rating Scale and the Menopausal Symptom Index.. The results indicate that patients receiving concomitant sertraline reported significantly less depressive symptoms, but did not differ significantly in physical symptoms than the group receiving a GnRH agonist alone.. Antidepressants, such as sertraline, appear to be significantly helpful in the treatment of mood symptoms during the course of GnRH agonist therapy.

Topics: 1-Naphthylamine; Adult; Affect; Antidepressive Agents, Second-Generation; Antineoplastic Agents, Hormonal; Depression; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Psychiatric Status Rating Scales; Retrospective Studies; Sertraline

Medical oestrogen suppressive therapy has to be considered as an important principle in the management of endometriosis. In the last years GnRHa became the "gold standard" as pre or postoperative measures before/after surgical intervention. We analyzed the data of 198 patients, most of them with recurrent endometriosis histologically confirmed during first-look laparoscopy. Patients were treated in a prospective, multicentre phase III study with the six months GnRHa leuprorelinacetate depot (LAD) followed by a second-look laparoscopy for precise assessment of therapeutic effects. In all stages of endometriosis a 35% reduction of the r-AFS-score compared to the baseline could be achieved due to surgical intervention during first-look laparoscopy with a further improvement of 64% after GnRHa-therapy and surgery during second-look laparoscopy. Two subgroups of patients (24 vs. 45) could be analyzed according to the time of second-look laparoscopy (< or = 30 days vs. > or = 60 days after last injection) showing a comparable r-AFS-score reduction. Both, superficial lesions and deep infiltrating nodules, endometriomas, peritoneal implants and obliterated cul de sac could successfully be treated through the combined medical-surgical approach. Pre- or postoperative therapy with a GnRHa facilitates surgical excision of the implants, a subtle adhesiolysis and often complete removal of all visible lesions. In a high percentage of patients, including advanced stages of the disease, a preservation of ovarian tissue to ensure the childbearing potential could be achieved by minimal-invasive techniques. These results can be claimed as the prerequisites for long-term relief of endometriosis complaints and encouraging pregnancy rates in endometriosis related infertility. This confirms great clinical benefit of the combined medical-surgical approach for the treatment of this enigmatic disease.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Delayed-Action Preparations; Endometriosis; Female; Humans; Laparoscopy; Leuprolide; Peritoneum; Pregnancy; Prospective Studies; Reoperation; Treatment Outcome

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.

Topics: Adult; Delayed-Action Preparations; Desogestrel; Double-Blind Method; Endometriosis; Ethinyl Estradiol; Female; Hot Flashes; Humans; Leuprolide; Placebos; Prospective Studies; Sleep Initiation and Maintenance Disorders; Sweating

This study was designed to evaluate the reliability, validity, and responsiveness of a newly developed, health-related quality-of-life measure.. A total of 137 women (122 from a Phase III clinical trial and 15 from a private practice setting) with endometriosis completed the questionnaire several times.. Reproducibility and internal-consistency reliability were acceptable with intraclass correlation coefficients ranging from 0.94 to 1.00 and Cronbach's alpha coefficients ranging from 0.84 to 0.97. Construct validity was demonstrated on the basis of correlations between items and scales. Health-related quality of life varied in a consistent manner according to clinician-rated measures of pelvic pain and dysmenorrhea and patient-reported levels of endometriosis pain, but no relationship emerged according to the revised American Fertility Society classification. In general, the questionnaire was moderately to highly responsive to change.. This is the first comprehensive health-related quality-of-life questionnaire available for use with endometriosis patients that has demonstrated reliability, validity, and responsiveness.

Topics: Adolescent; Adult; Demography; Endometriosis; Female; Humans; Leuprolide; Pain Measurement; Psychometrics; Quality of Life; Reproducibility of Results; Surveys and Questionnaires

After bioptical diagnosis of endometriosis, 81 patients were treated with GnRH-agonists buserelin or leuprolide for six months. Biopsies before and after treatment were used to test a semiquantitative score-system, regarding atrophy of glands and stroma cells. Furthermore glandular diameter, circumference and area of nuclei were examined morphometrically using a microscopic semiautomatical measuring system. Morphometrical and histological alterations during therapy were evaluated. Additionally, data suitable for predicting a possible therapeutic success were described. After therapy 40 patients still showed endometriotic implants (partial responder) in contrast to 41 cases without foci (total responder). Therapeutic effect of GnRH-agonists was proved in every respect: clinical complaints decreased markedly during GnRH-agonists therapy. Both buserelin and leuprolide treated groups revealed increase of atrophy and reduction of extension of stroma. Correspondingly morphometrical analysed parameters such as diameter, circumference and area of glands decreased during therapy as well as area of cytoplasm and nuclei. Except the diameter of glands, the leuprolide treated partial responder group (residual foci after GnRH-therapy) revealed a stronger therapeutic effect than the buserelin treated partial responder group. Obviously this effect seems to be produced by the stronger estradiol suppression of leuprolide. Pretherapeutic comparison of measured values pointed out a minor distinct endometriosis in the total responder group. Success or failure of therapy seems to depend more on the pretherapeutic degree of expression of endometriosis. Obviously the kind of applicated GnRH-agonist plays a minor distinct role. Morphometrical data of endometriotic foci appear to be appropriate to predict a possible therapeutic success of GnRH-agonist therapy. But because of many exceptions only a roughly estimated prediction is possible.

Topics: Adult; Buserelin; Dose-Response Relationship, Drug; Endometriosis; Fallopian Tubes; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Treatment Outcome

To assess the changes in the subpopulations of lymphocytes and in lymphocyte mitogenic activity in women with endometriosis receiving GnRH-agonist treatment.. Twenty-six women with advanced endometriosis from the National Cheng Kung University Medical College were studied. Each received a total of six doses of GnRH agonist at 4-week intervals. Immunologic responses at various times after receiving GnRH-agonist treatment, including numbers of peripheral blood lymphocytes subsets and the lymphocyte proliferative activity, were analyzed using a repeated measures analysis of variance. Twenty-six healthy women who visited our gynecologic clinics for routine Papanicolaou smear examination at the time of the recruitment were enrolled as controls. The responses for each patient receiving GnRH agonist were normalized with respect to those of her matched control at each of the time points. The differences between post- and pretreatment data were estimated using generalized estimating equations.. There was no significant difference in the sizes of lymphocyte subsets between patients and controls before treatment. After GnRH-agonist treatment, there was a trend in the rise of natural killer cell numbers early in the treatment period, with P values of .05 and .07 at 1-2 weeks and 2-3 weeks, respectively. This rise in natural killer cell numbers was not significant until 3-4 weeks and the second month after the treatment. There were no significant changes in the CD4+ and CD8+ T-cell subsets and B cells, although a slight increase in total T cells (ie, CD3+ T) was observed 1-2 weeks after receiving GnRH agonist. The T-cell mitogenic activities at the end of 2 and 4 months after GnRH-agonist treatment were 1.5 and 1.8 times, respectively, of those before treatment.. The increase in natural killer cell numbers and the upregulation of T-lymphocyte mitogenic activity, which might be caused by a direct effect of GnRH agonist or a consequence resulting from the depression of estradiol by GnRH agonist, may have implications in the clinical treatment of endometriosis.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets

To compare intranasal nafarelin and intramuscular leuprolide acetate (LA) depot in the management of endometriosis.. A multicenter, prospective, randomized, double-placebo, double-blind study was conducted on subjects who had symptoms and signs of endometriosis and bone mineral density (BMD) within the age-appropriate normal range. For 6 months, 99 subjects received nafarelin, 200 micrograms twice daily, and placebo injections once monthly; 93 subjects received LA depot injections, 3.75 mg once monthly, and placebo nasal spray, twice daily. Subjects were followed throughout treatment and for six months after treatment. The main outcome measures were changes in endometriosis symptoms and signs, BMD measurements, subject-reported and objectively measured hot flushes and circulating estradiol concentrations.. Nafarelin was as effective as LA depot in alleviating symptoms and signs of endometriosis. LA depot recipients lost significantly more BMD, had more days with subjective hot flushes and more objectively measured hot flushes than did nafarelin recipients. In the nafarelin group, estradiol levels were consistently higher than in the leuprolide depot group, with significant differences by month 3 of dosing.. Nafarelin and LA depot were equally effective despite higher estradiol levels in nafarelin recipients. Nafarelin-treated subjects lost less BMD, had fewer days with hot flushes and had fewer objectively measured hot flushes.

Topics: Adult; Bone Density; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Estradiol; Female; Humans; Leuprolide; Nafarelin; Ovary; Placebos; Prospective Studies; Vasomotor System

To assess the utility of urinary cross-linked N-telopeptides in monitoring bone resorption and predicting bone loss during GnRH agonist administration.. Ninety patients who were prescribed GnRH agonist therapy for 3-6 months for treatment of endometriosis, leiomyomas or other gynecologic disorders participated in this prospective multicenter study. N-telopeptides, serum estradiol (E2), and bone mineral density were monitored before, during and up to 3 months after the course of GnRH agonist therapy.. N-telopeptide levels increased significantly throughout GnRH agonist therapy and returned to baseline levels by 3 months after treatment was completed. A significant negative correlation was seen between N-telopeptide and E2 measurements after 3 months (r=-0.23, P<.05), 4 months (r=-0.32, P < .05), and 5 months (r=-0.41, P<.005) of GnRH agonist therapy. The percent change in bone mineral density at L1-L4 at 6 months of GnRH agonist treatment correlated inversely with the percent change in N-telopeptides from baseline to 2,3,4, and 5 months of treatment; the percent change of bone mineral density at the femoral neck at 6 months correlated inversely with the percent change of N-telopeptides from baseline to month 4.. Urinary N-telopeptide determinations provide a quantitative measure of bone resorption, due to GnRH agonist-induced hypoestrogenism. Increases in resorption as measured by N-telopeptides parallel decreases in in E2 levels. Increases in N-telopeptides on GnRH agonist therapy may provide a tool to predict decreases in bone mineral density.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Bone Resorption; Collagen; Collagen Type I; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Genital Neoplasms, Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Leiomyoma; Leuprolide; Middle Aged; Nafarelin; Peptides; Prospective Studies; Uterine Neoplasms

To study the effect of GnRH agonist (GnRH-a) treatment on memory and to assess the role of psychological factors.. A randomized prospective study.. An academic teaching hospital.. Women with endometriosis and infertility or endometriosis alone.. Memory Observation Questionnaire, Profile of Mood States, Health Concerns scale, a weekly diary of adverse effects.. Perceived memory functioning decreased during GnRH-a administration and by the final week of treatment 44% of women reported moderate to marked impairment in comparison to community norms. Prospective memory was most affected and withdrawal of GnRH-a treatment resulted in a return to normal memory functioning. Impairment was not related to excessive health concerns or mood changes and was uncorrelated with other adverse effects.. Memory disruption may be a more common side effect of GnRH-a treatment than currently is recognized. Problems were temporary and more likely a result of rapid estrogen depletion than a consequence of mood, somatic distress, or personality factors.

Topics: Adult; Endometriosis; Estradiol; Female; Humans; Leuprolide; Memory Disorders; Nafarelin; Prospective Studies

Thirty-six women with ultrasonographic diagnosis of ovarian endometrioma (bilateral in nine of them), have been treated laparoscopically. After the surgical procedure the patients were assigned to one of the following regimes: Gn-RH-a for 3 months, oral contraceptives if they wanted to avoid pregnancy, or nothing. The follow-up consisted in 1-3-6-12 months ultrasound. The first recurrences were observed at the 6-month ultrasound with an overall recurrence rate after 12 months of 11%. Improvement of pain symptoms occurred in 87% of the patients and fertility rate was 45%.

Topics: Adult; Antineoplastic Agents, Hormonal; CA-125 Antigen; Combined Modality Therapy; Contraceptives, Oral; Delayed-Action Preparations; Endometriosis; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Laparoscopy; Leuprolide; Ovarian Diseases; Ovary; Pregnancy; Pregnancy Rate; Recurrence; Triptorelin Pamoate; Ultrasonography

Administration of superactive agonistic analog of gonadotropin-releasing hormone (GnRH) has shown to induce a paradoxic and reversible suppression of gonadotropins, so that gonadal steroid concentrations are suppressed and hypoestrogenemia is induced. In order to compare the efficacy and safety of leuprorelin acetate depot (LA) and danazol in the treatment of endometriosis, we conducted this study.. A total of forty-five patients with pelvic endometriosis of different severity at laparoscopy with biopsy of peritoneal implants (n = 33) and surgical procedure (enucleation of ovarian chocolate cysts, cystectomy, or fulguration, n = 12) were included in the study and followed during the 20 weeks of treatment. LA 3.75 mg was injected subcutaneously every 28 days, while the daily oral dose of danazol was 800 mg.. Both treatments were associated with a lowering of severity score. There was a consistent decrease in women with stage IV disease in the LA group and an increase in patients with stage I disease in the danazol group, but no difference was found between both treatments. Hot flushing was the most common side effect reported in 97% of LA but occurred only in 13% of danazol-treated patients. In contrast, the androgenic, anabolic side effects of weight gain and myalgia were common in those receiving danazol. The CA-125 levels were significantly lower in both treatment groups compared with their pretreatment levels (p < 0.01). During the five months of the LA treatment, biochemical evaluation revealed no pathologic alternation. Only total protein albumin, alkaline phosphatase, total bilirubin, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, uric acid and calcium increased significantly. Danazol was also associated with adverse metabolic effects and significantly increased low-density lipoprotein-cholesterol concentrations (p < 0.05). In the fourth week, serum estradiol (E2) levels decreased to nearly castrated levels (13.87 +/- 1.63 pg/ml) in all patients treated with LA, and remained at this level thereafter. On the contrary, a slight but significant increase of the serum E2 levels was noted during the danazol treatment. After five months of treatment with LA, no significant changes in bone density were observed at the femoral neck or the anteroposterior (AP) view of lumbar spine, but there was a significant loss in bone density at the lateral view of lumbar spine (-7.1%, p < 0.05).. Both LA and danazol are effective in the treatment of endometriosis. The hypoestrogenic side effects of LA may be better tolerated than the androgenic, anabolic effects of danazol. However, the danazol treatment costs less than LA and has no significant side effect with osteoporosis.

Topics: Adult; Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Leuprolide; Luteinizing Hormone

To evaluate the efficacy of gestrinone versus leuprolide acetate (LA) in improving pelvic pain in women with endometriosis and to compare their effects on bone mineral density and serum lipid profile.. Multicenter, double-blind, double-dummy, randomized clinical trial.. Six academic departments specialized in the study of endometriosis.. Fifty-five women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis.. Six-month treatment with oral gestrinone (n = 27) or IM depot LA (n = 28) followed by 6-month follow-up.. Variations in severity of dysmenorrhea, deep dyspareunia, and nonmenstrual pain as shown by a visual analog scale and a verbal rating scale, modifications in bone mineral content as shown by dual-roentgenogram absorptiometry, and variations in serum cholesterol subfractions and lipoprotein(a) concentrations.. Significant improvements were observed in all three symptoms considered in both treatment arms. Moderate or severe pain symptoms recurrence on both pain scales was observed in 2 of 17 (11.8%) patients given gestrinone compared with 9 of 17 (52.9%) of those given LA (odds ratio, 0.12; 95% confidence interval, 0.02 to 0.69). Lumbar bone mineral density increased slightly in the gestrinone group but decreased by 3% in the LA one. High-density-lipoprotein cholesterol fell by 25% and lipoprotein(a) decreased by approximately 40% in the gestrinone-treated women but did not vary in those receiving LA.. Oral gestrinone is at least as effective as depot LA for pain relief in women with symptomatic endometriosis. A tendency to prolonged pain reduction was observed after gestrinone compared with LA treatment. Gestrinone does not negatively affect bone density but variations in serum lipids need further evaluation.

Topics: Absorptiometry, Photon; Adolescent; Adult; Bone Density; Double-Blind Method; Dysmenorrhea; Endometriosis; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lipids; Pelvic Pain; Progesterone Congeners

An open-label randomized pilot study was conducted to evaluate the efficacy and acceptability of 6 months treatment with leuprolide in a 3-monthly versus a monthly i.m. depot injection for the relief of chronic pelvic pain in women with endometriosis. A total of 30 women aged 18-38 years were allocated to the 3-monthly depot arm (n = 15) or to the monthly depot arm (n = 15) after laparoscopic diagnosis of pelvic endometriosis. Mean (SD) deep dyspareunia scores according to a 0-3 point verbal rating scale decreased from 1.8 (0.9) at baseline to 1.3 (0.7) at the end of treatment in the 3-monthly depot group and from 2.1 (1.2) to 1.3 (0.7) in the monthly depot group. Corresponding values in non-menstrual pain scores fell from 2.1 (0.6) to 1.1 (0.3), and from 2.1 (0.8) to 1.2 (0.4) respectively, without statistically significant differences between the groups. Serum luteinizing hormone (LH) and 17 beta-oestradiol concentrations were significantly suppressed at 12 and 24 weeks compared with baseline values, without differences between the groups. The monthly depot caused a slightly more marked inhibition of serum follicle stimulating hormone (FSH) levels with respect to the 3-monthly preparation. Mean (SD) endometriosis scores at baseline and at 6-month follow-up laparoscopy were respectively 32.8 (25.1) and 12.2 (9.3) in the 3-monthly depot group and 29.0 (22.7) and 13.1 (15.3) in the monthly depot group (paired t-test, P < 0.05). Mean percentage decrease in lumbar spine bone mineral density was 5.2% in the former and 4.9% in the latter subjects. In the 3-monthly depot group, 13 women graded the tolerability of their treatment schedule as "good' compared with seven in the monthly depot group (chi 2 = 5.40, P = 0.02).

Topics: Adolescent; Adult; Dyspareunia; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Luteinizing Hormone; Pain; Pilot Projects

Activated B cells have recently been shown to produce soluble CD23 from their membranes. The serum-soluble CD23 concentration in 21 patients with pelvic pain diagnosed as having endometriosis and confirmed by histology, and in 18 patients without pelvic pain, who had a normal pelvis during laparoscopic sterilization, was studied by chemiluminescent enzyme-linked immunosorbent assay. The endometriosis patients were randomized to 3 months of either danazol or leuprolide acetate injection. Serum was taken before and after 3 months of therapy. The serum-soluble CD23 concentration was significantly elevated in patients with endometriosis when compared with the controls (P < 0.0001). There was no correlation between soluble CD23 concentrations and the severity of endometriosis (r = 0.48, P > 0.05). The serum concentration of soluble CD23 decreased significantly on treatment with danazol but not leuprolide acetate (P < 0.05). We conclude that the elevation of soluble CD23 in patients with endometriosis suggests that there is activation of B cells, which respond to danazol but not leuprolide acetate injection.

Topics: B-Lymphocytes; Danazol; Delayed-Action Preparations; Endometriosis; Female; Humans; Leuprolide; Lymphocyte Activation; Receptors, IgE

To determine changes in trabecular vertebral bone mass, serum E2, and serum calcitonin during and after therapy of pelvic endometriosis with depot leuprolide acetate (LA) or danazol.. Prospective, randomized, double-blind study.. Academic university hospital and department of obstetrics and gynecology.. Twelve women with symptomatic pelvic endometriosis diagnosed and staged by laparoscopy.. All patients received blinded treatment with either 3.75 mg JM depot LA given every month and daily placebo tablets (n = 6) or 800 mg oral danazol daily with a monthly placebo injection (n = 6) for 24 weeks.. Quantitated computerized tomography of bone density of thoracic 12 to lumbar 4 vertebral bodies were determined before, at the end of 24 weeks of treatment, and 6 and 12 months after completing treatment. Gain or loss of bone mass was based against pretreatment levels. Serial serum levels of E2 and calcitonin before, throughout, and after therapy were compared with changes in bone mass.. Bone loss with LA was 14.0% +/- 0.5% (mean +/- SEM), recovering to a deficit of 4.2% +/- 3.8% and 3.3%, 6 and 12 months after stopping therapy. Danazol increased bone by 5.4% +/- 2.2%, with a further gain to 8.2% +/- 3.5% and 7.5%, 6 and 12 months after stopping treatment. Serum E2 levels usually were < 25 pg/mL (conversion factor to SI unit, 3.671) with LA but > 47.3 pg/mL with danazol. Calcitonin levels did not change significantly with either treatment.. Depot LA produced marked sustained hypoestrogenemia and significant bone loss with incomplete recovery 1 year after stopping treatment. Danazol maintained normoestrogenemia and increased bone mass with the gain maintained even 1 year after stopping therapy.

Topics: Adult; Bone Density; Calcitonin; Danazol; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Estradiol; Female; Humans; Leuprolide; Osteoporosis; Phosphates; Potassium Compounds; Prospective Studies; Spine

To compare the efficacy of a 3-month trial of leuprolide acetate (LA; Lupron; TAP Pharmaceuticals, Deerfield, IL) versus danazol (Danocrine; Scenofi Winthrup Pharmaceuticals, New York, NY) therapy on laparoscopically proven endometriosis.. Endometriosis severity was assessed at the time of laparoscopy and patients were randomized to receive 0.1 mg SC LA (n = 22) or 800 mg danazol orally (n = 18) daily for 3 months. A second laparoscopy and/or laparotomy was performed to assess the change in the extent of endometriosis and for surgical therapy.. Private practice at a university-affiliated hospital.. Forty patients with mild, moderate, or severe endometriosis. Ten patients were excluded.. Three-month treatment randomly assigned to either LA or danazol.. Prospective measurement of American Fertility Society endometriosis scores and size of ovarian endometriomata before and after therapy via laparoscopy.. The mean endometriosis score including adhesions decreased significantly from 36 +/- 4.9 to 29 +/- 5.0 (mean +/- SEM) with LA and from 34 +/- 6.4 to 29 +/- 6.5 with danazol. The mean laparoscopic endometriosis score not including adhesions decreased from 27 +/- 3.5 to 22 +/- 3.4 with LA and 22 +/- 3.5 to 19 +/- 3.1 with danazol. Seven of 18 (39%) endometriomata responded to LA and 6 of 15 (40%) endometriomata responded to danazol.. We conclude that both danazol and LA will reduce endometriosis scores after a 3-month course of therapy. Larger clinical trials are needed to compare short courses of therapy with the more established 6-month trials. A 3-month versus a 6-month course of therapy offers obvious benefits including decreased cost and decreased side effects.

Topics: Danazol; Endometriosis; Female; Humans; Laparoscopy; Laparotomy; Leuprolide; Prospective Studies; Reoperation; Time Factors; Tissue Adhesions

To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis.. Prospective randomized open label study.. Tertiary care university-affiliated reproductive medicine program.. Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis.. All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III volunteers (n = 18) were untreated and followed for bone density changes.. Disease extent at follow-up laparoscopy; pain, vasomotor, and vaginal symptom scores; bone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge.. Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group III untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II.. The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved.

Topics: Adult; Bone Density; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Endometriosis; Estradiol; Etidronic Acid; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lipids; Norethindrone; Prospective Studies; Time Factors; Vasomotor System; Weight Gain

In an open, non-randomized prospective phase-III-study the clinical and endocrine efficacy as well as the safety of leuprorelin acetate depot (Enantone-Gyn Monats-Depot) were investigated. The therapeutic results of 198 patients, gathered from 5 university institutions and two city hospitals, are reported. Endometriosis was classified by the revised American Fertility Society score (r-AFS) before and at the end of treatment. Serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, testosterone and leuprorelin acetate were determined by radioimmunoassay. The mean total r-AFS score changed as follows: before surgical intervention during first-look laparoscopy 21 +/- 24 at the end of first-look laparoscopy 15 +/- 19 at the end of the GnRH-treatment 8 +/- 14 During leuprorelin acetate treatment the r-AFS stages changed as follows: [table; see text] Using the scoring system 85.2% of the patients improved. Relief of dysmenorrhoea could be achieved in 95.4%, relief of dyspareunia in 64% and of pelvic pain in 69.4% of patients. Baseline hormone levels dropped sharply during treatment. [table; see text] Androstenedione, testosterone, blood pressure, body weight, haematological parameters, liver enzymes, creatinine, electrolytes and HDL-/LDL-cholesterin remained more or less unchanged. Side effects being hot flushes, sweating, sleeplessness, headache, nausea, depression and vaginal dryness were due to estradiol deprivation. In 135 patients resumption of menstruation occurred in 95.6% within the first three months post-treatment. 23 patients of whom 21 were judged as infertile, became pregnant immediately after treatment was finished. The study results confirm the efficacy of leuprorelin acetate depot in the treatment of even advanced stages of endometriosis.

Topics: Adolescent; Adult; Delayed-Action Preparations; Endometriosis; Female; Gonadal Steroid Hormones; Humans; Laparoscopy; Leuprolide; Middle Aged; Peritoneum; Prospective Studies

Hypo-oestrogenaemia following surgical oophorectomy leads to a regression of the ectopic endometrial tissue. A medical and transitory oophorectomy can be obtained using leuprolide ac., an analogue of LH-RH. In this study we compare the results of therapy with danazol or leuprolide in the treatment of endometriosis. Fifty patients affected by endometriosis were selected laparoscopically and recorded under the classification of American Fertility Society. 20-40 year old women who were admitted had not received any therapy for endometriosis within the previous 12 months. They were allocated at random to open treatment with intramuscular injection of leuprolide (3.75 mg/monthly) or oral danazol. The dose regimen used for this last drug was 600 mg/daily in the majority of patients. 47 women completed a six months therapy, and 42 underwent to a second laparoscopy to evaluate the effects of the treatment. Both danazol and leuprolide were associated to a decreasing of clinical symptoms and to adverse effects that we described in this paper.

Topics: Administration, Oral; Adult; Danazol; Endometriosis; Female; Humans; Injections, Intramuscular; Laparoscopy; Leuprolide

This is the first multicenter, double-blind randomized clinical trial that compares a depot gonadotropin-releasing hormone agonist with danazol in the treatment of endometriosis. Efficacy results have been previously reported; this report focuses on safety data.. A total of 270 patients from 22 centers were randomly selected to receive either leuprolide acetate depot (3.75 mg injected monthly) or danazol (800 mg administered orally daily). Safety outcomes included adverse effects, clinical laboratory changes, and bone mineral density changes.. Most patients receiving either drug reported side effects, most of which were related to the hypoestrogenism of leuprolide (e.g., vasodilatation) and relative hyperandrogenism of danazol (e.g., weight gain). Similarly small numbers of patients dropped out of the two treatment groups because of the side effects encountered. Leuprolide depot caused a greater decrease in bone density; preliminary data suggest a return to baseline on cessation of the drug. Danazol was associated with alteration of serum lipids, specifically a significant decrease in high-density lipoprotein.. Although side effects were commonly reported in both groups, the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy. Side effects were largely reversible on discontinuation of medication. More longitudinal data are necessary before the possibility of long-term risks can be excluded, especially as they pertain to bone mineral density and lipids.

Topics: Adolescent; Adult; Bone Density; Danazol; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Female; Humans; Leuprolide

To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone.. Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially.. The significant vasomotor instability (P < .01) and bone mineral density loss (-4.8 +/- 0.9%; P < .05) experienced by patients in group III was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state. Bone density changes in groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone.. These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.

Topics: Bone Density; Bone Resorption; Drug Therapy, Combination; Endometriosis; Estrogens; Etidronic Acid; Female; Humans; Leuprolide; Lipids; Norethindrone; Prospective Studies; Vasomotor System

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to suppress symptomatic endometriosis effectively but to elicit vasomotor symptoms and loss of bone mineral density. The role of norethindrone as a supplement to GnRHa in eliminating such side effects was assessed by enrolling 20 patients with symptomatic endometriosis diagnosed laparoscopically in a randomized, prospective, double-blinded trial. All patients received the long-acting GnRHa leuprolide acetate 3.75 mg im every 4 weeks for 24 weeks. Ten patients self-administered norethindrone 5 then 10 mg by mouth daily, whereas the remainder self-administered placebo tablets. Results of this study showed that combination therapy was as effective as GnRHa alone in significantly reducing circulating gonadotropin and estrogen levels (P less than 0.01), extent of visible endometriotic implants (P less than 0.01), and painful symptoms (P less than 0.01). Marked vasomotor and vaginal symptoms experienced by patients given GnRHa alone were minimized in those receiving GnRHa with norethindrone. Lumbar spine bone mineral density loss, measured by dual energy x-ray absorptiometry, was significantly reduced and more completely reversed in patients receiving combination therapy (P less than 0.05). A reversible decrease in high density lipoprotein-cholesterol and increase in low density lipoprotein:high density lipoprotein ratio was noted only in the patients receiving combination therapy, but not in those receiving GnRHa only. The addition of norethindrone to GnRHa is an effective means of treating symptomatic endometriosis while ameliorating side effects induced by GnRHa alone.

Topics: Bone Density; Drug Combinations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leuprolide; Lumbosacral Region; Norethindrone; Pain; Prospective Studies; Spine; Vasomotor System

We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis.. A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods.. When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis.. Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain.

Topics: Adolescent; Adult; Danazol; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Estradiol; Female; Genital Neoplasms, Female; Humans; Laparoscopy; Leuprolide

A national multicentre trial was organized in order to compare the efficacy and safety of leuprorelin acetate depot and danazol in the treatment of endometriosis. Sixty-seven patients with pelvic endometriosis of different severity at laparoscopy were included in the study and followed during the 24 weeks of treatment. Leuprorelin acetate depot 3.75 mg was injected every 24 days, while the daily dose of danazol was 600-800 mg. At the end of the study objective improvements induced by the two drugs were observed by a second laparoscopic examination. In addition, at regular intervals during the study semiquantitative evaluation of subjective symptoms were monitored. Scoring the final objective changes in the two patient groups revealed no significant difference, however the women treated with leuprorelin acetate depot registered significantly better control of pelvic pain. Due to its efficacy, tolerability and ease of use, leuprorelin acetate appears to be an excellent drug for the treatment of endometriosis.

Topics: Adult; Danazol; Delayed-Action Preparations; Endometriosis; Female; Humans; Italy; Laparoscopy; Leuprolide; Pelvic Neoplasms

During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. T

Topics: Adult; Delayed-Action Preparations; Endometriosis; Estradiol; Female; Follow-Up Studies; Germany; Gonadotropins, Pituitary; Humans; Laparoscopy; Leuprolide; Pelvic Neoplasms; Progesterone

Topics: Adult; Clinical Trials as Topic; Embryo Transfer; Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Pregnancy; Pregnancy Outcome

Topics: Chemistry, Pharmaceutical; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotropin-releasing hormone (GnRH) analog was assessed in 19 women with uterine leiomyomas and 19 women with endometriosis. There was a significant reduction in individual fibroid volumes at 3 months (P less than .05) and at 6 months (P less than .005) in the drug group, whereas there was no significant change in the placebo group. Vessel conspicuity significantly decreased at 3 months (P less than .02) and at 6 months (P less than .01) in the drug group but not in the placebo group. In the patients with endometriosis, there was a significant decrease (P less than .0006) in the number of endometriomas visualized. Significant changes were also noted in the pelvis in women who were receiving the GnRH analog. After 6 months of therapy, the identifiability of the ovaries was significantly poorer (P less than .05). The authors conclude that the utility of conservative therapy with a GnRH analog can be quantitatively assessed with MR imaging.

Topics: Abdominal Neoplasms; Adult; Antineoplastic Agents; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Uterine Neoplasms

The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients. Dysmenorrhea, pelvic pain, and pelvic tenderness all responded significantly to LA treatment in comparison with placebo. Menses were suppressed in all of the LA patients. Estradiol decreased significantly to menopausal levels in the LA group. There were small to moderate changes in a variety of laboratory parameters, but these were not clinically significant. The most common adverse event was vasodilatation, occurring significantly more frequently in the LA group. Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of pain symptoms.

Topics: Adult; Antineoplastic Agents; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Multicenter Studies as Topic; Pain; Randomized Controlled Trials as Topic

A prospective, randomized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis. Both regimens induced anovulation and ovarian suppression in all subjects. Mean estradiol (E2) and progesterone (P) levels were suppressed with both regimens, but were lower with leuprolide. There was no difference in cumulative follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, although at times during treatment mean levels of these hormones were lower with leuprolide. Higher P levels in the danazol group, most likely of adrenal origin, indicated a suppressive effect on adrenal steroidogenesis. Symptomatic improvement was significant in both groups. Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups. At 12 months after treatment, cumulative pregnancy and live birth rates were similar in both groups. Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis.

Topics: Administration, Intranasal; Adult; Body Weight; Danazol; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Laparoscopy; Leuprolide; Luteinizing Hormone; Pelvic Neoplasms; Pregnadienes; Pregnancy; Progesterone; Prognosis; Prospective Studies; Random Allocation

Topics: Endometriosis; Female; Humans; Laparoscopy; Leuprolide

Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects?. Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.. Significant reductions in the endometriotic implant surface area (P = 0.0213), serum TOS (P = 0.0491), OSI (P = 0.0056), IL-6 (P = 0.0236), TNF-α (P = 0.0083) and peritoneal fluid OSI (P = 0.0401), IL-6 (P = 0.0205) and TNF-α (P = 0.0045) concentrations were observed in the CBD5 group when compared with the saline solution group. Compared with the saline solution group, increased TAS concentrations in serum (P = 0.0012) and peritoneal fluid (P = 0.0145) were found in the CBD5 group. The CBD5 and leuprolide acetate groups were similar regarding inflammatory and oxidative stress parameters of serum and peritoneal fluid samples. The CBD5 group showed significantly lower mean intensity in both surface epithelium and stromal cells for VEGF (both P = 0.002) and only in surface epithelium cells for IL-6 (P = 0.0108), when compared with the leuprolide acetate group.. Due to its anti-inflammatory, antioxidative and antiangiogenic effects, CBD might be a therapeutic agent candidate for endometriosis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cannabidiol; Disease Models, Animal; Endometriosis; Female; Humans; Interleukin-6; Leuprolide; Rats; Rats, Wistar; Saline Solution; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

We evaluated elagolix and leuprolide from the patient's perspective for the treatment of endometriosis-related pain.. Preference weights from a published discrete choice experiment were used to evaluate preferences for treatment profiles simulating elagolix (150 mg/day and 200 mg/twice-daily dosages) and leuprolide for the treatment of moderate to severe endometriosis-related pain. Sensitivity analyses were conducted by varying the range of risk for pregnancy-related problems, moderate to severe hot flashes, and bone fracture across scenarios.. The 200 mg twice daily dosage of elagolix is more likely to be preferred over leuprolide by patients with moderate to severe endometriosis-related pain in all scenarios explored in the evaluation and sensitivity analyses. The probability that an average respondent would select a treatment was sensitive to increases in risk of moderate to severe hot flashes for leuprolide and possible variations in the risk of pregnancy-related problems for both treatments but was not influenced by an increased risk of bone fracture.. Patients' preferences for treatment of endometriosis-related pain should be evaluated using the benefits and risks of each pharmacological option. Respondents were more likely to prefer the treatment profile similar to 200 mg twice daily elagolix over that of leuprolide in all scenarios.

Topics: Adolescent; Adult; Choice Behavior; Endometriosis; Female; Humans; Hydrocarbons, Fluorinated; Leuprolide; Middle Aged; Pain; Patient Preference; Pregnancy; Pregnancy Complications; Pyrimidines; Severity of Illness Index; Surveys and Questionnaires; United States; Young Adult

Endometriosis (EMS) is one of the common diseases in women, which seriously affects the quality of life of women. Leuprorelin acetate can control the development of EMS, but long-term use can cause perimenopausal symptoms in women. Clinical studies have shown that Kuntai capsule combined with leuprorelin acetate is effective in the treatment of EMS, which can relieve perimenopausal symptoms, but it lacks of evidence-based medical evidence. Therefore, this study aims to systematically evaluate the efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS.. CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, PubMed, The Cochrance Library, Embase, Web of Science, and other databases were searched by computer to collect randomized controlled trials of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS. The retrieval time was from the establishment of the database to February 2021. Two researchers screened the literatures and extracted the data and meta-analysis was performed using RevMan 5.3 software.. This study evaluated the efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS by clinical effective rate, serum sex hormone levels estradiol, follicle-stimulating hormone, luteinizing hormone, visual analogue scale, Kupperman score and incidence of adverse reactions.. This study will provide reliable evidence-based evidence for the clinical application of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS.. Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.. DOI 10.17605/OSF.IO/AZU47.

Topics: Drug Therapy, Combination; Drugs, Chinese Herbal; Endometriosis; Female; Humans; Leuprolide; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Research Design; Systematic Reviews as Topic; Treatment Outcome

Thoracic endometriosis syndrome (TES) is a rare condition that occurs in women when endometriosis implants into the thoracic cavity. Catamenial hemoptysis, the occurrence of hemoptysis with menstruation, is a recognized clinical manifestation of TES commonly treated with hormonal therapy.. We present the first documented case describing the recrudescence of catamenial hemoptysis in the setting of Lumacaftor/Ivacaftor administration in a 25-year-old woman with cystic fibrosis (CF).. We review the literature on TES, pharmacologic management, and reported cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug interactions. We propose that our patient's recrudescence of catamenial hemoptysis was secondary to a drug-drug interaction between Lumacaftor/Ivacaftor and oral contraceptive therapy.. Our case suggests that women with CF who have catamenial hemoptysis and a genetic mutation approved for Tezacaftor/Ivacaftor or Elexacaftor/Tezacaftor/Ivacaftor can be managed effectively with either CFTR modulator and hormonal contraceptive therapy.

Topics: Adult; Aminophenols; Aminopyridines; Benzodioxoles; Bronchoscopy; Chloride Channel Agonists; Cystic Fibrosis; Drug Combinations; Drug Therapy, Combination; Endometriosis; Female; Fertility Agents, Female; Hemoptysis; Humans; Indoles; Leuprolide; Pyrazoles; Pyridines; Quinolines; Quinolones; Radiography, Thoracic; Thoracic Diseases; Tomography, X-Ray Computed

The aim of this study was to compare long-term use of combined oral contraceptive (COC) after gonadotropin-releasing hormone (GnRH) agonist plus add-back therapy with dienogest (DNG) treatment as medical treatments after surgery for ovarian endometrioma.. This prospective cohort study analyzed 52 reproductive-aged women who underwent surgery for ovarian endometrioma and received postoperative medical treatment with either COC after GnRH agonist (n = 20) or DNG (n = 32) for 24 months. Changes in quality-of-life (QOL) and bone mineral density (BMD) were compared according to treatment. In addition, recurrence of pain and lesions were compared.. Baseline characteristics did not differ in demographic profiles and factors associated with endometriosis or QOL. During 24 months of treatment, no differences in any component of QOL were found between the two groups. BMD at the lumbar spine significantly decreased after the first 6 months of treatment in both COC after GnRH agonist (-3.5%) and DNG (-2.3%) groups, but the groups did not differ statistically. After 6 months, further decrease in BMD was not observed until 24 months in both groups. In addition, no cases of pain or endometrioma recurrence were found.. Our results suggest that long-term use of COC after GnRH agonist plus add-back therapy is comparable to dienogest as a long-term postoperative medical treatment for endometriosis.

Topics: Adult; Contraceptives, Oral, Combined; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Nandrolone; Ovarian Diseases; Prospective Studies; Secondary Prevention; Young Adult

Prolonged gonadotrophin-releasing hormone agonist (GnRHa) administration before IVF with fresh embryo transfer to patients with endometriosis or aberrant endometrial integrin expression (-integrin) improves outcomes but may suppress ovarian response and prevents elective cryopreservation of all embryos. This retrospective cohort pilot study evaluates freeze-all cycles with subsequent prolonged GnRHa before embryo transfer in these populations. Patients from 2010 to 2015 who met inclusion criteria and received a long-acting GnRHa every 28 days twice before FET were evaluated. A subset underwent comprehensive chromosomal screening (CCS) after trophectoderm biopsy. Three groups were identified: Group 1: + CCS, +endometriosis (20 patients, 20 transfers); Group 2: +CCS, -integrin (12 patients, 13 transfers); Group 3: no CCS, +endometriosis or -integrin (10 patients, 12 transfers); Group 4: all transfers after CCS for descriptive comparison only (n = 2809). Baseline characteristics were similar among Groups 1-3 except that the mean surgery to oocyte aspiration interval was longer for Group 1 than Group 3. Implantation and ongoing pregnancy rates were statistically similar among the three groups and compared favourably to Group 4. A non-significant trend towards improved outcomes was noted in Group 1. Prolonged GnRHa after freeze-all in these patients avoids excessive ovarian suppression and results in excellent outcomes.

Topics: Adult; Embryo Transfer; Endometriosis; Endometrium; Female; Fertilization in Vitro; Freezing; Gonadotropin-Releasing Hormone; Humans; Integrin beta3; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies

As endometrioma frequently recurs after conservative surgery, long-term postoperative medical treatment for the prevention of recurrence is necessary. However, it has not been elucidated whether long-term postoperative medical treatment is crucial to all patients until menopause. Thereupon, this study was conducted to evaluate the age-related recurrence patterns after conservative surgery for endometrioma.. A retrospective cohort study was performed on a total of 420 reproductive-aged women who underwent conservative surgery for endometrioma between January 2000 and December 2010. Ultrasonography was used during the follow-up period to detect endometrioma recurrence. Patients were classified into two groups according to the use of postoperative medications. The first group was observation only, while the second received gonadotropin releasing hormone agonists followed by cyclic oral contraceptives. The cumulative recurrence rate of endometrioma was compared according to the age at surgery (20-29 years, 30-39 years, 40-45 years) within each group. Subgroup analysis was performed according to the age between the two groups.. The median follow-up duration after surgery was 29.0 months (range 6-159 months) for all patients. After adjusting for parity, size and bilaterality of cyst, and stage with American Society for Reproductive Medicine classification of endometriosis which was statistically different, within the group of no treatment, the cumulative recurrence rate in 40-45 years (10.2%) was significantly lower compared with those in 20-29 years (43.3%; hazard ratio (HR)=0.04; 95% confidence interval (CI)=0.01-0.52) and 30-39 years (22.5%; HR=0.19; 95% CI=0.04-0.92). However, there were no differences within the group of postoperative medical treatment. When we compared between the two groups, the cumulative recurrence rate was significantly different in 20-29 years (8.1 vs 43.3%; p<0.001) and 30-39 years (5.4 vs 22.5%; p=0.007), but there was no difference in 40-45 years (4.5 vs 10.2%; p=0.901).. Our preliminary results demonstrate that the risk of endometrioma recurrence decreases with age. After the age of forty, the recurrence rate does not differ according to the use of postoperative medication. Based on our results, postoperative medical treatment may be individualized according to the patient's age at the time of surgery. Further studies are needed to identify patients who may benefit from postoperative medication.

Topics: Adult; Aging; Combined Modality Therapy; Contraceptives, Oral, Sequential; Endometriosis; Female; Fertility Agents, Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leuprolide; Middle Aged; Organ Sparing Treatments; Ovarian Diseases; Ovary; Republic of Korea; Retrospective Studies; Risk; Secondary Prevention; Ultrasonography; Young Adult

Increased intrauterine microbial colonization by bacteria culture method and occurrence of endometritis have been reported in women with endometriosis. Here we investigated microbial colonization in intrauterine environment and cystic fluid of women with and without endometriosis by molecular approach.. This is a case-controlled biological study with a total of 32 women each with and without endometriosis. Among them, 16 each in these two groups of women received treatment with gonadotropin-releasing hormone agonist (GnRHa). Pattern of microbial colonization in endometrial swabs and endometrioma/non-endometrioma cystic fluid was examined using broad-range polymerase-chain reaction (PCR) amplification of bacteria targeting 16S rRNA gene (rDNA). After quantification of index PCR product, 16S rDNA metagenome sequence analysis was done by Illumina Miseq system.. A wide proportion (0.01-97.8%) of multiple bacteria was detected in both endometrial swabs and cystic fluid collected from women with and without endometriosis. 16S metagenome assay indicated that proportion of Lactobacillacae was significantly decreased (p<0.01) and of Streptococcaceae, Staphylococaceae, Enterobacteriaceae was significantly increased (p<0.05 for each) in GnRHa-treated women with endometriosis than in GnRHa-untreated women. While bacteria culture method failed to detect a single colony, 16S metagenome assay could detect significantly higher percentage of Streptococcaceae (p<0.01) and Staphylococaceae (p<0.05) in the cystic fluid derived from women with ovarian endometrioma comparing to that in cystic fluid collected from non-endometrioma cysts.. These findings indicate the occurrence of sub-clinical infection in intrauterine environment and in the cystic fluid of ovarian endometrioma. Additional side effect of GnRHa treatment in promoting silent intrauterine and/or ovarian infection should be considered.

Topics: Adult; Case-Control Studies; Endometriosis; Endometritis; Female; Gonadotropin-Releasing Hormone; Humans; Lactobacillaceae; Leuprolide; Metagenome; Middle Aged; RNA, Ribosomal, 16S; Streptococcaceae; Uterus; Young Adult

Objective To compare subsequent endometriosis-related surgery following initial laparoscopy among women treated with leuprolide acetate (LA) or other endometriosis therapies versus women who received no pharmacotherapy. Research design and methods This retrospective cohort analysis utilized MarketScan Commercial claims data. Women with endometriosis aged 18-49 who underwent laparoscopy between 1 January 2005 and 31 December 2011 were identified using diagnosis and procedures codes and were categorized into four cohorts based on claims within 90 days of laparoscopy: surgery plus adherent LA, surgery plus non-adherent LA, surgery plus other therapy, and surgery alone. Patients with proportion of days covered ≥0.80 in the 6 months after laparoscopy were considered adherent to LA. Main outcome measures Subsequent endometriosis-related surgery (laparoscopy, laparotomy or other excision/ablation/fulguration of endometriosis lesions, oophorectomy, or hysterectomy) was measured in the 6 and 12 months following initial laparoscopy. Risk of subsequent surgery was compared using multivariable Cox proportional hazards modeling. Results Most women were treated with surgery only (n = 9865); fewer were treated with LA (adherent: n = 202; non-adherent: n = 490) or other therapies (n = 230). The proportion of patients with subsequent surgery ranged from 2.0% to 10.0% during the 6 month follow-up (12 month: 9.7% to 13.5%). Adherent LA use was associated with significantly lower risk of surgery compared to surgery alone (hazard ratio [HR] = 0.31, p = 0.020) while use of other therapies was associated with significantly higher risk (HR = 1.51, p = 0.045) over the 6 month follow-up. There was no significant difference between the surgery plus non-adherent LA and surgery only cohort over 6 months (p = 0.247). The association between adherent LA and subsequent surgery was not significant over the 12 month follow-up. Conclusion Therapy with LA after laparoscopy for endometriosis was associated with lower risk of subsequent surgery at 6 months among women who were adherent to LA. Key limitations include lack of ability to capture disease severity which may have resulted in uncontrolled confounding.

Topics: Adolescent; Adult; Endometriosis; Female; Humans; Hysterectomy; Laparoscopy; Laparotomy; Leuprolide; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

Endometriosis affects over 10 million women in the United States. Depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, has been used extensively for the treatment of women with endometriosis but is associated with hypoestrogenic symptoms and bone mineral density loss. The concomitant use of add-back therapies, specifically norethindrone acetate (NETA), can alleviate these adverse effects.. To compare adherence to and persistence with LA treatment and time to endometriosis-related surgery among women treated with NETA and women treated with LA plus other add-back therapies or LA only.. This retrospective analysis was conducted using Truven Health MarketScan Commercial Claims and Encounters Database. Women with a diagnosis of endometriosis (ICD-9-CM code 617.xx) who initiated LA (index date) in 2005-2011 were selected for inclusion. Additional requirements were 12 months of continuous enrollment pre- and post-index and no evidence of endometriosis-related surgeries pre-index or up to 30 days post-index; no pre-index use of estrogen or noncontraceptive hormones; and no diagnoses of uterine fibroids, malignant neoplasms, infertility, or pregnancy. Patients were characterized as using NETA; other add-back therapies (estrogens, progestins, or estrogen-progestin combinations); or no add-back therapy. Adherence to and persistence with LA were measured over the 6 months following the index date using outpatient medical and pharmacy claims. Patients were considered adherent if their proportion of days covered was greater than or equal to 0.80. Persistence was operationalized as time to discontinuation, defined as a continuous gap of > 60 days without LA on hand. Time to endometriosis-related surgery (laparotomy, laparoscopy, excision/ablation/fulguration, oophorectomy, and hysterectomy) was measured over the 12 months following the index date. Surgeries were identified from inpatient and outpatient medical claims using procedure codes. Outcomes were compared among cohorts using multivariable logistic and Cox proportional hazards regression models controlling for demographics and baseline clinical characteristics.. The final sample included 3,114 women, with a mean age of 36.9 years. The majority of women used LA only with no add-back therapy (n = 1,963, 63.0%), while 15.1% (n = 470) used NETA, and 21.9% (N = 681) used other add-back therapies. During the 6-month follow-up, more patients in the LA plus NETA cohort were adherent to LA therapy compared with LA only (47.2% vs. 31.5%, P < 0.001), and fewer patients discontinued (37.9% vs. 59.6%, P < 0.001). Additionally, fewer patients underwent endometriosis-related surgery in the 12 months after LA initiation in the LA plus NETA cohort (12.6% vs. 16.9%, P = 0.021). In multivariable models, women who initiated LA plus NETA or LA plus other add-back therapies had a higher likelihood of being adherent to LA than LA only patients (OR = 1.91, 95% CI = 1.55-2.36 and OR = 1.95, 95% CI = 1.63-2.34) and lower likelihood of LA discontinuation (HR = 0.54, 95% CI = 0.46-0.63 and HR = 0.59, 95% CI = 0.52-0.68). NETA patients had a lower surgery rate in the 12-month post-index period compared with other add-back patients (HR = 0.68, 95% CI = 0.50-0.93) or LA only patients (HR = 0.69, 95% CI = 0.52-0.92).. For women with endometriosis, treatment with LA and concomitant add-back therapies was associated with better adherence to and persistence with LA over the 6 months following initiation, compared with treatment with LA only. The increased adherence and persistence to LA may translate into decreased need for surgical intervention, although fewer endometriosis-related surgeries were only observed in the 12 months following LA initiation for patients using concomitant NETA add-back therapy. These results support an increased and earlier use of NETA add-back therapy among women who initiate LA.. This study was funded by AbbVie, which also markets the endometriosis drugs Lupron and Lupaneta Pack. AbbVie participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. Soliman and Castelli-Haley are employees of AbbVie and may own AbbVie stock or stock options. Bonafede and Farr are employees of Truven Health Analytics, which received a research contract to conduct this study with and on behalf of AbbVie. Winkel is a clinical professor in the Department of Obstetrics and Gynecology at Georgetown University in Washington, DC, and has served in a consulting role on research to AbbVie for this project. An earlier version of the current research was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting; Philadelphia, PA; May 2015. All authors participated in data analysis and interpretation and contributed to the development of the manuscript.

Topics: Adult; Bone Density; Drug Therapy, Combination; Endometriosis; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; International Classification of Diseases; Leuprolide; Medication Adherence; Norethindrone; Norethindrone Acetate; Retrospective Studies

Micro ribonucleic acids (miRNAs) play an important pathological role in endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone, is widely used to treat endometriosis; however, the molecular mechanisms involved in endometriotic tissue regression remain unclear. We performed miRNA expression profiling of clinical ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment.. We obtained clinical samples from nine normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide acetate-treated endometriotic tissues. We compared the miRNA expression profiles of the three groups by performing TaqMan Array MicroRNA Card and bioinformatic analysis.. Two miRNAs, miR-939 and miR-154, were upregulated in endometriotic tissue and downregulated in leuprolide acetate-treated endometriotic tissue. Five miRNAs (miR-146a, miR-142-3p, miR-136*, miR-125b-1* and miR-15b*) were unchanged in endometriotic tissue but were upregulated under leuprolide acetate treatment. Ingenuity pathway analysis using predicted target genes for the seven identified miRNAs suggested the involvement of a range of pathways, including axonal guidance, bone morphogenetic protein, phosphatase and tensin homolog and nitric oxide signaling; molecular mechanisms of cancer; and the adipogenesis and signal transducer and activator of transcription 3 (STAT3) pathways.. To our knowledge, this is the first report profiling the miRNAs of endometrioma under leuprolide acetate treatment. The expression of seven miRNAs was modulated, concomitant with the disease state. This result gives new insight into the effects of leuprolide acetate treatment. Further investigation using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry will allow us to validate the results of this study and to explore new therapeutic targets and biomarkers of endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Endometriosis; Female; Humans; Leuprolide; MicroRNAs; Middle Aged; Ovarian Neoplasms; Signal Transduction

Topics: Adult; Ascites; Endometriosis; Female; Hormone Antagonists; Humans; Leuprolide; Nandrolone; Ovarian Cysts; Paracentesis; Peritoneal Cavity; Pleura; Pleural Effusion; Treatment Outcome

To determine the effect of dopamine agonists in a surgically induced endometriosis model on rats.. In this prospective randomized experimental study, surgical induction of endometriosis was performed by autotransplantation technique on 52 adult female Wistar-Albino rats. Endometriosis formation was confirmed by a second-look laparotomy (n:48) 1 month later. Four study groups were randomly generated according to their treatment regimens: group 1 (leuprolide acetate, n = 12), group 2 (bromocriptine, n = 12), group 3 (cabergoline, n = 12) and group 4 (control, n = 12). Endometriotic implants were excised for histopathological examination after treatment at the setting of laparotomy. The mean surface areas and histopathological glandular tissue (GT) and stromal tissue (ST) scores of endometriotic implants were studied and compared among groups.. After 30 days of treatment, the mean surface area of the endometriotic implants of leuprolide acetate, bromocriptine and cabergoline groups was significantly decreased. The regression of endometriotic foci size in comparison to control was highest in group 1, followed by group 2, then group 3. In the histopathological evaluation both the ST and GT scores of group 1, 2 and 3 were significantly decreased in comparison to controls without a statistically significant difference between the groups.. Dopamine agonists are as effective as GnRH agonists in the regression of experimental endometriotic implants in rats. Further trials are needed to elucidate the pathways affected by dopamine agonists.

Topics: Adult; Animals; Antineoplastic Agents; Bromocriptine; Cabergoline; Disease Models, Animal; Dopamine Agonists; Endometriosis; Endometrium; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Laparotomy; Leuprolide; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Triptorelin Pamoate

The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p < 0.01) and decreased mean histopathological scores of the implants (p < 0.05), mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and MCP-1 (p = 0.01) levels after treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

Topics: Angiogenesis Inhibitors; Animals; Ascitic Fluid; Disease Models, Animal; Endometriosis; Endometrium; Female; Inflammation; Leuprolide; Neovascularization, Pathologic; Rats; Rats, Wistar; Resveratrol; Stilbenes; Therapeutics

Resveratrol, a phytoalexin polyphenol, has anti-angiogenic, antioxidant, anti-inflammatory properties. We aimed to compare the anti-inflammatory and anti-angiogenic effects of resveratrol and leuprolide acetate (LA) in an experimental endometriosis model.. A prospective experimental study was conducted in a University Surgical Research Center. Thirty-three non-pregnant female Sprague-Dawley rats, in which experimental model of endometriosis were surgically induced were randomly divided into four groups. Group 1 was administered 30 mg/kg resveratrol i.m. for 14 days, group 2 was given 1mg/kg s.c. single dose LA, group 3 was administered both resveratrol and LA, and group 4 had no medication. After two weeks medication rats were sacrificed and size, histopathology and immunreactivity to matrix metalloproteinase (mmp)2, mmp9, vascular endothelial growth factor (VEGF) of the endometriotic implants were evaluated. Plasma and peritoneal fluid levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were analyzed.. The endometriotic implant volumes, histopathological grade and immunreactivity to mmp2, mmp9 and VEGF were significantly reduced (p<0.001), and plasma and peritoneal fluid levels of IL-6, IL-8 and TNF-α were significantly decreased in group 1 and group 2 in comparison to group 3 and group 4 (p < 0.001).. Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to LA. In contrast, the combination of LA and resveratrol decreased the anti-inflammatory and anti-angiogenic effects of each agent. Since resveratrol is widely used as an alternative therapy for a variety of conditions, it can undermine the effectiveness of LA. Therefore, caution should be exercised when used in combination with other agents.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Endometriosis; Endometrium; Female; Leuprolide; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Treatment Outcome; Vascular Endothelial Growth Factor A

Montelukast, a selective antagonist of Type 1 cysteinyl leukotriene receptors (CysLT1Rs), antagonizes the proinflammatory and proasthmatic activities of CysLT1Rs. We investigated the effect of montelukast on a surgically induced endometriosis rat model.. Thirty-two sexually mature, cycling, female Wistar-Albino rats, in which endometriotic implants were surgically induced, were randomly divided into three groups. Group I [Montelukast (M), 10 rats)] was given 1.6 mg/kg/day of oral montelukast sodium. Group II [Leuprolide acetate (L), 11 rats] was given 1 mg/kg single dose of s.c.leuprolide acetate. Group III [Control (C), 11 rats] received saline solution through an orogastric tube and served as controls. After a 3-weeks medication, the rats were sacrificed to investigate the endometriotic implants for size and morphological and histological characteristics, including immunoreactivity of MMP-2 and VEGF.. The mean area of implants decreased from 48.2 ± 24.7 to 29.3 ± 15.8mm(2) in Group I (M) (P = 0.008) and from 62 ± 32.1 to 39.9 ± 18.1mm(2) in Group II (L) (P=0.003). In Group III (C), the mean area increased from 41.1 ± 31.1 to 60.4 ± 37.1mm(2) (P = 0.025). Histopathological analysis showed statistically significant lower scores in rats treated with montelukast compared to leuprolide and controls. MMP H scores were not different between the groups in both epithelial and stromal MMP-2 immunostaining. VEGF H scores were statistically lower in Group 1 (M) in epithelial VEGF immunostaining when compared to Group II (L) and Group III (C) (P=0.006).. Montelukast may effectively cause a significant decrease in the area of endometriotic implants.

Topics: Acetates; Animals; Anti-Inflammatory Agents; Cyclopropanes; Disease Models, Animal; Endometriosis; Endometrium; Female; Leuprolide; Matrix Metalloproteinase 2; Quinolines; Rats; Rats, Wistar; Sulfides; Treatment Outcome; Vascular Endothelial Growth Factor A

The aim of this study was to compare the effects of pre-surgical medication with dienogest or leuprorelin on post-surgical ovarian function.. We conducted an exploratory study in two centers in Japan that comprised 30 patients with ovarian endometrial cysts for whom surgical excision was planned. Patients were enrolled and divided into pre-surgical medication groups with dienogest or leuprorelin for 12 weeks. Thereafter, patients were treated by laparoscopic cystectomy. The primary outcome was ovarian function post-surgery, as assessed by serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC) and resumption of menses. Secondary outcome was the effect of pre-surgical medication, as assessed by the size of endometrial cysts and visual analog scale (VAS) score. Serum AMH, AFC, size of endometrial cysts, and VAS scores were measured at baseline (before medication), after medication (1 day before surgery), and at 4 and 12 weeks post-surgery.. Serum AMH levels did not change after pre-surgical medication with either dienogest or leuprorelin. Although AMH decreased after surgery, it recovered by 12 weeks post-surgery in both groups with no statistically significant difference. Mean AFC did not change after surgery in either group. Menses returned by 12 weeks post-surgery in all patients except for those who were pregnant. The rate of reduction of endometrial cyst volume did not differ between the groups. Both dienogest and leuprorelin were associated with substantial reductions in VAS scores.. There were no statistically significant differences between pre-surgical medication with dienogest and leuprorelin in post-surgical ovarian function. Both medications were effective in reducing endometrial cyst volume and VAS score.

Topics: Adult; Anti-Mullerian Hormone; Endometriosis; Female; Humans; Laparoscopy; Leuprolide; Nandrolone; Ovarian Cysts; Ovary; Visual Analog Scale

Topics: Adult; Endometriosis; Fallopian Tube Diseases; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Leuprolide; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic

To demonstrate that adenomyosis is a rare cause of dysmenorrhea or chronic pelvic pain (CPP) in the adolescent population that can be identified with magnetic resonance imaging (MRI) and to report resolution of adenomyosis by MRI after a course of hormonal suppression in 4 adolescents.. Retrospective case series of 4 adolescents with adenomyosis on pelvic MRI at Texas Children's Hospital.. Continuous oral contraceptive (COC) therapy or leuprolide acetate.. Lesions on pelvic MRI after treatment.. We reviewed medical records of 4 adolescents with CPP and adenomyosis on T2-weighted pelvic MRI. All patients had initial diagnostic pelvic MRI and then definitive hormonal intervention. Repeat imaging was obtained after a symptom-free interval.. Patient ages ranged from 12 to 16 years. One patient had resolution of symptoms with COC therapy. MRI performed 3 years later showed no adenomyosis. Three patients failed COC therapy. All were symptomatically improved after therapy with a gonadotropin-releasing hormone agonist. Follow-up MRI performed at intervals between 6 months and 3 years showed resolution of adenomyosis.. MRI can raise suspicion for the diagnosis of adenomyosis in adolescents with refractory CPP. Subsequent MRI can show regression of lesions after symptom resolution with hormonal therapy.

Topics: Adenomyosis; Adolescent; Antineoplastic Agents, Hormonal; Child; Chronic Pain; Contraceptives, Oral; Dysmenorrhea; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Pelvic Pain; Retrospective Studies; Texas; Treatment Outcome

Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment.. We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis.. Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18.. These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Cluster Analysis; Endometriosis; Female; Gene Expression Profiling; Humans; Leuprolide; Middle Aged; Ovary

Gonadotropin releasing hormone agonists (GnRHa) decrease the expression of growth factors involved in the development of human endometriotic tissue. As endometriosis has been found to be associated with a mild increase in prolactin (PRL) serum levels, we aimed to evaluate changes in PRL serum levels as well as other hormones relevant to endometriosis and infertility during long-term administration of GnRHas in women with endometriosis.. In this prospective pilot study we obtained blood samples on the first day of leuporeline administration and then subsequently after 4, 8 and 12 weeks in 22 patients.. Median PRL levels were unchanged after 4 weeks, but significantly decreased 8 and 12 weeks after the first leuporeline administration (p1=0.085, p2=0.020, p3=0.001). There was no significant decrease in serum anti-Mullerian hormone (AMH) levels over the whole period of down regulation with leuporeline (p1-3>0.05).. Our data support the hypothesis that the decrease of PRL levels might contribute to the known effect of GnRH treatment in patients with endometriosis via suppression of VEGF expression in endometriotic lesions. Moreover this study lends support to the thesis that AMH remains stable under GnRHa therapy and therefore can be also used as a marker of ovarian function prior to IVF-stimulation during down regulation.

Topics: Adult; Androstenedione; Anti-Mullerian Hormone; Delayed-Action Preparations; Down-Regulation; Endometriosis; Estrogens; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Luteinizing Hormone; Pilot Projects; Progesterone; Prolactin; Prospective Studies; Radioimmunoassay; Testosterone; Thyrotropin

A 13-yr-old female nulliparous Allen's swamp monkey (Allenopitchecus nigroviridis) presented with intermittent excessive vaginal bleeding, cyclical lethargy, and a history of irregular menstrual cycles. Abdominal ultrasonography revealed a subjectively thickened, irregular endometrium, multiple leiomyomata (uterine fibroids), and bilateral anechoic foci on the ovaries. Treatment was initiated with leuprolide acetate i.m. monthly for 6 mo. Recheck ultrasound at 3 mo showed a decrease in leiomyoma diameter and no evidence of active follicles on the ovaries. Eleven months following completion of treatment, clinical signs recurred and the animal was treated with a deslorelin implant. Since implant placement, no vaginal bleeding has been noted.

Topics: Animals; Antineoplastic Agents, Hormonal; Cercopithecinae; Drug Implants; Endometriosis; Enzyme Inhibitors; Female; Leiomyoma; Leuprolide; Monkey Diseases; Triptorelin Pamoate

To assess the effects of amifostine, N-acetyl cysteine (NAC), and leuprolide as a scavenger in a rat endometriosis model.. This is a prospective randomized animal study. Setting The Animal Laboratory of Medical University. Animals 40 rats were used for transplantation of an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. After allowing 3 weeks for growth, laparotomies were performed to check the implants. Then animals were randomized into four groups: Group I amifostine (200 mg/day loading dose after 20 mg/kg/day, p.o.); Group II NAC (200 mg/day, p.o.); Group III leuprolide acetate 1 mg/kg single dose, sc; and Group IV (controls) no medication. Three weeks later, implants were evaluated morphologically. Serum and peritoneal TNF-alpha levels were evaluated. The transmission electron microscopic examination of the peritoneal samples and ovaries was also performed.. Leuprolide acetate, amifostine and NAC caused significant decreases in the mean implant areas and significant decreases in serum and peritoneal TNF-alpha levels. On comparing all groups, these reductions were higher in Group II. According to the transmission electron microscopic findings, leuprolide seems to be protecting normal structure of peritoneum best when compared to the other groups.. Amifostine, NAC and leuprolide caused regression of endometriosis in this experimental rat model by a yet unsettled mechanism.

Topics: Abdominal Wall; Acetylcysteine; Amifostine; Animals; Disease Models, Animal; Endometriosis; Endometrium; Female; Leuprolide; Peritoneal Diseases; Peritoneum; Random Allocation; Rats; Rats, Wistar; Treatment Outcome

Long-term pituitary down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist for 3–6 months prior to IVF/intracytoplasmic sperm injection (ICSI) improves clinical pregnancy rates in endometriosis patients. However, some discussion about this treatment strategy still exists. This retrospective study from a tertiary-care university hospital examined the efficacy and safety of IVF/ICSI with and without long-term pituitary down-regulation in severe endometriosis patients (surgically confirmed American Society for Reproductive Medicine stages III and IV). All first IVF/ICSI treatment cycles between January 2009 and January 2012 were analysed. In patients treated with (n = 68) and without (n = 45) long-term pituitary down-regulation, 13 (19.1%) versus nine (20.0%) ongoing pregnancies after fresh embryo transfer (adjusted OR 0.58, 95% CI 0.18–1.86,) and 24 (35.3%) versus 10 (22.2%) ongoing pregnancies after fresh and cryopreserved embryo transfers (adjusted OR 1.62, 95% CI 0.60–4.38) were accomplished, respectively. Three complications (2.7%) and three recurrences (2.7%) were reported, only in patients treated with long-term pituitary down-regulation. The 1-year cumulative endometriosis recurrence rate was 7.3%. IVF/ICSI in patients with severe endometriosis is safe with low complication and recurrence rates. A favourable effect, albeit non-significant, of long-term pituitary down-regulation in achieving an ongoing pregnancy was observed only after including cryopreserved embryo transfers.

Topics: Down-Regulation; Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Life Tables; Logistic Models; Pituitary Gland; Pregnancy; Pregnancy Rate; Recurrence; Retrospective Studies; Sperm Injections, Intracytoplasmic; Statistics, Nonparametric; Treatment Outcome

Although the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in reducing the recurrence of endometriosis-associated pain, its efficacy in preventing endometrioma recurrence is questionable. We compared the efficacy of postoperative use of LNG-IUS with oral contraceptives (OC) for preventing endometrioma recurrence.. A retrospective cohort study.. Medical university hospital.. Ninety-nine women with endometriomas.. A chart review was performed of women of reproductive age who had undergone laparoscopic surgery for endometrioma followed by three cycles of gonadotropin-releasing hormone agonist (leuprolide acetate) treatment. Women were categorized into two groups: a group that had postoperative LNG-IUS placement (n = 42) and a group that received postoperative, cyclic, low-dose, monophasic, OCs (n = 57). Main outcome measures. Endometrioma recurrence was analyzed according to several clinical variables and postoperative treatment modalities.. During the follow-up period (median 17 months), recurrent endometriomas were detected in eight women (8.1%). Patients with LNG-IUS had a recurrence rate of 4.8% (2/42), whereas women receiving OC had a recurrence rate of 10.5% (6/57). Cumulative recurrence-free survival assessment revealed that mean disease-free survival times for both groups were similar, but that for LNG-IUS was slightly longer than that for OC, with statistical significance (34.4 ± 1.0 months, 95% confidence interval 32.3–36.5, vs. 33.4 ± 1.3 months, 95% confidence interval 30.8–36.0, p = 0.045). Univariate analysis revealed a hazard ratio of 0.178 (95% confidence interval 0.029–1.075) (p = 0.060) for postoperative LNG-IUS use and endometrioma recurrence. However, for the multivariate regression analysis, only postoperative serum CA 125 levels were significantly associated with endometrioma recurrence (hazard ratio 1.012, p = 0.010).. Postoperative LNG-IUS use seemed to be comparable to the use of cyclic OC in preventing endometrioma recurrence.

Topics: Adult; Contraceptives, Oral, Hormonal; Disease-Free Survival; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices, Medicated; Leuprolide; Levonorgestrel; Middle Aged; Retrospective Studies; Secondary Prevention

The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis.. Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups.. Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05).. Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.

Topics: Analgesics; Animals; Atorvastatin; C-Reactive Protein; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Endometriosis; Endometrium; Female; Heptanoic Acids; Humans; Leuprolide; Nociception; Nociceptive Pain; Pyrroles; Rats; Rats, Wistar; Treatment Outcome; Tumor Necrosis Factor-alpha

To determine the effects of captopril on experimentally induced endometriosis in a rat model.. Twenty-four adult, mature female Wistar-Albino rats in which endometriotic implants were induced by transplanting autologous uterine tissue to ectopic sites on the peritoneum. After the endometriotic implants were formed surgically, the 24 rats were randomly divided into three groups. Group 1 (captopril group, eight rats) were given 50 mg kg(-1)d(-1) of oral captopril for 21 d. Group 2 (leuprolide acetate group, eight rats) were given a single 1 mg kg(-1) subcutaneous injection of leuprolide acetate. Group 3 (control) were given no medication and served as controls (eight rats). The surface area of the endometriotic implants and the score of histologic analysis. Also, VEGF and MCP-1 levels in peritoneal fluids and bloods were analyzed.. At the beginning of the medical treatment, the mean surface areas of the endometriotic implants were comparable in all three groups. At the end of the treatment the mean implant surface area in the captopril group and leuprolide acetate group was less than that in the control group. Mean histopathological examination score for the implants post treatment was lower in the captopril and leuprolide acetate groups. Peritoneal fluids VEGF level in the captopril and leuprolide acetate groups was lower than that in the control group. The post-treatment MCP-1 level was also lower in the captopril and leuprolide acetate groups than in the control group. The serum VEGF and MCP-1 levels post treatment were significantly lower in the captopril and leuprolide acetate groups than in the control group.. Administration of captopril reduced the size and progression of endometriotic lesions in a rat model.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Ascitic Fluid; Captopril; Chemokine CCL2; Disease Models, Animal; Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Leuprolide; Peritoneal Diseases; Peritoneum; Rats; Rats, Wistar; Transplantation, Autologous; Vascular Endothelial Growth Factor A

GPR30 is a seven-transmembrane G protein-coupled estrogen receptor that regulates endometrial cellular responses to estrogen. GPR30 is often highly expressed in cancer cells from aggressive tumors. The aim of this study was to evaluate the expression patterns of GPR30 in endometriosis during medical treatment.. A total of 38 females, 28 patients with endometriosis and 10 patients with leiomyoma who underwent laparoscopic surgery were included this study.. Eutopic endometrial tissue sampling from women without endometriosis and ectopic endometrial tissue sampling from women with endometriosis.. A quantitative real-time polymerase chain reaction analysis of the mRNA expression in eutopic and ectopic endometrial tissues with or without GnRH agonist treatment. The expression of GPR30 was confirmed by immunohistochemistry.. There was an increased level of GPR30 mRNA in eutopic endometrium during the proliferative phase, whereas higher expression was observed in the ectopic endometrium during the secretory phase. Increased GPR30 mRNA was observed in ectopic endometrium in comparison to eutopic endometrium. GnRH agonist treatment before laparoscopic surgery decreased GPR30 mRNA in ectopic endometrium. The immunohistochemical analysis also revealed that GPR30 was strongly expressed in epithelial cells in ectopic endometrium, whereas GnRH agonist treatment decreased the GPR30 expression.. High levels of GPR30 expression can play an important role in the progression of endometriosis.

Topics: Adult; Endometriosis; Endometrium; Female; Follicular Phase; Gene Expression; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Leuprolide; Luteal Phase; Middle Aged; Real-Time Polymerase Chain Reaction; Receptors, Estrogen; Receptors, G-Protein-Coupled; RNA, Messenger

The aim of this study was to compare the effects of theranekron, medroxyprogesterone acetate (MPA), and leuprolide acetate (LA) on surgically induced endometriosis in a rat model.. Endometriosis was surgically induced in forty female rats during estrus. After 3 weeks, a second operation was performed and the rats were randomized using a randomization table into theranekron, MPA, LA, and control groups. These treatments were continued for 3 weeks. A third operation was performed to evaluate treatment results. Then, the experimental treatments were halted and estrogen was initiated again to maintain estrus. After three additional weeks; i.e. after 9 weeks, the recurrence rate of endometrial foci was evaluated in a fourth operation and the rats were sacrificed. The volume of endometriotic foci and histopathology scores before and after treatment were compared.. The respective mean volumes of the endometriotic foci after 3, 6, and 9 weeks were 86.4±21.2, 16.4±8.2, and 20.1±9.6 mm(3) in the theranekron group, 78.3±20.4, 42.6±13.5, and 66.7±16.2 mm(3) in the MPA group, and 91.8±30.2, 34.4±11.4, and 72.4±21.9 mm(3) in the LA group. The respective mean histopathology scores were 2.4±0.6, 1.8±0.6, and 1.6±0.6 in the theranekron group, 2.5±0.8, 2.0±1.1, and 2.7±1.0 in the MPA group, and 2.3±0.5, 2.1±1.2, 2.4±0.8 in the LA group. After 9 weeks, the mean volume of endometriotic foci and histopathology scores were significantly lower in the theranekron group.. Theranekron caused more evident regression of endometriotic foci than MPA or LA in a rat model. After stopping the theranekron treatment, the recurrence rate was also lower than that of the other groups.

Topics: Animals; Antineoplastic Agents, Hormonal; Disease Models, Animal; Endometriosis; Endometrium; Female; Leuprolide; Medroxyprogesterone Acetate; Random Allocation; Rats; Secondary Prevention; Spider Venoms

To study the efficacy and safety of Gonadotropin-releasing hormone agonists (GnRH-a) combined with laparoscope conservative surgery in treatment of moderate or severe endometriosis.. From Jan. 2007 to Jan. 2010, 68 patients with moderate or severe undergoing treatment in Renmin Hospital of Wuhan University were enrolled in this retrospective study. Three groups were classified, which were 25 patients in GnRH-a group, subcutaneous injection Leuprorelin on the second day of menstruation, every 4 weeks for 3 months. Twenty-three patients in Marvelon group, orally one marvelon tablet on the second day of menstruation, continuous 21 days for one period of treatment for 3 courses. Twenty patients in surgery group, without any medicine used preoperatively. All patients were followed by 12 months and compare their surgery time, blood loss, recovery, visual analog scale (VAS), and recurrence and so on.. The operating time were (68 ± 18) min in GnRH-a group, (80 ± 21) min in Marvelon group and (90 ± 24) min in surgery group. The amount of bleeding were (118 ± 15) ml in GnRh-a group, (161 ± 18) ml in Marvelon group and (193 ± 13) ml in surgery group. There was significant lower in the operating time and amount of bleeding in GnRH-a group than those in other two groups (P < 0.05). The activity time and the anus exhaust time were shorter in patients in GnRh-a group than those in the other two groups significantly (P < 0.05). When followed up in 12 months after treatment, visual analogue scale had dropped from 3.8 (1.9 - 6.8) to 1.9 (1.1 - 2.8) in GnRh-a group, from 2.7 (1.3 - 5.5) to 1.8 (1.2 - 3.2) in Marvelon group and from 1.9 (1.0 - 4.9) to 1.6 (1.0 - 3.6) in surgery group. It was showed the most remarkable decreased VAS in GnRHa group when compared with the other two groups (P < 0.05). The recurrence rates were 12% (3/25) in GnRH-a group, 22% (5/23)in Marvelon group and 25% (5/25) in surgery group. It was found that the most significant lower recurrence was in GnRH-a group when compared with the other two groups (P < 0.05).. It was safe and efficacy that GnRH-a combined with laparoscopic conservative surgery were used in treatment of endometriosis. It could bring shorter operation time, less intraoperative blood loss, quick postoperative recover, the lower recurrence rate.

Topics: Administration, Oral; Adult; Desogestrel; Dyspareunia; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Laparoscopy; Leuprolide; Operative Time; Pain Measurement; Recurrence; Retrospective Studies; Severity of Illness Index; Treatment Outcome

To evaluate the short-term effect of leuprorelin acetate microspheres in preventing recurrence of ovarian endometrioma after conservative surgery.. From January 2011 to September 2011, 190 ovarian endometrioma patients undergoing conservative laparoscopic surgery at Affiliated Obstetrics and Gynecology Hospital Affiliated to Fudan University were enrolled in this retrospective study. Among 184 patients were followed up, the range of following up were 12 to 21 months. 116 cases presented dysmenorrheal. Based on postoperative treatment, they were classified into 124 cases treated by domestic gonadotropin releasing hormone agonist(GnRH-a) post-operatively for 3-6 months and 60 cases without postoperative treatment. Among all, 63 patients were treated with, that was leuprorelin acetate microspheres for injection (Beiyi, 3.75 mg, q28 d), 61 patients were treated with imported GnRH-a post-operatively for 3-6 months, that were either Zoladex(3.6 mg, q28 d), Dophereline(3.75 mg, q28 d) or Enatone (3.75 mg, q28 d). The recurrence and pain improvement were compared among those groups.. (1) The total rate of cyst recurrence was 12.5% (23/184) while the average recurrent time was (13.7 ± 2.6) months (2-21 months). The cyst recurrence rate was significantly lower in patients treated with GnRH-a post-operatively than those who didn't take medications [21.7% (13/60) versus 8.1% (10/24), P < 0.05]. However, there was no significant difference between domestic GnRH-a group and the imported one [7.9% (5/63) versus 8.2% (5/61), P > 0.05]. (2) After conservative surgery, symptoms were found to be relieved in 87.1% (101/116) patients among 116 patients complaining of dysmenorrheal pre-operatively and the pain recurrence rate was 12.9% (13/101). However, there was no significant difference in either symptom relief rate or pain recurrence rate among different groups. The symptom relief rate were 87% (33/38), 86% (37/43) and 89% (31/35) while the pain recurrence rate were 12% (4/33), 14% (5/37) and 13% (4/31) respectively in none, imported GnRH-a group and domestic GnRH-a group.. Leuprorelin acetate microspheres could be effective in preventing recurrence of ovarian endometrioma, but not in symptom relieving after conservative surgery in short term. The effect of domestic and imported GnRH-a was similar.

Topics: Adult; Dysmenorrhea; Endometriosis; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Laparoscopy; Leuprolide; Middle Aged; Ovarian Diseases; Retrospective Studies; Secondary Prevention; Treatment Outcome; Young Adult

The aim of this study was to evaluate the improvement in catamenial chronic pelvic pain (CPP) after Gonadotropin Releasing Hormone analogue (GnRH-a) administration in women affected by adenomyosis or endometriosis. We retrospectively analysed clinical data of 63 premenopausal women with clinical suspect of adenomyosis (15 women, Group A) or endometriosis (48 women, Group B), which received GnRH-a in order to reduce CPP intensity during the time on surgery waiting list. Main outcome measures were variation of CPP intensity, numbers of days requiring analgesics and lost work productivity before and three months after GnRH-a administration. Compared to baseline, a significant decrease in CPP intensity (p < 0.05) was observed in both groups, even if this reduction was significantly higher in Group A than in Group B (p < 0.001). In both groups, moreover, a significant reduction in number of days requiring analgesics (p < 0.05) and lost work productivity (p < 0.05) was detected. In conclusion, GnRH-a administration in women with clinical suspect of adenomyosis induces a greater reduction in CPP when compared to women with endometriosis, thus representing a potential ex adiuvantibus criteria, helping TV-US in the clinical diagnosis of adenomyosis.

Topics: Adenomyosis; Adult; Chronic Pain; Endometriosis; Female; Humans; Leuprolide; Middle Aged; Ovarian Diseases; Pelvic Pain; Retrospective Studies; Treatment Outcome

Topics: Adult; CA-125 Antigen; Carcinoma, Endometrioid; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovarian Neoplasms

Topics: Aged; Antineoplastic Agents, Hormonal; Endometriosis; Ethinyl Estradiol; Female; Humans; Leuprolide; Male; Prostatic Neoplasms; Urinary Bladder Diseases

While chronic pain is a main symptom in endometriosis, the underlying mechanisms and effective therapy remain elusive. We developed an animal model enabling the exploration of ectopic endometrium as a source of endometriosis pain. Rats were surgically implanted with autologous uterus in the gastrocnemius muscle. Within two weeks, visual inspection revealed the presence of a reddish-brown fluid-filled cystic structure at the implant site. Histology demonstrated cystic glandular structures with stromal invasion of the muscle. Immunohistochemical studies of these lesions revealed the presence of markers for nociceptor nerve fibers and neuronal sprouting. Fourteen days after surgery rats exhibited persistent mechanical hyperalgesia at the site of the ectopic endometrial lesion. Intralesional, but not contralateral, injection of progesterone was dose-dependently antihyperalgesic. Systemic administration of leuprolide also produced antihyperalgesia. In vivo electrophysiological recordings from sensory neurons innervating the lesion revealed a significant increase in their response to sustained mechanical stimulation. These results are consistent with clinical and pathological findings observed in patients with endometriosis, compatible with the ectopic endometrium as a source of pain. This model of endometriosis allows mechanistic exploration at the lesion site facilitating our understanding of endometriosis pain.

Topics: 4-Aminopyridine; Action Potentials; Amifampridine; Animals; Antineoplastic Agents, Hormonal; Biophysics; Calcitonin Gene-Related Peptide; Cells, Cultured; Chronic Pain; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Endometriosis; Endometrium; Estrous Cycle; Female; Ganglia, Spinal; GAP-43 Protein; Hyperalgesia; Lectins; Leuprolide; Muscle, Skeletal; Nerve Fibers; Patch-Clamp Techniques; Potassium Channel Blockers; Progesterone; Progestins; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; Tetraethylammonium; Time Factors; Transplants; Uterus

To evaluate the efficacy and tolerability of a low-dose estrogen-only regimen as a short-term add-back therapy during post-operative GnRH agonist (GnRHa) treatment of patients with endometriosis.. Retrospective cohort study. One hundred seventeen women of reproductive age who were treated with post-operative GnRHa after conservative laparoscopic surgery for endometrioma were eligible for this study. The patients were divided into two groups: group A (n = 56) received tibolone (2.5mg) between 2002 and 2004 and group B (n = 61) received estradiol valerate (1mg) between 2005 and 2007 as an add-back therapy for five months, beginning at the time of the second injection of a GnRHa. The incidence of hypoestrogenic symptoms and the degree of pelvic pain according to a verbal rating scale (VRS) scoring system, the incidence and patterns of uterine bleeding during add-back therapy, the endometrial thickness by ultrasonography two months after the last GnRHa treatment, and the serum CA-125 level were evaluated.. The incidence of uterine bleeding, hypoestrogenic symptoms such as hot flashes and sweating, and pelvic pain did not differ significantly between the two treatment groups. However, the endometrium was thicker in group A than group B (p = 0.022). In group B, the frequency of uterine bleeding was lower from the second month after starting add-back therapy than in group A, but without statistical significance (at the sixth month, p = 0.086).. The low-dose estrogen-only regimen was efficacious and tolerable as a short-term add-back therapy during post-operative GnRHa treatment after surgery for endometriosis.

Topics: Adult; Cohort Studies; Endometriosis; Endometrium; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Norpregnenes; Pelvic Pain; Ultrasonography

Uterine leiomyomas are the most common benign tumors of reproductive age women, but there is no effective medical therapy to data. Aim of this study was to examine and compare the efficacy of gonadotropin-releasing hormone agonist (GnRHa) versus dienogest in premenopausal women with uterine myoma.. We retrospectively analyzed the medical records of 55 premenopausal patients with endometriosis, who received dienogest (2 mg daily) for 6 months regarding coexistence of uterine myoma between January 2008 and June 2010. To compare these data in a case-control study, we analyzed a matched control group of 12 patients treated with leuprolide acetate (1.88 mg monthly) for 6 months having uterine myoma.. Of the 55 patients treated with dienogest, six were associated with coexistent myoma node. Total myoma volume significantly decreased to 59.7 ± 7.0% of initial in dienogest group and 51.9 ± 5.5% in GnRHa group. Reduction rate in myoma volume was similar in both groups.. Uterine myoma volume was successfully reduced by use of dienogest. Consideration of GnRHa disadvantages may lead to short- or long-term management of women with myoma who are to be managed transiently, and who wish to avoid surgical intervention, especially perimenopausal women.

Topics: Adult; Antineoplastic Agents, Hormonal; Case-Control Studies; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyoma; Leuprolide; Middle Aged; Nandrolone; Premenopause; Retrospective Studies; Tumor Burden; Uterine Neoplasms

Anaphylactic reactions to gonadotropin-releasing hormone (GnRH) agonists are exceedingly rare, but if they occur, they can be life threatening. This case describes a 33-year-old patient with endometriosis who developed an acute allergic reaction on leuprolide (Lucrin) administration. Although skin tests with the replacement goserelin (Zoladex) were negative, usage of this medication resulted in a similar allergic reaction. This is the first case report that shows that, in case of a proven allergy to one GnRH agonist, a switch to another GnRH agonist should not be made even if allergy tests are negative for this medication.

Topics: Adult; Anaphylaxis; Anti-Allergic Agents; Clemastine; Diagnosis, Differential; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Histamine H1 Antagonists; Humans; Leuprolide

To study the effect of bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of surgically induced endometriosis in an experimental model.. This is an experimental study conducted in the Center for Health and Biological Sciences at the Pontifical Catholic University of Parana, Brazil. Endometriotic implants were surgically induced in 120 female Wistar rats. The animals with viable endometrial implant (larger than 25 mm(2)) were randomically divided into 3 groups to receive an intraperitoneal injection of 0.2 cc of saline solution (C group; n=30), a subcutaneous injection of 1mg/kg of leuprolide (L group; n=34), or an intraperitoneal injection of 5×10(6) bone marrow derived-mononuclear stem cells (SC group; n=36). They were sacrificed after 21 days to assess the implants' size and the tissue expression of vascular endothelial growth factor receptor (VEGF-R) and tumor necrosis factor-alpha (TNF-alpha).. Treatment with leuprolide decreased the surface area of the endometriotic implant compared to the SC group and the C group. The absolute reduction in the surface area of the implant was 16.5mm, 0mm, and 0mm (p=0.007), respectively, and the percent reduction was 40.2%, 0%, and 0% (p=0.001). VEGF-R expression in the endometriotic implant decreased after treatment in the L and SC groups compared to the C group (409.6 μm(2) vs. 465 μm(2) vs. 920.9 μm(2), respectively; p=0.021). TNF-alpha expression also reduced in the L and SC groups compared to the C group (585.7 μm(2) vs. 549.3 μm(2) vs. 2402.1 μm(2), respectively; p<0.001).. Bone marrow derived-mononuclear stem cells transplantation decreased the expression of VEGF-R and TNF-alpha in the endometriotic implant but did not reduce the surface area of the lesion.

Topics: Animals; Bone Marrow; Disease Models, Animal; Endometriosis; Female; Fertility Agents, Female; Injections, Intraperitoneal; Leuprolide; Rats; Rats, Wistar; Receptors, Vascular Endothelial Growth Factor; Stem Cell Transplantation; Tumor Necrosis Factor-alpha

Endometriosis is a debilitating disease that affects women of reproductive age and may lead to impaired fertility. Cell attachment, invasion of the underlying tissue, and vascular ingrowth are important processes in endometrial lesion development. However, the degree of cellular exchange between host peritoneum and endometrial tissue is unclear.. An experimental endometriosis model was employed whereby uterine horn fragments from wild-type mice were implanted into genetically identical eGFP (enhanced green fluorescent protein) host mice and vice versa. Hormone sensitivity of the ectopic lesions was assessed and cellular exchange determined histologically.. White cyst-like lesions developed from implanted fibrin-rich fragments by day 7. Lesions consisted of a well-developed stroma with glandular and luminal epithelium. Both ovariectomy and treatment with a GnRH agonist, leuprorelin, resulted in the suppression of ectopic lesion growth, whereas estradiol treatment increased the size of the ectopic lesion (4 mice per group on day 14). Ingrowth and outgrowth of blood vessels was apparent as well as the exchange of cells between host peritoneum and lesion.. These findings support the proposal that there is a close cellular interplay between host peritoneum and ectopic tissue and the suitability of this mouse model to study these interactions.

Topics: Animals; Cell Adhesion; Disease Models, Animal; Endometriosis; Epithelial Cells; Estradiol; Female; Green Fluorescent Proteins; Leuprolide; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovariectomy

Information is limited regarding the multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated the pattern of changes in inflammatory reaction, micro-vessel density and apoptosis in the tissues collected from women with endometriosis, adenomyosis and uterine myoma who were treated with or without GnRHa therapy.. Biopsy specimens were collected from lesions, myometria and corresponding endometria of 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma. A fraction of these women were treated with GnRHa therapy for a variable period of 3-6 months before surgery. We performed immunohistochemical analysis of CD68, a macrophage (Mvarphi) marker and von Willebrand factor (VWF), a vessel marker, using respective antibodies. Changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy.. The infiltration of CD68-positive Mvarphi and VWF-positive micro-vessel density were significantly decreased in the endometria of women with endometriosis, adenomyosis and uterine myoma in the GnRHa-treated group when compared with that in the non-treated group. Marked decreases in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with the non-treated group, a significant increase in apoptotic index (apoptotic cells per 10 mm(2) area) and quantitative-histogram scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases.. GnRHa was able to markedly reduce the inflammatory reaction and angiogenesis and to significantly induce apoptosis in tissues derived from women with endometriosis, adenomyosis and uterine myoma. These multiple biological effects at the tissue level may be involved in the regression of these reproductive diseases.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Apoptosis; Caspase 3; Chemokine CCL2; Endometriosis; Enzyme Activation; Female; Gonadotropin-Releasing Hormone; Humans; Inflammation; Leiomyoma; Leuprolide; Macrophages; Uterine Neoplasms; von Willebrand Factor

Persistence and compliance in women with endometriosis who are receiving gonadotropin-releasing hormone agonists (GnRH-a) may be limited by its hypoestrogenic side effects. Use of concomitant therapy with norethindrone acetate (NA), estrogen, estrogen/progestin combinations, or other progestin (i.e., 'add-back therapy' [ABT]) is recommended to alleviate these side effects. This retrospective study evaluated ABT utilization and its effect on compliance and persistence in patients with endometriosis taking the GnRH-a leuprolide acetate (LA) depot suspension.. A retrospective analysis of a large pharmacy claims database identified patients who started LA therapy from 2002 to 2004 for the treatment of endometriosis. Patients were identified as having received ABT if they started 7 days before, or within 45 days of the last LA fill.. A total of 1285 women with endometriosis who began using LA were identified with 12 months of evaluable data: 211 (16.4%) used concomitant NA therapy, 116 (9.0%) used concomitant estrogen-based therapy, 28 (2.2%) used concomitant combination estrogen- and progestin-based therapies, 56 (4.4%) used concomitant progestin-based therapy, and 874 (68.0%) did not use any ABT. Mean (+/-SD) LA persistence in women receiving NA-based ABT was 5.83 +/- 2.98 months, compared with 4.25 +/- 2.62 months for those not using ABT (P < 0.0001). Average medication possession ratio was 0.43 +/- 0.20 for women receiving NA-based ABT versus 0.32 +/- 0.18 for those not receiving any ABT (P < 0.0001). Patients < 30 years of age were most likely to continue therapy longer and have greater compliance compared with the older age group cohorts (P < 0.01). Patients who used ABT continued to do so for 3.79 +/- 3.21 months.. Limitations of this study include those associated with the use of retrospective claims databases: It does not include any information regarding the patient's pain symptoms, disease severity, or other factors, which could correlate to compliance and persistence.. Among women using LA therapy for endometriosis, only 32% used any type of ABT, and these patients had significantly higher persistence and compliance with LA therapy compared to no ABT user group.

Topics: Adult; Contraceptives, Oral, Synthetic; Databases, Factual; Endometriosis; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Norethindrone; Norethindrone Acetate; Patient Compliance; Progesterone Congeners; Retrospective Studies

The aim of this study was to evaluate the effect of vascular endothelial growth factor (VEGF) and interleukin-1beta (IL-1beta) on apoptosis induced by leuprolide acetate (LA) in endometrial epithelial cell cultures from patients with endometriosis. Primary endometrial epithelial cell cultures were obtained from uterine endometrial biopsies of patients with endometriosis and control women. Endometrial epithelial cells were incubated with LA; a combination of LA and VEGF; a combination of LA and IL-1beta; or in basal conditions. LA was added 3h prior to addition of VEGF and IL-1beta. After stimulation, the percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique and Bax expression was assessed by western blot. Treatment with LA enhanced the percentage of apoptotic cells in endometrial epithelial cells from subjects with endometriosis and control subjects. Addition of either VEGF or IL-1beta after exposure to LA restored the percentage of apoptotic cells to basal levels. Moreover, treatment with LA increased Bax expression in endometrial epithelial cells from patients with endometriosis. This effect was reverted by the addition of either VEGF or IL-1beta. Our results show that VEGF and IL-1beta reduce apoptosis and decrease Bax expression in endometrial epithelial cells from patients with endometriosis. This study suggests that VEGF and IL-1beta may protect endometriotic cells from undergoing apoptosis in addition to exerting their pro-angiogenic role.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Culture Techniques; Cells, Cultured; Cytoprotection; Endometriosis; Endometrium; Female; Humans; Interleukin-1beta; Leuprolide; Vascular Endothelial Growth Factor A

To establish the effect of adenomyosis on IVF/ICSI outcomes in infertile patients with endometriosis who were pretreated with long-term (>/=3 months) GnRH-agonist prior to IVF/ICSI.. Retrospective study in 74 infertile patients with surgically proven endometriosis who were treated with IVF/ICSI between January 2002 and March 2007. The diagnosis of adenomyosis was based on transvaginal ultrasound criteria. All patients were pretreated with long-term (>or=3 months) GnRH-agonist prior to IVF/ICSI.. 90.4% of the patients were diagnosed with endometriosis rASRM stages III-IV. Adenomyosis was demonstrated in 27% of them and was predominantly located in the posterior wall of the uterus. The following IVF/ICSI outcomes were found: a mean duration of GnRH-agonist use prior to IVF/ICSI of 5.35 months (3-26); a mean dosage of FSH used of 208IU (75-450); the mean number of oocytes retrieved was 8.73 (1-30); the mean number of embryos obtained was 3.86 (0-16); the mean number of embryos transferred was 1.6; a mean fertilization rate of 43.6%; a mean implantation rate of 26.3%; a mean miscarriage rate of 24.3%; and a clinical pregnancy rate (fetal heart activity on ultrasound beyond 12 weeks of gestation) of 31.7%. No significant differences were found for any of the IVF/ICSI outcomes between women with and without adenomyosis.. Adenomyosis had no adverse effects on IVF/ICSI outcomes in infertile women with proven endometriosis who were pretreated with long-term GnRH-agonist.

Topics: Adult; Down-Regulation; Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovulation Induction; Pituitary Gland; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome; Ultrasonography

We recently demonstrated the effect of gonadotrophin-releasing hormone agonist (GnRHa) on tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma. Here, we investigated expression of GnRH receptors (GnRHRs) and effect of GnRHa on the proliferation of cells derived from endometria and pathological lesions of women with these reproductive diseases.. Biopsy specimens were collected from lesions and corresponding endometria of 35 women with pelvic endometriosis, 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma during laparoscopy or laparotomy. The gene and protein expressions of GnRHR in eutopic/ectopic cells and tissues were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The immunoreactivity of GnRHR in tissue was analysed by quantitative-histogram (Q-H) scores. The exogenous effect of GnRHa on cell proliferation was examined by 5-bromo-2-deoxyuridine incorporation assay. The Ki-67-immunoreactive cell proliferation index was analysed in biopsy specimens derived from GnRHa-treated and -non-treated women.. Types I and II GnRHRs mRNA and proteins were expressed in eutopic endometria and pathological lesions derived from women with endometriosis, adenomyosis and uterine myoma. GnRHR expression was the highest in the menstrual phase when compared with other phases of the menstrual cycle. Higher Q-H scores of GnRHR immunoreaction were found in blood-filled opaque red lesions than in other peritoneal lesions. Exogenous treatment with GnRHa significantly suppressed the proliferation of cells derived from respective endometria and pathological lesions when compared with GnRHa-non-treated cells.. Local tissue expression of GnRHR was detected in endometriosis, adenomyosis and uterine myoma. In addition to a hypo-estrogenic effect, a direct anti-proliferative effect of GnRHa may be involved in the regression of these reproductive diseases with consequent remission of clinical symptoms.

Topics: Adult; Cell Proliferation; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Ki-67 Antigen; Leiomyoma; Leuprolide; Ovarian Neoplasms; Receptors, LHRH; Uterine Neoplasms

Patients with severe extraperitoneal endometriosis require rapid remission and cannot wait for the effects of oral contraceptive hormones (OCs) to appear.. We successfully achieved personalized gonadotropin-releasing hormone agonist (GnRHa) therapy for a patient with catamenial right shoulder joint pain and right inguinal pain associated with extraperitoneal endometriosis, which was completely unable to be suppressed by OCs. A total of 15 subcutaneous GnRHa depot injections over a period of 19 months was performed according to the serum estradiol and LH levels, in order to maintain long-term amenorrhea without any estrogen-deprivation effects. No recurrence of the catamenial symptoms has been observed for more than 35 months after the final GnRHa depot injection.. Personalized GnRHa therapy should become the first-choice therapy for OC-resistant inoperable extraperitoneal endometriosis.

Topics: Endometriosis; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Inguinal Canal; Injections, Subcutaneous; Leuprolide; Middle Aged; Shoulder Pain

Doxycycline (Dox) has a number of non-antibiotic properties. One of them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of this study was to assess the effects of Dox in a rat endometriosis model.. Endometriosis was surgically induced in 40 rats by transplanting of endometrial tissue. After 3 weeks, repeat laparotomies were performed to check the implants and the animals were randomized into four groups: Group I, low-dose Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The treatment, initiated on the day of surgery and continuing for 3 weeks, was administered to the study groups. Three weeks later, the rats were euthanized and the implants were evaluated morphologically and histologically for immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the peritoneal fluid was assayed.. Treatment with leuprolide acetate, or high-dose or low-dose Dox caused significant decreases in the implant areas compared with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP H scores were significantly lower in the group that received low-dose Dox in both epithelial and stromal MMP-2 and -9 immunostaining when compared with the control group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2 (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)].. Low-dose Dox caused regression of endometriosis in this experimental rat model.

Topics: Animals; Doxycycline; Endometriosis; Endometrium; Female; Immunohistochemistry; Interleukin-6; Leuprolide; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Wistar

To investigate whether the GnRH agonist may reduce aromatase P450 and COX-2 in the eutopic endometrium of patients with endometriosis and ovarian endometrioma.. Endometrial specimens and ovarian endometrioma were obtained from 15 women with endometriosis undergoing laparoscopic surgery. The stromal cells of the eutopic endometrium and ovarian endometroma were cultured in the presence of the GnRH agonist (leuprolide acetate 0, 1, 5 and 10 microM) for 24 h. To investigate the effects of the GnRH agonist on the eutopic endometrium in vivo, biopsy samples of the endometrium (n = 5) among the patients who underwent laparoscopy were obtained after GnRH agonist therapy. The protein production of aromatase cytochrome P450 and COX-2 was examined by Western blot.. Proteins of aromatase P450 and COX-2 were reduced in the eutopic endometrium of patients with endometriosis treated with the GnRH agonist for 3 months. The stromal cells in the culture of endometrial explants and ovarian endometrioma which were treated with the GnRH agonist reduced the aromatase P450 and COX-2.. The GnRH agonist reduced aromatase P450 and COX-2 by direct action on the eutopic endometrium of patients with endometriosis and ovarian endometrioma.

Topics: Aromatase; Cell Culture Techniques; Cyclooxygenase 2; Cytochrome P-450 Enzyme System; Endometriosis; Endometrium; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Laparoscopy; Leuprolide

To evaluate the effect of combined surgical-medical treatment on endometriosis progression in adolescents as measured by disease stage.. Retrospective chart review.. Two academic medical centers.. Sequential cases of young women identified on chart review with chronic pelvic pain unresponsive to dysmenorrheal treatment who underwent initial laparoscopy for diagnosis and surgical destruction of endometriosis. All patients were then treated with standard continuous medical therapy. Patients with exacerbation of pain on anti-endometriosis medical therapy who elected a subsequent laparoscopic procedure were eligible for this study.. Retrospective chart review. Endometriosis stage and adhesions at subsequent laparoscopy as compared to the initial surgical procedure.. 90 patients met inclusion criteria. Eligible patients were 12 to 24 years of age at the time of the initial laparoscopy. The median endometriosis stage at first and second laparoscopy was I. No stage change was observed in 70% of patients, 19% improved by one stage, 1% improved by two stages, and 10% worsened by one stage. Regardless of initial stage, a trend toward disease progression was not observed. There was a significant likelihood for stage improvement at second laparoscopy, with those initially diagnosed as stage II or III most likely to exhibit improvement.. Based on the concept that endometriosis can be progressive, these data suggest that combined surgical-medical management retards disease progression in adolescents and young adults.

Topics: Adolescent; Child; Combined Modality Therapy; Contraceptives, Oral, Combined; Disease Progression; Electrocoagulation; Endometriosis; Female; Fertility Agents, Female; Humans; Laparoscopy; Lasers, Gas; Leuprolide; Medroxyprogesterone Acetate; Peritoneal Diseases; Retrospective Studies; Treatment Outcome; Young Adult

We report the case of a patient with adenomyosis complicated by deep vein thrombosis in whom low-dose gonadotropin-releasing hormone agonist (GnRHa) therapy was useful as a uterus-conserving therapeutic option. The patient was a 34-year-old nulliparous woman who presented with edema and pain in the left lower leg. The patient had been treated with four cycles of GnRHa therapy for adenomyosis and repeatedly experienced chronic pelvic pain, dysmenorrhea and anemia due to hypermenorrhea. Leg venography confirmed deep vein thrombosis, and thrombolytic therapy was performed to eliminate symptoms. Because the patient strongly wanted to conserve the uterus, low-dose GnRHa therapy was initiated. The patient is currently taking 450 microg/day buserelin acetate nasally (regular dose: 900 microg/day), and estradiol levels have been maintained at 24-50 pg/ml. Anemia, leg numbness and chronic pelvic pain have dissipated, and the patient has not experienced estrogen deficiency symptoms for more than two years.

Topics: Administration, Intranasal; Adult; Buserelin; Drug Administration Schedule; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Venous Thrombosis

Topics: Abdominal Pain; Danazol; Diagnosis, Differential; Dysmenorrhea; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysterectomy; Laparoscopy; Leuprolide; Menorrhagia; Nafarelin; Nursing Assessment; Physical Examination; Progesterone; Severity of Illness Index

In the present study, we aimed to compare the effects of cetrorelix and leuprolide on endometriosis.. This randomized, placebo-controlled, single-blind, experimental study was performed on 45 Wistar adult female rats in the Experimental Surgery Laboratory at Ondokuz Mayis University. After the peritoneal implantation of endometrial tissue, rats were randomized to three equal intervention groups: (i) control group, (ii) leuprolide group, and (iii) cetrorelix group. Six weeks later, following implant volume measurements (volume-1) by performing a second laparotomy, saline (0.1 cc/rat) was administered subcutaneously to the control group once a week, leuprolide (0.075 mg/kg) subcutaneously to the leuprolide group twice at 4-week intervals and cetrorelix (0.001 mg/rat/day) subcutaneously to the cetrorelix group for 8 weeks. At the end of the treatment, by performing a third laparotomy, implant volumes were remeasured (volume-2) and implants were totally excised for histopathological examination. The volume-1 and volume-2 values within the groups, and stromal and glandular tissue scores between the groups were compared.. In both the leuprolide group and the cetrorelix group, volume-2 as compared to volume-1 had significantly reduced (P < 0.01, P < 0.01 respectively), while there was no significant volume change in the control group (P > 0.05). In this group, when compared with the control group, glandular and stromal tissues had significantly lessened (P < 0.01, P < 0.01 respectively).. Leuprolide and cetrorelix were found to have similar efficacy in the regression of both the size and the histological structure of experimental endometriotic implants.

Topics: Animals; Antineoplastic Agents, Hormonal; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Laparotomy; Leuprolide; Random Allocation; Rats; Rats, Wistar; Single-Blind Method

Our purpose was to evaluate the effect of the GnRH agonist (GnRHa), leuprolide acetate (LA), and the GnRH antagonist (GnRHant), Antide, on apoptosis and expression of apoptosis-related proteins in endometrial epithelial cell (EEC) cultures from patients with endometriosis and controls (infertile women without endometriosis).. Biopsy specimens of eutopic endometrium were obtained from 22 patients with endometriosis and from 14 women that served as controls. Apoptosis was examined in EEC after incubation with LA and Antide. Bax, Bcl-2, Fas and FasL expression was evaluated after exposure to LA, Antide or a combination of both. The percentage of apoptotic cells (%ApC) was assessed by the acridine orange-ethidium bromide technique, and protein expression was evaluated by western blot and immunocytochemistry.. LA 100 and 1000 ng/ml increased the %ApC in EEC from patients with endometriosis (both P < 0.05) and controls (p < 0.05 and P < 0.01, respectively). Antide 10(-5) M increased the %ApC in EEC from patients with endometriosis and controls (P < 0.01). In EEC from women with endometriosis, Bax expression increased after treatment with LA, Antide and LA + Antide (P < 0.05, P < 0.001 and P < 0.001), whereas Bcl-2 expression decreased after exposure to LA and Antide (P < 0.001 and P < 0.01). FasL expression increased after LA, Antide and LA + Antide treatments (P < 0.01, P < 0.001 and P < 0.01). No significant changes were observed on Fas expression.. GnRH analogues enhanced apoptosis in EEC, and this was accompanied by an increase in expression of the pro-apoptotic proteins Bax and FasL and a decrease in expression of the anti-apoptotic protein Bcl-2.

Topics: Apoptosis; bcl-2-Associated X Protein; Cells, Cultured; Endometriosis; Endometrium; Epithelial Cells; Fas Ligand Protein; fas Receptor; Female; Gene Expression Regulation; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Infertility, Female; Leuprolide; Oligopeptides; Proto-Oncogene Proteins c-bcl-2

This prospective randomized-controlled animal study was designed to determine the effects of atorvastatin on experimentally induced endometriosis in a rat model.. Thirty-seven Wistar-Albino rats in which endometriotic implants were induced were randomly divided into four groups. Group I (Low-dose atorvastatin group, eight rats) were given 0.5 mg kg(-1) day(-1) oral atorvastatin. Group II (High-dose atorvastatin group, 10 rats) were given 2.5 mg kg(-1) day(-1) oral atorvastatin. Group III were given a single dose of 1 mg kg(-1) s.c. leuprolide acetate (GnRH agonist group, nine rats). Group IV were given no medication and served as controls (10 rats). All rats received the treatment for 21 days and were then euthanized to assess the implants' size, vascular endothelial growth factor (VEGF) level in peritoneal fluid and histological score.. At the end of the treatment, the mean areas of implants were smaller and VEGF levels in peritoneal fluid were lower in Groups II and III than those in Group I and the control group (all P < 0.05). The mean areas of implants decreased from 41.2 +/- 13.9 to 22.7 +/- 13.9 mm(2) after medication in Group II and decreased from 41.2 +/- 18.1 to 13.1 +/- 13.8 mm(2) in Group III (both P < 0.05), whereas in Group I, the mean area increased from 43.0 +/- 12.7 to 50.5 +/- 13.9 mm(2) (P < 0.05).. High-dose atorvastatin caused a significant regression of endometriotic implants.

Topics: Animals; Atorvastatin; Disease Models, Animal; Dose-Response Relationship, Drug; Endometriosis; Endometrium; Female; Heptanoic Acids; Leuprolide; Pyrroles; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A

To report a rare complication of GnRH agonist therapy for intestinal endometriosis.. Case report.. University hospital.. A 45-year-old nulliparous Japanese woman with catamenial digestive symptoms.. GnRH agonist therapy.. Acute abdomenal crisis with free air in the abdominal X-ray.. An emergency laparotomy showed both an ileal constriction and perforation. An ileocecal enterectomy with an end-to-end anastomosis was performed. A pathological examination of the ileum revealed ileal endometriosis.. Flare-up of intestinal endometriosis induced by GnRH agonist has the potential to lead to intestinal perforation. Careful diagnosis and treatment are necessary for cyclic and periodic gastrointestinal manifestation.

Topics: Abdomen, Acute; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Ileal Diseases; Intestinal Perforation; Leuprolide; Middle Aged

Topics: Adult; Antineoplastic Agents, Hormonal; Baths; Endometriosis; Female; Headache; Hot Temperature; Humans; Leuprolide

To investigate the efficacy of levamisole on experimental endometriosis.. After the implantation of endometrial tissue on abdominal peritoneum, 40 rats were randomized to 1 of 4 equal intervention groups. Levamisole (2 mg/rat) was applied subcutaneously to group "L" once a week. Depot medroxyprogesterone acetate (3 mg/kg) was applied intramuscularly to group "M" twice at 4-week intervals. Leuprolide (0.075 mg/kg) was applied subcutaneously to group "G" twice at 4-week intervals. Saline (0.1 cm(3)/rat) was applied subcutaneously to group "C" once a week for 8 weeks. The efficacy of levamisole was determined by volume measurement and characterizing the histological structure of the implants.. Volume increase of the implants in group C (P<0.05), and volume decrease in groups M, G, and L was found (P<0.05, P<0.01, and P<0.01, respectively.) Stromal tissue and glandular activity were not different between groups L and G.. Levamisole was found to be as effective as leuprolide in regression of the volume of endometriotic implants.

Topics: Adjuvants, Immunologic; Animals; Contraceptive Agents, Female; Delayed-Action Preparations; Disease Models, Animal; Endometriosis; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Levamisole; Medroxyprogesterone Acetate; Random Allocation; Rats; Rats, Wistar

To examine the effect of the GnRH agonist leuprolide on the growth of cultured endometrioma cells.. Experimental study in an academic setting on endometrioma cell lines cultured from 15 women undergoing laparoscopy or laparotomy for excision of endometrioma.. Mean cell counts resulting from treatment with lower concentrations were not significantly different from those of the controls. Increasing concentrations of leuprolide resulted in inhibition of cell growth. The inhibitory effect of leuprolide was statistically significant when the 1,000 ng/mL concentration was compared with the control concentration.. Increased concentrations of leuprolide has suppressive effects on the growth of cultured endometrioma cells. This suggests a direct effect of GnRH agonists acting via GnRH agonist receptors. Long-acting gonadotropin-releasing hormone (GnRH) agonists cause pituitary receptor down-regulation and ovarian suppression, a function that has made this class of agents useful for the treatment of endometriosis. Recent work has also revealed that this class of agents may also have a direct suppressive effect on peripheral target tissue, mediated by GnRH and GnRH agonist receptors. Preliminary work has suggested that there are GnRH receptors in endometriotic cells and that the growth of these cells is inhibited by GnRH agonists. This activity, however, has not been extensively studied in the growth of endometrioma cells. The present study evaluated the effect of the GnRH agonist leuprolide on 15 endometrioma cell lines.

Topics: Cell Proliferation; Cells, Cultured; Endometriosis; Female; Gonadotropin-Releasing Hormone; Growth Inhibitors; Humans; Leuprolide

To evaluate the bone density of adolescents with endometriosis treated with a GnRH-agonist and "add-back" therapy with norethindrone acetate.. Retrospective chart review.. Pediatric gynecology clinic at a tertiary care center.. 36 adolescents, ages 13 to 21 years, with endometriosis.. Bone mineral density (BMD, g/cm(2)) by dual energy x-ray absorptiometry (DXA); BMD Z-scores of hip and spine.. The mean BMD Z-score at the total hip was -0.24 +/- 1.0, with a range of -2.4 to 1.7. At this site, 6 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 2 had a Z-score < or = -2.0 SD. The mean BMD Z-score at the lumbar spine was 0.55 +/- 1.1, with a range of -2.8 to 1.4. At the spine, 11 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 3 had a Z-score < or = -2.0 SD. There was no correlation noted between duration of therapy with the GnRH-agonist plus add-back and BMD at the hip or spine.. BMD at the hip was normal in most adolescents with endometriosis who were receiving a GnRH-agonist plus add-back therapy with norethindrone acetate. Almost one third of subjects exhibited skeletal deficits at the spine. These data suggest that BMD should be carefully monitored in adolescents receiving treatment with GnRH agonists.

Topics: Absorptiometry, Photon; Adolescent; Adult; Bone Density; Cohort Studies; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hip; Humans; Leuprolide; Lumbar Vertebrae; Norethindrone; Norethindrone Acetate

To clarify the effect of Pycnogenol (Horphag Research, Geneva, Switzerland), French maritime pine bark extract, on endometriosis.. Fifty-eight women were included in this study. They were operated on conservatively for endometriosis and surgically diagnosed with the condition. All patients were followed at 4, 12, 24 and 48 weeks after starting treatment to check for endometriosis signs and symptoms, including changes in CA-125 and estrogen levels (E2). Thirty-two patients in the Pycnogenol treatment group took 60 mg Pycnogenol orally a day for 48 weeks. The 26 patients who received gonadotropin-releasing hormone agonist (Gn-RHa) were treated in the standard way.. Treatment with Pycnogenol slowly but steadily reduced the symptom scores. Treatment with Gn-RHa reduced the scores more efficiently; however, 24 weeks after the end of treatment, the scores suggested a recurrence of signs. No influence of treatment on menstrual cycles or E2 was observed in the Pycnogenol group. CA-125 decreased in both treatment groups. Patients with smaller endometriomas responded better to treatment as compared to patients with larger endometriomas. In the Gn-RHa group, the lowering of CA-125 concentrations was far more pronounced; however, a clear rebound effect was observed.. Pycnogenol is a therapeutic alternative to Gn-RHa in the treatment of endometriosis.

Topics: Adjuvants, Immunologic; Adolescent; Adult; CA-125 Antigen; Dose-Response Relationship, Drug; Drug Administration Schedule; Endometriosis; Estrogens; Female; Fertility Agents, Female; Flavonoids; Follow-Up Studies; Humans; Leuprolide; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Time Factors

A patient with diaphragmatic endometriosis who showed immediate relapse following radical thoracoscopic surgery received personalized GnRH agonist (GnRHa) therapy. GnRHa depots were subcutaneously injected by modulating injection intervals according to serum estradiol and LH levels in order to maintain long-term amenorrhea without any adverse effects. A leuprolide acetate depot was injected 24 times for 34 months. Therefore, so far, 1.88 mg of leuprolide acetate depot have been injected every seven weeks to achieve a stable endocrine condition with 15-30 pg/ml serum estradiol, 3-10 IU/l serum LH, and 7-15 IU/lI serum FSH.

Topics: Adult; Diaphragm; Endometriosis; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Menstrual Cycle; Pneumothorax

The major symptom is dysmenorrhea. Chronic, sometimes non-cyclic pain due to pelvic adhesions is often seen in the long course of the disease. Infiltration into the blader or bowel is a rare but serious complication. A group of patients presents with sterility. Endometriosis histologically resembles endometrium. There can be ovarian cysts and foci either on the peritoneum or in the muscularis of the uterus. The etiology is unknown. There are a number of existing theories. A rare condition is an endometriosis caused iatrogen during a caesarean section. It can develop between uterus and bladder or within the suture or scar tissue. Since we know so little, the treatment options are unsatisfying. Operative resection followed by endocrine medication is the standard therapy. Alternative medicine can be an useful additional factor in the treatment concept.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Buserelin; Complementary Therapies; Contraceptive Agents, Female; Cyclooxygenase 2 Inhibitors; Dysmenorrhea; Endometriosis; Female; Fertility Agents, Female; Humans; Infertility, Female; Leuprolide; Medroxyprogesterone Acetate; Middle Aged; Postoperative Care; Pregnancy; Time Factors

Evaluate the incidence of aberrant endometrial integrin (alphavbeta(3) vitronectin) expression in patients at high risk for implantation defects.. Retrospective case-control trial of 74 consecutive infertile patients with prior failed IVF cycles despite good embryo quality and/or endometriosis who underwent endometrial biopsy 9-11 days after an LH surge to assess the presence or absence of alphavbeta(3) vitronectin. Patients were separated into two groups for analysis based on the presence (Gr. A) or absence (Gr. B) of integrin expression. A subset of Gr. B patients (86.1%) was treated with a 2 month course of a GnRH agonist prior to IVF (Gr. B1). No Gr. A patients were so treated.. Absent alphavbeta(3) vitronectin expression was noted in 48.6% of patients evaluated. A trend towards more severe endometriosis was noted in Gr. B (57.1 vs 31.5%). Responses to controlled ovarian hyperstimulation and IVF cycle outcomes including ongoing pregnancy rates were similar between Gr. B1 patients untreated Gr. A controls (55.6 vs 63.9%).. A high incidence of absent endometrial alphavbeta(3) vitronectin expression is noted in patients at increased risk for implantation defects. Prolonged GnRH agonist therapy prior to an IVF cycle resulted in outcomes similar to untreated controls with positive expression.

Topics: Adult; Case-Control Studies; Danazol; Endometriosis; Endometrium; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility, Female; Integrin alphaVbeta3; Leuprolide; Retrospective Studies; Risk Factors

Topics: Adult; Endometriosis; Female; Humans; Intestinal Diseases; Intestinal Polyps; Leuprolide

To evaluate the efficiency and side-effects of depot medroxyprogesterone acetate in the treatment of moderate or severe endometriosis after conservative surgery.. Ninety-four women with moderate or severe endometriosis after conservative surgery were divided into three groups: 34 cases in the group of depot medroxyprogesterone acetate (DMPA) received intramuscularly depot medroxyprogesterone acetate 150 mg every 28 - 30 days for 6 months; 30 cases in the group of gonadotropin releasing hormone agonists (GnRH-a) received hypodermically leuprorelin acetate 3.75 mg every 28 - 30 days for 6 months; 30 cases in the group of control did not receive any postoperative medical treatment. Patients' symptoms and signs including pelvic pain, pelvic tenderness, menstrual and weight changes were recorded before and after treatment. Liver and renal functions, sex hormone level were also examined at the same time.. Both DMPA and GnRH-a treatment achieved similar significant relief of pelvic symptoms and signs (88% and 93%) compared with the control group (chi(2) = 12.273, P < 0.01; chi(2) = 9.604, P < 0.01). The cumulative recurrence rates of DMPA and GnRH-a groups were 6% and 7%, significantly lower than that of the control group (chi(2) = 5.222, P < 0.05; chi(2) = 4.320, P < 0.05). There were no significant differences between DMPA and GnRH-a groups (chi(2) = 0.488, P > 0.05; chi(2) = 0.017, P > 0.05). Serum estradiol (E(2)) level was significantly reduced in both DMPA and GnRH-a groups, but serum E(2) was maintained at the level of early follicular phase in the group of DMPA (120 +/- 9) pmol/L and menopause phase level in the group of GnRH-a (62 +/- 9) pmol/L. The main side effects of DMPA were menstrual changes, weight gain and delay of ovulation.. Depot medroxyprogesterone acetate seems to be an effective, safe, and convenient treatment for endometriosis with low-cost, good compliance, and few side effects.

Topics: Adult; Combined Modality Therapy; Delayed-Action Preparations; Drug Administration Schedule; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leuprolide; Luteinizing Hormone; Medroxyprogesterone Acetate; Treatment Outcome; Uterine Hemorrhage

Our objective was to assess the effects of 6 months' treatment with two types of gonadotropin-releasing hormone (GnRH) analogues on lumbar bone mineral density (BMD) and bone metabolism. We studied 27 women who had been given a diagnosis of endometriosis or uterine myoma. The subjects received drug therapy for 6 months and were subsequently followed up for 1 year. The BMD of the lumbar spine (L2, L3, L4) was measured by dual energy X-ray absorptiometry four times: at baseline, after 6 months, after 12 months, and after 18 months. The serum concentrations of sex steroids and bone metabolic markers were measured at the same times as BMD. Compared with the baseline value, the mean decrease in the buserelin group L2-4 BMD was 3.7% at 6 months, 1.7% at 12 months, and 0.4% at 18 months. In the leuprolide group, L2-4 BMD decreased respectively by 5.1%, 6.2%, and 4.3%. Serum concentrations of calcium increased significantly after 6 months of treatment (P < 0.05) and returned to the baseline level at 12 months in both groups. In the leuprolide group, the intact osteocalcin concentration after 6 months was significantly higher than the baseline value, and after 12 months, it decreased to the baseline level. Our results indicate that the effect on BMD of 6 months' treatment with GnRH analogues virtually resolves by 1 year after treatment, provided that drugs affecting bone metabolism are not given during this period.

Topics: Absorptiometry, Photon; Adult; Bone and Bones; Bone Density; Buserelin; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Japan; Leuprolide; Lumbar Vertebrae; Osteocalcin; Osteoporosis; Time Factors; Uterus

Trends in the use of laparoscopy as a diagnostic and treatment tool for endometriosis are changing in the United States and the use of empirical treatment for chronic pelvic pain is on the rise. Although it is regarded as the gold standard for the diagnosis of endometriosis, laparoscopy has a positive predictive value of only 43-45%. Furthermore, chronic pelvic pain can be treated medically without a diagnosis confirmed by laparoscopy and histology. Therapy with the gonadotropin-releasing hormone (GnRH) agonist leuprorelin acetate is effective in relieving pelvic pain regardless of the presence of endometriosis. The current treatment algorithm for chronic pelvic pain in the United States comprises physical examination, medical history and ultrasound, and if the cause of the pain is not identified, treatment with oral contraceptives and nonsteroidal antiinflammatory drugs is undertaken. On lack of response to these treatments, GnRH agonist therapy is initiated. The American College of Obstetrics and Gynecology supports therapy with GnRH agonists in the management of women with chronic pelvic pain, even in the absence of confirmation of endometriosis, provided that a detailed investigation reveals no other cause of the pain. Laparoscopy is the final option if pain is not relieved by medical treatments.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; United States

It is estimated that 1% of patients with endometriosis have involvement of the urinary tract, with the bladder being the most common location. Ureteral endometriosis is a rare entity, and the majority of cases are found at exploratory laparotomy for extensive involvement of the pelvic organs. Obstruction of the ureter may be caused by extrinsic or intrinsic disease, with the extrinsic form occurring four times as often. Progressive ureteral obstruction can be insidious in onset and ultimately lead to renal failure. Hormone therapy has had variable success, and open surgery has been the mainstay of treatment. Only one case of ureteral endometriosis, both intrinsic and extrinsic, diagnosed at ureteroscopy has been reported previously. We present a case of ureteral obstruction secondary to isolated intrinsic endometriosis diagnosed at ureteroscopy and treated endoscopically with holmium laser ablation and leuprolide therapy.

Topics: Antineoplastic Agents, Hormonal; Endometriosis; Endoscopy; Female; Humans; Leuprolide; Middle Aged; Radiography; Stents; Ureter; Ureteral Diseases; Ureteral Obstruction

One of the most common gynaecological causes of chronic pelvic pain is endometriosis. A lack of correlation between laparoscopic findings and pelvic pain has been reported. As endometriotic lesions are under hormonal influence, the effects of the gonadotrophin-releasing hormone (GnRH) analogues cause shrinkage of the deposits, reducing symptoms caused by them. We carried out a longitudinal, interventional pilot study, examining the effect of leuprorelin acetate 3.75 mg (Prostap SR, Wyeth) on pelvic pain prospectively. Preliminary data shows a decrease in pain scores from before to after treatment which is statistically significant (P<0.0001) as well as a general improvement in other symptoms. Laparoscopy showed that symptom intensity is not always related to severity of endometriosis and the worst symptoms may not necessarily be due to pathology. Therefore, it is beneficial to treat women with CPP with GnRH analogues as first-line management to relieve painful symptoms, avoid surgical risks and save money.

Topics: Adult; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Endometriosis; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Laparoscopy; Leuprolide; Longitudinal Studies; Pain Measurement; Patient Satisfaction; Pelvic Pain; Periodicity; Pilot Projects; Prospective Studies; Sampling Studies; Severity of Illness Index; Treatment Outcome

To observe the long-term changes in bone metabolism induced by GnRH agonist (GnRHa) treatment and to determine the factor that affected the change in bone mineral density (BMD).. Prospective observational study.. Department of obstetrics and gynecology in university and general hospitals.. Fifty women with endometriosis treated with GnRHa between 1994 and 1996.. Leuprolide acetate administered for 24 weeks. Bone mineral density measurement by dual energy x-ray absorptiometry and collection of blood and urine samples were conducted until 12 months of posttreatment.. Spinal BMD and bone turnover markers.. Mean BMD percent changes from pretreatment were -4.9% and -3.4% at 6 months of treatment and at 12 months of posttreatment, respectively. When the patients were divided by the median pretreatment deoxypyridinoline (DP) level, recovery of BMD after GnRHa discontinuation was slower in the Low-DP group than in the High-DP group. A significant positive correlation was found between the pretreatment DP level and the percent change in BMD at 12 months of posttreatment. No significant relation between BMD and the other bone turnover markers was noted.. Bone mineral density changes were diverse among patients who were administered GnRHa. The pretreatment DP level may be the predictive factor for GnRHa-induced BMD change.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Density; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Peptide Fragments; Predictive Value of Tests; Procollagen; Prospective Studies

The purpose of this study was to assess the in vitro effect of gonadotropin-releasing hormone agonist on natural killer cell activity in women with and without endometriosis and to ascertain whether gonadotropin-releasing hormone agonist effects on natural killer cell activity are direct or mediated solely through the hypoestrogenic state that they produce in vivo.. With use of a chromium 51 release microcytotoxicity assay with K562 target cells, natural killer cell activity was measured after the incubation of mononuclear cells with leuprolide acetate that was obtained from 16 patients with endometriosis and 11 control subjects.. The cytotoxicity of natural killer cells that were obtained from patients with endometriosis was reduced significantly (P<.001) with leuprolide. Natural killer cell cytotoxicity from control patients was also significantly decreased (P=.005) with gonadotropin-releasing hormone agonist. Natural killer cell cytotoxicity was significantly lower in patients with endometriosis than in control patients (P=.029).. These findings suggest a direct immunomodulatory role of gonadotropin-releasing hormone agonist on natural killer cell activity and confirm previous findings that patients with endometriosis have reduced natural killer cell cytotoxicity.

Topics: Adjuvants, Immunologic; Adult; Case-Control Studies; Cell Line, Tumor; Cytotoxicity, Immunologic; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Killer Cells, Natural; Leuprolide

Topics: Antineoplastic Agents, Hormonal; Blood Chemical Analysis; Blood Specimen Collection; Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Leuprolide; Platelet Count; Vascular Endothelial Growth Factors

Topics: Adult; Antineoplastic Agents, Hormonal; Colonic Polyps; Colonoscopy; Endometriosis; Female; Humans; Leuprolide; Menstruation; Recurrence

To quantify levels of macrophage migration inhibitory factor (MIF) in the peritoneal fluid (PF) of women with endometriosis, and to correlate these levels with the extent of disease.. Controlled clinical study.. Academic medical center.. Peritoneal fluid samples were collected during laparoscopic surgery in 60 women with endometriosis and 16 controls undergoing tubal ligation; 52 of the women with endometriosis had received no hormonal treatment in the 6 months prior to surgery, while 8 were using gonadotropin-releasing hormone (GnRH) agonists.. Peritoneal fluid migration inhibitory factor (PF MIF) levels.. Women with endometriosis had significantly higher PF MIF levels (10.8 +/- 0.9 ng/mL) than controls (3.0 +/- 0.7 ng/mL). However, no correlation existed between MIF levels and the stage of disease (r = 0.05) or the depth of endometriotic invasion (r = 0.08). Moreover, treatment with a GnRH agonist did not suppress PF MIF levels. Peritoneal fluid MIF levels did not vary significantly between the proliferative and secretory phases of the cycle, and did not distinguish women with endometriosis-associated infertility from women with endometriosis-associated pain.. Peritoneal fluid migration inhibitory factor levels are markedly elevated in women with endometriosis but are independent of the extent of disease.

Topics: Ascitic Fluid; Case-Control Studies; Delayed-Action Preparations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Macrophage Migration-Inhibitory Factors; Neoplasm Invasiveness

To clarify the inhibitory effect of GnRH agonist on estrone (E(1)) sulfatase expression.. Retrospective immunohistochemical study.. The Jikei University Hospital, Tokyo, Japan.. Thirty-three women who had undergone cystectomy of the ovary or oophorectomy and were proved histopathologically to have cystic endometriosis in the ovary.. Fifteen of the 33 patients were treated with GnRH agonists monthly for 2-6 months before surgery. The other 18 patients did not receive any hormonal therapy. Tissue sections were immunostained with an anti-E(1) sulfatase monoclonal antibody (KM1049) originating from human placenta.. Microscopic evaluation to assess the presence and localization of E(1) sulfatase and to describe any variations in its expression with or without treatment with GnRH agonist.. Immunostaining showed that E(1) sulfatase was localized only on the glandular epithelial cells of cystic endometriosis in the ovary. The immunostaining with anti-E(1) sulfatase proved that GnRH agonist inhibited E(1) sulfatase expression in the cystic endometriosis in the ovary.. Gonadotropin-releasing hormone agonist inhibits E(1) sulfatase expression in cystic endometriosis in the ovary.

Topics: Adult; Delayed-Action Preparations; Endometriosis; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Leuprolide; Middle Aged; Ovarian Cysts; Retrospective Studies; Sulfatases

To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor rofecoxib on endometrial explants and on peritoneal vascular endothelial growth factor (VEGF) levels in the rat endometriosis model.. Prospective, placebo-controlled study.. Laboratory at Dokuz Eylül University.. Twenty-six rats with experimentally induced endometriosis.. Rats were treated for 3 weeks with oral rofecoxib (3 mg/kg per day; n = 9); single subcutaneous injection of depot leuprolide acetate (1 mg/kg; n = 9); or vehicle (control; n = 8).. Change in explant area and histologic examination by semiquantitative analysis of endometriotic explants and measurement of peritoneal VEGF levels.. Three weeks of treatment with rofecoxib statistically significantly decreased the implant size (62.4%) compared with control (16.6%), and this effect was comparable with the decrease in leuprolide (64.3%). Histologic examination of the explants indicated mostly atrophy and regression in treatment groups, and semiquantitative analysis showed statistically significantly lower scores in rats treated with rofecoxib and leuprolide compared with controls. Both rofecoxib and leuprolide statistically significantly decreased VEGF levels compared with controls.. Rofecoxib causes regression and atrophy of the endometriotic lesions and is as effective as a GnRH agonist with an accompanying decrease in the VEGF levels.

Topics: Administration, Oral; Animals; Ascitic Fluid; Atrophy; Cyclooxygenase Inhibitors; Endometriosis; Female; Gonadotropin-Releasing Hormone; Injections, Subcutaneous; Lactones; Leuprolide; Rats; Rats, Wistar; Sulfones; Vascular Endothelial Growth Factor A

To investigate whether GnRH agonists or danazol therapy normalizes estrogen metabolism in the eutopic endometrium of women with endometriosis, adenomyosis, or leiomyomas.. Prospective clinical study.. University hospital.. Fifty-three women with endometriosis, adenomyosis, or leiomyomas.. Patients received GnRH agonist or danazol. Biopsy samples of the endometrium were obtained before and after endocrine therapy. Nontreated endometrial explants were cultured in the presence of either drug.. Reverse transcription polymerase chain reaction-Southern blot and immunohistochemical analyses of the endometrial expression of aromatase cytochrome P450, estrogen receptor, progesterone receptor, and Ki-67. Nontreated endometrial explants were cultured in the presence of either drug.. Messenger RNA and protein of aromatase cytochrome P450 were greatly reduced in the eutopic endometrium of patients treated with GnRH agonist for 2 months or more or with danazol for 1 month or more. Culture of endometrial explants with GnRH agonist (10(-9)-10(-7) M) did not change the amount of aromatase cytochrome P450, whereas danazol (10(-7)-10(-6) M) efficiently reduced aromatase cytochrome P450 expression.. Therapy with GnRH agonist or danazol decreases expression of aromatase cytochrome P450 in diseased eutopic endometrium. Endocrine therapy normalized in part the impaired hormonal expression of the eutopic endometrium. GnRH agonist reduced aromatase cytochrome P450 expression mainly by promoting a hypoestrogenic state, whereas danazol reduced aromatase cytochrome P450 in part by direct action on the eutopic endometrium.

Topics: Adult; Antineoplastic Agents, Hormonal; Aromatase; Buserelin; Danazol; Endometriosis; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Ki-67 Antigen; Leiomyoma; Leuprolide; Middle Aged; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; RNA, Neoplasm; Uterine Diseases; Uterine Neoplasms

Catamenial pneumothorax is a rare clinical entity of unknown etiology. The most well known hypothesis is passage of air from the genital tract through endometrial fenestrations in the diaphragm. Although some reports are associated with diaphragmatic endometriosis, few have been confirmed endometrial implants in the visceral pleura. We describe a very rare case of catamenial pneumothorax caused by ectopic endometriosis in the visceral pleura confirmed histopathologically in a woman 1-year after hysterectomy.

Topics: Adult; Endometriosis; Female; Follow-Up Studies; Humans; Hysterectomy; Immunohistochemistry; Leiomyoma; Leuprolide; Periodicity; Pleural Diseases; Pneumothorax; Rare Diseases; Recurrence; Thoracoscopy; Treatment Outcome; Uterine Neoplasms

The aim of the present study was to evaluate the effect of GnRH analogues on the in-vitro eutopic endometrial cell apoptosis and release of interleukin-1beta (IL-1beta) and vascular endothelial growth factor (VEGF).. Biopsy specimens of eutopic endometrium obtained from 16 women with untreated endometriosis and 14 controls were studied. Apoptosis, IL-1beta and VEGF release were evaluated in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA) as GnRH agonist, antide as GnRH antagonist, and a combination of both. The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique, and IL-1beta and VEGF concentrations were assessed by using commercial enzyme-linked immunosorbent assay (ELISA) kits.. We found that LA (100 ng/ml) enhanced apoptosis in endometrial cell cultures from endometriosis patients and controls and this effect was reversed by antide at 10(-7) mol/l. IL-1beta and VEGF release was downregulated by LA in cultures from controls and endometriosis patients. The addition of antide 10(-7) mol/l reversed this inhibition. Endometrial cultures treated with antide at 10(-7) mol/l did not show any significant effects compared with basal conditions.. GnRH agonists appear to have a direct effect in endometrial cells cultures, by enhancing the percentage of apoptotic cells and decreasing the release of pro-mitogenic cytokines such as IL-1beta and VEGF.

Topics: Apoptosis; Case-Control Studies; Cells, Cultured; Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Humans; Interleukin-1; Leuprolide; Oligopeptides; Vascular Endothelial Growth Factor A

There is growing evidence that suggests a direct action of gonadotropin-releasing hormone agonist (GnRH-a) on endometrial growth. Consequently, our purpose was to evaluate the effect of GnRH-a on in vitro eutopic endometrial cell growth and apoptosis.. Prospective study.. Research institute and clinical fertility center.. Sixteen women with untreated endometriosis and 14 controls.. Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA), antide, and a combination of both.. The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique; cell proliferation was assessed by (3)H-thymidine incorporation.. Leuprolide acetate (LA) (100 ng/mL) enhanced apoptosis in endometrial cultures from patients with endometriosis and controls, and this effect was reversed by antide 10(-7)M. Cell proliferation was down-regulated by LA at 1, 10, and 100 ng/mL in cultures from women without and with endometriosis. The addition of antide 10(-7)M reversed this inhibition.. GnRH-a appears to have a direct effect by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells.

Topics: Acridine Orange; Apoptosis; Biopsy; Cell Division; Endometriosis; Epithelial Cells; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Oligopeptides; Prospective Studies; Thymidine; Transforming Growth Factor beta

It has been hypothesized that circulating androgens may be involved in the development of ovarian cancer. The androgenic medication, danazol, and the antiandrogenic medications, leuprolide and nafarelin, are commonly used in the treatment of endometriosis. We assessed the associations between the use of these medications and ovarian cancer.. We pooled information on self-reported use of danazol and leuprolide/nafarelin from two population-based case-control studies of incident ovarian cancer, comprising 1373 cases and 1980 controls. Odds ratios for the association between danazol and ovarian cancer, and leuprolide/nafarelin and ovarian cancer were adjusted for age, parity, oral contraceptive use, and family history of ovarian cancer. These analyses were repeated among the 120 cases and 124 controls who reported having had endometriosis.. Danazol users (n = 19) were at a significantly elevated 3.2 fold (95% confidence interval, 1.2-8.5) risk of developing ovarian cancer, whereas leuprolide/nafarelin users (n = 23) were not at significantly elevated risk (odds ratio, 1.0; 95% confidence interval, 0.4-2.4). Similar results were obtained among the subset of women with endometriosis.. Danazol, but not leuprolide/nafarelin, increased the risk of ovarian cancer. This supports the hypothesis that androgen excess may be associated with the development of ovarian cancer.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Case-Control Studies; Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Genetics, Population; Humans; Leuprolide; Middle Aged; Nafarelin; Ovarian Neoplasms

A novel cytokine termed osteoprotegerin (OPG) that is also called osteoclastogenesis-inhibitory factor, which inhibits osteoclast maturation and activity, was recently isolated. In order to determine the influence of estrogen deficiency on the levels of circulating OPG in women, we studied the changes in the levels of circulating OPG in 10 Japanese women ages 25-49 (mean +/- SD, 34.0 +/- 6.9) years with endometriosis receiving gonadotropin-releasing hormone agonists (GnRH-a) therapy. We further analyzed whether the levels of circulating OPG have relations with the levels of the biomarkers of bone turnover or those of circulating mineral components in these patients during GnRH-a treatment. The patients were treated with a monthly injection of 3.75 mg leuprolide acetate depot for 6 months. In all patients, the concentrations of serum estradiol decreased after 6 months of GnRH-a treatment. The bone mineral density of the lumber spines in these patients significantly (P < 0.01) decreased (percentage change: mean +/- SD, -5.4 +/- 2.1%), while circulating OPG levels significantly (P < 0.01) increased after 6 months of treatment. The values of circulating OPG had significant correlations with those of urinary pyridinoline (r = 0.59, P < 0.01), urinary deoxypylridinoline (Dpd) (r = 0.46, P < 0.05), and serum alkaline phosphatase (r = 0.66, P < 0.01) but not with those of serum carboxy-terminal propeptide of type I procollagen during GnRH-a treatment. The values of circulating OPG also correlated significantly with those of serum calcium (Ca) and phosphorus (P) (r = 0.65 and 0.72, P < 0.01). Further analyses revealed that the percentage change in the value of circulating OPG had a significant correlation with that of urinary Dpd (r = 0.84, P < 0.01). These results suggest that circulating OPG levels rise against the increase in osteoblastic bone resorption and circulating Ca levels in the case of estrogen deficiency, possibly as a compensatory mechanism serving to limit circulating Ca levels and bone density.

Topics: Adult; Bone Density; Bone Remodeling; Endometriosis; Female; Glycoproteins; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Statistics, Nonparametric

To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas.. Retrospective study with prospective selection of participants and controls.. Instituto de Ginecología y Fertilidad Buenos Aires, Argentina.. Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B).. Laparoscopic endometrioma cystectomy, IVF-ET cycle.. E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate.. There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B.. Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

Topics: Adult; Embryo Transfer; Endometriosis; Estradiol; Female; Fertilization in Vitro; Humans; Infertility, Female; Laparoscopy; Leuprolide; Ovarian Diseases; Ovary; Ovulation Induction; Pregnancy; Retrospective Studies

Chronic, painful bladder symptoms are diagnostic and therapeutic challenges for urologists and gynecologists. The aims of this study were to evaluate women with menstrual cycle-related changes in their interstitial cystitis symptoms, to treat them with hormonal manipulation, and to follow them long term.. The cases of women who were referred to a tertiary care center with interstitial cystitis and menstrual cycle exacerbation of symptoms were evaluated in a retrospective study. Fifteen women had undergone laparoscopy that was followed immediately by cystoscopy and bladder hydrodistension. Patients were then treated with leuprolide acetate or oral contraceptive pills.. Patient age ranged from 23 to 48 years. The duration of symptoms ranged from 1 to 26 years. Ten patients (67%) had findings of both interstitial cystitis and peritoneal endometriosis. Five of 15 patients (33%) had interstitial cystitis, but no endometriosis was found. Symptoms improved for 8 of 9 women who were treated with leuprolide acetate and for 5 of 6 women who were treated with oral contraceptive pills. Patients were followed up for an average of 55 months.. Diagnostic laparoscopy should be considered together with hydrodistension of the bladder for women with pelvic pain and irritative bladder symptoms that are exacerbated premenstrually. Endometriosis is often present in patients with these complex symptoms. This is the first report of hormonal treatment for chronic, cyclic irritative bladder symptoms; improvement appears to occur even when endometriosis is not identified by laparoscopy.

Topics: Adult; Chronic Disease; Contraceptives, Oral; Cystitis, Interstitial; Cystoscopy; Dilatation; Endometriosis; Female; Follow-Up Studies; Humans; Laparoscopy; Leuprolide; Menstrual Cycle; Middle Aged; Pelvic Pain; Peritoneal Diseases; Retrospective Studies; Treatment Outcome; Water

Topics: Antineoplastic Agents, Hormonal; Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Leuprolide; Ovarian Neoplasms

To report a rare case of a patient with catamenial hemoptysis, secondary infertility, and endometriosis associated with a unicornuate uterus and noncommunicating rudimentary horn.. Case report.. University hospital.. A 29-year-old woman who developed progressive catamenial hemoptysis and secondary infertility was evaluated at the University Hospital of Crete.. The complete history, laboratory data, laparoscopic findings, and chest magnetic resonance image of this patient were analyzed. A GnRH agonist, leuprolide acetate, was successfully administered.. Diagnosis and appropriate treatment of pulmonary endometriosis in a patient with rudimentary uterine horn.. Treatment with a GnRH agonist achieved suppression of both menstruation and hemoptysis. After 6 months of normal menstrual activity, the symptoms reappeared. The patient was again treated with leuprolide acetate (3.75 mg/mo IM) for 6 months and remained asymptomatic. In fact, the patient became pregnant after cessation of therapy. Finally, the patient was treated successfully with removal of the rudimentary uterine horn during cesarean section. Three-year follow-up showed disappearance of the chest symptoms.. Pulmonary endometriosis and unicornuate uteri are rare. To our knowledge, this is the first case of catamenial hemoptysis with a congenital müllerian anomaly. We describe successful management using a combination of GnRH agonist and surgical resection of the rudimentary uterine horn.

Topics: Adult; Endometriosis; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hemoptysis; Humans; Infertility, Female; Leuprolide; Lung Diseases; Pregnancy; Uterus

To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues.. In 32 women with endometriomas (17 untreated and 15 treated with GnRH analogue) and 21 with ovarian cystadenomas, we examined the expression of secretory leukocyte protease inhibitor messenger RNA (mRNA) by Northern blot analysis; protein distribution was measured immunohistochemically. Concentrations of secretory leukocyte protease inhibitor in peritoneal fluid were measured by enzyme-linked immunosorbent assay. Expression of secretory leukocyte protease inhibitor in endometrioma explants in vitro was also studied with and without the GnRH analogue treatment.. Secretory leukocyte protease inhibitor mRNA expression was identified only in untreated endometriomas. In the GnRH agonist-treated endometriomas, the semiquantitative H-score for secretory leukocyte protease inhibitor immunostaining was significantly lower than that for untreated endometriomas (P <.001). The peritoneal fluid of the GnRH agonist-treated women also contained significantly lower concentrations of secretory leukocyte protease inhibitor (median 76 ng/mL, interquartile range 51-131 ng/mL; P <.001) than untreated women (124 ng/mL, 70-186 ng/mL). Secretory leukocyte protease inhibitor in endometrioma explants in vitro was significantly inhibited by the GnRH analogue (P <.05).. Expression of secretory leukocyte protease inhibitor in tissue and peritoneal fluid of women with ovarian endometriomas was decreased by GnRH agonist treatment.

Topics: Adult; Ascitic Fluid; Blotting, Northern; Case-Control Studies; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Leuprolide; Middle Aged; Ovarian Diseases; Proteinase Inhibitory Proteins, Secretory; Proteins

The therapeutic effects of certain Japanese herbal medicines on menopausal symptoms induced by gonadotropin-releasing hormone agonist therapy were examined in Japanese women with endometriosis, adenomyosis, or leiomyoma. Menopausal symptoms occurred in 17 of the 22 patients. Toki-shakuyaku-san, Shakuyaku-kanzo-to, Keishi-bukuryo-gan, Kami-shoyo-san, Tokaku-joki-to, or Keishi-to was administered to 13 of the 17 patients with menopausal symptoms, and efficacy was observed in all 13. Eleven patients with hot flashes were treated with Toki-shakuyaku-san, and all II patients experienced some relief; four experienced total relief. Three patients complaining of severe shoulder stiffness were treated with Shakuyaku-kanzo-to and were completely relieved of symptoms. There was no significant change in serum estradiol levels after treatment with the Japanese herbal medicines. Our results indicate that Japanese herbal medicines can be recommended for menopausal symptoms induced by gonadotropin-releasing hormone agonists without a negative effect on serum estradiol levels.

Topics: Adult; Endometriosis; Female; Hot Flashes; Humans; Leiomyoma; Leuprolide; Middle Aged; Phytotherapy; Uterine Neoplasms

We report the case of a woman treated with a gonadotrophin-releasing hormone analogue for endometriosis who developed typical clinical features of fibromyalgia, with widespread musculoskeletal pain, sleep difficulties, neuropsychological complaints and tender points on clininal examination. The gonadotrophin-releasing hormone analogue treatment probably induced disturbances in the neuroendocrine system and the secretion of neurotransmitters, and may be suspected to be the cause of this case of fibromyalgia.

Topics: Adult; Antineoplastic Agents, Hormonal; Endometriosis; Female; Fibromyalgia; Humans; Leuprolide

Endometriosis is defined as an inflammatory condition of the female reproductive tract, a state often associated with infertility and miscarriage. Many exogenously administered factors (treatments) control the disease via as yet unknown pathways. Possible candidate molecules involved in these mechanisms could be the serum-soluble human leukocyte antigens (sHIA) that have been detected in a variety of human body fluids and that are associated with several diseases.. We here examine how danazol and leuprorelin acetate depot treatments exert their anti-inflammatory action. It is plausible that subtle alterations mediated by these treatments and in relation to sHLA may explain the pathophysiology of endometriosis and provide insights towards new therapeutic protocols.. Indirect enzyme-linked immunosorbent assay (ELISA), using specific monoclonal antibodies, determined serum-soluble class-I and class-II HLA levels. ELISA readings from treated women were compared with normal healthy subjects.. Serum-soluble class-I and class-II HLA levels are statistically significantly lower (P < 0.001) in women with endometriosis than in the control groups. However, danazol but not leuprorelin acetate depot administration augments soluble HLA class I and class II (P < 0.01 and P < 0.001, respectively) to normal levels during the treatment period, an increase that may account for the anti-inflammatory effect and the remission observed.. It is shown that one of the underlying causes of endometriosis may be the lack of both circulating class-I and class-II antigen levels. Danazol administration acts via an induced release of these antigens, whose presence correlates with the degree of the inflammatory alleviation obtained. We thus provide evidence that the inflammatory state of the disease appears to be associated with soluble HLA levels because, 3 months after ceasing therapy, the circulating antigens in the serum return to the same levels that correspond to the pathological condition.

Topics: Adult; Anti-Inflammatory Agents; Danazol; Endometriosis; Estrogen Antagonists; Female; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; HLA Antigens; Humans; Leuprolide

Endometriosis is a common disease found in reproductive age women, but pulmonary endometriosis is rare. We present a 21-year-old female with catamenial chest pain, chest tightness, severe cough, and hemoptysis. Though we could not find any definite intrapulmonary endometriotic lesion by computed tomography and bronchoscope, she was diagnosed to have pulmonary endometriosis due to the typical clinical symptoms. After 6 months of GnRH agonist application, the symptoms were completely relieved. She has been followed up and has been symptoms free for at least 6 months after administration of GnRH agonist.

Topics: Adult; Endometriosis; Female; Humans; Leuprolide; Lung Diseases

The present study was conducted to investigate whether GnRH-receptor (GnRH-R) gene is expressed in endometriosis ovarian implants and whether a GnRH-analogue (GnRH-a) may exert an effect on endometriosis cell proliferation in vitro. The presence of GnRH-R transcripts in ovarian endometriosis cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and further confirmed by Southern blot analysis. GnRH-R mRNA was detected in all the 13 samples examined. In contrast, GnRH-R transcripts were not detectable in endometriosis-free peritoneal tissue. In the second part of the study, endometriosis cells were cultured for 9 days with different doses of leuprolide acetate (ranging from 0 to 10(-5) M). In 4 out of 13 cases, a significant anti-proliferative effect was observed at doses of leuprolide acetate ranging from 10(-9) to 10(-5) M. In one case, a significant inhibition of cell proliferation was observed only at 10(-5) M leuprolide acetate concentration. In contrast, the GnRH-a did not affect cell growth, regardless of the expression of GnRH-R transcripts and the given doses, in the remaining 8 experiments. To date, this is the first evidence indicating that GnRH-R mRNA is expressed in human ovarian endometriomas. Moreover, the inhibition of endometriosis cell proliferation induced by the GnRH-a in vitro suggests that, at least in some cases, this compound might exert a direct effect on endometriosis lesions.

Topics: Adult; Base Sequence; Cell Division; DNA Probes; Endometriosis; Female; Gene Expression; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Leuprolide; Ovarian Diseases; Receptors, LHRH; RNA, Messenger

We describe a low-grade endometrial stromal sarcoma coexistent with leiomyoma and adenomyosis treated with leuprolide acetate. We describe its histologic characteristics and clinical significance.

Topics: Adult; Endometrial Neoplasms; Endometriosis; Female; Humans; Leiomyoma; Leuprolide; Neoplasms, Multiple Primary; Sarcoma

Impaired sensitivity of endometrial tissue to spontaneous apoptosis in women with endometriosis contributes to the abnormal implantation and growth of endometrium at ectopic sites. Our purpose was to examine the effect of gonadotropin-releasing hormone analog, widely used in the treatment of endometriosis, on the reduced rate of endometrial apoptosis in endometriosis.. Paired ectopic and eutopic endometrial tissue specimens were obtained from 13 patients with endometriosis, and control samples were taken from 8 patients with uterine myoma. Apoptotic cell death was assessed biochemically and morphologically with an enzyme-linked immunoassay and Hoechst No. 33342 staining of deoxyribonucleic acid fragment, respectively.. Spontaneous apoptosis was significantly lower in ectopic and eutopic endometrial tissue from patients with endometriosis (0.22 +/- 0.082 in absorbance) than in endometrial tissue from control subjects (0.52 +/- 0.483)(P < 0.001). Incubation with a gonadotropin-releasing hormone analog (1 micromol/L) increased the apoptotic rate of endometrial cells from patients with endometriosis to 0.56 +/- 0.501 (P <.001). The effect of this gonadotropin-releasing hormone revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L; however, the control endometrium was not affected.. Exposure to gonadotropin-releasing hormone results in changes of the sensitivity of endometriotic endometrium to spontaneous apoptosis; these changes in sensitivity may, in turn, release endometrial cells from resistance to apoptosis and result in reduced survival and growth. This phenomenon could, at least in part, account for the therapeutic action of gonadotropin-releasing hormone analog on endometriosis.

Topics: Apoptosis; Benzimidazoles; Buserelin; Coloring Agents; DNA Fragmentation; Endometriosis; Endometrium; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Dyes; Humans; Leuprolide; Propidium

We reported a case of catamenial pneumothorax that was recurrent after surgical treatment. A 43-year-old woman had sudden chest pain and dyspnea during menstruation. Right pneumothorax and pleural effusion were pointed out on chest X-ray films. When the patient was 31 years old, she received a diagnosis of catamenial pneumothorax and underwent thoracotomy for resection of diaphragmatic endometriosis. However, after surgery she experienced recurrence of right pneumothorax, and was accordingly treated with danazol. The patient decided to terminate medication by herself because her symptoms had disappeared. Several years after the cessation of medication, she experienced chest pain frequently during menstruation, but did not seek a medical check-up. She visited our department because of persistent chest pain in 1997. After the patient was hospitalized, pneumothorax was diagnosed and continuous drainage was performed. Although pneumothorax was alleviated by drainage, it recurred during the patient's next menstrual period. Open lung surgery was performed. Diaphragmatic endometriosis with a small hole and inflammatory thickened lesions on the visceral pleura of the lower lobe (S 6) were found and excised. Microscopic examination of the excised specimens showed endometriosis. Visceral pleural endometriosis has been histologically demonstrated in very few cases. After surgery, hormonal therapy was started. The patient has been well for 12 months without recurrence of pneumothorax. Both surgical and hormonal treatment were considered necessary for the treatment of catamenial pneumothorax in this case.

Topics: Combined Modality Therapy; Diaphragm; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Menstruation; Middle Aged; Muscular Diseases; Pleural Diseases; Pneumothorax; Recurrence; Treatment Outcome

To quantify messenger RNA (mRNA) levels of the two estrogen receptor isoforms, estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta) in the eutopic endometrium and ovarian endometriotic cysts.. Prospective study.. University hospital.. Patients with endometriosis and patients with uterine leiomyoma or carcinoma in situ.. Gonadotropin-releasing hormone agonist (GnRH-a)-treated (n = 12) or untreated (n = 24) endometriotic cysts were obtained from 36 patients during laparoscopic cystectomy. Eutopic endometrium tissues were obtained from 24 patients during or immediately after surgery.. ER-alpha and ER-beta mRNA levels, using a real-time reverse transcription (RT)-polymerase chain reaction (PCR) assay, TaqMan RT-PCR.. Eutopic endometrium and ovarian endometriotic cysts showed predominantly higher levels of ER-alpha mRNA than ER-beta mRNA. Although ER-alpha and ER-beta mRNA levels in the eutopic endometrium were affected by a cyclic change in ovarian hormones, ovarian endometriotic cysts were less affected. Moreover, a long-term hypoestrogenic state induced by GnRH-a especially decreased ER-alpha mRNA levels in endometriotic cysts. Consequently, the relative ratios of ER-alpha to ER-beta mRNA levels in both GnRH-a-treated and untreated endometriotic cysts were significantly lower than those in the eutopic endometrium.. The results suggest that the principal and regulatory effects of estrogens may be mediated mainly via ER-alpha rather than ER-beta in both the eutopic endometrium and endometriotic cysts.

Topics: Adult; Delayed-Action Preparations; Endometriosis; Endometrium; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Humans; Leuprolide; Ovary; Prospective Studies; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

We report the rare case of a patient with adenomyosis who showed thyroid dysfunction of unknown etiology during treatment for endometriosis. She responded to nafarelin acetate and danazol when she was euthyroid but not to buserelin acetate when she was hyperthyroid. This suggests that the response to anti-endometriotic medicine in our patient was altered by impaired thyroid function and that this could occur in other such patients.

Topics: Adult; Buserelin; CA-125 Antigen; Cinnamomum zeylanicum; Danazol; Endometriosis; Estrogen Antagonists; Female; Hormones; Humans; Hyperthyroidism; Japan; Leuprolide; Magnoliopsida; Medicine, East Asian Traditional; Nafarelin; Phytotherapy; Plant Extracts; Thyrotropin; Thyroxine; Triiodothyronine

This study was undertaken to evaluate the effectiveness of a 6-month course of gonadotropin-releasing hormone agonist treatment for patients with symptomatic endometriosis of the rectovaginal septum.. Fifteen patients with rectovaginal endometriosis and moderate to severe pain symptoms were the subjects of the study. None of these patients had either clinical or objective evidence of ovarian endometriosis, nor was there evidence of any obstructive lesions of the intestine or ureters. All patients were given leuprolide acetate depot at 3.75 mg, 1 ampule intramuscularly every 28 days, and treatment had a planned duration of 6 months. Follow-up evaluations were set every 2 months during the treatment phase and every 3 months thereafter until the completion of 1 year after discontinuation of medical therapy. At each follow-up visit pain symptoms were recorded, and clinical exploration, transvaginal ultrasonography, and transrectal ultrasonography were performed.. Two patients stopped the treatment early after the second and fourth leuprolide doses; in both cases the reason was persistence of pain, and both requested a surgical solution. The other 13 patients showed a marked improvement with respect to pain during the 6-month treatment course but had early pain recurrence after drug suspension; 11 of them required further treatment within the first year of follow-up. The failure rate of gonadotropin-releasing hormone agonist therapy to produce 1-year pain relief after treatment discontinuation was 87% (13/15) on an intent-to-treat basis. The endometriotic lesions showed a slight but significant reduction in size during therapy but had returned to the original volume within 6 months after cessation of the gonadotropin-releasing hormone analog treatment.. Our results suggest that gonadotropin-releasing hormone analogs should not be considered a real therapeutic alternative to surgical treatment for patients with symptomatic endometriosis of the rectovaginal septum, except possibly in a limited and unpredictable number of cases.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pain; Rectal Diseases; Treatment Failure; Ultrasonography; Vaginal Diseases

Gonadotropins and sex hormones are intimately related to the stability of affective states. Patients with affective disorders may demonstrate abnormal levels of sex hormones and gonadotropins. It is therefore possible that affective disorder patients may experience mood dysregulation by synthetic sex hormones and gonadotropins like lupron.. A case report of a young woman with a history of endometriosis and a past history of irritability and depression is described. Treatment of the endometriosis with lupron induced a manic episode.. The lupron-induced mania was successfully treated with a mood-stabilizing agent, lithium carbonate.. Patients with a history of affective disorder may develop manic episodes when treated with Lupron. Mood-stabilizing agents are helpful in ameliorating this unwanted effect.

Topics: Adult; Antimanic Agents; Bipolar Disorder; Endometriosis; Female; Fertility Agents, Female; Humans; Leuprolide; Lithium Carbonate

Laparoscopy is the most frequent surgical approach in gynecologic patients with acute or chronic pelvic pain. The symptomatology is frequently related to a specific gynecological pathology such as endometriosis or associated adhesive disease. During an eight year period, January 1990 to December 1997, 26 patients (aged 16-20 years) with endometriosis were diagnosed endoscopically and managed pharmaceutically in our clinic. The disease was evaluated and staged according to the American Society of Reproductive Medicine. The disease was evaluated as first stage in 16 patients (61.6%), as second stage in eight patients (30.8%), as third stage in one patient (3.8%) and as fourth stage in one patient (3.8%). Patients underwent adhesiolysis and management according to their laparoscopic findings. Postoperative pharmaceutical treatment (Danazol, GnRH analogues, Oral Contraceptives) was given. Patients were followed for the evaluation of the treatment. The efficacy of the combination of endoscopic and pharmaceutical management of the disease is discussed.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Ascitic Fluid; Contraceptives, Oral; Danazol; Disease Management; Electrocoagulation; Endometriosis; Estrogen Antagonists; Evaluation Studies as Topic; Female; Humans; Laparoscopy; Leuprolide; Pain; Tissue Adhesions; Treatment Outcome

A gonadotropin-releasing hormone agonist, leuprolide acetate, was administered every 4 weeks for treatment of rectovaginal endometriosis. Degrees of apoptosis (percentage of in situ deoxyribonucleic acid 3'-end-labeled cells) and cell proliferative activity (percentage of cells with immunostaining for proliferating cell protein Ki-67) were examined in endometriotic glands of biopsy specimens taken before and during gonadotropin-releasing hormone agonist therapy. Gonadotropin-releasing hormone agonist induced apoptosis and suppressed cell proliferative activity in endometriotic glands.

Topics: Adult; Apoptosis; Biopsy; Cell Division; Endometriosis; Female; Humans; Ki-67 Antigen; Leuprolide; Rectal Diseases; Vaginal Diseases

To assess the efficacy and diagnostic value of GnRH agonist (GnRH-a) therapy in cases of hidden sciatic nerve endometriosis.. Case report.. Academic tertiary referral center for endometriosis treatment.. Three patients with cyclic, catamenial sciatica associated with pelvic endometriosis who had electromyographic evidence of sciatic nerve damage but negative computed tomography and magnetic resonance imaging findings.. Monthly administration of the GnRH-a leuprolide acetate plus daily transdermal E2 (25 microg).. Relief of pain symptoms and improvement in motor function.. All three patients had clear decreases in pain and partial amelioration of claudication.. Endometriosis of the sciatic nerve may be hard to diagnose with the use of current imaging techniques but may be proved by clinical response to GnRH analogue treatment and may be more frequent than previously thought.

Topics: Administration, Cutaneous; Adult; Drug Administration Schedule; Electromyography; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Movement; Pain; Palliative Care; Peripheral Nervous System Diseases; Sciatic Nerve; Tomography, X-Ray Computed

Although laparoscopy has been considered the gold standard for the diagnosis of endometriosis, it often fails to detect the disease and provide lasting pain relief. Motivated by concerns for patient well-being, treatment efficacy, and cost containment, Lovelace Health Systems of Albuquerque, New Mexico, turned to the Lovelace Chronic Pelvic Pain Protocol, based on a chronic pelvic pain algorithm used to identify potential candidates for therapy with gonadotropin-releasing hormone agonist (GnRH agonist). Since the protocol's introduction in January 1997, empiric therapy with GnRH agonist has proved beneficial to patients, physicians, and healthcare system budgets.

Topics: Algorithms; Chronic Disease; Clinical Protocols; Decision Making; Endometriosis; Female; Gonadotropin-Releasing Hormone; Health Care Costs; Humans; Hysteroscopy; Leuprolide; New Mexico; Organizational Case Studies; Pelvic Pain; Program Evaluation

A 30-year-old female had twice experienced right pneumothorax within 2 months that was related to the onset of menstruation, suggesting catamenial pneumothorax. Right thoracoscopy revealed the presence of "blue berry spots" and pinhole at the lateral part of central tendon in the diaphragm. No bulla or bleb was found on the right lung. Partial resection of the diaphragm including these lesions was performed under small thoracotomy assisted by thoracoscopy. Histological findings showed endometriosis of the diaphragm. She was followed without hormonal therapy, but recurrent right pneumothorax occurred. Therefore she was given leuprorelin acetate for 5 months, and she is asymptomatic 7 months after surgery.

Topics: Adult; Diaphragm; Endometriosis; Endoscopy; Female; Fertility Agents, Female; Humans; Leuprolide; Menstruation; Muscular Diseases; Pneumothorax; Recurrence; Thoracoscopy; Thoracotomy

Topics: Clinical Trials as Topic; Drug Implants; Endometriosis; Female; Humans; Leuprolide; Male; Prostatic Neoplasms

Topics: Drug Therapy, Combination; Endometriosis; Estrogens, Conjugated (USP); Female; Humans; Leuprolide; Norethindrone; Norethindrone Acetate

The aim of this study was to investigate the indications and treatment options in patients with lower-extremity neuropathies and radiculopathies caused by endometriosis.. The authors identified five patients whose symptoms included catamenial pain, weakness, and sensory loss involving the sciatic and femoral nerves and multiple lumbosacral nerve roots. Radiographic studies supported the diagnosis of catamenial neuropathy or radiculopathy, but definitive diagnosis depended on surgical and pathological examination. Treatment of symptoms, including physical therapy and a course of antiinflammatory or analgesic medication, was not helpful. Patients responded favorably to hormonal therapy. Laparoscopy or open exploration for extrapelvic lesions was performed for diagnosis or for treatment when hormone therapy failed. Pain and sensory symptoms responded well to therapy. Weakness improved, but never recovered completely.. Catamenial neuropathy or radiculopathy should be considered when evaluating reproductive-age women with recurring focal neuropathic leg pain, weakness, and sensory loss.

Topics: Adult; Analgesics; Anti-Inflammatory Agents; Antineoplastic Agents, Hormonal; Endometriosis; Female; Femoral Nerve; Humans; Hypesthesia; Laparoscopy; Leuprolide; Low Back Pain; Lumbosacral Plexus; Menstruation; Middle Aged; Muscle Weakness; Muscular Diseases; Neuralgia; Paresthesia; Peripheral Nervous System Diseases; Physical Therapy Modalities; Radiography; Sciatic Nerve; Sciatica; Spinal Nerve Roots; Thigh; Treatment Outcome

To evaluate the effects of a gonadotropin-releasing hormone agonist (GnRH-a) on plasminogen activator (PA), matrix metalloproteinase (MMP), plasminogen activator inhibitor (PAI) and matrix metalloproteinase inhibitor (MMPI) activities in peritoneal fluid relative to GnRH-a-induced reduction of adhesion formation.. Continuation of prospective randomized study using surgical models for adhesion formation.. Department of Obstetrics and Gynecology research laboratory at the University of Missouri School of Medicine.. Forty reproductively cycling female Sprague-Dawley rats.. Female rats were injected with depot GnRH-a or diluent and randomly assigned to adhesion and endometriosis surgeries. Peritoneal fluid was collected prior to (time 1) and 7 weeks from (time 2) initial surgery.. Peritoneal fluid was analyzed for PA, PAI, MMP, and MMPI activities.. At time 1, MMP and MMPI activities were similar in all rats; however, PA and PAI activities were less in rats pretreated with GnRH-a than with diluent. Between time 1 and time 2, GnRH-a-treated rats showed an increase in PAI and MMPI activities without significant changes in PA or MMP activities, whereas rats receiving diluent showed a significant increase in PAI and MMP activities but no significant changes in PA or MMPI activities. At time 2, rats receiving GnRH-a had less PA and MMP activities than those receiving diluent. Adhesion scores showed a positive correlation with MMP activity.. In the absence of GnRH-a therapy, surgical tissue manipulation increased peritoneal fluid MMP and PAI activity. Gonadotropin-releasing hormone agonist therapy decreased PA and MMP activities and also increased PAI and MMPI activities. This GnRH-a-induced shift to a less invasive phenotype may alter fibrinolysis and extracellular matrix remodeling and thereby play a role in the mechanism of GnRH-a-induced reduction in adhesion formation.

Topics: Animals; Disease Models, Animal; Endometriosis; Female; Leuprolide; Metalloendopeptidases; Plasminogen Activators; Plasminogen Inactivators; Rats; Rats, Sprague-Dawley; Tissue Adhesions

We report a prospective pilot study which evaluated the feasibility of combined ultrasonographically guided drainage and laparoscopic excision after pre-operative administration of a gonadotrophin-releasing hormone analogue for 3 months in the management of ovarian endometriotic cysts >5 cm. Ten patients with an ultrasonographic diagnosis of large unilateral or bilateral ovarian endometriotic cysts received an intramuscular injection of leuprorelinum acetate 3.75 every 4 weeks for 12 weeks. After 4 weeks of medical treatment, the endometrioma was carefully drained transabdominally under ultrasonographic control. Within 8 weeks since the last injection, the patients were submitted to a second ultrasonography, and laparoscopy-guided stripping of the endometrioma was performed. A videotape review was undertaken to evaluate duration and complexity of the different phases of surgery. Stripping of endometriomas with preservation of residual ovarian parenchymas was obtained in all cases; adhesiolysis was complete in 6 cases. There were neither intra-operative complications nor conversions in laparotomy. In conclusion, gonadotrophin-releasing hormone analogue and cyst drainage seem to permit an easy laparoscopic approach of large endometriomas; the findings of our pilot phase seem to justify a randomized trial to better define the effectiveness of this approach with respect to standard procedures.

Topics: Adult; Drainage; Endometriosis; Feasibility Studies; Female; Humans; Laparoscopy; Leuprolide; Ovarian Cysts; Pilot Projects; Prospective Studies; Ultrasonography

Changes in the specific antiendometrial IgM antibodies in an endometriotic patient, who were treated with leuproride acetate and in turn with Keishi-bukuyogan, were investigated by the flowcytometric analysis which was developed in our laboratory. The oriental therapy decreased the specific IgM antibody titer gradually and kept the patient symptom-free for more than 7 months without any suppression of serum CA125 and estradiol levels. On the other hand, leuproride acetate therapy suppressed both serum CA125 and serum estradiol levels but not the IgM antibody titer. The results suggest that the specific antiendometrial IgM autoantibody could be a pathogenic molecule in endometriosis and it could also serve as a clinical marker for the oriental therapy of endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Autoantibodies; Cells, Cultured; Drugs, Chinese Herbal; Endometriosis; Female; Humans; Immunoglobulin M; Leuprolide

Adenomyosis is a common pathologic finding significantly related to the menstrual and reproductive characteristics of women. Although noted during younger reproductive years, it usually presents in women over 35 years of age. For those with a strong desire to preserve fertility, there is presently no uniform agreement on the most appropriate therapeutic methods to manage the condition. Herein, we present a case of long-term secondary infertility with successful pregnancy after treatment of deep adenomyosis with cytoreductive surgery and a subsequent six-month course of gonadotropin-releasing hormone agonist (GnRHa) therapy. For those who want to conceive, early combined GnRHa therapy immediately following cytoreductive surgery and a delay of four to six months before attempting to fall pregnant is advisable. This is because adenomyosis tends to recur rapidly and the myometrium can be significantly disrupted during surgery. The major obstetric complications, such as uterine atony, rupture or placenta accreta, do not increase with adenomyosis during pregnancy. Although two events of threatened abortion and one of preterm labor were encountered during the pregnancy course, a healthy 2,900-g female was delivered by low transverse cesarean section at term. A cesarean section was performed because of previous large cytoreductive surgery. In contrast to GnRHa therapy alone, we report an effective alternative to hysterectomy in order to maintain fertility and achieve successful pregnancy.

Topics: Adult; Combined Modality Therapy; Endometriosis; Female; Humans; Leuprolide; Pregnancy

To compare the outcome of in vitro fertilization and embryo transfer (IVF-ET) after laparoscopic surgery in women with endometriosis with that of patients with tubal factor infertility.. Retrospective survey of hospital and office charts using a computerized worksheet.. Lin-Kou medical center of Chang Gung Memorial Hospital.. Sixty-seven women with minimal to mild or moderate to severe endometriosis. Women with tubal factor infertility without other associated disorders (60 cycles) made up the control group.. Seventy-five consecutive cycles of IVF-ET were performed in these patients who failed to conceive after laparoscopic conservative surgery.. The concentration of serum estradiol on the day of human chorionic gonadotropin (hCG) injection, the day of hCG injection, clinical pregnancy rates per transfer, number of follicles larger than 14 mm, number of embryos transferred, and implantation rate were not significantly different between women with endometriosis and those with tubal factor infertility. The number of oocytes retrieved and number fertilized were decreased, and the basal level of follicle-stimulating hormone on cycle day 3 was higher in women with both degrees of endometriosis. Women in both endometriosis groups received more follicle-stimulating hormone and human menopausal gonadotropin than those with tubal factor infertility.. The outcome of IVF-ET in patients with endometriosis after laparoscopic surgery did not differ from that in the group with tubal factor infertility, but the former required more ampules of gonadotropin to achieve the same response. The advantages of laparoscopic surgery in women with endometriosis should be probably correlated with success of IVF-ET.

Topics: Adult; Case-Control Studies; Chorionic Gonadotropin; Danazol; Embryo Transfer; Endometriosis; Estrogen Antagonists; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility, Female; Laparoscopy; Leuprolide; Menotropins; Pregnancy; Retrospective Studies; Treatment Outcome

To investigate monocyte chemotactic protein-1 concentrations in the peritoneal fluid (PF) of women with or without endometriosis, then assess peritoneal mesothelial cells as a potential source of monocyte chemotactic protein-1.. Prospective study.. University medical center.. Women with (n = 60) or without (n = 18) endometriosis.. First monocyte chemotactic protein-1 levels in PF were measured, then mesothelial cells in culture were treated with cytokines.. In PF and culture supernatants, monocyte chemotactic protein-1 was measured by ELISA. In vitro monocyte chemotactic protein-1 messenger RNA expression was evaluated by Northern analysis.. The median concentration of monocyte chemotactic protein-1 in PF of control women was 137 pg/mL (conversion factor to SI unit, 0.115; range, 12 to 418 pg/mL); that of women with moderate endometriosis was 205 pg/mL (range 65 to 6,000 pg/mL); and that of those with severe endometriosis was 1,165 pg/mL (0 to 2,602 pg/mL). Within the moderate to severe endometriosis group, monocyte chemotactic protein-1 levels were higher in women with untreated endometriosis (354 pg/mL range 0 to 6,000 pg/mL) than in women receiving GnRH agonist (128 pg/mL, range 0 to 216 pg/mL). In the control group, monocyte chemotactic protein-1 levels were higher in the proliferative phase than in the secretory phase. Mesothelial cells produced constitutively monocyte chemotactic protein-1; moreover, both interleukin-1 alpha and tumor necrosis factor-alpha induced higher levels of monocyte chemotactic protein-1.. Levels of monocyte chemotactic protein-1 in PF were higher during the proliferative phase than secretory phase of control women and increased in moderate to severe endometriosis. The regulated expression of monocyte chemotactic protein-1 may recruit macrophages into PF and contribute to the pathogenesis of endometriosis.

Topics: Antineoplastic Agents, Hormonal; Ascitic Fluid; Cells, Cultured; Chemokine CCL2; Endometriosis; Epithelial Cells; Epithelium; Female; Humans; Interleukin-1; Leuprolide; Menstrual Cycle; Prospective Studies; Reference Values; RNA, Messenger; Sterilization, Tubal; Transcription, Genetic; Tumor Necrosis Factor-alpha

We report a case of parenchymal pulmonary endometriosis in combination with severe endometriosis genitalis externa. The difficulties on the way to final diagnosis are described, also the different possibilities of hormonal treatment that results in ovarian suppression. In our case the patient is without any symptoms since three years using a GnRH-Agonist as first line therapy and as second line therapy high-dose medroxyprogesterone acetate. Because of the very good clinical results after hormonal suppression surgical intervention might become necessary only in certain cases. This can be the case when after intolerance of hormonal treatment angiography of lung vascular system on the bases of number and localization of endometrial lesions shows good operative conditions.

Topics: Adult; Angiography; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Drug Therapy, Combination; Endometriosis; Fallopian Tubes; Female; Hemoptysis; Humans; Laparoscopy; Leuprolide; Lung Diseases; Medroxyprogesterone Acetate

Gonadotropin-releasing hormone (GnRH) agonists are synthetic derivatives of the native decapeptide produced by the hypothalamus. These agents cause a reversible suppression of the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland. With GnRH agonist therapy, there is a resulting loss of endogenous ovarian gonadotropin stimulation and a severe hypo-estrogen state consistent with castrate levels of estrogen. Recently, GnRH agonists such as leuprolide and goserelin have been noted to be effective in treating mild to severe endometriosis. Side effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. However, despite some reports of emotional lability as an adverse effect of GnRH agonists, it appears that the occasional, rather severe psychiatric consequences of these agents are underappreciated. In this article, we present the case reports of 4 women of reproductive age with no prior psychiatric history who were treated with a GnRH agonist for endometriosis. These women developed symptoms consistent with various psychiatric disorders, including panic disorder and major depression with and without psychotic features. Three of these patients were given sertraline while on GnRH agonist therapy, which improved their mood and anxiety symptoms. Women undergoing GnRH agonist therapy may provide a model with which to investigate mood disorders during the perimenopausal stage of life.

Topics: 1-Naphthylamine; Adult; Antidepressive Agents; Antineoplastic Agents, Hormonal; Anxiety Disorders; Depressive Disorder; Endometriosis; Female; Humans; Leuprolide; Sertraline

Endometriosis is undoubtedly an extremely complex disease from both a diagnostic and therapeutic point of view. The finding that the continuous administration of GnRH analogs suppresses gonadotropin release by the hupophysis, thus blocking ovary function, has promoted researchers to use these drugs in the treatment of endometriosis.. Having reviewed the data reported in the literature, the authors selected from the numerous drugs used to resolve implants (oestroprogestogens, danazol, progestogens, clomiphene citrata, GnRH analogs), a GnRH analog with a depot action known as leuprorelin (D-Leu6-Pro9-NH-Ethylamide).. This drug was administered to 98 patients suffering from endometriosis at a dose of one intramuscular phial every 30 days for six months.. The results obtained (complete resolution of disease in 610.2% of cases, partial remission in 30.6% of cases, transient improvement in 9.2% of cases owing to reduced patient compliance, percentage of pregnancies after treatment 12%), allow the authors to conclude that the use of a GnRH antagonist, like leuprorelin, owing to its efficacy and good tolerability, represents a valid alternative to oestroprogestogens and Danazol in the treatment of implants and the symptoms of endometriosis.

Topics: Adult; Dose-Response Relationship, Drug; Endometriosis; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Leuprolide; Middle Aged

Abdominal wall endometriosis usually occurs in the surgical scar of previous cesarean sections. This condition often presents as a mass with cyclical pain and swelling. Two cases of abdominal scar endometriosis are reported. The definitive diagnosis was established by pathologic analysis. Both patients were premenopausal with no history of endometriosis. Pelvic endometriosis was not detected in the patient undergone laparotomy. The management consisted in perform and adequate excision to prevent recurrence. The utility of drug therapy is evaluated.

Topics: Abdominal Muscles; Adult; Antineoplastic Agents, Hormonal; Cesarean Section; Cicatrix; Danazol; Endometriosis; Estrogen Antagonists; Female; Humans; Leuprolide; Muscular Diseases; Postoperative Care; Time Factors

The fact that RU 486 curtailed estrogen-induced endometrial proliferation in primates and relieved pelvic pain in women with endometriosis is the reason for continuing research on antiprogestins. Thirty-two adult female cynomolgus monkeys demonstrating menstrual regularity had surgery for the induction of endometriosis. After lesion staging, four treatment groups (n = 8), each of 1-yr duration, were made. Group I received combination/sequential therapy with depot GnRH agonist (GnRH-a) for 3 months, followed by weekly RU 486 for 9 months. Group II received weekly RU 486, group III received monthly GnRH-a, and group IV served as a vehicle control. A staging laparotomy was performed every 3 months to assess the area of peritoneal endometriosis (square centimeters) and the thickness of in situ endometrium. Bone density was measured serially by dual x-ray absorptiometry. Serum was collection weekly. Mean (+/- SE) serum estradiol levels were lower after GnRH-a (77.1 +/- 2.6 pmol/L) than after RU 486 (231 +/- 12 pmol/L) treatment and lower than those in untreated cycling controls (231 +/- 13 pmol/L). GnRH-a produced significant atrophy of endometriotic plaques within 3 months of therapy; this lesion reduction was sustained with RU 486. Both GnRH-a and RU 486 alone produced profound thinning of ectopic and eutopic endometrium throughout 1 yr of continuous therapy. Bone density decreased significantly after 6 months of GnRH-a alone (P < 0.05), without significant changes in the other groups. After RU 486 treatment, there were no significant changes in testosterone, androstenedione, sex hormone-binding globulin, or cortisol. Like GnRH-a, long term antiprogestin therapy produced a reduction in the volume of pelvic endometriotic lesions as well as atrophy of in situ endometrium; however, RU 486 allowed maintenance of tonic ovarian estradiol secretion, suggesting that efficacious endometriosis therapy can be sustained long term without the sequelae of hypoestrogenism, specifically bone density loss.

Topics: Animals; Bone Density; Endometriosis; Endometrium; Estradiol; Female; Hormone Antagonists; Leuprolide; Macaca fascicularis; Mifepristone; Progestins; Time Factors; Vagina

Therapy of endometriosis with a GnRH-agonist (Leuprorelin) demonstrated a good therapeutical efficiency. As a side effect it had a significant negative impact on trabecular bone mass (non significant on cortical bone) as measured by DXA. Rising levels of Osteocalcin indicated the stimulation of bone remodelling. Three years after the end of the therapy a long term follow up control was able to detect the complete recovery of the mean density values in the extremities with even higher values in some patients compared with the initial measurement. In the spine half of the patients reached or surpassed the initial values. Regarding the patients history the differences in the recovery were obviously due to a different lifestyle especially body exercise, and not due to a different reaction to the GnRH-agonist therapy. Without being able to predict the individual bone loss due to a GnRH agonist therapy the results of this study indicate that the transient oestrogen deficiency does not result in a relevant long term bone loss or an elevated risk of osteoporosis. On the other hand in case of known risk factors or of a prolonged or repeated GnRH-agonist therapy the individual bone density and the individual bone loss should be controlled by DXA. Those patients with a significant negative impact on their bone mass then can be treated directly.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Bone Density; Bone Remodeling; Delayed-Action Preparations; Endometriosis; Female; Follow-Up Studies; Humans; Leuprolide; Long-Term Care; Osteocalcin; Osteoporosis

In a previous study 198 patients with histologically confirmed endometriosis underwent a "three-step" therapy, where surgical removal of endometriosis implants was followed by a 6 months treatment with 3.75 mg leuprorelinacetate depot as monthly subcutaneous injections and a second look laparoscopy with removal of residuals. In the following report long-term follow-up data generated in 112 of the above 198 patients on the post-treatment effect in respect to symptoms and pregnancy outcome in infertility are reported. For this purpose a special questionnaire was used. The follow-up period was up to 60 months with a median time of 33.5 months. Out of 112 patients 91 complained of infertility. 43 out of these 91 (47.3 %) became pregnant during the follow-up period, resulting in 55 pregnancies and 36 newborns. More than half of these patients conceived spontaneously, whereas in the rest stimulation programs became necessary. Recurrence of dysmenorrhoea, dyspareunia and pelvic pain was defined as recurrence of disease. During the follow-up period 70/112 (62.5 %) of the patients complained recurrence of symptoms with median first onset at 11 months. In two third symptoms were still less severe than at admission and classified as mild and moderate. The r-AFS score at first and second look laparoscopy did not differ in patients with and without recurrence of disease (p = 0.311 and 0.750). Only 28.6 % (20/70) of patients required an additional medical or surgical treatment. A subgroup of 51 patients could be evaluated in respect to quality of life and improvement of subjective conditions. Regain of quality of life and improvement of subjective conditions were reported in 54.9 % (28/51) and 52.9 % (27/51) respectively. The study results suggest that although the physiological effects of leuprorelin acetate treatment as suppression of ovarian function is rapidly reversible, the therapeutic effects linger, as evidenced by ongoing reduction of symptoms from baseline, leaving many patients asymptomatic or much improved longer than 1 year after treatment has ended. Besides long term relief and/or sustained reduction in symptom severity, the high pregnancy rate in infertility, as well as regain of quality of life and well being favour this therapeutic approach in endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Endometriosis; Female; Follow-Up Studies; Humans; Infant, Newborn; Infertility, Female; Injections, Subcutaneous; Leuprolide; Pregnancy; Quality of Life; Recurrence; Treatment Outcome

Ureteral obstruction due to endometriosis is an infrequent condition which can be asymptomatic for a long time. Irreversible loss of renal function may result in cases with delayed diagnosis. Our report concerns a case of unilateral hydronephrosis and hypertension due to retroperitoneal endometriosis occurring in a 24-year-old woman. The management of patients bearing obstructive uropathy caused by endometriosis is discussed. In the present case, a conservative operation followed by medical treatment, including GnRH analogs, was used to preserve reproductive capacity.

Topics: Adult; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Contraceptives, Oral, Synthetic; Desogestrel; Endometriosis; Estradiol Congeners; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Hydronephrosis; Hypertension, Renal; Leuprolide; Retroperitoneal Space; Ureteral Obstruction

To evaluate the effect of hormonal suppression on the size of ovarian endometriomas and to develop a predictive model for changes in the size of these lesions.. The study consisted of 80 women of reproductive age with the diagnosis of stage IV pelvic endometriosis, according to the revised American Fertility Society (rAFS) classification, and included 48 women with endometriomas > or = 3 cm. After the initial laparoscopic and sonographic evaluation, ovarian suppression was achieved with either danazol or a gonadotropin-releasing hormone agonist (GnRH-a) for six months. In all patients, pretreatment and posttreatment pelvic sonograms were performed, and at the end of treatment residual disease was evaluated and resected by laparotomy or laparoscopy. Seven of 80 women with endometriomas > or = 3 cm had serial sonograms during the course of therapy. Serial pelvic sonograms in this subgroup were used to develop a statistical model for predicting the size of endometriomas after treatment. The model was then tested in another subgroup of 41 women with endometriomas > or = 3 cm.. At the end of treatment, there was a significant decrease in the r-AFS score in both the danazol and GnRH-a groups. Medical treatment facilitated surgical resection of residual disease and preservation of ovarian tissue. There was no difference in this respect between danazol and GnRH-a. Endometriomas decreased by 51% in both treatment groups. The predictive model, when tested on 41 patients, underestimated the actual change by 11%, but the difference was within the 95% confidence limits.. This study documented, for the first time, that ovarian endometriomas decrease in size during hormonal suppression. Both danazol and GnRH-a were equally effective.

Topics: Adult; Antineoplastic Agents, Hormonal; Danazol; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Laparotomy; Leuprolide; Ovarian Diseases; Preoperative Care; Prospective Studies; Regression Analysis; Ultrasonography

Our purpose was to verify regional immune modulations and to test the effect of gonadotropin-releasing hormone agonist in women with endometriosis.. Concentrations of peritoneal cytokines, including interleukin-1 beta, interleukin-2, soluble interleukin-2 receptor, interleukin-6, granulocyte-monocyte colony-stimulating factor, interferon gamma, and tumor necrosis factor-alpha were compared in women with and without endometriosis. Peritoneal cytokine and interleukin-2 production were examined by adding various mitogens to peritoneal fluid mononuclear cells of women with advanced endometriosis before and after gonadotropin-releasing hormone agonist treatment.. A significant increase in peritoneal interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha and a decrease in interferon gamma were noted in women with endometriosis. After gonadotropin-releasing hormone agonist treatment interleukin-6 decreased and interferon gamma increased. A significant impairment of interleukin-2 production of peritoneal fluid mononuclear cells by phytohemagglutinin and pokeweed mitogen stimulation was demonstrated in endometriosis, and production could be restored after gonadotropin-releasing hormone agonist treatment.. These results indicate that regional immunologic dysfunction might be invoked in the disease process of endometriosis.

Topics: Ascitic Fluid; Endometriosis; Female; Humans; Interferon-gamma; Leuprolide; Lymphocyte Activation; T-Lymphocytes

A case is presented of massive ascites and right sided pleural effusion caused by endometriosis. The final diagnosis was not made for a considerable time. Massive ascites and a right sided pleural effusion caused by endometriosis is rare, with fewer than 10 reports in the literature worldwide. Physicians should be aware of this potentially tentially treatable cause, having excluded other possibilities such as malignancy and tuberculosis.

Topics: Adult; Ascites; Endometriosis; Female; Humans; Leuprolide; Pleural Effusion

A spontaneous colonic adenocarcinoma and endometriosis was diagnosed in a 34-year-old female rhesus macaque (Macaca mulatta). The tumor caused partial obstruction of the ascending colon and histologically resembled the commonly described napkin-ring tumors of the descending and sigmoid colon found in humans. Serum levels of CA 125, a high-molecular-weight glycoprotein antigen that has been reported elevated in a variety of pathological conditions of the pelvic cavity in humans, was severely elevated. Both the adenocarcinoma and the endometriosis may have contributed to this finding.

Topics: Adenocarcinoma; Animals; Carcinoembryonic Antigen; Colonic Neoplasms; Endometriosis; Female; Humans; Hysterectomy; Leuprolide; Macaca mulatta; Primate Diseases

To report a case of intestinal obstruction that developed shortly after preoperative administration of a GnRH analogue (GnRH-a) that caused flare-up and rapid progression of enteric endometriosis.. Case report.. University tertiary reproductive endocrinology practice.. A 34-year-old nulligravid female with progressive severe symptomatic endometriosis.. Planned preoperative administration of GnRH-a for 3 months followed by extirpative surgery and hormone replacement therapy. Instead, total abdominal hysterectomy, bilateral salpingoophorectomy, resection of the obstructed ileocecal junction, and side-to-side ileo-ascending enterocolostomy was performed.. Preoperative GnRH-a administered in the midfollicular phase resulted in flare-up of preexisting ileocecal endometriosis that rapidly progressed, resulting in partial small bowel obstruction.. Gonadotropin-releasing hormone agonist should be used with caution when there is known or suspected enteric endometriosis. Consideration should be given to blocking the agonistic effect of GnRH-a in this setting by the prior or concomitant use of progestins or danazol.

Topics: Adult; Endometriosis; Female; Humans; Hysterectomy; Ileal Diseases; Ileocecal Valve; Intestinal Obstruction; Leuprolide

To investigate the impact of endometriosis stage on IVF.. A retrospective study of 214 patients diagnosed with endometriosis who underwent 360 cycles of IVF at The New York Hospital-Cornell Medical Center. Meanwhile, 111 pure mechanical (tubal) infertility patients treated in 160 cycles at the same time were designated as the control group for comparison.. Patient's hormone and semen profiles, hormonal response and outcome to stimulation, as well as the outcome of pregnancy, abortion, and delivery rate were analyzed.. No differences in the pregnancy outcome between the endometriosis and control groups were noted when compared among the subgroups of pure endometriosis, endometriosis plus tubal factor, endometriosis plus others (primarily endometriosis plus male factor), and control. Comparing the outcomes in pure endometriosis cases by staging, we could not find any discrepancies in terms of pregnancy rates (PRs) according to the severity of the disease. The addition of GnRH analogur down-regulation to gonadotropin stimulation resulted in an increase in PR. A relatively high delivery rate (38.9% per cycle, 41.9% per retrieval, and 43.2% per transfer) was achieved when the pure endometriosis patients were treated with concomitant leuprolide acetate down-regulation and gonadotropin.. We have observed that pregnancy outcome in patients with endometriosis was not different than the outcome for patients with mechanical (tubal) infertility. There were no differences in PRs by stage of endometriosis.

Topics: Adult; Endometriosis; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Menotropins; Pregnancy; Pregnancy Outcome; Retrospective Studies

Progestin or estrogen-progestin combination therapy has not proven useful in the treatment of endometriosis of the abdominal scar after cesarean delivery. We report our experience in managing this condition with a gonadotropin agonist.. A 22-year-old black woman with a history of two previous cesareans developed endometriosis of the abdominal scar. The extent of the lesion was estimated by computed tomographic (CT) scan, and a 6-month preoperative course of leuprolide acetate was administered. The patient exhibited prompt symptomatic response to the gonadotropin agonist, but the physical examination and CT scan findings were unchanged. Pathologic examination after surgical removal of the lesion confirmed the clinical diagnosis.. Leuprolide acetate administered to a patient with cesarean scar endometriosis was associated with an improvement in symptoms, but there was no change in lesion size.

Topics: Adult; Cesarean Section; Cicatrix; Endometriosis; Female; Humans; Leuprolide; Postoperative Complications; Pregnancy; Tomography, X-Ray Computed

Sciatic nerve endometriosis was previously treated primarily with surgery. Most commonly hysterectomy and bilateral salpingo-oophorectomy have been used; however, two reports also describe successful conservative surgery with resection of the endometriosis from the sciatic nerve. Only one case of sciatic nerve endometriosis has been reported to have responded to medical management. This report details the rapid and complete resolution of sciatica secondary to endometriosis after medical treatment with the gonadotropin releasing hormone analog leuprolide acetate for depot suspension.

Topics: Adult; Endometriosis; Female; Humans; Leuprolide; Peripheral Nervous System Diseases; Sciatic Nerve

Cutaneous or subcutaneous endometriosis is a rare entity that should be suspected in any female presenting with cyclic pain emanating from a mass in the vicinity of an abdominal surgical scar or the umbilicus.. The purpose of this report is to examine the diagnostic procedures for endometriosis and to review the therapeutic value of surgical excision alone or in combination with hormonal treatment.. Endometriosis presenting cutaneously in an infraumbilical laparoscopy scar and endometriosis occurring subcutaneously in a cesarean section scar were both diagnosed via incisional biopsy. Both lesions were treated with hormonal therapy followed by surgical excision.. Hormonal therapy with danazol or with leuprolide resulted in reduction of symptoms but was associated with amenorrhea in both cases and with dyspareunia in the second patient. Subsequent laparoscopy and surgical excision of the endometrioma were curative.. Preoperative hormonal therapy, although sometimes associated with such side effects as amenorrhea, may be used in cases of large endometriotic masses to reduce the size of the surgical defect, but surgical excision remains the treatment of choice.

Topics: Adult; Combined Modality Therapy; Danazol; Endometriosis; Female; Humans; Leuprolide; Skin Diseases

Pharmacological inhibition of ovarian function (PIOF) in young women is associated with hypoestrogenism and very low estrogen levels. These alterations can trigger osteopenia, either by delayed peak bone mass or by active bone destruction, and therefore, an increased risk of osteoporosis at later years. Twenty-one women (mean age: 32 years) with diagnosis of endometriosis, who were submitted to PIOF with leuprolide acetate, were prospectively studied. As a result of treatment for bone resorption with nasal spray salmon calcitonin, 200 UI/day, a decreased femoral and lumbar bone mass density was identified in these women through densitometry. Regarding bone remodelling biochemistry, changes were seen in urinary markers suggesting bone destruction inhibition, while bone formation markers showed stimulation. Biochemical markers of bone turnover and bone mass measurements are useful during follow-up of young women with osteopenia.

Topics: Administration, Intranasal; Adult; Analysis of Variance; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Calcitonin; Depression, Chemical; Endometriosis; Female; Humans; Leuprolide; Ovary; Prospective Studies

To investigate the effects of leuprolide acetate (LA), a GnRH agonist (GnRH-a), and of danazol on the hypothalamic-pituitary-ovarian axis in patients with endometriosis.. Ten patients were divided into LA and danazol treatment groups.. Serum levels of E2, immunoreactive and bioactive LH, pulsatility of LH, and gonadotropins release by GnRH. Changes in serum E2 levels by hMG administration during LA treatment.. Serum E2 level decreased to near castrated levels during the LA treatment, while it remained unchanged during the danazol treatment. Leuprolide acetate administration resulted in a significant suppression of the serum level of bioactive LH, of the pulsatility of LH release, of the pituitary response to GnRH injection, and of the elevation in the serum E2 level by hMG administration, but danazol treatment did not show these suppressive effects.. Our results suggest that the hormonal actions of LA and danazol on endometriosis are different from each other, especially in the suppression of serum E2 level.

Topics: Adult; Danazol; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Leuprolide; Luteinizing Hormone; Menotropins; Ovary; Pulsatile Flow

A patient with a 10-year history of secondary infertility underwent GnRH-a therapy with LA for 5 months to control symptoms of severe adenomyosis and to avoid an unwanted hysterectomy. Shortly after cessation of treatment, the patient conceived. A healthy male was delivered at term by cesarean section, which makes this the first report of a live birth after treatment of severe adenomyosis with a GnRH-a.

Topics: Adult; Endometriosis; Female; Humans; Infertility, Female; Injections, Intramuscular; Leuprolide; Pregnancy; Pregnancy Outcome; Treatment Outcome; Ultrasonography; Uterine Diseases; Uterus

Endometriosis is a disease observed in women in fertile age, it causes pelvic pain characterized by dysmenorrea and dyspareunia. Moreover, there is an association with infertility. Between the alternative of the medical therapeutics of endometriosis drugs with hipogonadotrofic and hypoestrogenic effects, as the danazol and gestrinona has been used. At present, there are analogies of GnRH factor where leuprolide acetate allow a continue liberation in a monthly administration. This is a case of a woman with extensive endometriosis that has hepatitis due to danazol and subsequently was treated with leuprolide acetate. The effectiveness of leuprolide acetate is analyzed in relation with the relief of pain and the laparoscopic evaluation of the endometriosis focus.

Topics: Adult; Danazol; Endometriosis; Female; Follow-Up Studies; Humans; Leiomyoma; Leuprolide; Neoplasms, Multiple Primary; Uterine Neoplasms

To evaluate the safety and efficacy of leuprolide acetate depot (LA, Lupron; TAP Pharmaceuticals, Deerfield, IL) plus daily conjugated equine estrogens (Es, Premarin; Wyeth-Ayerst Laboratories, Philadelphia, PA), and medroxyprogesterone acetate (MPA, Provera; The Upjohn Company, Kalamazoo, MI) "add-back" treatment of endometriosis-associated pelvic pain.. Retrospective case series.. Tertiary care, academic medical center.. Eight patients with moderate to severe pelvic pain and laparoscopically documented endometriosis.. Leuprolide acetate depot 3.75 mg IM every 4 weeks for 24 months. Oral conjugated equine Es 0.625 mg/d plus MPA 2.5 mg/d were also taken from treatment months 3 through 24.. Six women completed the 2-year study. Mean revised endometriosis scores for implants, adhesions, and total values were significantly reduced at the conclusion of treatment from pretreatment scores. Self-reported pelvic pain scores were significantly lower at treatment months 3, 6, 12, 18, 24, and 6 months after therapy than pretreatment scores. Dual X-ray absorptiometry bone density measurements of the lumbar spine did not change significantly during the 24-month treatment period. The proportion of women experiencing hot flushes was significantly reduced after E-progestin add-back treatment from the proportion at treatment month 3.. Treatment with LA depot plus conjugated equine Es and MPA for 2 years was a safe and effective therapy for women with endometriosis and pelvic pain in this small retrospective study.

Topics: Adult; Bone Density; Drug Implants; Endometriosis; Estrogens; Female; Humans; Leuprolide; Menstruation; Pain; Pelvis; Progestins

GnRH agonists are known to suppress LH, FSH, and subsequent ovarian estradiol production by down-regulation of pituitary gonadotropin receptors. Previous investigations have demonstrated that GnRH agonists also suppress GHRH-stimulated GH release in normal men and women and PRL levels in subjects with hyperprolactinemia. Little is known about the effects of GnRH agonists on the hypothalamic-pituitary-adrenal axis. The purpose of the present investigation was to determine the secretion of ACTH and cortisol after an iv infusion of hCRH in control women (n = 11) and in women undergoing treatment with GnRH agonists (n = 10). The plasma and serum levels of ACTH and cortisol increased after infusion of CRH in all women. The basal and CRH-stimulated plasma levels of ACTH and cortisol at each time point were not statistically different between GnRH agonist-treated women and controls. Thus, the chronic use of GnRH agonists is known to suppress the hypothalamic-pituitary-ovarian axis and is associated with GH and PRL suppression as well, but does not apparently alter the hypothalamic-pituitary-adrenal axis.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Endometriosis; Female; Humans; Hydrocortisone; Kinetics; Leiomyoma; Leuprolide; Menstrual Cycle; Reference Values; Uterine Neoplasms

A woman with longstanding primary infertility and progressive, symptomatic rectal endometriosis was treated with daily leuprolide acetate for nine months. All bowel symptoms subsided. The patient was treated with human menopausal gonadotropin and intrauterine insemination prior to discontinuation of the leuprolide acetate, resulting in a twin pregnancy.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Endometriosis; Female; Humans; Infertility, Female; Insemination, Artificial, Heterologous; Leuprolide; Menotropins; Pregnancy; Rectal Diseases

Leuprolide acetate was used to produce a constant hypoestrogenic environment in a young patient with histologically confirmed adenomyosis. Conservative medical therapy was initiated because of the patient's complaint of severe dysmenorrhea coupled with her strong desire for uterine conservation. The initial daily subcutaneous dose was eventually converted to monthly intramuscular depot formulation for patient convenience. A dramatic therapeutic response was observed with each course of therapy. This included a marked reduction in uterine size, amenorrhea, and complete resolution of pelvic pain. Cyclic use of an OC agent following LA was associated with a return of symptoms and uterine growth. The patient did, in fact, conceive immediately on cessation of analogue therapy.

Topics: Adult; Contraceptives, Oral; Delayed-Action Preparations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Laparotomy; Leuprolide; Postoperative Care; Time Factors; Triptorelin Pamoate

We investigated the mechanisms of desensitization induced by gonadotropin-releasing hormone agonist in the pituitary.. Effects of gonadotropin-releasing hormone agonist on the pituitary were studied in vitro and in vivo in the rat. In the clinical study serum luteinizing hormone was measured by radioimmunoassay with a polyclonal luteinizing hormone antibody (luteinizing hormone-radioimmunoassay) and by immunoradiometric assay with monoclonal luteinizing hormone antibodies (luteinizing hormone-immunoradiometric assay) during gonadotropin-releasing hormone agonist treatment.. In the in vitro study bead-attached pituitary cells that were desensitized with a continuous infusion of 10(-7)mol/L gonadotropin-releasing hormone responded to 50 mmol/L K+. In the in vivo study gonadotropin-releasing hormone binding sites and rat luteinizing hormone beta-messenger ribonucleic acid in the pituitary decreased during gonadotropin-releasing hormone agonist treatment, but serum levels of rat luteinizing hormone did not decrease. In addition, a disparity between luteinizing hormone-radioimmunoassay and luteinizing hormone-immunoradiometric assay was demonstrated during gonadotropin-releasing hormone agonist treatment.. Pituitary desensitization in response to gonadotropin-releasing hormone agonist may not be wholly receptor mediated and a nonreceptor process may be involved.

Topics: Animals; Buserelin; Cells, Cultured; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Luteinizing Hormone; Male; Nafarelin; Pituitary Gland; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, LHRH; RNA, Messenger

To determine the effect of baseline complex ovarian cysts on controlled ovarian hyperstimulation and in vitro fertilization (IVF) outcome.. Retrospective analysis with stratification by stimulation regimen and the presence or absence of surgically documented endometriosis.. Two hundred sixty-one women undergoing IVF from May 1, 1989 to December 31, 1990.. The outcome measures assessed were the maximum estradiol (E2) concentration on day of human chorionic gonadotropin (hCG) administration, number of follicles with maximum diameter greater than or equal to 15 mm, number of follicles with maximum diameter greater than or equal to 12 mm, number of days to hCG administration, number of ampules of human menopausal gonadotropin (hMG) used, number of oocytes retrieved and fertilized, number of embryos transferred, and pregnancy and cycle cancellation rates.. There were no statistical differences between cyst and noncyst groups in any of the above parameters of IVF performance. In a single subgroup, patients with endometriosis stimulated with hMG and patients with cysts had significantly lower E2 concentrations than patients without cysts.. The presence of a complex cyst on a baseline ultrasound does not appear to adversely affect IVF cycle outcomes.

Topics: Endometriosis; Female; Fertilization in Vitro; Humans; Leuprolide; Ovarian Cysts; Pregnancy; Retrospective Studies

The plasmatic parameters of coagulatory and fibrinolytic activity were studied in 15 patients with biopsy-proven endometriosis treated with leuprorelin acetate for 6 months. Bleeding time remained constant, indicating the absence of increased bleeding tendencies. The activity of the main inhibitor of the fibrinolytic response, plasminogen activator inhibitor, was reduced by 25%, suggesting an improvement in fibrinolytic reactivity. Plasma levels of fibrin degradation fragments were reduced by 35%, suggesting a marked reduction in the rate of fibrin generation and degradation. A simultaneous reduction in thrombin-antithrombin III complexes and prothrombin fragment 1 + 2 (-10%) indicated that this effect was induced by reduced procoagulant activity, ie, thrombin generation. These data indicate that in gonadotrophin-releasing hormone (Gn-RH) analogue therapy the basal rate of coagulatory processes is reduced. The frequency and extent of fibrin-generating and degrading processes are reduced, suggesting a beneficial effect of Gn-RH analogues on the risk of thromboembolic disease.

Topics: Antithrombin III; Blood Coagulation; Delayed-Action Preparations; Endometriosis; Female; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Leuprolide; Plasminogen Inactivators; Thrombin; von Willebrand Factor

Leuprorelin acetate, a highly potent gonadotrophin-releasing hormone agonist, was originally launched in the USA as a daily injection for the treatment of metastatic prostatic cancer. A once-monthly injectable depot form was subsequently developed. Biodegradable copoly(DL-lactic/glycolic) acid was chosen as the release-controlling polymer, and microspheres containing leuprorelin acetate were prepared by the in-water drying method. Results of studies in rats showed that a copolymer with a molecular weight of 14,000 and a lactic/glycolic acid ratio of 75/25 had the most satisfactory release-controlling properties. Microspheres given once monthly reduced serum testosterone levels in male rats. Microspheres also reduced serum oestradiol levels and caused a marked regression in experimental endometriosis in female rats. In clinical studies of prostatic cancer, use of the depot formulation has effectively reduced the dose required to as low as one-eighth of that needed for administration by daily injection. A sophisticated manufacturing system has now been developed and products now available have many advantages.

Topics: Animals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Endometriosis; Female; Humans; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Microspheres; Prostatic Neoplasms; Rats; Testosterone

Endometriosis was diagnosed in an aged dysmenorrheic rhesus monkey (Macaca mulatta) after biopsy of a 7 cm abdominal mass which could not be completely resected due to extensive adhesions. A 6-month course of treatment with leuprolide, a gonadotropin-releasing hormone agonist, resulted in cessation of menstrual cycles and marked clinical improvement. Dysmenorrhea and hypovolemic shock occurred 2 months after therapy was completed. Despite supportive treatment and resumption of leuprolide, the primate's clinical deterioration and abdominal mass enlargement necessitated euthanasia. To our knowledge, this is the first report of a case of endometriosis in a rhesus macaque treated with a gonadotropin-releasing hormone agonist. Although prolonged leuprolide therapy was clinically effective, its cost and the difficulty in early diagnosis of endometriosis may limit its use in nonhuman primate medicine.

Topics: Animals; Endometriosis; Female; Leuprolide; Macaca mulatta; Monkey Diseases

The lung is an infrequent location of extragenital endometriosis, an exceptional cause of hemoptysis or pneumothorax. Adequate management has not yet been well established. We present two cases of pulmonary endometriosis, parenchymal and pleural. The presenting symptoms were catamenial hemoptysis and pneumothorax, respectively, which were treated with GnRH analogues. The first patient received Buserelin (900 micrograms/day intranasally) for 6 months. After 15 months of normal menstrual activity, the symptoms reappeared. The patient was then treated with Triptorelin (3.75 mg/month intramuscularly) for 6 months and remains asymptomatic and menstruating 14 months after discontinuing treatment. The patient presenting with pneumothorax was treated with leuprolide (1 mg/day subcutaneously) for 6 months and is asymptomatic 1 year after stopping treatment. These results suggest that GnRH analogues may be an acceptable alternative to danazol in the medical management of pulmonary endometriosis.

Topics: Administration, Intranasal; Adult; Antineoplastic Agents; Buserelin; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hemoptysis; Hormones; Humans; Leuprolide; Lung Neoplasms; Pneumothorax; Triptorelin Pamoate

Gonadotropin-releasing hormone (GnRH), a decapeptide synthesized and released by the hypothalamus, regulates production and release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the adenohypophysis. Parenterally administered GnRH was initially used diagnostically as a test of adenohypophyseal reserve of LH and FSH. Subsequently, native GnRH was used therapeutically to treat hypothalamic hypogonadal and infertility states in both men and women. Because of the low potency and short half-life of native GnRH, long-acting, potent analogs have been developed that suppress secretion of native pituitary gonadotropins, resulting in medical gonadectomy. When administered parenterally and, more recently, intranasally, these compounds are useful in the management of prostate and breast carcinoma, endometriosis and uterine leiomyomata, precocious puberty and nontumorous ovarian hyperandrogenic syndromes.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Male; Nafarelin; Prostatic Neoplasms

Topics: Adult; Antineoplastic Agents; Danazol; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Rectal Neoplasms

We report a case of ascites and bilateral pleural effusions associated with an endometrioma in a 26-year-old woman of Chinese descent. She had a right salpingo-oophorectomy and partial omentectomy performed, and she received leuprolide acetate depot injections after the operation. We believe this is the first description of use of a GnRH agonist to treat this rare condition.

Topics: Adult; Antineoplastic Agents; Ascites; Endometriosis; Fallopian Tubes; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Omentum; Ovarian Neoplasms; Ovariectomy; Pelvic Neoplasms; Pleural Effusion

Presented here is the first reported case of biopsy-proved adenomyosis treated medically with long-term GnRH analogue. Uterine volume, as calculated by serial ultrasound measurements, was reduced by 65% after 4 months and remained small several months after discontinuation of therapy. Size reduction was accompanied by amenorrhea and relief of severe dysmenorrhea. Though not proposed as a substitute for surgery, GnRH analogue may be useful as a surgical adjuvant or for temporary reduction of symptoms.

Topics: Adult; Antineoplastic Agents; Endometriosis; Female; Genital Neoplasms, Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Injections, Subcutaneous; Leuprolide; Ovarian Neoplasms; Uterine Neoplasms

A new, simple experimental endometriosis model was established by auto-transplanting endometrial tissue fragments beneath kidney capsules in female rats. The transplanted endometrial tissue grew well, forming a fluid-filled cyst, which reached maximal size 2 to 3 weeks after transplantation. The growth and maintenance of the transplants was dependent on the ovary: ovariectomy induced regression of well grown transplants. The therapeutic effects of TAP-144-SR (biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model. A single sc injection of TAP-144-SR (corresponding to 1, 10 or 100 micrograms/kg/day of TAP-144), suppressed the growth of the transplanted endometrial tissues and uterine weight in a dose-dependent manner. At 100 micrograms/kg/day, the suppressive effect was more marked in rats given TAP-144-SR than in those given TAP-144 solution. The extent of suppression was comparable to that caused by ovariectomy. Serum and pituitary concentrations of LH and FSH were also reduced more markedly by the administration of TAP-144-SR than by TAP-144 solution. From these results, the present endometriosis model was found to be useful for the evaluation of compounds with potential therapeutic activity. The sustained-release formulation of TAP-144 seems to be beneficial over its solution in terms of both convenience and efficiency for therapy of patients with endometriosis.

Topics: Animals; Antineoplastic Agents; Delayed-Action Preparations; Disease Models, Animal; Dose-Response Relationship, Drug; Endometriosis; Endometrium; Female; Follicle Stimulating Hormone; Leuprolide; Luteinizing Hormone; Organ Size; Ovariectomy; Ovary; Pituitary Gland; Rats; Rats, Inbred Strains; Uterine Neoplasms; Uterus

Experience with depot forms of hormonal preparations suggests that severe adverse reactions are infrequent and immediate hypersensitivity reactions are rare. We report a case of recurrent anaphylaxis to a depot form of GnRH analogue requiring both acute and chronic management.

Topics: Adult; Anaphylaxis; Delayed-Action Preparations; Emergencies; Endometriosis; Female; Humans; Leuprolide; Skin Tests; Time Factors; Uterine Neoplasms

Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. The standard therapy is surgical. However, medical treatment has been reported using danazol, progestins, and estrogen-progestin combinations, although solid documentation of the effect of hormonal therapy against ureteral endometriosis is lacking. Gonadotropin-releasing hormone (GnRH) agonist treatment of endometriosis has yielded good results but has not been adequately reported in patients with ureteric involvement. We report three patients treated with a GnRH agonist, leuprolide acetate, for 6-9 months as a preoperative course. One patient had bilateral and two had unilateral obstruction. The preoperative course relieved the obstruction in the patient with bilateral disease and in one with unilateral changes. The failure occurred in a patient with intrinsic ureteric endometriosis. This early experience suggests a place for GnRH agonist therapy for patients with ureteric obstruction due to endometriosis, probably, but not necessarily, in conjunction with a planned surgical procedure. If medical therapy is attempted, close surveillance of renal function is mandatory.

Topics: Adult; Antineoplastic Agents; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Hydronephrosis; Leuprolide; Middle Aged; Pelvic Neoplasms; Radiography; Ureteral Neoplasms; Ureteral Obstruction

We report the case of a patient who was successfully treated with a long-acting GnRH agonist for pulmonary endometriosis. This 28-year-old woman had symptomatic pleural endometriosis, documented by biopsies, as well as symptomatic pelvic endometriosis. Two surgical procedures, consisting of excision of pleural endometriotic tissue and partial pleurectomies, failed to relieve her chest symptoms. Little relief was achieved with pseudopregnancy treatment. Satisfactory symptomatic improvement was obtained with danazol, but this medication had to be discontinued because of severe side effects. Trial of a GnRH agonist, leuprolide acetate, achieved complete remission of her chest symptoms; in addition, the patient became pregnant immediately after cessation of therapy. Gonadotropin-releasing hormone agonist therapy may be an important therapeutic alternative for women with pulmonary endometriosis who cannot tolerate danazol treatment and in whom surgical therapy fails to relieve the chest symptoms.

Topics: Adult; Antineoplastic Agents; Danazol; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pelvic Neoplasms; Pleural Neoplasms

Effects of danazol, gonadotropin-releasing hormone agonist (leuprolide), and danazol-leuprolide combination on experimental endometriosis were evaluated in female rats. A complete resorption of the fluid and a marked decrease in the volume of endometrium autotransplanted under the renal capsule were found after castration (1.4 +/- 0.1 mm3 in castrated, n = 14, vs 26.7 +/- 5.6 mm3 in intact control, n = 16). Histologic examination indicated atrophy and regression of the endometrial explant. These atrophic changes of endometrial explant were also induced by danazol, leuprolide, and the combination treatment. However, the volume of explants after combination therapy with danazol and leuprolide (1.8 +/- 1.0 mm3, n = 17) was significantly less than that after therapy with danazol (11.6 +/- 2.8 mm3, n = 20) or leuprolide alone (5.9 +/- 1.4 mm3, n = 24). The combination therapy (16/17) was also shown to be superior to danazol (9/20) or leuprolide alone (14/24) to induce the regression of fluid in experimental endometriosis. As expected, administration of leuprolide decreased the serum estradiol level, but use of danazol did not. These findings suggest that a combination therapy of danazol and gonadotropin-releasing hormone agonist, which show different modes of action, may be a potential modality in treatment of patients with advanced endometriosis.

Topics: Analysis of Variance; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Danazol; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Kidney Neoplasms; Leuprolide; Ovariectomy; Rats; Rats, Inbred Strains; Remission Induction; Transplantation, Autologous; Transplantation, Heterotopic

We report a case of an insulin-dependent diabetic female who received leuprolide acetate and Depo-Lurpon for the treatment of endometriosis. Their use was associated with hyperglycemia and a deterioration in glucose control that necessitated changes in insulin dosage.

Topics: Adult; Antineoplastic Agents; Blood Glucose; Diabetes Mellitus, Type 1; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide

The therapeutic effect of sustained-release microspheres of a potent LHRH agonist (leuprorelin acetate) on experimental endometriosis in female rats was examined histologically. Endometriosis was produced in rats by autotransplantation of endometrial tissue obtained from the left uterine horn into the renal subcapsular space. In the nontreated rats, the transplants were well established and had formed large cysts containing fluid. The walls of the cysts were composed of epithelium and stroma resembling that of normal endometrium. In the rats which received the microspheres of leuprorelin acetate, growth of the transplant was markedly suppressed as evidenced by the reduced size of the cystic cavity and the flattened and pyknotic epithelium. Also, the uterine and ovarian weight decreased significantly. In the ovariectomized rats, growth of the transplant was also markedly suppressed, and the uterine weight decreased. The present results clearly indicate that a single injection of the sustained-release microspheres of leuprorelin acetate markedly suppresses growth of the transplant and produces uterine and ovarian atrophy in the rats.

Topics: Animals; Antineoplastic Agents; Capsules; Danazol; Delayed-Action Preparations; Disease Models, Animal; Endometriosis; Female; Gonadotropin-Releasing Hormone; Leuprolide; Male; Organ Size; Ovariectomy; Ovary; Rats; Uterine Neoplasms; Uterus

Repeated application of GnRH agonists causes a reversible suppression of ovarian function. Suppression on estrogen release is the fundamental idea of this hormonal therapy of endometriosis. We treated twelve patients with histologically proved endometriosis with leuprolide acetate depot in a dose of 3.75 mg s.c. every 4 weeks over a period of 6 months. In the first week of therapy the estrogen level decreased to a post-menopausal niveau along with amenorrhoea during the entire period of therapy. Complaints previous to therapy such as dysmenorrhoea, pelvic pain and dyspareunia were relieved or completely disappeared after therapy. The clinical finding on palpation also diminished or disappeared. In addition to this finding pelvis copy showed a shift from severe endometriosis stage III and stage IV to stage I and stage II of the AFS classification 1985. Regular menstruation appeared in 5 to 9 weeks after the last application to all patients. Out of six cases of infertility, four patients became pregnant. Except for one case, typical menopausal symptoms appeared, such as flush, increased perspiration and sleeping disorders. During and after therapy we could not prove any changes in the lipid metabolism under estrogen therapy. Mineralization of the bone decreased under therapy by about 3%. Simultaneously, serum osteocalcin increased. Demineralization occurred with one exception within the normal range for the corresponding age. With identical efficiency but less side effects, we see therapy with GnRH agonists as an alternative to current hormonal therapy of endometriosis.

Topics: Adolescent; Adult; Amino Acid Sequence; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Menstruation; Molecular Sequence Data; Uterine Neoplasms

Gonadotropin-releasing hormone agonists are effective in the treatment of endometriosis and myomas, both of which are estrogen-dependent processes, but there is a high clinical recurrence rate after therapy is discontinued. Long-term continuous therapy (2 years or more) has a cumulative effect on bone loss and causes other uncomfortable or harmful side effects. Noninvasive assessments of disease response in patients with myomas have shown that bone changes might be prevented and other side effects of long-term therapy can be alleviated by adding back small amounts of estrogen or progestin. No comparable data are available for patients with endometriosis because the need for repeated laparoscopy has made long-term studies impractical. Nevertheless, a short-term study of patients with endometriosis showed that adding small amounts of progestin during treatment with a gonadotropin-releasing hormone agonist may help prevent bone changes.

Topics: Drug Therapy, Combination; Endometriosis; Estrogen Replacement Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Medroxyprogesterone; Medroxyprogesterone Acetate; Norethindrone; Uterine Neoplasms

In this study, in-vitro fertilization (IVF) cycles were examined in patients with endometriosis who received gonadotrophin releasing hormone agonist (GnRHa) therapy in an effort to improve their response to stimulation. Twelve patients treated with an identical gonadotrophin stimulation protocol, with and without GnRHa, were evaluated using paired analysis. In the GnRHa cycles, the total number of oocytes retrieved and transferred per cycle was higher than in the control cycles. In addition, use of the agonist lowered the cancellation rate from 33 to 0%, while a trend towards better pregnancy results was observed. When analysed according to the stage of the disease, the patients with stage III or IV endometriosis had a more dramatic improvement with GnRHa. These data suggest that GnRHa therapy may be beneficial in some patients with endometriosis undergoing IVF.

Topics: Embryo Transfer; Endometriosis; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Hormones; Leuprolide; Pituitary Hormone-Releasing Hormones; Retrospective Studies

GnRH agonist and synthetic steroid such as Danazol, Medroxyprogesterone acetate (MPA) and Gestrinone are useful for the treatment of patients with endometriosis. These compounds induce atrophy and regression of endometriotic tissue, but the action mechanisms are still unclear. The present study, therefore, was undertaken to elucidate the mechanisms of these compounds in the treatment of endometriosis. In addition, a combination therapy with these compounds for endometriosis was also evaluated with an experimental animal model. Effects of GnRH agonist, Danazol and GnRH/Danazol combination on experimental endometriosis were evaluated in female rats. Endometrium autotransplanted under the renal capsule markedly decreased in size following castration. Histologic examination indicated atrophy and regression of the endometrial explant. The changes of endometrial explant were also induced by GnRH agonist, Danazol and combination treatment. However, a combination therapy with GnRH agonist and Danazol (93%) was shown to be superior to GnRH agonist (65%) and Danazol alone (45%) to induce atrophy and regression of experimental endometriosis. As expected, GnRH agonist significantly decreased serum E2, but Danazol did not at all. It is suggested that a combination therapy with GnRH agonist and Danazol may be a potential modality in the treatment of endometriosis. In order to evaluate whether Danazol, MPA, and Gestrinone has a direct inhibitory effect to synthesize estrogen, immature female rats were hypophysectomized and the ovaries were stimulated by a daily PMS injection. Administration of Danazol to the rats for two weeks stimulated the synthesis of 17, 20-lyase, 17 beta-HSD and aromatase activity, but did not inhibit any enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Buserelin; Danazol; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Medroxyprogesterone; Medroxyprogesterone Acetate; Ovary; Pregnadienes; Rats; Rats, Inbred Strains

Luteinising hormone-releasing hormone (LHRH) analogues administered by a continuous release system produce a more complete and constant inhibition of the pituitary-ovarian axis than do multiple, daily intranasal insufflations or a once daily subcutaneous injection. In the present study, results were too limited to make a valid comparison between the clinical efficacy of various formulations in the treatment of endometriosis. A slow-release formulation is more effective in inducing amenorrhoea, but also produces more frequent and more severe clinical symptoms of oestrogen deprivation. There is no significant change in serum cholesterol levels during 6 months of treatment with any of the formulations used. During LHRH analogue treatment, the increase in urinary excretion of calcium is related to the rate and degree of serum oestradiol inhibition but the loss in bone mineral content is small and reversible after cessation of treatment. Both short-term and long-term treatment with LHRH analogues is feasible.

Topics: Buserelin; Delayed-Action Preparations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Nafarelin; Triptorelin Pamoate

Leuprolide acetate is a highly potent analog of luteinizing hormone-releasing hormone. We have prepared 1-month release injectable microcapsules of leuprolide acetate using a biodegradable polymer, poly (dl-lactide-co-glycolide), to treat an endocrine-dependent tumor, prostate cancer. In the present study, the possibility using the microcapsules to treat endometriosis was investigated. In rats, the microcapsules exhibited a pseudo-zero order release from the injection site for 1 month after being administered s.c. and i.m., and maintained effective constant serum levels of the analog during the 4-week treatment. A single injection of the microcapsules (100 micrograms/kg/day as leuprolide acetate) suppressed luteinizing hormone, follicle-stimulating hormone and estradiol for more than 4 weeks, and caused a dramatic regression of growth of Jones experimental endometriosis model in female rats. These results encourage the belief that a 1-month release parenteral preparation of leuprolide acetate may be potentially useful in the therapy of endometriosis in human beings.

Topics: Animals; Capsules; Delayed-Action Preparations; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Injections; Lactic Acid; Leuprolide; Male; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rats; Rats, Inbred Strains

The chemical structure of luteinizing-hormone-releasing hormone (LHRH) was discovered in 1971 after more than a decade of intensive effort. Subsequent physiologic studies in primates and humans showed that the biologic activity of LHRH depends on the way in which the hormone is administered. Pulsatile administration of LHRH, which mimics the natural secretory pattern, causes sustained secretion of the gonadotrophins. This method of administration has been used to induce ovulation in women with hypothalamic amenorrhea and to induce puberty and spermatogenesis in men with hypogonadotrophic hypogonadism. Continuous infusion, however, produces only transient stimulation of gonadotrophin secretion, followed by a "desensitization" response in which gonadotrophin secretion is inhibited. Thus, LHRH can either augment or inhibit gonadotrophin secretion depending on the mode of administration. Recently, long-acting synthetic analogs of LHRH have been shown to desensitize the pituitary gland and inhibit gonadotrophin release when administered as a single daily subcutaneous injection. These LHRH analogs have proved highly effective in the treatment of prostatic carcinoma and central precocious puberty. They are also being studied as a new approach to contraception and to the treatment of endometriosis and polycystic ovary syndrome.

Topics: Animals; Child; Contraceptive Agents, Male; Endometriosis; Estrogens; Female; Follicle Stimulating Hormone; Genital Diseases, Female; Genital Diseases, Male; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamic Diseases; Infertility; Leuprolide; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Ovulation Induction; Polycystic Ovary Syndrome; Prostatic Neoplasms; Puberty, Precocious; Spermatogenesis; Time Factors; Triptorelin Pamoate

This study was designed to test the efficacy of a long-acting GnRH agonist (alpha) for inhibition of ovulation and menses in monkeys as well as suppression of mild to moderate endometriosis through an individualized, intermittent regimen. Endometriosis was surgically induced in 21 cynomolgus monkeys; ectopic tissue viability was verified histologically. GnRH alpha (leuprolide, D-Leu6-Pro9-Net-LHRH, Abbott Laboratories) was injected weekly in treatment cycle 1 (10 microgram/kg, sc; n = 15). Ovulation and menses ceased in 6 of 15 females. For the remaining 9 monkeys, the GnRH alpha dose was increased to 15 microgram/kg weekly in treatment cycle 2. Still, 4 monkeys resisted suppression; in treatment cycle 3, their regimen increased to 15 microgram/kg every fourth day. Thus, anovulation and amenorrhea was achieved in 14 of 15 monkeys within 90 days, seemingly as a result of ovarian desensitization, since GnRH alpha injections usually enhanced serum LH and FSH levels (P less than 0.05). Frequent laparotomies and daily hormonal profiles of estradiol, progesterone, FSH, and LH in serum confirmed these findings. After treatment, 12 of 15 monkeys manifested resolution of ectopic endometrial tissue; concurrently, there was no change in the severity of endometriosis in the 6 saline-injected controls. Six of 15 monkeys became pregnant within 90 days after cessation of GnRH alpha injections; 1 of 6 control females conceived. These findings may encourage consideration of clinical investigations employing individualized and/or intermittent GnRH alpha administration for the treatment of endometriosis or to achieve contraception.

Topics: Animals; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Leuprolide; Luteinizing Hormone; Macaca fascicularis; Menstruation; Ovulation; Pregnancy; Progesterone