leuprolide and Uterine-Neoplasms

Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013.. To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials.. All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.. Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach.. This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report. Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.

Topics: Adult; Antineoplastic Agents, Hormonal; Bias; Contraceptives, Oral; Desogestrel; Female; Goserelin; Humans; Intrauterine Devices, Medicated; Leiomyoma; Leuprolide; Levonorgestrel; Lynestrenol; Medroxyprogesterone Acetate; Menstruation; Middle Aged; Nandrolone; Norethindrone Acetate; Premenopause; Progestins; Randomized Controlled Trials as Topic; Tumor Burden; Uterine Neoplasms

To-date, the only cure for symptomatic uterine fibroids (UFs) is surgical intervention. However, surgery may eliminate the hope of future pregnancies; moreover, the intrinsic risks of surgery make it a less favorable to women with UFs. Because of this, conservative medical therapies have become an attractive and prior option for those women. Leuprolide acetate (LA), a gonadotropin-releasing hormone (GnRH) agonist, is the only pharmacological agent currently approved for the short-term and pre-operative management of symptomatic UFs in the USA. Areas covered: This systematic review covers the successes and failures of prominent drugs that have been researched for UFs in the past and agents that have shown promise in recent clinical trials. The most recent clinical trials and advances in drug therapy are presented in a comprehensive overview outlining the direction UF drug discovery is heading. Expert opinion: Experts in the field are already on the forefront leading the responsibility to uncover potential drugs as long term fertility friendly viable options for non-invasive treatment/prevention of UFs. Indeed, a shift in the UF management is expected in the future.

Topics: Animals; Antineoplastic Agents, Hormonal; Drug Design; Drug Discovery; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

Uterine fibroids are smooth muscle tumours arising from the uterus. These tumours, although benign, are commonly associated with abnormal uterine bleeding, bulk symptoms and reproductive dysfunction. The importance of progesterone in fibroid pathogenesis supports selective progesterone receptor modulators (SPRMs) as effective treatment. Both biochemical and clinical evidence suggests that SPRMs may reduce fibroid growth and ameliorate symptoms. SPRMs can cause unique histological changes to the endometrium that are not related to cancer, are not precancerous and have been found to be benign and reversible. This review summarises randomised trials conducted to evaluate the effectiveness of SPRMs as a class of medication for treatment of individuals with fibroids.. To evaluate the effectiveness and safety of SPRMs for treatment of premenopausal women with uterine fibroids.. We searched the Specialised Register of the Cochrane Gynaecology and Fertility Group, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinical trials registries from database inception to May 2016. We handsearched the reference lists of relevant articles and contacted experts in the field to request additional data.. Included studies were randomised controlled trials (RCTs) of premenopausal women with fibroids who were treated for at least three months with a SPRM.. Two review authors independently reviewed all eligible studies identified by the search. We extracted data and assessed risk of bias independently using standard forms. We analysed data using mean differences (MDs) or standardised mean differences (SMDs) for continuous data and odds ratios (ORs) for dichotomous data. We performed meta-analyses using the random-effects model. Our primary outcome was change in fibroid-related symptoms.. We included in the review 14 RCTs with a total of 1215 study participants. We could not extract complete data from three studies. We included in the meta-analysis 11 studies involving 1021 study participants: 685 received SPRMs and 336 were given a control intervention (placebo or leuprolide). Investigators evaluated three SPRMs: mifepristone (five studies), ulipristal acetate (four studies) and asoprisnil (two studies). The primary outcome was change in fibroid-related symptoms (symptom severity, health-related quality of life, abnormal uterine bleeding, pelvic pain). Adverse event reporting in the included studies was limited to SPRM-associated endometrial changes. More than half (8/14) of these studies were at low risk of bias in all domains. The most common limitation of the other studies was poor reporting of methods. The main limitation for the overall quality of evidence was potential publication bias. SPRM versus placebo SPRM treatment resulted in improvements in fibroid symptom severity (MD -20.04 points, 95% confidence interval (CI) -26.63 to -13.46; four RCTs, 171 women, I. Short-term use of SPRMs resulted in improved quality of life, reduced menstrual bleeding and higher rates of amenorrhoea than were seen with placebo. Thus, SPRMs may provide effective treatment for women with symptomatic fibroids. Evidence derived from one RCT showed no difference between leuprolide acetate and SPRM with respect to improved quality of life and bleeding symptoms. Evidence was insufficient to show whether effectiveness was different between SPRMs and leuprolide. Investigators more frequently observed SPRM-associated endometrial changes in women treated with SPRMs than in those treated with placebo or leuprolide acetate. As noted above, SPRM-associated endometrial changes are benign, are not related to cancer and are not precancerous. Reporting bias may impact the conclusion of this meta-analysis. Well-designed RCTs comparing SPRMs versus other treatments are needed.

Topics: Amenorrhea; Antineoplastic Agents, Hormonal; Estrenes; Female; Humans; Leiomyoma; Leuprolide; Menstruation; Mifepristone; Norpregnadienes; Oximes; Pelvic Pain; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Progesterone; Uterine Neoplasms

Uterine fibroids are the most common premenopausal benign uterine tumours. Fibroids can cause symptoms including heavy menstrual bleeding, pelvic pressure and pain. Progestogens can be administered by various routes. Intramuscular injection of depot medroxyprogesterone acetate (DMPA) has dual actions (stimulatory or inhibitory) on fibroid cell growth. Progestogen-releasing intrauterine systems (IUS) decrease menstrual blood loss associated with fibroids by inducing endometrial atrophy and reduction of uterine fibroid size. Currently, their effectiveness for the treatment of uterine fibroids has not been evaluated.. To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.. We searched the Menstrual Disorders and Subfertility Group Specialised Register (inception to 17 August 2012), CENTRAL (inception to 17 August 2012) and Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, MEDLINE (inception to 17 August 2012), Ovid EMBASE (1 January 2010 to 17 August 2012), Ovid PsycINFO (inception to 17 August 2012), CINAHL database, and trials registers for ongoing and registered trials.. All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.. We assessed all potentially eligible studies identified as a result of the search strategy. Two review authors extracted data from each included study using an agreed form and assessed the risk of bias. We resolved discrepancies through discussion.. This review included three studies. However, data for progestogen-releasing intrauterine systems were available from only one study that compared 29 women with a levonorgestrel (LNG)-IUS versus 29 women with a combined oral contraceptive (COC) for treating uterine fibroids. There was a significant reduction of menstrual blood loss (MBL) in women receiving the LNG-IUS compared to the COC using the alkaline hematin test (mean difference (MD) 77.5%, 95% CI 71.3% to 83.67%, 58 women) and a pictorial assessment chart (PBAC) (MD 34.5%, 95% CI 14.9% to 54.1%, 58 women). The reduction in uterine fibroid size was significantly greater in the leuprorelin group at 16 weeks compared to the progestogen lynestrenol group (MD -15.93 mm, 95% CI -18.02 to -13.84 mm, 46 women). There was no RCT evaluating the effect of DMPA on uterine fibroids.. Progestogen-releasing intrauterine systems appear to reduce menstrual blood loss in premenopausal women with uterine fibroids. Oral progestogens did not reduce fibroid size or fibroid- related symptoms. However, there was a methodological limitation and the one included study with data had a small sample size. This evidence is insufficient to support the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Intrauterine Devices, Medicated; Leiomyoma; Leuprolide; Levonorgestrel; Lynestrenol; Medroxyprogesterone Acetate; Menstruation; Premenopause; Progestins; Randomized Controlled Trials as Topic; Tumor Burden; Uterine Neoplasms

To evaluate novel hormonal therapies in patients with unresectable benign metastasizing leiomyoma (BML) disease.. Case series.. National Institutes of Health (NIH).. Five subjects with the diagnosis of BML based on imaging and/or histopathologic diagnosis.. Four patients were treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor. One patient was treated with an antiprogestin (CDB-2914).. Response to therapy was measured by tumor burden on cross-sectional imaging employing RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 guidelines.. Four patients treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor demonstrated stable disease with reduction in tumor burden. The fifth patient treated with antiprogestin (CDB-2914) had degeneration of her tumor, progression of its size, and an improvement in symptoms.. Hormone treatment with GnRH agonist and/or aromatase inhibition may be a therapeutic option to reduce tumor burden in unresectable BML disease or for those patients who wish to avoid surgical intervention. RECIST 1.1 guidelines, while traditionally used to evaluate tumor response to cancer therapeutics, may be useful in evaluating BML tumor burden response to hormone therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyomatosis; Leuprolide; Middle Aged; Norpregnadienes; Tomography, X-Ray Computed; Treatment Outcome; Tumor Burden; Uterine Neoplasms

Uterine fibroids are benign tumours that arise from individual smooth muscle cells of the uterus. Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) ligands that act as estrogens in some tissues while blocking estrogen activity in others. There have been many clinical studies of various SERMs for uterine fibroids. However, their effectiveness is controversial.. To evaluate the effectiveness and safety of selective estrogen receptor modulators in women with uterine fibroids.. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, EMBASE, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database (Chinese Biomedical Disc), VIP, and China National Knowledge Infrastructure. We handsearched a number of journals and searched reference lists, and searched databases of ongoing trials and the Internet. The searches were conducted in March and April 2012.. We included randomised controlled studies of selective estrogen receptor modulators versus other forms of medical therapy, placebo or no treatment in women of reproductive age (18 to 45 years old) with confirmed uterine fibroids.. Two review authors independently extracted data and assessed trial quality. As the studies identified were not sufficiently similar, we did not do a meta-analysis but summarised the data in a narrative format.. Three studies involving 215 participants were included, the trial size varied from 25 to 100 women. The SERM in all cases was raloxifene. In one study women in both arms received gonadotrophin releasing hormone (GnRH) analogue. Comparison interventions included no treatment and placebo. Two of the three included studies found a significant benefit from raloxifene, but the third study found no benefit at three or six-month follow-up. The overall quality of the evidence was low or very low. All three studies mentioned adverse reactions but data were limited.. There is no consistent evidence from the limited number of studies that SERMs reduce the size of fibroids or improve clinical outcomes. Further studies are required to establish evidence of benefit of SERMs in treating women with uterine fibroids. This updated review did not find any new study for inclusion.

Topics: Adult; Female; Humans; Leiomyoma; Leuprolide; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Uterine Neoplasms; Young Adult

Uterine fibroids are benign tumors that arise from individual smooth muscle cells of the uterus. Selective estrogen receptor modulators (SERMs) are ER ligands that act as estrogens in some tissues, while blocking estrogen action in others. There have been many clinical studies of various SERMs for uterine fibroid. However, their effectiveness is controversial.. To evaluate the evidence for the effectiveness and safety of selective estrogen receptor modulators in women with uterine fibroids.. We searched The Cochrane Library, MEDLINE, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database, Chinese Biomedical Disc (CBMDisc 1978 to July 2004); VIP (1989 to October 2005)); China National Knowledge Infrastructure (CNKI 1994 to 2003) in October 2005. We hand searched a number of journals, and searched reference lists, databases of ongoing trials and the Internet.. We included randomized controlled studies of selective estrogen receptor modulators versus other forms of medical therapy or placebo in women in the reproductive age (18 to 45 years old) with confirmed uterine fibroid.. Two review authors independently extracted data and assessed trial quality. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarized the data in a narrative format.. Three studies involving 215 participants were included, trial size varied from 25 to 100. Comparison interventions included no treatment, Poly vitamins, and leuprolide acetate depot plus raloxifene versus leuprolide plus placebo tablet. There was a tendency towards fibroid reduction with selective estrogen receptor modulators (SERMs), although this was not significant in all studies. All three studies mentioned adverse reactions but no detailed data were acquired in the included studies.. There is no evidence from the limited number of studies that SERMs reduce the size of fibroids or improve clinical outcomes. Further studies are required to establish evidence of benefit of SERMs in treating women with uterine fibroids.

Topics: Female; Humans; Leiomyoma; Leuprolide; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Uterine Neoplasms

Uterine fibroids are benign tumors that arise from individual smooth muscle cells of the uterus. Selective estrogen receptor modulators (SERMs) are ER ligands that act as estrogens in some tissues, while blocking estrogen action in others. There have been many clinical studies of various SERMs for uterine fibroid. However, their effectiveness is controversial.. To evaluate the evidence for the effectiveness and safety of selective estrogen receptor modulators in women with uterine fibroids.. We searched The Cochrane Library, MEDLINE, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database, Chinese Biomedical Disc (CBMDisc 1978 to July 2004); VIP (1989 to October 2005)); China National Knowledge Infrastructure (CNKI 1994 to 2003) in October 2005. We hand searched a number of journals, and searched reference lists, databases of ongoing trials and the Internet.. We included randomized controlled studies of selective estrogen receptor modulators versus other forms of medical therapy or placebo in women in the reproductive age (18 to 45 years old) with confirmed uterine fibroid.. Two review authors independently extracted data and assessed trial quality. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarized the data in a narrative format.. Three studies involving 215 participants were included, trial size varied from 25 to 100. Comparison interventions included no treatment, Poly vitamins, and leuprolide acetate depot plus raloxifene versus leuprolide plus placebo tablet. There was a tendency towards fibroid reduction with selective estrogen receptor modulators (SERMs), although this was not significant in all studies. All three studies mentioned adverse reactions but no detailed data were acquired in the included studies.. There is no evidence from the limited number of studies that SERMs reduce the size of fibroids or improve clinical outcomes. Further studies are required to establish evidence of benefit of SERMs in treating women with uterine fibroids.

Topics: Female; Humans; Leiomyoma; Leuprolide; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Uterine Neoplasms

Topics: Diphosphonates; Drug Therapy, Combination; Epidermal Growth Factor; ErbB Receptors; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

To evaluate the safety, efficacy, and techniques of laparoscopic myomectomy as treatment for symptomatic uterine myomas.. Medline literature review and cross-reference of published data.. Results from randomized trials and clinical series have shown that laparoscopic myomectomy provides the advantages of shorter hospitalization, faster recovery, fewer adhesions, and less blood loss than abdominal myomectomy when performed by skilled surgeons. Improvements in surgical instruments and techniques allows for safe removal and multilayer myometrial repair of multiple large intramural myomas. Randomized trials support the use of absorbable adhesion barriers to reduce adhesions, but there is no apparent benefit of presurgical use of GnRH agonists. Pregnancy outcomes have been good, and the risk of uterine rupture is very low when the myometrium is repaired appropriately.. Advances in surgical instruments and techniques are expanding the role of laparoscopic myomectomy in well-selected individuals. Meticulous repair of the myometrium is essential for women considering pregnancy after laparoscopic myomectomy to minimize the risk of uterine rupture. Laparoscopic myomectomy is an appropriate alternative to abdominal myomectomy, hysterectomy, and uterine artery embolization for some women.

Topics: Catheter Ablation; Embolization, Therapeutic; Female; Humans; Laparoscopy; Leiomyoma; Leuprolide; Pregnancy; Randomized Controlled Trials as Topic; Tissue Adhesions; Uterine Neoplasms

Topics: Antineoplastic Agents, Hormonal; Diagnosis, Differential; Drug Therapy, Combination; Estrogen Receptor Modulators; Female; Gynecologic Surgical Procedures; Humans; Laparoscopy; Leiomyoma; Leiomyomatosis; Leuprolide; Norpregnenes; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Uterine Neoplasms

More women are delaying child-bearing such that gynaecologists can no longer resort as frequently to definitive treatments, such as a hysterectomy, in the management of uterine fibroids. A review of newer conservative medical, radiological and surgical therapies and minimal access approaches to the organ-preserving myomectomy operation are discussed.. Data from published literature describing newer modalities of treatment and reviewing updated information of the impact of fibroids and myomectomy on fertility potential were collated.. Medical treatments serve to retard the growth of fibroids temporarily and have short-term success in the amelioration of symptoms. Uterine artery embolisation is a novel non-surgical approach to debulking of uterine fibroids and the relieve of symptoms. Hysterectomy is a treatment choice that is curative. Laparoscopic hysterectomy carries a 3% risk of major complications compared to 1% via a laparotomy. Laparoscopic myomectomy is a viable alternative to open myomectomy but due diligence must be exercised in ensuring meticulous and secure myomectomy defect repair. The risk of uterine dehiscence has been reported to be about 0.5% which is comparable to that in traditional open myomectomy which has been somewhat understated. Hysteroscopic resection of submucous fibroids is very efficacious and preserves reproductive potential. This procedure and myomectomy of intramural fibroids associated with intracavitary distortion are clearly indicated as these types of fibroids have been implicated as a cause of infertility and pregnancy loss at least 2 to 3 times higher than controls. This relationship prevailed in patients undergoing assisted reproduction.. The management of uterine fibroids has undergone a revolution in the past few decades with better understanding of its impact on fertility and technical advances in endoscopy and radiologic embolisation techniques and also pharmaceutical alternatives such as gonadotrophin-releasing hormone agonist and progesterone intrauterine contraceptive devices. Advances in molecular biology may provide an opportunity to manipulate receptors and cellular biology in order to arrest tumourigenesis altogether.

Topics: Adult; Complementary Therapies; Embolization, Therapeutic; Female; Follow-Up Studies; Humans; Hysterectomy; Infertility, Female; Laser Therapy; Leiomyoma; Leuprolide; Maternal Age; Middle Aged; Minimally Invasive Surgical Procedures; Pregnancy; Pregnancy, High-Risk; Risk Assessment; Singapore; Treatment Outcome; Uterine Neoplasms

Leuprolide acetate has been used to decrease uterine size and shrink leiomyomata. In carefully selected patients, its treatment benefits are well recognized. However, if leuprolide acetate is inadvertently given to a patient with an unsuspected leiomyosarcoma, complications may occur.. A patient presumed to have leiomyomata was treated with monthly injections of leuprolide acetate. In the third month of treatment, unusual manifestations, including increased bleeding, aborting mass, urinary retention, and severe pain, occurred suggesting a possible malignancy and requiring immediate operation.. The use of leuprolide acetate can delay the diagnosis and treatment of leiomyosarcoma and thus may increase the risk of morbidity and affect the treatment outcome of patients with leiomyosarcoma. The histologic changes ascribed to leuprolide acetate treatment in leiomyomata also were seen in this leiomyosarcoma.

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Leiomyosarcoma; Leuprolide; Middle Aged; Uterine Neoplasms

Topics: Antineoplastic Agents, Hormonal; Blood Vessels; Female; Humans; Leiomyoma; Leuprolide; Regional Blood Flow; Ultrasonography, Doppler; Uterine Neoplasms; Uterus

To clarify whether preoperative treatment with gonadotropin-releasing hormone (GnRH) agonists offers substantial advantages to patients undergoing conservative or definitive surgery for uterine leiomyomas.. A review of data from the most recent English-language literature.. Inducing amenorrhea in patients with heavy menorrhagia and severe sideropenic anemia before both conservative and definitive surgery for uterine fibroids raises hemoglobin and hematocrit values to within the normal range, limits homologous blood transfusions and enables operations to be scheduled with the patients in better condition. A temporary 30-50% reduction in mean uterine volume theoretically may convert an abdominal into a vaginal hysterectomy in "borderline" cases or sometimes allow a transverse instead of longitudinal abdominal incision. No trial has yet demonstrated "clinically" significant reductions in operating time, operative blood loss or postoperative morbidity in patients undergoing myomectomy or hysterectomy after a course of GnRH agonists as compared with those operated on immediately. There seems insufficient scientific evidence to justify the routine use of GnRH agonists before myomectomy at laparotomy, except possibly in the case of extremely bulky uteri. GnRH agonist treatment before hysteroscopic myomectomy induces endometrial thinning, reduces bleeding and mucous debris, and decreases the diameter of submucous leiomyomas, improving visibility and limiting operating time and fluid intravasation.. The available data seem to support the use of GnRH agonist treatment before surgery for uterine leiomyomas in selected circumstances. Administration of GnRH agonist for only two or three months preoperatively seems to achieve all the advantages of this treatment, limiting side effects and cost.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysterectomy; Leiomyoma; Leuprolide; Preoperative Care; Treatment Outcome; Uterine Neoplasms

This article is an overview of uterine neoplasms that demonstrate mesenchymal differentiation. Major clinical and pathologic features are described, with a focus on those lesions that cause diagnostic difficulty. Brief discussions on more recent observations made concerning these entities are also included.

Topics: Adenofibroma; Adenomyoma; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Female; Humans; Leiomyomatosis; Leuprolide; Myometrium; Receptors, Cell Surface; Sarcoma; Stromal Cells; Uterine Neoplasms; Uterus

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

Hysteroscopic surgery has been widely used in gynaecology for the treatment of endocavitary fibroids, synechias, uterine septum and abnormal uterine bleeding. Reports proposed preoperative medical therapy to improve the endometrials conditions. Attempts at inhibiting the thickness and vascularity of the endometrium and to reduce the fibroids size in preparation for hysteroscopic surgery by using different types of hormones have been reported. The suppression provided for a long period of time after the procedure by gonadotropin releasing hormone (GnRH) analogs, is likely to help inhibit endometrial regeneration and provided even better long time success, in endometrial ablation and submucous leiomyomatas hysteroscopic surgery. A literature review of the efficiency of the gonadotropins releasing hormone agonist, in endometrial inhibition before surgery and small regional experience is shown.

Topics: Animals; Endometrium; Female; Gonadotropin-Releasing Hormone; Humans; Hysteroscopy; Leiomyoma; Leuprolide; Male; Patient Selection; Preoperative Care; Uterine Neoplasms

The current literature reflects a trend toward alternatives to abdominal hysterectomy for the treatment of symptomatic leiomyomata uteri. Precision in diagnosis is aided by new techniques in ultrasound and magnetic resonance imaging. Gonadotropin-releasing hormone agonists reduce tumor and uterine bulk; relieve symptoms of bleeding and discomfort; are clearly useful as an adjunct to surgery; and in some patients may resolve symptoms, thus obviating the need for surgery, at least in the short-term. Repeated courses or long-term therapy with gonadotropin-releasing hormone agonists remain limited by the potential risks associated with long-term hypoestrogenemia. Myomectomy can be offered to symptomatic women desiring preservation of reproductive potential without incurring significant alteration in operative risk compared with hysterectomy and with a likelihood of subsequent conception exceeding 50%. Endoscopic removal of submucous or intracavitary leiomyomata is clearly technically feasible with acceptable risk by hysteroscopy and with good conception rates thereafter. Laparoscopic removal of intramural and subserosal leiomyomata uteri is also technically feasible with acceptable perioperative risk, but the need for removal of small tumors and the safety of subsequent pregnancy after removal of large intramural tumors has yet to be put into appropriate perspective.

Topics: Adult; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Hysterosalpingography; Laparoscopy; Leiomyoma; Leuprolide; Middle Aged; Neoplasm Recurrence, Local; Reoperation; Tourniquets; Uterine Neoplasms

The gonadotropin-releasing hormone agonists have potential benefit as presurgical adjuncts in the management of uterine leiomyomas or fibroids. Uterine fibroids contain estrogen receptors and are responsive to therapeutic hormonal manipulation; gonadotropin-releasing hormone agonists are effective by inducing a state of hypoestrogenism. Clinical trials with gonadotropin-releasing hormone agonists consistently have demonstrated efficacy for decreasing both myoma size and uterine volume. The advantages of the preoperative use of gonadotropin-releasing hormone agonists include a reduction in uterine and myoma size and vascularity and potentially improved operative technique and uterine cavity integrity. Ongoing clinical trials will be needed to confirm the role of gonadotropin-releasing hormone agonists in the treatment of uterine fibroids.

Topics: Analysis of Variance; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Nafarelin; Remission Induction; Uterine Neoplasms; Uterus

This review covers literature published between December 1990 and November 1991. It shows a continuous outpouring of publications on the use of gonadotropin-releasing hormone agonists and operative hysteroscopy as part of the background of alternatives to hysterectomy. The new technologies question traditional management of fibroids, which may vary considerably in different areas. Abdominal myomectomy, which never received adequate recognition as an alternative in the past, is also discussed. The review concludes with a section on abdominal hysterectomy.

Topics: Buserelin; Female; Goserelin; Humans; Hysteroscopy; Leiomyoma; Leuprolide; Methods; Uterine Neoplasms

Use of GnRH-A offers a promising medical approach to treating uterine leiomyomas. This therapy can be useful in selected patients, preserving fertility by delaying the need for imminent surgical treatment. In selected perimenopausal women, agonist therapy may, in fact, be an alternative to surgical intervention. Shrinking the size of myomas and reducing uterine volume with these agents have been reported to control symptoms of myoma, making myomectomy or vaginal hysterectomy a safer procedure. Used preoperatively, GnRH-A therapy can also reduce the risk of surgical complications and excessive blood loss.

Topics: Antineoplastic Agents; Buserelin; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Leuprolide; Nafarelin; Premedication; Uterine Neoplasms

To evaluate the efficacy and safety of ulipristal acetate (UPA) for uterine fibroids (UFs), a phase III study was conducted with leuprorelin (LEU) as a comparator. This is the first confirmatory trial of UPA for UFs among Asians.. Multicenter, randomized, double-blind, double-dummy, parallel-group study.. Thirty-two sites in Japan.. Patients were assigned to 2 arms, with 82 patients in the UPA group and 79 patients in the LEU group.. In the UPA group, 10 mg of UPA was orally administered once a day for 12 weeks. In the LEU group, 1.88 mg or 3.75 mg of LEU was subcutaneously administered at weeks 0, 4, and 8.. The primary endpoint was the percentage of patients with amenorrhea for 35 days. For safety evaluation, adverse events (AEs) were recorded.. The percentage of patients with amenorrhea for 35 days was 87.0% in the UPA group and 81.8% in the LEU group, and the efficacy of UPA for causing amenorrhea for 35 days was confirmed to be noninferior to that of LEU. AEs occurred in 78.0% of the patients in the UPA group and 88.8% of the patients in the LEU group.. The effect of UPA on heavy menstrual bleeding was shown to be comparable with that of LEU in Japanese patients with symptomatic UFs. No notable AEs occurred because of the UPA treatment, and the incidence of AEs in the UPA group was comparable with that of AEs in the LEU group. This result demonstrates the clinical utility of UPA for Asians.

Topics: Adult; Amenorrhea; Double-Blind Method; Female; Humans; Japan; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Norpregnadienes; Time Factors; Treatment Outcome; Uterine Neoplasms

To investigate the noninferiority of relugolix compared with leuprorelin acetate in reducing heavy menstrual bleeding associated with uterine leiomyomas.. In a double-blind, double-dummy trial, premenopausal women with uterine leiomyomas and heavy menstrual bleeding defined as a pictorial blood loss assessment chart score of at least 120 were randomized in a 1:1 ratio to relugolix (40 mg, oral, once daily) or leuprorelin acetate (1.88 mg or 3.75 mg, monthly injection) for 24 weeks. The primary endpoint was the proportion of patients with a total pictorial blood loss assessment chart score of less than 10 for weeks 6-12. Secondary endpoints included myoma and uterine volumes, and hemoglobin levels. A sample size of 144 patients per group (n=288) was estimated to provide at least 90% power to demonstrate noninferiority (prespecified noninferiority margin -15%; one-sided 0.025 level of significance).. From March 2016 to September 2017, 281 patients were randomized (relugolix, n=139, leuprorelin n=142). Demographic and baseline characteristics were well balanced; mean pictorial blood loss assessment chart score was 254.3 in the relugolix group and 263.7 in the leuprorelin group. The proportion of patients with total pictorial blood loss assessment chart score of less than 10 for weeks 6-12 was 82.2% in the relugolix group and 83.1% in the leuprorelin group, demonstrating noninferiority of relugolix compared with leuprorelin (relugolix-leuprorelin difference -0.9%; 95% CI: -10.10 to 8.35; prespecified noninferiority margin -15%; P=.001). Reductions in myoma and uterine volumes and increases in hemoglobin levels were comparable in the two groups. Relugolix was associated with an earlier effect on menstrual bleeding than leuprorelin (pictorial blood loss assessment chart score of less than 10, 64.2% vs 31.7% [relugolix-leuprorelin difference 32.5%; 95% CI: 20.95-44.13%] for weeks 2-6 and pictorial blood loss assessment chart score of 0, 52.6% vs 21.8% [30.7%; 95% CI: 19.45-42.00%] for weeks 2-6) and faster recovery of menses after treatment discontinuation (relugolix median [Q1, Q3], 37 days [32.0, 46.0]; leuprorelin median, 65 days [54.0, 77.0]). Adverse events and bone mineral density loss were similar between relugolix and leuprorelin treatment groups.. In women with uterine leiomyomas, once-daily treatment with relugolix, an oral gonadotropin-releasing hormone antagonist, demonstrated noninferiority to monthly leuprorelin for improvement of heavy menstrual bleeding at 6-12 weeks of treatment, had a more rapid effect on menstrual bleeding, and was generally well tolerated.. ClinicalTrials.gov, NCT02655237; JAPIC Clinical Trial Information, JapicCTI-163128.. Takeda Pharmaceutical Company Limited and an affiliate of NovaQuest Capital Management LLC.

Topics: Administration, Oral; Adult; Antineoplastic Agents, Hormonal; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Hemoglobins; Humans; Injections; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Organ Size; Phenylurea Compounds; Pyrimidinones; Severity of Illness Index; Tumor Burden; Uterine Neoplasms; Uterus

The study aimed to evaluate the safety and efficiency of ultrasound-guided high-intensity focused ultrasound (USgHIFU) combined with gonadotropin-releasing hormone analogue (GnRHa)-ablating symptomatic uterine leiomyoma with homogeneous hyperintensity on T. A total of 34 patients with 42 symptomatic uterine leiomyomas with homogeneous hyperintensity on T. The treatment time and sonication time of the combination group were 102.0 min (55.8-152.2 min) and 25.4 min (12.2-34.1 min); however, they were 149.0 min (87.0-210.0 min) and 38.9 min (14.0-46.7 min) in the simple USgHIFU group. The treatment and sonication time for the combination group was significantly shorter than that for the simple USgHIFU group. Treatment efficiency, NPV ratio and energy effect ratio were 46.7 mm. Our data suggest that USgHIFU combined with GnRHa may be performed to ablate symptomatic uterine leiomyoma with homogeneous hyperintensity on T

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; High-Intensity Focused Ultrasound Ablation; Humans; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Ultrasonography, Interventional; Uterine Neoplasms; Young Adult

To assess the factors associated with future pregnancy and successful delivery in women who were treated for uterine adenomyoma with combination (surgical-medical) therapy using ultramini- or mini-laparotomy conservative surgery and gonadotropin-releasing hormone agonist.. One hundred and two women were evaluated. Items for analysis included: age, body mass index, and conception history; clinical symptoms of dysmenorrhea and menorrhagia; tumor location and preoperative serum level of cancer antigen 125 (CA125); the intraoperative findings of the weight of the removed tumor, and the uterine cavity opening.. After excluding those patients using contraception or searching for an assisted reproductive technique, a total of 56 women were enrolled for analysis. Twenty-three (41.1%) women had 27 clinical pregnancies after 3 years of follow-up; 15 went on to deliver a healthy live-born child; two delivered preterm but healthy babies; seven had elective abortions; four had spontaneous abortions; and one had an ectopic pregnancy. The women who had a successful delivery during the 3-year follow-up after treatment tended to be younger, with a lower body mass index, lower baseline analgesic usage score, and lower preoperative serum level of CA125, be nulliparous, and with an adenoma in an anterior location. The linear regression model showed that age and baseline analgesic usage score were independent predictors of successful delivery and accounted for 56.5% of the total variance related to successful delivery.. Age was an important factor associated with future successful delivery, therefore, caution should be taken in considering the maintenance of future fertility in older women treated with surgical-medical therapy.

Topics: Adenomyoma; Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Dysmenorrhea; Female; Follow-Up Studies; Humans; Infertility, Female; Laparotomy; Leuprolide; Linear Models; Menorrhagia; Middle Aged; Postoperative Complications; Pregnancy; Severity of Illness Index; Treatment Outcome; Uterine Neoplasms; Uterus

The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear.. In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%.. Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate).. Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Topics: Administration, Oral; Adult; Double-Blind Method; Endometrium; Female; Humans; Injections, Intramuscular; Intention to Treat Analysis; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Norpregnadienes; Uterine Neoplasms; Young Adult

The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity.. Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined.. In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased.. Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Glucose; Body Mass Index; C-Reactive Protein; Chemokine CCL2; Cytokines; E-Selectin; Female; Gonadotropin-Releasing Hormone; Humans; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Leiomyoma; Leuprolide; Middle Aged; Premenopause; Sex Hormone-Binding Globulin; Testosterone; Uterine Neoplasms

The aim of the present study was to determine the influence of acute estrogen deficiency induced by administration of a gonadotropin-releasing hormone (GnRH) agonist on circulating levels of cytokines and chemokines. Eighty-three women with uterine leiomyoma were assigned in open, parallel-group fashion to a no-treatment (control) group and a GnRH-agonist group. Serum levels of nine cytokines and chemokines as well as vascular inflammatory markers were measured. Serum levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-α (TNFα) in the GnRH-agonist group were increased significantly at 6 months. There were also significant differences in percentage changes in interleukin (IL)-6, IL8, MCP1, and macrophage inflammatory protein-1β (MIP1β) between the control and GnRH agonist groups. Soluble intercellular adhesion molecule-1 (sICAM1) and E-selectin levels showed significant increases in the GnRH agonist group at 6 months. Serum MCP1 concentrations showed weak correlations with levels of sICAM and E-selectin. We conclude that a hypo-estrogenic state due to administration of a GnRH agonist increases circulating levels of cytokines and chemokines, especially MCP1.

Topics: Adult; Chemokine CCL2; Cytokines; E-Selectin; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Intercellular Adhesion Molecule-1; Leiomyoma; Leuprolide; Time Factors; Uterine Neoplasms

To compare the efficacy of surgical-medical treatment and surgery alone in the treatment of uterine symptomatic adenomyoma.. Prospective nonrandomized study.. Medical centers.. One hundred sixty-five women treated with conservative adenomyomectomy.. Surgery followed by six-course treatment (n = 114, surgical-medical group) or no treatment (n = 51, surgery-alone group) with a gonadotropin-releasing hormone (GnRH) agonist regimen.. Symptom relief (scale: 0, no symptoms, to 5, worst symptoms) and relapse (when any one scale was > or =2 after treatment) during the 2-year follow-up period.. The general characteristics of the patients were similar in both groups, except for the diameter of the adenomyoma and age. Patients in both groups had statistically significant symptom relief, and all symptom scores declined from a mean of 3 or 4 to a mean of 1 or less at the end of the 2-year follow-up period. The symptom-relapse rates in the surgical-medical group were statistically significantly lower than those in the surgery alone group (n = 32, 28.1% vs. n = 25, 49.0%, respectively).. Conservative surgery, regardless of GnRH agonist treatment, may be acceptable for management of a selected population with severe symptomatic adenomyoma. However, surgical-medical treatment provided more effective symptom control (a lower symptom relapse rate) than surgery alone during the 2-year follow-up period.

Topics: Adenomyoma; Adult; Combined Modality Therapy; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Gynecologic Surgical Procedures; Humans; Leuprolide; Middle Aged; Prospective Studies; Secondary Prevention; Treatment Outcome; Uterine Neoplasms

To determine the acceptability and effectiveness of a gonadotropin-releasing hormone (GnRH) agonist for the treatment of perimenopausal women with symptomatic uterine myomas.. The participants included 43 women with symptomatic myomas who wished to retain their uteri. All the women were older than 45 years old, agreed to use the GnRH agonist for menopause induction, and were without any underlying malignancy. They were treated with six courses of GnRH agonist between 2004 and 2005. The definition of re-intervention included: (1) surgical intervention, such as hysterectomy, myomectomy or laparoscopic uterine vessel occlusion, or (2) modification of GnRH agonist use. Modification of GnRH agonist use included either failure to complete a 6-month GnRH agonist treatment course, or re-use of GnRH agonist with/without interruption of continuity. Failure was defined as women who underwent surgical intervention or failed to complete the 6-month GnRH agonist treatment. Evaluations were performed every 6 months, for up to 2 years.. Re-intervention rates were 14.0% (n = 6), 23.3% (n = 10) and 32.6% (n = 14), and failure rates were 7.0% (n = 3), 11.6% (n = 5) and 16.3% (n = 7), at the end of the 6-, 12- and 24-month follow-up periods, respectively. Three patients failed to complete the 6-month GnRH agonist treatment, and four received surgical interventions.. More than 80% of women in this study benefited from the use of GnRH agonist to produce menopause, suggesting that this can be an alternative choice for managing perimenopausal women with symptomatic uterine myomas.

Topics: Antineoplastic Agents, Hormonal; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Leuprolide; Middle Aged; Patient Satisfaction; Perimenopause; Treatment Outcome; Uterine Neoplasms

To determine if 3 months of preoperative gonadotropin-releasing hormone agonist (GnRH-a) treatment decreases postoperative uterine adhesions after open abdominal surgery for the removal of uterine fibroids.. Prospective, randomized, clinical study.. A tertiary care medical center.. Women of reproductive age with symptomatic uterine fibroids not amenable to hysteroscopic removal.. Twenty patients underwent an initial abdominal myomectomy followed by a second-look laparoscopy for evaluating uterine adhesions after random allocation to groups receiving either GnRH analog or placebo for 3 months before the initial surgery.. Adhesion formation between treatment groups and by incision number and aggregate length.. Presurgical GnRH-a treatment did not decrease adhesion formation compared with placebo. For every additional centimeter of incision length, the total adhesion area over the uterine serosal surface increased by 0.55 cm(2). The number of myomas removed and the number of incisions were positively correlated with total adhesion area.. Preoperative treatment with GnRH-a for 3 months before open abdominal myomectomy did not decrease postoperative uterine adhesions. Following the standards of good surgical technique, adhesions are minimized with fewer and smaller incisions.

Topics: Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Postoperative Complications; Prospective Studies; Tissue Adhesions; Uterine Neoplasms

To prospectively determine if semiquantitative assessment of R2* images and T1-weighted magnetic resonance (MR) images of leiomyomas correlates with the efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment for volume reduction.. Internal review board approval and informed consent were obtained for this study. Twenty women (mean age, 36.3 years) with intramyometrial leiomyomas were enrolled in this study. Single-section double-echo dynamic MR imaging was performed before GnRH agonist administration. T2-weighted images were obtained before and after two or three GnRH agonist injections (1.88 mg leuprorelin acetate). The steepest signal intensity (SI) upslope on T1-weighted images and the area under the curve (AUC) on R2* images were determined by using a 16 x 16-voxel matrix that was placed in the center of a leiomyoma. Pearson correlation analysis was performed to compare the percentage of volume reduction with SI upslope and AUC. Unpaired t test was performed to evaluate the difference between leiomyomas with AUC and SI upslope values that were less than or greater than the mean.. Percentage of volume reduction ranged from 6.2% to 51.1%. The mean AUC and mean SI upslope were 39.2 and 9.83% per second, respectively. There was a significant correlation between the AUC and the percentage of volume reduction (r = 0.81, P < .001), although no significant correlation was observed between the SI upslope and the percentage of volume reduction. A significant difference in percentage of volume reduction was observed in leiomyomas by using mean AUC as a cutoff value (P = .003).. AUC on R2* images correlates with the efficacy of GnRH agonist before initiation of treatment for volume reduction of leiomyoma.

Topics: Adult; Algorithms; Antineoplastic Agents, Hormonal; Female; Gonadotropin-Releasing Hormone; Humans; Image Interpretation, Computer-Assisted; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Pilot Projects; Prognosis; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Uterine Neoplasms

To compare the effectiveness of leuprorelin and cetrorelix, when used as preoperative endometrial thinning agents prior to transcervical resection of endometrium (TCRE).. A prospective, double-blind randomised controlled trial.. Gynaecological department of a UK district general hospital.. A total of 106 premenopausal women with dysfunctional uterine bleeding, undergoing TCRE.. Women were equally randomised to 3.75 mg of leuprorelin acetate (3-4 weeks) or 3 mg cetrorelix (4-7 days) prior to TCRE. About 1 ml saline was given as placebo in both arms.. Amenorrhoea rate at 6 months, endometrial thickness using transvaginal ultrasound on the day of operation.. A total of 100 women completed the trial with no loss to follow up. Amenorrhoea rate at 6 months after surgery was high in both groups (80% cetrorelix and 84% leuprorelin) with no statistical significance. All endometrial outcome measures including endometrial thickness on ultrasound, histology and operative appearance were more favourable in leuprorelin group as compared with cetrorelix (P values 0.013, <0.001 and 0.003 respectively). More women in leuprorelin group had hot flushes as compared with cetrorelix (15/50 versus 6/50; P = 0.047). No significant differences were seen in other outcome measures.. In dosages used, leuprorelin produced more consistent thinning of the endometrium as compared with cetrorelix, although this did not make any significant difference to operative or menstrual outcomes. The endometrial thinning effect with cetrorelix does appear to be more favourable than that seen at postmenstrual phase in other studies. The optimum (possibly higher) dosage of cetrorelix for this purpose has not yet been established.

Topics: Adult; Double-Blind Method; Endometrium; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyoma; Leuprolide; Menorrhagia; Menstruation; Patient Satisfaction; Postmenopause; Preoperative Care; Prospective Studies; Treatment Outcome; Uterine Neoplasms

To investigate the effects of tibolone co-administration with GnRH agonist treatment in terms of cognition, mood, and quality of life.. Randomized, controlled, single-blind, clinical trial.. Department of gynecology and obstetrics at a university in Italy.. One hundred ten premenopausal women with symptomatic uterine leiomyomas.. Six months of treatment with leuprolide acetate depot (11.25 mg IM, every 3 mo) associated with either tibolone (2.5 mg/d orally; group A) or placebo (1 tablet per d; group B).. At baseline and after 6 months of treatment, uterine and leiomyoma sizes, leiomyoma-related symptoms, climacteric-like symptoms, cognition, mood, and quality of life.. At study entry, no difference was detected between groups in any parameters assessed. After treatment, the leiomyoma-related symptoms were significantly reduced in both groups, without any statistically significant differences between them. The Kupperman Index was statistically significantly higher in group B in comparison with baseline and group A. The cognition scores were statistically significantly different in comparison with baseline in group B, whereas no change was observed in group A. After treatment, mood and quality of life were statistically significantly improved in both groups, even though the improvement was significantly higher in group A than in group B.. Tibolone administration reverses the deleterious effect on cognition that is caused by leuprolide acetate depot and improves mood and quality of life in patients who receive GnRH agonist for symptomatic uterine leiomyomas.

Topics: Administration, Oral; Adult; Affect; Antineoplastic Agents, Hormonal; Central Nervous System Agents; Cognition; Delayed-Action Preparations; Female; Humans; Leiomyoma; Leuprolide; Middle Aged; Norpregnenes; Quality of Life; Single-Blind Method; Time Factors; Treatment Outcome; Uterine Neoplasms

To compare goserelin and leuprolide given before hysterectomy for symptomatic large fibroid uteri.. A randomized study of 66 premenopausal women with fibroid uteri at least 14 weeks of gestation in a gravid uterus. Women were randomized to receive either subcutaneous depot 3.6 mg goserelin or 3.75 mg leuprolide every 4 weeks for a total of 3 doses. Hysterectomy was performed within 1 month of the last dose.. A total of 34 women randomized to the goserelin group and 31 women to the leuprolide group were available for analysis. Preoperative hemoglobin level (P=0.89), operative blood loss (P=0.72), and operating time (P=0.39) were not different between the 2 groups. Postoperative hemoglobin was higher in the leuprolide group (P=0.003), but blood transfusion requirement was not different between the groups (P=1.0). Other outcomes and side effects of the drugs were similar.. Goserelin and leuprolide administered before hysterectomy for uterine fibroids have similar perioperative outcomes.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Leuprolide; Middle Aged; Treatment Outcome; Uterine Neoplasms

To evaluate the clinical features and the expression of transforming growth factor-beta3 (TGF-beta3) and connective tissue growth factor (CTGF) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs (GnRH-a) and tibolone.. Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months. Twenty-two patients received the same therapy plus 2.5 mg tibolone daily. Patients underwent uterine surgery after therapy. Twenty-two untreated patients underwent surgery directly. Hematologic tests, bone mineral density (BMD) measurement, and ultrasonographic evaluation of uterine volume were performed before and after treatment. Menorrhagia and pelvic pain were evaluated with a visual analog scale. Hot flushes were recorded in daily diaries. Immunohistochemical expression of TGF-beta3 and CTGF in myometrium and myoma samples was evaluated semiquantitatively.. After therapy, hemoglobin and iron levels similarly increased in both groups. BMD significantly decreased only in the GnRH-a group. Uterine volume similarly decreased in both groups. No patient had menorrhagia or pelvic pain at the end of therapy. The number of hot flushes increased after the first month in the GnRH-a group; in the GnRH-a plus tibolone group, it remained constant and was lower. In untreated cases, TGF-beta3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas. After medical treatment, growth factor immunoexpression remained unchanged in myometrial samples and was reduced in leiomyomas. Endothelial cells showed strong immunopositivity, both in untreated and in treated cases.. This study focuses on the effects of GnRH-a and tibolone on TGF-beta3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Connective Tissue Growth Factor; Drug Therapy, Combination; Female; Hemoglobins; Hot Flashes; Humans; Immediate-Early Proteins; Immunohistochemistry; Injections, Subcutaneous; Intercellular Signaling Peptides and Proteins; Iron; Leiomyoma; Leuprolide; Myometrium; Neoadjuvant Therapy; Norpregnenes; Transforming Growth Factor beta; Transforming Growth Factor beta3; Uterine Neoplasms

Basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) are involved in the pathogenesis of leiomyomas and influence angiogenesis, which is necessary for growth of leiomyomas. Gonadotropin-releasing hormone analogue (GnRH-a) treatment might modify the growth factor expression and the blood supply in myomas. We investigated the effects of GnRH-a treatment on some clinical parameters, on the immunohistochemical expression of bFGF, VEGF, and PDGF, and on the vasculature of leiomyomas.. Thirty-one women were treated with leuprolide acetate for 3 months; 55 untreated patients formed the control group. Hematologic parameters were assessed at the admission, after GnRH-a treatment, and after surgery. Uterine volume was evaluated by ultrasonography. The immunoexpression of bFGF, VEGF, and PDGF and of the endothelial markers CD34 and CD105, as well as the vascular pattern, were studied in leiomyomas, comparing treated and untreated patients.. Hematologic parameters improved and uterine volumes decreased after GnRH-a treatment. The immunoexpression of bFGF, VEGF, and PDGF decreased in treated myomas, together with the total number of vessels and the angiogenetic vessels.. This study confirms the clinical response of uterine shrinkage after GnRH-a treatment. A pathogenetic role of bFGF, VEGF, and PDGF in myoma growth and vascularization is suggested. Finally, this study indirectly confirms the importance of the vasculature in leiomyoma growth.

Topics: Adult; Antigens, CD; Antigens, CD34; Antineoplastic Agents, Hormonal; Endoglin; Female; Fibroblast Growth Factor 2; Hemoglobins; Humans; Immunohistochemistry; Iron; Leiomyoma; Leuprolide; Neovascularization, Pathologic; Platelet-Derived Growth Factor; Receptors, Cell Surface; Uterine Neoplasms; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A

Short-term treatment with gonadotropin-releasing hormone agonist (GnRHa) is a useful preoperative medical therapy of uterine leiomyomas. However, adverse effects caused by the hypo-estrogen state sometimes appear, suggesting the necessity of add-back therapy. In this study, we investigated effects of three kinds of add-back therapies on the proliferative activity of uterine leiomyoma cells by examining the expression of Ki-67 in leiomyoma cells by immunostaining. Thirty patients who were to undergo hysterectomy or myomectomy were injected with 3.75 mg depot leuprolide acetate every four weeks until the end of the 12th week. Twenty patients underwent add-back therapy from the 5th week to the end of the 12th week, 8 patients receiving 0.625 mg of conjugated equine estrogen (CEE) /day, 6 patients 5.0 mg of medroxyprogesterone acetate (MPA)/day, 6 patients 0.625 mg CEE plus 2.5 mg of MPA /day. The add-back of CEE or CEE plus MPA suppressed decreases in the proliferative activity of leiomyoma cells caused by GnRHa therapy, but that of MPA did not. These results suggest that the add-back therapy with MPA is of use in preventing the adverse effects caused by hypo-estrogen in the preoperative short-term GnRHa therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Cell Proliferation; Drug Administration Schedule; Estrogens, Conjugated (USP); Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Leuprolide; Medroxyprogesterone Acetate; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Treatment Outcome; Uterine Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Norpregnenes; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Uterine Neoplasms

To evaluate the effectiveness and safety of triptorelin in the treatment of uterine leiomyoma.. A multi-center, prospective, randomly controlled clinical trial was carried out from Dec. 2002 to Mar. 2004 in three university hospitals. A total of 125 qualified patients with uterine leiomyoma were randomly divided into either triptorelin group (63 cases) treated with 3.75 mg triptorelin injected intramuscularly or leuprorelin group (62 cases) treated with 3.75 mg leuprorelin injected subcutaneously. Both drugs were injected every 28 days for a total of 3 months.. All 125 patients finished the trial. The uterine volumes were similar before treatment between the triptorelin group and the leuprorelin group and were decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 51% and 49%, respectively, without significant difference between two groups (P > 0.05). The volumes of the largest leiomyoma decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 50% and 48% in the triptorelin and leuprorelin groups, respectively, without significant difference between them (P > 0.05). Patients with serum level of 17beta-estradiol < 183 pmol/L accounted for 94% in both groups. The hemoglobin and serum ferrum levels were both significantly increased in the two groups after treatment (P < 0.05). The amenorrhea rates after 3 months of treatment were 97% in the triptorelin group and 95% in the leuprorelin group (P > 0.05). Dysmenorrhea, noncyclic pelvic pain and pressure-like symptoms were relieved quickly and remarkably in both groups after treatment. The rates of adverse event occurred in 71% of patients in both groups. The main side effects included flare-up effects and hypoestrogenic symptoms. Nine patients in the triptorelin group and 6 in the leuprorelin group received add-back therapy with tibolone 1.25-2.50 mg/d because of remarkable climacteric-like symptoms.. Treatment of uterine leiomyoma with triptorelin for 3 months is both effective and safe in Chinese women.

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Leuprolide; Prospective Studies; Treatment Outcome; Triptorelin Pamoate; Uterine Neoplasms

Although GnRH analogues are widely used to treat a variety of sex hormone-related diseases, little is known about their effect on metabolism. Therefore, we have evaluated the effect of a GnRH analogue, administered with or without raloxifene, on serum levels of lipoproteins, glucose, insulin and homocysteine (Hcy).. One hundred premenopausal women with symptomatic uterine leiomyomas were initially enrolled and randomized to receive 3.75 mg/28 days leuprolide acetate depot associated with 60 mg/day raloxifene hydrochloride (group A) or 1 placebo tablet/day (group B) for six cycles of 28 days. At entry and at cycle 6, subjects underwent anthropometric measurements, including body mass index and waist-to-hip ratio measurements, and blood chemistry assays for serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, Hcy, vitamin B(12) and folate concentrations. Insulin resistance was evaluated with the homeostasis model assessment (HOMA) score.. Baseline parameters were similar in the two groups. At cycle 6, TC, HDL-C, LDL-C and TG levels were significantly increased (P < 0.05) in group B. In group A, LDL-C levels were unchanged, and TC, HDL-C and TG levels were increased (P < 0.05). Serum TC and LDL-C levels differed (P < 0.05) between the groups. Glucose levels were unchanged between and within groups, whereas insulin levels and HOMA scores increased (P < 0.05) versus baseline in group B. Post-treatment Hcy levels were higher (P < 0.05) versus baseline in group B; they were unchanged in group A. Serum vitamin B(12) and folate concentrations were unchanged in both groups.. GnRH analogues alter serum lipoprotein and Hcy levels and increase insulin resistance. These acute metabolic changes may be prevented or reduced by raloxifene.

Topics: Adult; Blood Glucose; Body Constitution; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Delayed-Action Preparations; Female; Folic Acid; Homeostasis; Homocysteine; Humans; Insulin; Insulin Resistance; Leiomyoma; Leuprolide; Lipids; Middle Aged; Placebos; Premenopause; Raloxifene Hydrochloride; Triglycerides; Uterine Neoplasms; Vitamin B 12

Our aim was to evaluate the long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with symptomatic uterine leiomyomas.. Fifty pre-menopausal women with uterine leiomyomas were treated with leuprolide acetate depot at dose of 3.75 mg/28 days and raloxifene hydrochloride at 60 mg/day for 18 cycles. At admission and after each six cycles of treatment, bone mineral density (BMD), uterine, leiomyoma and non-leiomyoma dimensions, serum bone metabolism markers, lipid, glucose and insulin levels were evaluated. Leiomyoma-related and climacteric-like symptoms were assessed using a daily diary.. Throughout the study, no significant change in BMD or in any bone metabolism markers was observed. A significant decrease in uterine, leiomyoma and non-leiomyoma sizes was detected in comparison with baseline already after 6 months. No other significant change was observed at the successive follow-up visits. No significant change in lipid and glucose profile was detected throughout the study. The treatments were well tolerated. All treatment withdrawals (16%, eight out of 50) were due to lack of compliance, and none to drug-related adverse experiences.. GnRH agonist plus raloxifene administration is an effective and safe treatment for pre-menopausal women with uterine leiomyomas.

Topics: Antineoplastic Agents, Hormonal; Blood Glucose; Bone Density; Bone Remodeling; Delayed-Action Preparations; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Lipids; Longitudinal Studies; Middle Aged; Patient Dropouts; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Severity of Illness Index; Treatment Outcome; Uterine Neoplasms; Vasomotor System

The purpose of the present study was to investigate changes in serum leptin levels during GnRH agonist therapy. Twenty regularly menstruating women with uterine leiomyomas were enrolled. These subjects were given GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Serum leptin and estradiol (E2) levels were measured at the two time points of day 1 or 2 of the menstrual cycle and the end of GnRH agonist therapy. Weight, total body fat mass, percentage of body fat, and total body lean mass were measured by whole body scanning with dual-energy X-ray absorptiometry. The ratio of serum leptin levels to total body fat mass (leptin-fat mass ratio), and the ratio of serum leptin levels to total body lean mass (leptin-lean mass ratio) were calculated. All subjects became amenorrheic after the initial administration of GnRH agonist. Baseline E2 levels were 45.4 +/- 21.0 pg/mL, which significantly decreased after GnRH agonist therapy (13.3 +/- 4.2 pg/mL, p<0.01). Baseline leptin levels were 8.7 +/- 8.1 ng/mL, which did not differ from the values after 4 months of GnRH agonist administration (8.9 +/- 6.8 ng/mL). Total body fat mass significantly increased from 20.0 +/- 10.4 to 21.0 +/- 9.4 kg (p<0.05), while total body lean mass significantly decreased (34.5 +/- 4.2 kg to 33.3 +/- 3.9 kg, p<0.01). However, leptin-fat mass ratio after GnRH agonist therapy did not differ from the baseline values (0.39 +/- 0.16 ng/mL/kg vs 0.38 +/- 0.16 ng/mL/kg). Hypogonadism does not have a major impact on circulating leptin levels.

Topics: Adult; Antineoplastic Agents, Hormonal; Body Composition; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leptin; Leuprolide; Longitudinal Studies; Middle Aged; Uterine Neoplasms

We investigated the effect of the GnRH agonist (GnRH-a) on the uterine volume and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) and the vasculature of leiomyomas. Twenty-five women were treated with leuprorelin acetate for 3 months; 46 untreated patients were enrolled as a control group. The uterine volume was measured by ultrasonography. After myomectomy or hysterectomy, the immunoexpression of bFGF and the endothelial marker, CD34, was studied and compared in treated and untreated leiomyomas. Uterine volume decreased after therapy. The number of cells expressing bFGF and the vascularity were diminished in treated leiomyomas. Reduction in the blood supply might be responsible, in part, for uterine-volume shrinkage after GnRH-a therapy.

Topics: Adult; Antigens, CD34; Antineoplastic Agents, Hormonal; Female; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Humans; Hysterectomy; Immunohistochemistry; Leiomyomatosis; Leuprolide; Treatment Outcome; Ultrasonography; Uterine Neoplasms

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

This prospective randomized, single-blind, placebo-controlled clinical trial was performed to evaluate the efficacy of raloxifene in preventing the bone loss associated with GnRH agonist (GnRH-a) administration. One hundred premenopausal women with uterine leiomyomas were treated with leuprolide acetate depot at a dosage of 3.75 mg/d for 28 d and then randomized into two groups to receive raloxifene hydrochloride at 60 mg/d (group A) or placebo (1 tablet/d; group B). Bone mineral density (BMD) and serum bone metabolism markers were evaluated at admission and after six treatment cycles. Posttreatment BMD differed significantly from baseline BMD in group B but not in group A. BMD was significantly higher in group A than in group B. In group A, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were unchanged vs. baseline. Differently, posttreatment concentrations of these bone turnover markers were significantly lower in group B compared with baseline and group A values. In conclusion, raloxifene prevents GnRH-a related bone loss in premenopausal women with uterine leiomyomas.

Topics: Adult; Body Mass Index; Bone and Bones; Bone Density; Calcium; Delayed-Action Preparations; Female; Femur; Humans; Leiomyoma; Leuprolide; Lumbar Vertebrae; Middle Aged; Osteoporosis; Phosphorus; Placebos; Premenopause; Prospective Studies; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Uterine Neoplasms

Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms.. After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method.. After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period.. In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes.

Topics: Delayed-Action Preparations; Female; Hot Flashes; Humans; Leiomyoma; Leuprolide; Menorrhagia; Pain; Patient Dropouts; Placebos; Premenopause; Prospective Studies; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Ultrasonography; Uterine Neoplasms

To study the bone metabolism in postmenopausal women who have been treated with gonadotropin-releasing hormone agonist (GnRH-a) and tibolone.. Prospective, open, controlled clinical trial.. Department of Gynecology and Obstetrics, University of Catanzaro, Catanzaro, Italy.. One hundred twenty perimenopausal women with symptomatic uterine leiomyomas (groups A and B), and 40 healthy control women who underwent a normal spontaneous menopause (group C).. Treatment for 12 months with leuprolide acetate plus tibolone (group A) or hysterectomy with bilateral oophorectomy (group B).. Lumbar spine bone mineral density (BMD) and bone turnover markers at entry into the study, after medical treatment (only group A), and 12 months after discontinuation medical treatment (group A) or after surgery (group B). The same parameters were noted in healthy women before and 12 months after menopause (retrospective control group, group C).. At the women's entry into the study, no significant difference in BMD and bone turnover markers was detected between groups A and B. In group A, no significant variation in BMD or bone turnover markers was observed 12 months after medical treatment in comparison with baseline. At 12 months after discontinuation of treatment (in women who had achieved menopause) and after surgery, we observed a statistically significant decrease in BMD and in bone turnover markers in both groups in comparison with baseline. At 12 months after they became menopausal, we also observed a statistically significant reduction in BMD and in bone turnover markers in control group C. At the same 12-month follow-up visit, a statistically significant difference in BMD and in bone turnover markers was detected when comparing groups A and B with group C.. Women previously treated with GnRH-a and tibolone similar to women who are menopausal as a result of surgery, have higher bone loss after menopause.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone and Bones; Bone Density; Bone Development; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Leuprolide; Lumbar Vertebrae; Middle Aged; Norpregnenes; Osteoporosis, Postmenopausal; Ovariectomy; Postmenopause; Prospective Studies; Reference Values; Uterine Neoplasms

To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy.. Prospective, randomized, open, placebo-controlled clinical trial.. Department of Gynecology and Obstetrics, University of Naples Federico II, Naples, Italy.. 66 women with symptomatic uterine leiomyomas.. Treatment for 2 months with leuprolide acetate and iron tablets, plus tibolone (group A) or placebo tablets (group B); or with leuprolide acetate and iron tablets (group C).. Laparoscopic myomectomy at the end of treatment. Operative time and blood loss during surgery were recorded. Uterine volume, volume and number of uterine leiomyomas, volume and echogenicity of the largest uterine leiomyomas, hematologic data, and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery.. Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B, compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery, hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B.. Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone.

Topics: Adult; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Iron; Laparoscopy; Leiomyoma; Leuprolide; Norpregnenes; Placebos; Prospective Studies; Treatment Outcome; Uterine Neoplasms

The purpose of this study was to evaluate the efficacy of ipriflavone in preventing bone loss, decreasing in serum cholesterol and decreasing the rate of appearance of vasomotor symptoms, as well as the effects of ipriflavone on reduction of myoma volume by estrogen deficiency during treatment with the GnRH analog leuprolide. One hundred two women (mean age, 44.3 +/- 0.53 yr) receiving leuprolide therapy for uterine leiomyoma were randomly allocated to two groups (group A, leuprolide only; group B, leuprolide with ipriflavone). Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after treatment for 6 months. Levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) were measured before treatment and after 3 and 6 months of treatment. Subjects were asked to report the appearance of vasomotor symptoms throughout treatment. Myoma node volumes were measured before treatment and after treatment for 6 months. Bone mineral density was reduced in both groups, with reduction rates of -5.26% in group A and -3.70% in group B (P < 0.01 vs. group A). Changes in bone markers were not significant in either group. TC was significantly increased in both groups, and TG levels were increased significantly after 3 and 6 months of treatment in group A but not in group B. There was no significant difference between these two groups in amount of increase of either TC or TG. LDL-C levels were increased significantly after 3 and 6 months of treatment in both groups, and the differences between the groups (11.7% in group A vs. 7.5% in group B at 3 month and 22.6% in group A vs. 8.4% in group B at 6 month) were significant. Severe vasomotor symptoms were reduced in group B. The rates of reduction of myoma volume were 49.8% in group A and 52.9% in group B; this difference between groups was not significant. Ipriflavone efficaciously alleviated the adverse effects of estrogen deficiency such as bone loss and increase in LDL-C level, and the ability of leuprolide therapy to reduce myoma volume was not decreased by ipriflavone administration.

Topics: Adult; Bone Density; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Estrogen Antagonists; Female; Humans; Isoflavones; Leiomyoma; Leuprolide; Middle Aged; Osteoporosis; Triglycerides; Uterine Neoplasms

To determine whether length of pre-operative treatment with gonadotrophin-releasing hormone agonists (GnRHa) may have different effects on uterine shrinkage and intra-operative blood loss, 36 patients with symptomatic uterine fibroids awaiting myomectomy were randomly divided into two groups.. Twenty patients received long-term GnRHa administration, six monthly depot injections of leuprolide acetate (LA), while 16 patients were treated with two monthly LA injections before surgery. The hemoglobin concentration and estradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured before and after treatment in both groups.. Uterine volume decreased in the long-term treated group from 680+/-276 cm3 to 486+/-195 cm3 (36%) after two and to 388+/-172 cm3 (51%) after six LA injections. In the short-term treated group the basal uterine volume decreased from 745+/-320 cm3 to 456+/-177 cm3 (39%) after two LA injections. The uterine volume decrease was statistically significant (p<0.05) after two LA injections in both groups while the decrease observed between two and six LA injections was not significant (p>0.05). The intra-operative blood-loss was not significantly different between the two groups studied, 315+/-93 cm3 and 336+/-88 cm3.. Two pre-operative GnRHa depot injections offer similar results, in terms of uterine shrinkage and intra-operative blood loss, and a longer treatment seems to be justified in cases of anemia.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Delayed-Action Preparations; Double-Blind Method; Estradiol; Female; Follicle Stimulating Hormone; Hemoglobins; Humans; Leiomyoma; Leuprolide; Luteinizing Hormone; Myometrium; Preoperative Care; Time Factors; Uterine Neoplasms

To assess the effect of gonadotropin-releasing hormone (GnRH) agonist treatment upon angiogenesis in uterine leiomyomata.. Uterine leiomyomata specimens of 49 consecutive patients who underwent myomectomy or hysterectomy following presurgical treatment with (n = 23) and without (n = 26) GnRH agonist were stained immunohistochemically with antibody to factor VIII-related antigen. For each subject, age, parity, number of Lupron treatments, leiomyoma size (cm), and mean microvessel counts calculated from three fields (x400) were recorded. Differences in patient age, parity, microvessel counts and leiomyoma size between GnRH agonist treated and untreated patients were tested by unpaired Student's t test. Differences among the various number of doses were tested by one-way ANOVA, with Bonferonni and Neuman-Keuls post hoc tests between specific dose-number groups. The relationship between microvessel counts and leiomyoma size was tested by Pearson correlation test. Multivariate stepwise regression tested the relationship between the number of Lupron doses and microvessel counts, correcting for age, parity, and leiomyoma size. p < 0.05 was considered significant.. Patient age and parity were similar in GnRH treated and untreated patients (mean 43.3 +/- 6.6 versus 43.9 +/- 7.5 years and median 2 (range 0-7) versus 1 (range 0-5), p = 0.78 and p = 0.45, respectively). Microvessel counts of leiomyomata specimens treated presurgically with GnRH agonist therapy (median 22.7, range 6.7-65.7) were not significantly different from microvessel counts of specimens without presurgical GnRH agonist treatment (median 19.8, range 6-53; p = 0.77). No correlation between leiomyoma size and microvessel counts was noted (r = 0.06, P = 0.7).. Angiogenesis as assessed by microvessel counts in surgically removed leiomyomata is not affected by presurgical medical management with GnRH agonist therapy.

Topics: Analysis of Variance; Antineoplastic Agents, Hormonal; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Immunohistochemistry; Leiomyoma; Leuprolide; Neovascularization, Pathologic; Paraffin Embedding; Preoperative Care; Regression Analysis; Uterine Neoplasms; Uterus

To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol, given prior to surgical treatment of symptomatic uterine myomas, on the pre-operative symptoms, tolerance, and operative blood loss.. Fifty-six women were randomly selected to receive, during 16 weeks, either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release (n=33) or lynestrenol 5 mg two tabs per day (5th to the 25th menstrual cycle) (n=23).. Intent-to-treat analysis of the main efficacy criterion, namely ultrasonographic reduction of myoma(s) diameter, showed a significant difference in favour of leuprorelin (P=0.02) with a mean decrease of 26.5+/-4.5% (n=29) as opposed to 7.3+/-5% in the lynestrenol group (n=17). Clinical improvement was satisfactory in both groups. Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one (P=0.02) (for hemoglobin: P=0.07).. Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity. The tolerance was good, reflecting each drug mechanism of action.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Lynestrenol; Preoperative Care; Ultrasonography; Uterine Neoplasms

To evaluate the feasibility of intermittent 6-month courses of leuprolide acetate for the long-term control of symptoms attributed to leiomyomata uteri.. Prospective open-label feasibility study.. University department of obstetrics and gynecology.. Thirty women with abnormal bleeding or discomfort (pain or pressure) due to leiomyomata uteri.. Patients received an initial 6-month course of the GnRH agonist leuprolide acetate, after which they were observed for symptom recurrence. Symptom recurrence was managed by repeated 6-month courses of leuprolide acetate.. Relief of symptoms, responses on a quality-of-life questionnaire, serum lipid levels, blood count, and ferritin level. The number of doses of leuprolide acetate required to maintain symptom control was recorded. Serial bone mineral density measurements were made in selected patients.. Twenty of the 30 women who began therapy with leuprolide acetate continued in the protocol. Each individual 6-month course of leuprolide acetate therapy was followed by a median of 9 additional months of symptom control (range, 2 to >25 months). Women remaining in the protocol experienced a mean decrease of 2.4% in bone mineral density of the lumbar spine; bone mineral density of the hip did not change.. Intermittent courses of leuprolide acetate can be used in the nonsurgical management of women with symptomatic leiomyomata uteri. Use of antiresorptive add-back therapy and monitoring of bone mineral density can be considered when repeated courses of leuprolide acetate are given.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Drug Administration Schedule; Female; Humans; Leiomyoma; Leuprolide; Time Factors; Uterine Neoplasms

Topics: Electrocoagulation; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Pain Measurement; Pain, Postoperative; Preoperative Care; Reference Values; Uterine Neoplasms; Uterus

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.

Topics: Absorptiometry, Photon; Adult; Antineoplastic Agents, Hormonal; Bone Density; Delayed-Action Preparations; Estriol; Female; Humans; Leiomyoma; Leuprolide; Lumbar Vertebrae; Middle Aged; Osteoporosis; Uterine Neoplasms

Aims of our study were as follows: (1) to evaluate the therapeutic efficacy of the preoperative administration of a gonadotropin-releasing hormone analog before laparoscopic myomectomy and (2) to assess whether any ultrasonographic parameter of the fibroids (number, size, Doppler velocimetry, or echogenicity) was of prognostic value.. A prospective randomized study was performed on 67 patients with symptomatic uterine fibroids that were mainly intramural; these patients were undergoing laparoscopic myomectomy. Patients were randomized either to preoperative administration of two injections of a depot formulation of leuprolide acetate 28 days apart (group A, n = 35) or to direct surgery (group B, n = 32). In each group we studied the number, volume, and echogenicity of the larger fibroids; the resistance index of uterine arteries and of fibroid vessels; hematologic parameters; operative time; and blood loss.. The two groups did not differ significantly in basal ultrasonographic parameters and hematologic data. Postoperatively, the red blood cell count and the serum hemoglobin and iron levels were significantly (p < 0.05) lower in group B. Both blood loss (p < 0.01) and operative time (p < 0.05) were significantly lower in group A. However, the operative time was significantly longer when the main fibroid was markedly hypoechoic, probably because the increased softness of the tumor after leuprolide acetate pretreatment makes its enucleation much more cumbersome.. Our data confirm the therapeutic efficacy of preoperative administration of a gonadotropin-releasing hormone analog before laparoscopic myomectomy in reducing the blood loss and in decreasing the operative time. This preoperative course of leuprolide acetate in hypoechoic fibroids, because of the further reduction of the density of the myomas, causes a significant (p < 0.05) increase in operative time.

Topics: Adult; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Hemoglobins; Hemorrhage; Humans; Injections, Intramuscular; Iron; Laparoscopy; Leiomyoma; Leuprolide; Middle Aged; Predictive Value of Tests; Prospective Studies; Time Factors; Treatment Outcome; Ultrasonography; Uterine Neoplasms

To assess ultrasonographic prediction of the efficacy of administration of a gonadotropin-releasing hormone (GnRH) analog before laparoscopic myomectomy.. Prospective, randomized study of women treated consecutively from September 1994 to July 1996 (Canadian Task Force classification I).. Endogyn Service, Private Endoscopic Associates, Naples, and Department of Gynecologic and Pediatric Sciences, Reggio Calabria University, Catanzaro, Italy.. Sixty-seven infertile women with symptomatic uterine myomata, mainly intramural, undergoing laparoscopic myomectomy.. Patients were prospectively randomized in two groups. Group A received preoperative administration of two injections of a depot formulation of leuprolide acetate 28 days apart, and group B underwent direct surgery. In each group we studied the number, diameter, and echogenicity of larger fibroids; resistance index of uterine arteries and myoma vessels; operating time; and blood loss.. The two groups did not significantly differ in baseline ultrasonographic parameters. Both blood loss (p <0.01) and operating time (p <0.05) were significantly lower in group A. However, operating time was significantly longer when the main myoma was markedly hypoechoic.. Our data confirm the therapeutic efficacy of administration of a GnRH analog before laparoscopic myomectomy in reducing blood loss and decreasing operating time in all cases except those with markedly hypoechoic fibroids.

Topics: Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Delayed-Action Preparations; Female; Humans; Laparoscopy; Leiomyoma; Leuprolide; Myometrium; Preoperative Care; Prospective Studies; Treatment Outcome; Ultrasonography; Uterine Neoplasms; Uterus; Vascular Resistance

The authors examined 33 patients with symptomatic uterine leiomyomas due to undergo total hysterectomy in order to evaluate the effects of treatment with GnRH analogues on leiomyoma and estrogen and progesterone receptors.. The patients were divided into two groups: one group was treated with leuprolide acetate (Group A) and the other did not receive treatment (Group B).. A significant reduction in the volume of leiomyomas and estrogen and progesterone receptors was noted in patients in Group A.. Treatment with GnRH analogues therefore represents a valid aid for patients with uterine leiomyomas and sideropenic anemia awaiting surgery.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Middle Aged; Preanesthetic Medication; Treatment Outcome; Uterine Neoplasms

In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism.

Topics: Absorptiometry, Photon; Analysis of Variance; Antineoplastic Agents, Hormonal; Bone Density; Bone Remodeling; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Isoflavones; Leiomyoma; Leuprolide; Lumbar Vertebrae; Menopause; Metrorrhagia; Osteoporosis, Postmenopausal; Treatment Outcome; Uterine Neoplasms; Uterus

In an open, non-comparative clinical phase IV multicentre study the efficacy and safety of the GnRH agonist leuprorelin acetate depot (LAD) for patients with at least one symptomatic uterine leiomyoma was assessed. 144 premenopausal patients were enrolled and treated with up to six injections of 3.75 mg LAD/month subcutaneously prior to surgical intervention, e.g. either hysterectomy or myoma enucleation. Due to a profound suppression of serum-estradiol levels to castration range (< or = 30 pg/ml) an average volume reduction of all myomas from 86.6 +/- 101.3 ml to 38.5 +/- 63.5 ml became obvious for 90% of all patients. In parallel a significant shrinkage of uterine volume was observed. At baseline 43 patients were planned to undergo a hysterectomy. 29 of these 43 patients could be switched after therapy with LAD to an enucleation as appropriate surgical treatment. In addition a number of patients with scheduled myoma enucleations which were planned to be performed via laparotomy could definitely be operated laparoscopically. Treatment was generally well tolerated. Most of the observed side effects were related to hypoestrogenism. The results of this study have shown that medical pretreatment for patients with uterine fibroids with LAD prior to surgical intervention is an effective measure to improve operability and could lead for several patients to minimal invasive surgery.

Topics: Adult; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Estradiol; Female; Humans; Hysterectomy; Injections, Subcutaneous; Leiomyoma; Leuprolide; Middle Aged; Prospective Studies; Uterine Neoplasms

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

Treatment of women with uterine myomas with GnRH agonists results in symptoms of hypoestrogenism which can be prevented by concurrent "add-back" estrogen administration. We took advantage of these induced endocrine changes to investigate their effects on cognitive functioning in young women with myomas. Nineteen women with uterine myomas were tested before treatment. They all received the GnRH agonist, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks and were then randomized to receive LAD plus estrogen or LAD plus placebo every 4 weeks for 8 additional weeks. Levels of all sex hormones decreased after 12 weeks of LAD treatment (P < 0.01), and only estradiol (E2) levels increased (P < 0.01) following 8 weeks of subsequent treatment in the group that received LAD plus E2. Scores on neuropsychological tests of verbal memory decreased from pretreatment to 12 weeks posttreatment with LAD (P < 0.05). These memory deficits were reversed in the group that received LAD plus E2 for 8 weeks coincident with an increase in plasma E2, whereas memory scores remained depressed in the group that received LAD plus placebo. These findings are consistent with those from studies on surgically menopausal women and strongly suggest that estrogen serves to maintain verbal memory in women. These results provide support for the efficacy of add-back estrogen regimens in women treated with GnRH agonists and also imply that estrogen may be important for maintaining memory in the postmenopause.

Topics: Adult; Cognition Disorders; Delayed-Action Preparations; Estradiol; Female; Humans; Leiomyoma; Leuprolide; Memory Disorders; Uterine Neoplasms

To determine the effectiveness of leuprolide acetate (LA) followed by medroxyprogesterone acetate (MPA) in the treatment of abnormal uterine bleeding attributed to leiomyomata uteri.. Randomized, double-blinded, controlled clinical trial.. Human volunteers in an academic research environment.. Premenopausal women with abnormal uterine bleeding attributed to leiomyomata uteri.. Subjects received 6 months of LA after which they were randomized to receive MPA or placebo.. Control of bleeding as assessed by menstrual calendar and self-report; hematologic parameters (hemoglobin and ferritin); uterine size by ultrasonography.. More than three quarters of subjects became amenorrheic on LA. The proportion of subjects with improvement in the bleeding abnormality after therapy was not different in the group receiving MPA compared with placebo; however, women who received MPA were less likely to be anemic after therapy than women receiving placebo. Among the women assigned to placebo, 55% experienced an improvement in bleeding compared with pre-GnRH agonist therapy that persisted after discontinuation of LA. There was a high dropout rate (51%), largely associated with failure of the regimens to control bleeding symptoms.. Approximately one half of women with abnormal bleeding attributed to leiomyomata uteri have sustained symptomatic improvement after 6 months of therapy with LA even when only placebo therapy is given, although MPA decreases the incidence of anemia. Leuprolide acetate with or without subsequent progestin may be useful as a component of nonsurgical management of these tumors, with monitoring of hematologic status. The interpretability of these data is limited by the high rate of therapy discontinuation in women with abnormal bleeding of the severity studied here.

Topics: Adult; Double-Blind Method; Female; Humans; Leiomyoma; Leuprolide; Medroxyprogesterone Acetate; Middle Aged; Uterine Neoplasms

To compare the size of arterial vessels in myomas from women treated with GnRH agonist (GnRH-a) or given placebo.. Our study group included 46 women about to undergo myomectomy or hysterectomy; 30 were treated with leuprolide acetate (3.75 or 7.5 mg) in three monthly doses, and 16 were given placebo. Arterial diameters of the intramyomatous vessels were measured using an ocular micrometer on hematoxylin and eosin-stained slides.. Clinically and radiologically, the uterine volume of GnRH-a-treated patients decreased by an average of 30%, and the diameter of the largest myoma decreased by 27%. The average diameter of intramyomatous arteries was 24% smaller in GnRH-a subjects compared with those receiving placebo (136 +/- 42 versus 178 +/- 60 microns, P < .01). In addition, arteriosclerotic changes, including intimal and medial fibrosis, were seen more often in the GnRH-a-treated subjects (48 versus 25%, P < .05).. Intramyomatous arteries were smaller and more often showed arteriosclerotic changes in leiomyomas removed from women treated with GnRH-a compared with those given placebo. The estrogen deprivation induced by GnRH-a may cause a relative vasoconstriction of myomatous vessels. Whether this decreased vessel size is the principal contributor to decreased myoma size will require further study.

Topics: Adult; Arteries; Combined Modality Therapy; Constriction, Pathologic; Double-Blind Method; Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Premedication; Uterine Neoplasms; Uterus

To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas.. This was a phase III, stratified, randomized, double-blind, placebo-controlled, parallel-group, 12-week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their pre-study hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater.. Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetate-treated groups than in the placebo group.. Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterine-myoma volume, and in alleviating bleeding and other leiomyoma-related symptoms.

Topics: Adult; Anemia, Iron-Deficiency; Bone Density; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Hematocrit; Hemoglobins; Humans; Iron; Leiomyoma; Leuprolide; Middle Aged; Preoperative Care; Uterine Hemorrhage; Uterine Neoplasms

To compare the effects of two different doses of a monthly depot injection of a GnRH agonist (GnRH-a) on uterine cavity area in patients with uterine leiomyomata.. Prospective, randomized study.. Hospital department of obstetrics and gynecology.. Thirty-six premenopausal women, 25 to 52 years of age, with uterine leiomyomata.. Leuprolide acetate (LA) depot, 1.88 or 3.75 mg, was administered SC every 4 weeks for 24 weeks.. Uterine cavity area before and after treatment was assessed by hysterosalpingography.. The 1.88- and 3.75-mg LA depots significantly reduced uterine cavity area by 40.8% and 40.2%, respectively. No significant difference was observed between the two groups.. Monthly injection of 1.88 or 3.75 mg LA depots appears to reduce uterine cavity area to a similar extent in patients with uterine leiomyomata.

Topics: Adult; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Leiomyomatosis; Leuprolide; Middle Aged; Prospective Studies; Uterine Neoplasms; Uterus

Topics: Adult; Arteries; Carotid Arteries; Double-Blind Method; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Middle Aged; Prospective Studies; Severity of Illness Index; Uterine Neoplasms; Uterus; Vascular Resistance

This study evaluated the microscopic changes in leiomyomata following the use of a gonadotropin releasing hormone (GnRH) agonist. Seventeen women with symptomatic leiomyomata were included. Nine were treated with a GnRH agonist for three to six months prior to surgery, and the remaining eight served as controls. Following myomectomy, paraffin sections were prepared from the tumors. These sections were examined microscopically by two gynecologic pathologists, who were blind to the patient groups. The results showed increased cellularity and hyalinization in leiomyomata following GnRH agonist treatment.

Topics: Adult; Cell Count; Female; Humans; Hyalin; Leiomyoma; Leuprolide; Mitotic Index; Nafarelin; Retrospective Studies; Severity of Illness Index; Single-Blind Method; Uterine Neoplasms

Six patients with symptomatic leiomyomata uteri and in whom surgical treatment was indicated received, during 3 months, intramuscular leuprolide acetate, 3,75 mg monthly, in order to 1) achieve a reduction of myomata size and 2) recover an anemic patient before surgery. In every patient, amenorrhea was induced since the second month of treatment. A significant decrease of myomas sizes was achieved. The reduction of the volume of the largest myoma in each case, varied between 51% and 77% (x = 60% +/- ES 4,3) LH and estradiol plasma levels diminished significantly and FSH did not changed in response to treatment. Side effects were well tolerated. Hot flashes were present in all patients, headaches in 2 and loss of strength in 2. Surgery was accomplished after 3 months of treatment. Myomectomy was performed in 5 cases and total hysterectomy in 1. Uterine shrinkage and the period of amenorrhea induced by Lupron-depot facilitated hysterectomy and myomectomy techniques and the recovery of one patient with a severe anemia.

Topics: Adult; Female; Humans; Injections, Intramuscular; Leiomyoma; Leuprolide; Preoperative Care; Uterine Neoplasms

This study measured the changes in uterine volume, uterine vascular resistive index and lumbar vertebral bone density before and after a six-month course of leuprolide acetate depot in women with uterine leiomyomas. All nine patients studied were black. The high baseline bone density of black women may provide a greater scope for the use of gonadotropin agonists as compared to women in the general population. A significant reduction in uterine volume was achieved in the patients with leuprolide therapy. Uterine vascular resistive indices were not altered consistently following leuprolide therapy in women with leiomyomas.

Topics: Adult; Black People; Bone Density; Delayed-Action Preparations; Female; Humans; Leiomyoma; Leuprolide; Organ Size; Uterine Neoplasms; Vascular Resistance

Treatment of women with leiomyomata with gonadotrophin-releasing hormone agonists (GnRHa) for > 6 months is not recommended because of concerns regarding adverse sequelae of prolonged hypoestrogenism. It has been postulated that addition of low-dose sex steroids to GnRHa treatment, i.e. 'add-back' therapy, may avert some of these adverse effects (accelerated bone resorption, vasomotor flushes) without altering the efficacy of GnRHa therapy. To evaluate the effects of long-term GnRHa therapy on uterine size, bleeding patterns, bone mass and lipids, 51 pre-menopausal women with leiomyomata were treated with the GnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2 years. After 3 months of leuprolide therapy, the women were randomized to receive either low-dose continuous oestropipate, 0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1-14 each month (the oestrogen-progestin add-back group) or higher-dose norethindrone, 10 mg daily (the progestin add-back group), for the remaining 21 months. Mean uterine volume decreased by 40% in both treatment groups during the first 3 months on leuprolide treatment. There was no significant change in uterine size following oestrogen-progestin add-back. However, mean uterine volume in the progestin add-back group increased to 87% of pre-treatment size by treatment month 12 and 95% of pre-treatment size by treatment month 24. Mean bone density of the lumbar spine as measured by dual X-ray absorptiometry decreased significantly by 2.6% during the first 3 months in all patients, but did not change significantly following steroid add-back in both treatment groups during the final 21 treatment months.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bone Density; Cholesterol, HDL; Delayed-Action Preparations; Estradiol Congeners; Estrone; Female; Hematocrit; Humans; Leiomyoma; Leuprolide; Middle Aged; Norethindrone; Prospective Studies; Time Factors; Uterine Neoplasms

It has been amply demonstrated that uterine leiomyoma possess estrogen receptors. On the basis of this presupposition, it is considered logical to use GnRH-agonists which, by reducing the level of estrogen, also reduce the volume of the leiomyoma, although to a varying extent. The maximum reduction which can be obtained occurs, according to published data, between 3 and 6 months of treatment, attaining mean values of approximately 50%. In the author's experience the treatment period was shortened even further by administering only 2 vials of leuprolide depot each month to women who subsequently underwent hysterectomy. The sample group comprised 30 women with uterine leiomyomatosis, of whom 15 were treated with a GnRH analogue and 15 with placebo. The reduction of uterine volume was evaluated by echography and was found to be 40% in the treated group, whereas non change was detected in the "placebo-group".

Topics: Adult; Combined Modality Therapy; Delayed-Action Preparations; Female; Humans; Hysterectomy; Leiomyomatosis; Leuprolide; Middle Aged; Premedication; Time Factors; Uterine Neoplasms

We wanted to correlate the degree of myoma shrinkage after luteinizing hormone-releasing hormone (LHRH)-analogue depot therapy to the estrogen and progesterone receptor content of the enucleated fibroids. Twenty premenopausal, regularly menstruating women wishing to preserve their childbearing capacity were treated for three to six months with 3.75 mg of leuprorelin acetate depot subcutaneously. Four weeks after the last injection, all fibroids were enucleated and investigated immunohistochemically by using monoclonal (rat) antibodies to human estrogen and progesterone receptors. The localization and distribution of nuclear staining was visualized through a light microscope and scored semiquantitatively by multiplying the staining intensity with the percentage of positive cells. Although LHRH-analogue depot therapy led to almost the same degree of ovarian suppression in all of the women, extent of myoma shrinkage varied from 0% to 87%. On the other hand the extent of myoma regression correlated significantly to the estrogen receptor content of the enucleated fibroid, while diminution of myoma size seemed to be independent of the progesterone receptor. This indicates an association between myoma shrinkage and the estrogen receptor status of the enucleated fibroid. It remains to be proved that pretreatment receptor analysis may predict the myomata that are sensitive to endocrine treatment.

Topics: Adult; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Infertility, Female; Injections, Subcutaneous; Leiomyoma; Leuprolide; Menstrual Cycle; Receptors, Estrogen; Receptors, Progesterone; Ultrasonography; Uterine Neoplasms

To evaluate the effects of two different doses (3.75 mg versus 7.5 mg) of leuprolide acetate (LA, Lupron; Tap Pharmaceuticals, Deerfield, IL) on myoma size, blood loss during myomectomy, on magnetic resonance imaging (MRI) signal quality, and histopathologic changes in women requiring myomectomy.. Prospective, nonrandomized, sequential study.. Urban center teaching hospital.. Twenty-eight women with uterine leiomyomata requiring myomectomy.. Nine women were entered as controls (group 1), 10 women received 3.75 mg IM (group 2), and 9 women received 7.5 mg IM of LA (group 3) each for 3 months before myomectomy.. The uterine size and hematocrit among the three groups of patients before treatment was not significantly different. A significant reduction of 34.5% and 34.6% in myomata size was seen in groups 2 and 3. The estimated average blood loss at myomectomy was 745 +/- 101 mL, 615 +/- 177 mL, and 722 +/- 192 mL in groups 1, 2, and 3, respectively. The postoperative hematocrit was not different among the three groups (29.8% +/- 0.9%, 30.4% +/- 1.6%, and 29.8% +/- 1.2%). There was no evidence of cytologic atypia, increased mitosis, or change in fibrosis in LA-treated women. There were no characteristic MRI or histologic changes seen after LA treatment as compared with controls.. The results of this study have demonstrated that both doses of LA (3.75 and 7.5 mg) can induce a significant and similar degree of size reduction in myomas and that neither dose of LA aided in the reduction of blood loss at myomectomy and therefore should not be used routinely.

Topics: Adult; Dose-Response Relationship, Drug; Female; Hematocrit; Humans; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Prospective Studies; Uterine Neoplasms; Uterus

Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume.. Patients were randomly assigned to group A (eight patients) receiving 25 mg of RU 486 daily for 3 months or group B (six patients) receiving 3.75 mg of leuprolide acetate monthly for 3 months. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography. Uterine volume was measured before and during the study with abdominal ultrasonography.. Both groups showed an increase in resistive index. Patients receiving RU 486 had uterine artery blood flow decreased by 40%, and those receiving leuprolide acetate had a 21% decrease. We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups.. Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery.. Fourteen women with uterine fibroids and scheduled to undergo either myomectomy or hysterectomy were randomly assigned to take RU-486 and leuprolide acetate over a period of three months to determine their effects upon uterine artery blood flow and uterine volume. Eight patients received 25 mg of RU-486 per day and six patients received 3.75 mg/month of leuprolide acetate over the same period. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography, while uterine volume was measured before and during the study with abdominal ultrasonography. Blood flow decreased 40% among those taking RU-486 compared to 21% among those administered leuprolide acetate. Uterine volume decreased significantly for both groups without significant difference in the extent of decrease between groups. Study findings would support the hypothesis that a significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery.

Topics: Female; Humans; Leiomyoma; Leuprolide; Mifepristone; Prospective Studies; Regional Blood Flow; Uterine Neoplasms; Uterus

Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy.. Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist.. All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms.. The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity.

Topics: Adult; Blood Loss, Surgical; Blood Transfusion; Blood Volume; Combined Modality Therapy; Female; Humans; Hysterectomy; Hysterectomy, Vaginal; Leiomyoma; Length of Stay; Leuprolide; Middle Aged; Organ Size; Uterine Neoplasms; Uterus

To test the hypothesis that the effects of estrogen reduction on uterine leiomyoma regression are mediated through changes in cell density or the extracellular matrix.. Uterine myomas were obtained from 20 women who had received randomly either the GnRH agonist leuprolide acetate depot for 3 months or placebo. The biochemical and morphologic characteristics studied included: total protein, DNA, and amino acid concentrations; histologic appearance; collagen content; and nuclear density.. The absolute and relative concentrations of hydroxylysine, hydroxyproline, glycine, and proline were significantly greater (P < .05) in uterine myomas from patients pretreated with a GnRH agonist compared with placebo-treated controls. The GnRH agonist was also associated with trends toward increased mean total protein, DNA, and nuclear density, but the differences did not reach statistical significance.. The concentrations of the amino acids contained in collagen were significantly greater in uterine myomas from patients treated with the GnRH agonist compared to myomas from placebo-treated controls. In addition, our observations suggest that the reduction in uterine myoma volume associated with GnRH agonist therapy is associated with alterations in the extracellular matrix.

Topics: Amino Acids; Collagen; DNA, Neoplasm; Double-Blind Method; Female; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

Women with symptomatic uterine myomas were randomized to receive LA depot or placebo for 12 weeks before myomectomy. Silver staining nucleolar organizer regions (AgNORs) per nuclei were assessed in the tissue obtained at the time of myomectomy. Myoma tissue from women treated with LA depot before myomectomy had significantly fewer AgNORs per nuclei than myoma tissue obtained from women treated with placebo. Leuprolide acetate depot may reduce the number of proliferating cells in myomas.

Topics: Adult; Delayed-Action Preparations; Estradiol; Female; Humans; Leiomyoma; Leuprolide; Nucleolus Organizer Region; Uterine Neoplasms

To evaluate leuprolide acetate (LA) depot (Enantone Depot, Takeda, Italy) when administered preoperatively in hysteroscopic surgery.. Prospective, comparative study.. University Clinic of Obstetrics and Gynecology.. One hundred ninety-three patients (114 pretreated with LA depot and 79 controls) who underwent hysteroscopic surgery for uterine septa (group A), submucous fibroids (group B), and abnormal uterine bleeding (group C).. In groups B and C there was a significant reduction in the operating time, bleeding during the operation, and the amount of distention medium required after LA depot administration, but no significant differences in surgical feasibility or efficacy were found in group A patients after treatment.. Preoperative treatment with LA depot is effective in making hysteroscopic surgery easier.

Topics: Adult; Delayed-Action Preparations; Endometrium; Female; Humans; Hysteroscopy; Leuprolide; Myometrium; Prospective Studies; Uterine Hemorrhage; Uterine Neoplasms; Uterus

Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.

Topics: Adult; Bone Density; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Middle Aged; Progestins; Prospective Studies; Spine; Triptorelin Pamoate; Ultrasonography; Uterine Neoplasms; Uterus

A short term therapy of leiomyomata uteri with leuprolide acetate depot 3.75 i.m. every 28 days for 4 months was started in 19 patients. Uterine volume, based on the ultrasound data, was calculated, utilizing the formula for a prolate ellipsoid, before and after treatment. Before the treatment the uterine mean volume was 207.3 cc and decreased to 122.2 cc after therapy. The efficacy of the treatment was evaluated by means of the "t" test for paired data and showed a p < 0.002.

Topics: Adult; Drug Evaluation; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Middle Aged; Uterine Neoplasms

The effect of leuprorelin acetate depot on the endocrine system and on lipid metabolism was evaluated in a multicentre, noncomparative study. During the first month of treatment, suppression of serum oestradiol levels to below 20 pg/ml was achieved and luteinising hormone and follicle-stimulating hormone levels were reduced to less than 50% of pretreatment values. A negative influence on lipid metabolism was not recorded. The high-density lipoprotein/low-density lipoprotein ratio did not change during therapy. Resumption of menstruation occurred within a mean period of 3 months after the last leuprorelin acetate depot injection.

Topics: Bone Density; Delayed-Action Preparations; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Leuprolide; Lipid Metabolism; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Luteinizing Hormone; Progesterone; Uterine Neoplasms

Between October 1988 and October 1990 in a noncomparative multicentre study, 114 patients were treated for uterine fibroids with the gonadotrophin-releasing hormone (Gn-RH) agonist, leuprorelin acetate depot. The mean age of the women was 33 years and 55.3% of them had a history of infertility. After confirmation of the diagnosis by ultrasound and/or operation, treatment began between day 1 and 3 of the cycle with leuprorelin acetate depot 3.75 mg subcutaneously. Therapy was carried out for a total of 6 months with one injection every 4 weeks. Treatment was paralleled by measurements of endocrine and metabolic parameters, estimation of myoma and uterine size by ultrasound and self-reporting of the patients of drug-related complaints. Four of the 114 women did not complete the whole treatment, two of them because of general side effects, one because of carcinophobia and unsatisfactory regression of the myoma and the last one for unspecified reasons. During treatment, a mean reduction of the uterine volume of about 67% was observed, in conjunction with shrinkage of the myoma in 92.1% of cases (mean decrease of 56% of the fibroids) with a large interindividual difference. Maximal diminution of uterine and fibroid size had been nearly completely reached within the first 12 weeks of therapy. After 4 weeks of the Gn-RH agonist depot most of the patients had achieved postmenopausal status, which continued throughout the remaining 20 weeks of treatment. In accordance with this finding, the majority of general side effects was due to the hypo-oestrogenic endocrine status. Liver and lipid metabolism was almost unaffected, although increasing calcium and alkaline phosphatase serum levels as well as an increased urinary calcium/creatinine ratio demonstrated an increased metabolic turnover of the bone. Haemoglobin concentrations, however, increased in those cases with fibroid-related anaemia. Thus the slow-release form of leuprorelin acetate is an adjunct to myomectomy especially in those women in whom family planning is not yet completed.

Topics: Adult; Delayed-Action Preparations; Estradiol; Female; Follicle Stimulating Hormone; Germany; Hemoglobins; Humans; Leiomyoma; Leuprolide; Luteinizing Hormone; Progesterone; Prolactin; Uterine Neoplasms

A total of 110 nonmenopausal women (mean age 42.1 years) presenting with symptomatic uterine leiomyomata and/or fibromatous uteri have been enrolled in this trial to evaluate the efficacy of the depot formulation of leuprorelin acetate in decreasing uterine volume and minimizing menorrhagia, dysmenorrhoea and pressure over the bladder. All patients were treated with an intramuscular injection of leuprorelin acetate depot 3.75 mg every 4 weeks for 16 weeks. Clinical examinations and hormonal and ultrasound determinations were performed before, during and at the end of treatment. Appropriate follow-up is still ongoing for most patients. At the end of the treatment period, of 88 women with enlarged fibromatous uteri, 33 (37.5%) showed a decrease in uterine volume of greater than or equal to 50% of the original size, while nine (10.2%) remained with unchanged uterine volume. Of 80 fibromas measurable separately, 47 (52.8%) decreased by greater than 50% of the initial volume and 16 (18%) remained unchanged or even increased. During treatment, clinically advantageous effects were observed in the associated symptomatology, mainly in the production of amenorrhoea and restoration of normal haemoglobin levels. Most of the patients were affected by irregular menstrual blood loss with consequent anaemia that in 29 patients was expressed by low levels of haemoglobin (mean 9.2 g/dl; SD 1.5; range 4.5-11.8 g/dl). By the end of the treatment, only one patient still had moderate vaginal blood loss. Haemoglobin levels rose to a mean value of 11.8 g/dl (SD 1.3; range 8.5-14.1 g/dl). Three patients (2.7%) failed to complete the 16-week treatment protocol, because of headache (one patient) and increased blood pressure (two patients). As a result of the treatment, of the 107 patients who were candidates for surgery and who were included in this study, only nine (8.4%) required surgery during leuprorelin acetate treatment. Of these, four operations were vaginal excision of the submucous myomata protruding into the cervix during treatment, and in five hysterectomy performed because of persistence of symptoms. In most patients the achievement of amenorrhoea minimized the fear of surgical emergency, facilitating an increased awareness of their clinical condition. With the exception of the three patients who dropped out, side effects were mild in all patients, consisting mainly of hot flushes, which were easily tolerated. In the following 8-12 months, the regrowth of uterine volume

Topics: Adult; Delayed-Action Preparations; Female; Follow-Up Studies; Humans; Injections, Intramuscular; Italy; Leiomyoma; Leuprolide; Uterine Neoplasms; Uterus

The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a randomized, double-blind, P-controlled study of the efficacy of LA depot before myomectomy. After 27 to 38 months of follow-up, the recurrence of myomas was found to be greater when at least four myomas were resected. Myoma recurrence was not associated with pretreatment or preoperative uterine volume, resected myoma mass, or preoperative medical therapy.

Topics: Adult; Combined Modality Therapy; Delayed-Action Preparations; Female; Follow-Up Studies; Humans; Incidence; Leuprolide; Myoma; Recurrence; Uterine Neoplasms

To compare the efficacy of two different doses, 1.88 mg and 3.75 mg, of a monthly depot injection of a gonadotropin-releasing hormone agonist (GnRH-a) in the treatment of uterine leiomyomata.. A prospective randomized study.. Hospital department of gynecology and obstetrics.. Forty-one premenopausal Japanese women, 25 to 53 years of age, with uterine leiomyomata.. Depot type of GnRH-a, leuprolide acetate (LA) 1.88 mg or 3.75 mg was administered subcutaneously every 4 weeks for 24 weeks.. Efficacy of treatment was assessed in terms of uterine volume, serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and adverse symptoms during treatment.. In both groups, a significant reduction in uterine volume, 52% in 1.88 mg group and 47% in 3.75 mg group, was obtained at week 24, with near maximal reduction (41%, 45%) apparent by 12 weeks. No significant difference was observed between the groups in percent uterine volume reduction at each treatment week. Both groups showed significant and equal suppression of serum levels of E2, LH, and FSH. In addition, the incidence of adverse symptoms was not significantly different between the two groups.. Monthly injection of 1.88 mg or 3.75 mg LA depot has equivalent treatment efficacy in reducing uterine volume. Twelve weeks of treatment is enough to obtain near maximal reduction.

Topics: Adult; Delayed-Action Preparations; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Japan; Leiomyoma; Leuprolide; Luteinizing Hormone; Middle Aged; Prospective Studies; Ultrasonography; Uterine Neoplasms; Uterus

The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms.

Topics: Adult; Antineoplastic Agents; Delayed-Action Preparations; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Injections, Intramuscular; Leiomyoma; Leuprolide; Uterine Neoplasms

Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas, which were the size of 14 to 18 weeks' gestation, were randomized into two groups to determine whether preoperative gonadotropin-releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy. The control group (group A; n = 25) did not receive preoperative gonadotropin-releasing hormone agonist, but patients in Group B (n = 25) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy. Patients in the two groups were similar with respect to age, gravidity, parity, pretreatment uterine size, and hemoglobin and hematocrit levels. Patients in group B had an increase in hemoglobin levels (10.75 to 12.12 gm/dl, p less than 0.05) and a decrease in uterine volume (1086.7 to 723.4 ml, p less than 0.05) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy (76.0% vs 16%). Patients in group B also had shorter hospitalizations (5.2 vs 3.8 days, p less than 0.05). We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas.

Topics: Female; Gonadotropin-Releasing Hormone; Hematocrit; Hemoglobins; Hormones; Humans; Hysterectomy; Leiomyoma; Leuprolide; Preoperative Care; Uterine Neoplasms; Uterus

Eighteen patients with leiomyomata uteri were randomized to receive either leuprolide acetate depot (n = 9) 3.75 mg intramuscularly (IM) or placebo (n = 9) IM every 4 weeks for four injections. Leuprolide acetate treated patients demonstrated a reduction in mean uterine volume of 34% and a decrease in serum estradiol (E2) concentrations from 120 +/- 21 pg/mL (mean +/- standard error) to 16 +/- 9 pg/mL. Leuprolide acetate treated patients also demonstrated significant decreases in serum growth hormone (GH) (3.0 +/- 0.4 ng/mL versus 1.4 +/- 0.4 ng/mL) and insulin-like growth factor-I (IGF-I) concentrations (3.3 +/- 0.4 U/mL versus 1.3 +/- 0.2 U/mL) over the 12 week treatment period. Serum IGF-II levels did not change. Mean uterine volume and serum E2, GH, IGF-I, and IGF-II concentrations did not change in placebo-treated patients. These data suggest that hypoestrogenism is associated with decreases in circulating GH and IGF-I.

Topics: Adult; Antineoplastic Agents; Clinical Trials as Topic; Estradiol; Fasting; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Hormones; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Leiomyoma; Leuprolide; Placebos; Somatomedins; Uterine Neoplasms; Uterus

Topics: Clinical Trials as Topic; Combined Modality Therapy; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leiomyoma; Leuprolide; Random Allocation; Uterine Neoplasms

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

Endometrium, myometrium and uterine leiomyomata (fibroids) all secrete PRL. Although the regulation of endometrial PRL secretion has been extensively studied, little is known about myometrial and fibroid PRL. This study investigated the effects of the GnRH agonist (GnRH-a) leuprolide acetate depot, administered in vivo, on fibroid and myometrial PRL secretion by explant cultures. Tissue was obtained from 17 patients enrolled in a prospective, randomized, double-blind, placebo-controlled clinical trial. Explant cultures of fibroid and myometrium were established in defined serum free media and harvested media assayed for PRL and total protein. Fibroid PRL secretion was substantially greater than myometrial PRL secretion. Fibroid PRL secretion increased with time whereas myometrial PRL secretion did not. Fibroid, but not myometrial, PRL secretion in GnRH-a treated patients was significantly lower when compared to controls. Fibroid protein secretion was not affected by GnRH-a administration in vivo. Progesterone supplementation in vitro inhibited fibroid PRL secretion; estrogen and GnRH-a in vitro had a minimal effect. Western blot analysis showed a small proportion of PRL secreted by fibroids to be glycosylated. These results demonstrate: 1) PRL secretion is greater from fibroids than myometrium; 2) fibroid PRL secretion in vitro is specifically reduced after 24 h after in vivo treatment with GnRH-a; 3) estrogen or progesterone in vitro does not reverse the suppression by in vivo administration of GnRH-a; and 4) GnRH-a in vitro has no effect on fibroid PRL secretion.

Topics: Antineoplastic Agents; Blotting, Western; Culture Techniques; Dose-Response Relationship, Drug; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Myometrium; Progesterone; Prolactin; Uterine Neoplasms

The reduction in uterine and fibroid volume associated with the chronic administration of a gonadotropin-releasing hormone agonist (GnRH-a) is thought to be secondary to the analogue induced hypoestrogenic state. Our hypothesis was that the concentration of bioactive estrogen receptors (ER) and progesterone receptors (PR) may be important in the regulation of fibroid growth. The purpose of this study was to determine ER and PR content in fibroids and myometria from women pretreated with GnRH-a compared with controls. Tissue was obtained from 20 premenopausal women with uterine fibroids who were randomized to receive either leuprolide acetate depot, 3.75 mg intramuscularly every 28 days for four injections (n = 10) or placebo (n = 10) before myomectomy. The mean fibroid ER and PR content was significantly greater than the mean myometrial ER and PR content. The mean fibroid ER content for GnRH-a-treated patients was significantly greater than in placebo-treated patients (143.3 +/- 22.8 versus 36.1 +/- 14.3 fmol/mg). The mean fibroid PR and the mean myometrial ER and PR content were not significantly different between treatment groups. Clinically, the significant increase in fibroid ER may be an explanation for the rapid regrowth of fibroids observed after the cessation of GnRH-a therapy.

Topics: Antineoplastic Agents; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Infant, Newborn; Leiomyoma; Leuprolide; Menstrual Cycle; Myometrium; Prolactin; Receptors, Estrogen; Receptors, Progesterone; Uterine Neoplasms

The gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate depot was used as a biologic probe to investigate the possible roles of insulin-like growth factors (IGFs) I and II in fibroid growth. The secretion of IGF-I and IGF-II by explant cultures of fibroids and myometria from women treated with a GnRH-a was compared with that of tissue obtained from placebo-treated controls. Patients were randomized to receive either leuprolide 3.75 mg every 28 days (N = 9) or placebo injections (N = 8) before myomectomy. Fresh tissue was diced into 2-mm3 explants and cultures were established in serum-free media. The media were assayed for IGF-I, IGF-II, and total protein. Patients treated with GnRH-a demonstrated a 34% reduction in uterine volume, whereas placebo-treated patients exhibited no change. The secretion of IGF-I and IGF-II by fibroid explants obtained from women treated with the GnRH-a was significantly less than that in tissue obtained from placebo-treated controls (P less than .01 and P less than or equal to .05, respectively). Similarly, the secretion of IGF-I and IGF-II by myometrial explants was significantly less in tissue obtained from women treated with GnRH-a (P less than .0001 for both IGF-I and IGF-II). Protein secretion by fibroid tissue obtained from women treated with GnRH-a was not significantly different when compared with tissue from placebo-treated controls. In conclusion, fibroids and myometria from women pretreated with the GnRH-a secreted significantly less IGF-I and IGF-II than did tissue obtained from placebo-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Female; Gonadotropin-Releasing Hormone; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Leiomyoma; Leuprolide; Prospective Studies; Randomized Controlled Trials as Topic; Somatomedins; Uterine Neoplasms; Uterus

Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment. Leiomyomas are common, estrogen-sensitive, benign neoplasms that decrease in size by 40% to 50% during gonadotropin-releasing hormone agonist treatment. During gonadotropin-releasing hormone agonist therapy most women are amenorrheic. After discontinuation of gonadotropin-releasing hormone agonist treatment, uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs. Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy. This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin "add-back" treatment as a potential long-term medical therapy for women with symptomatic leiomyomas. Finally, an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues, is presented.

Topics: Buserelin; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Leuprolide; Middle Aged; Pilot Projects; Preoperative Care; Progestins; Time Factors; Uterine Neoplasms; Uterus

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

Topics: Adult; Antineoplastic Agents; Cholesterol; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Estradiol; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leiomyoma; Leuprolide; Middle Aged; Placebos; Random Allocation; Uterine Neoplasms

Eighteen premenopausal women with symptomatic leiomyomata uteri were enrolled in a stratified, randomized, double-blind, placebo-controlled study evaluating the efficacy of leuprolide acetate (LA) depot treatment before myomectomy. Stratification was based on pretreatment uterine volume (less than 600 cm3 versus greater than or equal to 600 cm3). Nine women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 12 weeks (group A); nine women received IM placebo with the same injection schedule (group B). All women underwent myomectomy within 4 weeks of their last injection. Mean total intraoperative blood loss was 213 +/- 44 mL (mean +/- standard error of the mean [SEM]) in group A and 302 +/- 43 mL in group B. When data from patients with large uteri (pretreatment uterine volumes of 600 cm3 or greater) were analyzed, mean total blood loss was 189 +/- 44 mL in group A and 390 +/- 20 mL in group B. These data suggest that leuprolide depot treatment before myomectomy may decrease intraoperative blood loss in women with large leiomyomata uteri.

Topics: Delayed-Action Preparations; Double-Blind Method; Estradiol; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hemorrhage; Hormones; Humans; Intraoperative Complications; Leiomyoma; Leuprolide; Placebos; Postoperative Complications; Premedication; Uterine Neoplasms; Uterus

Several studies have shown that treatment with a gonadotropin-releasing hormone (GnRH) analogue can reduce uterine volume in women with leiomyomata. However, no study to date has used a controlled population for comparison, nor has any study delineated the physiologic mechanism of volume reduction. We performed a double-blind, placebo-controlled study of a depot form of a GnRH analogue (leuprolide) given monthly for 24 weeks in 11 patients with symptomatic uterine leiomyomata. Patients initially treated with placebo were subsequently treated with active drug for 24 weeks. Magnetic resonance imaging was used to identify specifically the total uterine volume, total myoma volume, and total non-myoma volume. Treated patients had a significant reduction in total uterine and non-myoma volumes as compared with placebo patients (P less than .02). Total myoma volume was also reduced, but only to a P = .06 level. Pre- versus post-therapy values for all 11 patients showed significant reduction in all three volumes (P less than .02). Most symptoms were markedly improved. By 24 weeks post-therapy, all volumes had returned to baseline levels, although symptomatic improvement commonly persisted. The non-myoma volume was proportionally reduced to a greater extent than the myoma volume (42.7 versus 30.4%), and we therefore could explain the reenlargement seen when treatment was discontinued. Side effects were well tolerated and there were no study dropouts. We conclude that temporary hypoestrogenism induced by GnRH analogues can produce significant though temporary reduction in uterine volumes, and that the non-myoma volume is responsible for much of the reduction and reenlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antineoplastic Agents; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Placebos; Pregnancy; Randomized Controlled Trials as Topic; Uterine Neoplasms

A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels.

Topics: Adult; Antineoplastic Agents; Cholesterol; Double-Blind Method; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Random Allocation; Uterine Neoplasms

Fourteen premenopausal women with uterine leiomyomata were randomized to receive a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide, either by daily subcutaneous (SC) injection (500 micrograms/day) or by intranasal (IN) spray (1600 micrograms/day) for 24 weeks. In the SC group, a significant reduction in uterine volume occurred from a pretreatment volume of 368 +/- 60 (mean +/- standard error of the mean [SEM]) cm3 to 202 +/- 61 cm3 at 12 weeks of therapy (P less than 0.01) and to 172 +/- 49 cm3 at 24 weeks of therapy (P less than 0.005). In the IN group, no significant reduction in uterine volume occurred. In addition, there was a significant negative correlation between the serum estradiol concentration during treatment and the percent decrease in uterine volume (r = -0.55, P less than 0.05). Four months after completing therapy, uterine volume increased to 296 +/- 104 cm3 in the SC group, which was not significantly different from pretreatment volume. These findings suggest that reduction in uterine volume depends on the degree of hypoestrogenism induced and that uterine volume increases soon after cessation of GnRH-a therapy.

Topics: Administration, Intranasal; Adult; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leiomyoma; Leuprolide; Middle Aged; Random Allocation; Self Administration; Uterine Neoplasms; Uterus

Gonadotropin-releasing hormone agonists are used to treat premenopausal uterine leiomyomas; however, leiomyoma volume reduction is not always achieved. The reduction rate after this treatment varies for each leiomyoma, even in the same patient. Therefore, an effective method for predicting uterine leiomyoma volume reduction is required to reduce the adverse hypoestrogenic effects and drug-related economic burden related to gonadotropin-releasing hormone agonists.. This study aimed to determine the predictive use of MED12 mutations for evaluating the effect of gonadotropin-releasing hormone agonist treatment concerning reducing uterine leiomyoma volume and to predict the MED12 mutation status based on the findings of magnetic resonance imaging performed before treatment.. MED12 exon 2 mutation and erythropoietin expression in uterine leiomyomas were evaluated concerning volume reduction, as measured using magnetic resonance imaging. We developed a system for classifying leiomyomas according to T2-weighted magnetic resonance imaging signals to noninvasively predict the presence or absence of MED12 mutations in leiomyomas. Leiomyoma samples (>5 cm) were obtained from 168 patients during surgery (hysterectomy or myomectomy) between 2005 and 2021 at Yokohama City University Hospital. To analyze the rate of leiomyoma volume reduction, 41 patients had been preoperatively administered the gonadotropin-releasing hormone agonist (leuprorelin acetate 3.75 mg, monthly subcutaneous injection) for 3 months; magnetic resonance imaging was performed before and after treatment without contrast material.. Patients with MED12 exon 2 mutations had smaller volume reduction after treatment with the gonadotropin-releasing hormone agonist (P<.001, Mann-Whitney U test) and displayed lower signal intensity on T2-weighted images than those with leiomyomas expressing wild-type MED12 exon 2. The newly proposed magnetic resonance imaging-based classification system showed that MED12 exon 2 mutations were more frequent in the low-signal group than in the high-signal group, with nearly equal proportions of mutated and wild-type MED12 exon 2 leiomyomas noted in the intermediate group. The low-signal group had significantly lower erythropoietin expression levels than the high-signal group (P<.001, Kruskal-Wallis test with the Dunn posthoc analysis).. MED12 mutation status can be a candidate marker for predicting the effect of gonadotropin-releasing hormone agonists on uterine leiomyoma reduction. Magnetic resonance imaging findings can be used to determine MED12 mutation status as a noninvasive strategy to select patients who will most likely benefit from gonadotropin-releasing hormone agonist treatment.

Topics: Erythropoietin; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Mediator Complex; Mutation; Uterine Neoplasms

Signal intensity (SI) of predominant fibroid (F1) on T2-weighted (T2W) images is useful for predicting the volume reduction response after gonadotropin-releasing hormone (GnRH)-agonist treatment. Few studies have been published regarding when and how to use GnRH agonist before UAE.. To investigate magnetic resonance imaging (MRI) prediction of volume reduction rate (VRR) of large fibroids after GnRH-agonist treatment before uterine artery embolization (UAE) as well as the efficacy of UAE based on MRI.. Data from 30 patients with a large fibroid and MRI results both before and after GnRH-agonist treatment were retrospectively analyzed. Indications for GnRH-agonist treatment are fibroids with a maximum diameter ≥10 cm or pedunculated submucosal fibroids ≥8 cm. GnRH agonist (3.75 mg leuprolide acetate) was administered subcutaneously once per month 2-6 times. SI of F1 on T2W imaging was measured: the SI was referenced to the SI of the rectus abdominis muscle (F/R).. Mean maximum fibroid diameter was 11.1 ± 1.9 cm (range = 8.0-15.5 cm). Mean number of GnRH-agonist injections before UAE was 2.8 (range = 2-6). For predicting VRR ≥50% and <30%, the optimal cut-off values of F/R were 2.58 (sensitivity 80%, specificity 80%) and 1.69 (sensitivity 100%, specificity 70%), respectively. Of the 30 patients, fibroid infarction was complete in 29 (96.7%).. SI of F1 on T2W imaging is useful for predicting the volume reduction response after GnRH-agonist treatment. After GnRH-agonist treatment for large fibroids, UAE is effective to achieve complete infarction of fibroids.

Topics: Female; Humans; Infarction; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Retrospective Studies; Treatment Outcome; Uterine Artery Embolization; Uterine Neoplasms

To investigate the efficacy of short-term administration of relugolix, a novel orally active gonadotropin-releasing hormone (GnRH) antagonist, before single-port laparoscopic-assisted vaginal hysterectomy (LAVH) for symptomatic uterine myomas, retrospectively compared with injection of leuprorelin, a GnRH agonist.. A retrospective comparative study of each 35 women with symptomatic myomas in the relugolix and leuprorelin groups.. Before administration of relugolix and leuprorelin, the median uterine volume did not differ significantly between the two groups (p = 0.53). Median uterine volume change from baseline after short-term administration of relugolix and leuprorelin did not differ significantly (p = 0.17). Surgical duration (p = 0.84) and estimated blood loss (p = 0.48) were not different between the two groups. According to a patient questionnaire, the side effects of the drugs were not different between the two groups (p = 0.27). When patients were was asked if they wanted to have either of these drugs again, some relugolix users preferred leuprorelin due to concern about forgetting daily medication, while some leuprorelin users preferred relugolix to avoid pain at injection.. Oral relugolix medication or leuprorelin injection administered before single-port LAVH for uterine myomas yielded an equivalent reduction of uterine volume and perioperative outcomes with no significant adverse events. Patient preference for either oral daily relugolix or a monthly injection of leuprorelin could be considered when preoperative management is determined.

Topics: Female; Humans; Hysterectomy, Vaginal; Laparoscopy; Leiomyoma; Leuprolide; Myoma; Phenylurea Compounds; Pyrimidinones; Retrospective Studies; Uterine Neoplasms

To investigate differences in volume and fibroid vascularity expressed in vascular index after three months of (pre-)treatment with leuprolide acetate (LPA) or ulipristal acetate (UPA).. Prospective pilot study of 23 premenopausal women with uterine fibroids. Patients who started with LPA or UPA and had at least one fibroid with a size between 3 and 12 cm, were included consecutively. Per patient one fibroid was evaluated. The ultrasound was performed at baseline and after three months using LPA or UPA using a standardized protocol. 3D scans were evaluated using VOCAL software to calculate outcomes of volume, vascular index (VI) without shell ("shell off") and of the inner shell.. Four patients in the LPA group were additionally excluded from analyses due to insufficient quality of 3D scans. In the ten remaining patients (pre-)treated with LPA both volume and vascular indices of the fibroid reduced significantly after three months from a median of 224.3 cm. In this pilot study we observed a consistent and statistically significant decrease in VI and fibroid volume after three months of LPA treatment in patients with uterine fibroids. The decrease in fibroid volume and VI was less consistent after UPA use. The strong correlation between the VI at baseline and volume reduction, may in theory be used to predict the volume reduction after LPA.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Leuprolide; Neovascularization, Pathologic; Netherlands; Norpregnadienes; Pilot Projects; Premenopause; Treatment Outcome; Tumor Burden; Uterine Neoplasms

The aim of this guideline is to provide clinicians with an update to the 2015 Clinical Practice Guideline on the Management of Uterine Fibroids. As new information and evidence has become available since 2015, the Gynaecology Clinical Practice Committee of the Society for Obstetricians and Gynaecologists of Canada has determined that an addendum to that document was necessary to inform members about treatment modalities for uterine fibroids.. Implementation of this guideline update should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options and reviewed the risks and anticipated benefits.. Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2015 to April 2018, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to April 2018. Most of the unpublished data have not been evaluated scientifically. The product monograph was also reviewed up to December 31st, 2018.. The majority of fibroids are asymptomatic and require no intervention or further investigations. For symptomatic fibroids such as those causing menstrual abnormalities (e.g., heavy, irregular, and prolonged uterine bleeding), iron deficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy is a definitive solution. However, it is not the preferred solution for women who wish to preserve fertility and/or their uterus. The selected treatment should be directed towards an improvement in symptomatology and quality of life. The cost of the therapy to the health care system and to women with fibroids must be interpreted in the context of the cost of untreated disease conditions and the cost of ongoing or repeat investigative or treatment modalities.. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

Topics: Anemia; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Female; Gonadotropin-Releasing Hormone; Hematinics; Humans; Iron Compounds; Leiomyoma; Leuprolide; Liver Function Tests; Menorrhagia; Norpregnadienes; Uterine Neoplasms

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures.. Laboratory study.. University research laboratory.. Women undergoing hysterectomy for symptomatic leiomyomas.. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry.. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points.. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones.. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy.

Topics: Antineoplastic Agents, Hormonal; Cell Culture Techniques; Cell Line, Tumor; Collagen Type I; Estradiol; Extracellular Matrix; Female; Fibronectins; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Medroxyprogesterone Acetate; Time Factors; Uterine Neoplasms; Versicans

Estrogen deprivation therapy for myoma/adenomyosis decreases bone mineral density and can only be applied in the short term, as temporizing measures in the premenopausal woman.. To examine the effects of bisphosphonate minodronic acid on markers of bone turnover over a 6-month period in women receiving gonadotropin-releasing hormone agonist (GnRHa).. We retrospectively analyzed the medical records of 19 premenopausal patients with myoma/adenomyosis, who received GnRHa (leuprolide acetate, 1.88 mg/month or buserelin acetate, 900 µg/day) for 6 months from January 2014 to December 2014. Eight patients concomitantly received minodronic acid 50 mg every month during GnRHa therapy, and 11 treated with GnRHa alone. To compare these data in a case-controlled study, we analyzed an age-matched group of seven (premature or natural) menopausal women treated with minodronic acid. The primary outcome was percent changes in bone turnover markers in urine at 6 months.. In menopausal women group, minodronic acid (50 mg once-monthly) for 6 months decreased urinary deoxypyridinoline (DPD) and cross-linked N-telopeptides of type 1 collagen (NTX). Women receiving a GnRHa had a significant increase in urinary DPD and TNX at 6 months while minodronic acid during GnRHa therapy improved urinary levels of DPD and NTX to near baseline.. Minodronic acid treatment appears to be promising in women with secondary bone loss receiving GnRHa treatment.

Topics: Adenomyosis; Adult; Biomarkers; Bone Remodeling; Bone Resorption; Buserelin; Diphosphonates; Female; Gonadotropin-Releasing Hormone; Humans; Imidazoles; Leiomyoma; Leuprolide; Middle Aged; Pilot Projects; Retrospective Studies; Uterine Neoplasms

To evaluate changes in proliferating and apoptotic markers of myoma tissue from patients treated with a selective progesterone receptor modulator (SPRM) or GnRH agonist by measuring expression of PDGF-A mRNA, IGF-1 mRNA, bcl-2 mRNA, and PCNA and caspase-3 protein.. Between December 2013 and July 2014, women with symptomatic leiomyoma were divided into control (no treatment before surgery), SPRM (treatment with ulipristal acetate [SPRM] for 3 months before surgery), and GnRHa (treatment with leuprolide acetate [GnRH agonist] for 3 months before surgery) groups. Tissue specimens were collected from the myoma core and normal myometrium of all patients. The expression of mRNA and protein was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot.. A total of 38 patients were enrolled (control group, n=14; SPRM group, n=13; GnRHa group, n=11). PDGF-A mRNA expression was lower in both the myoma core and normal myometrium tissues of the SPRM compared with the control group, but there was no difference between the control and GnRHa group. There were also no group differences in bcl-2 mRNA or IGF-1 mRNA expression. Both PCNA and caspase-3 protein expression were higher in the leiomyoma tissue of the SPRM compared with the control group, but there was no difference between the control and GnRHa groups in the expression of either protein.. Both proliferation and apoptosis were increased in the leiomyoma of patients after SPRM treatment, but there was no change following GnRH agonist treatment, in vivo. However, PDGF-A mRNA was decreased after SPRM treatment, indicating a dual effect of progesterone on the regulation of growth factors. Furthermore, there was an increase in caspase-3 protein, but not bcl-2 mRNA, expression in the SPRM group suggesting that SPRM may exert its effects in pathways other than the bcl-2 apoptotic pathway.

Topics: Adult; Antineoplastic Agents, Hormonal; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Caspase 3; Cell Proliferation; Combined Modality Therapy; Female; Gene Expression Regulation, Neoplastic; Humans; Leiomyoma; Leuprolide; Middle Aged; Myometrium; Neoplasm Proteins; Norpregnadienes; Proliferating Cell Nuclear Antigen; Receptor, Platelet-Derived Growth Factor alpha; Receptors, LHRH; Receptors, Progesterone; Uterine Neoplasms

Topics: Adenomyoma; Adult; Antineoplastic Agents, Hormonal; Female; Humans; Leuprolide; Polyps; Uterine Neoplasms

Uterine fibroids (UFs), also known as uterine leiomyomas, are benign, fibrotic smooth muscle tumors. Although the GnRH analog leuprolide acetate that suppresses gonadal steroid hormones is used as a treatment, it has significant side effects, thereby limiting its use. Availability of more effective therapy is limited because of a lack of understanding of molecular underpinnings of the disease. Although ovarian steroid hormones estrogen and progesterone and their receptors are clearly involved, the role of other nuclear receptors (NRs) in UFs is not well defined. We used quantitative real-time PCR to systematically profile the expression of 48 NRs and identified several NRs that were aberrantly expressed in UFs. Among others, expression of NR4A subfamily members including NGFIB (NR4A1), NURR1 (NR4A2), and NOR1 (NR4A3) were dramatically suppressed in leiomyoma compared with the matched myometrium. Restoration of expression of each of these NR4A members in the primary leiomyoma smooth muscle cells decreased cell proliferation. Importantly, NR4As regulate expressions of the profibrotic factors including TGFβ3 and SMAD3, and several collagens that are key components of the extracellular matrix. Finally, we identify NR4A members as targets of leuprolide acetate treatment. Together, our results implicate several NRs including the NR4A subfamily in leiomyoma etiology and identify NR4As as potential therapeutic targets for treating fibrotic diseases.

Topics: Adult; Binding Sites; Cell Proliferation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Leiomyoma; Leuprolide; Middle Aged; Models, Biological; Myocytes, Smooth Muscle; Myometrium; Orphan Nuclear Receptors; Protein Binding; Response Elements; Uterine Neoplasms

Hematopoietic stem cell transplant is an effective treatment strategy for a variety of hematologic disorders, but patients are at risk for dysfunctional coagulation and abnormal bleeding. Gynecologists are often consulted before transplant for management of abnormal uterine bleeding, which may be particularly challenging in this context.. A premenopausal woman with MonoMAC (a rare adult-onset immunodeficiency syndrome characterized by monocytopenia and Mycobacterium avium complex infections resulting from mutations in GATA2, a crucial gene in early hematopoiesis) presented with pancytopenia, evolving leukemia, and recent strokes, necessitating anticoagulation. During preparation for hematopoietic stem cell transplant, she experienced prolonged menorrhagia requiring transfusions. Surgical therapy was contraindicated, and medical management was successful only when combined with balloon tamponade.. Balloon tamponade may be a potentially life-saving adjunct to medical therapy for control of uterine hemorrhage before hematopoietic stem cell transplant.

Topics: Adult; Antineoplastic Agents, Hormonal; Contraceptives, Oral, Synthetic; Estrogens; Female; GATA2 Transcription Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Induction Chemotherapy; Leiomyoma; Leuprolide; Medroxyprogesterone; Menorrhagia; Stroke; Uterine Balloon Tamponade; Uterine Neoplasms

Benign metastasizing leiomyoma and lymphangioleiomyomatosis (LAM) both are characterized by abnormal proliferation of smooth muscle-like cells in the lung.. A 32-year-old African woman with a diagnosis of LAM underwent myomectomy for uterine leiomyomas. An alternative diagnosis of benign metastasizing leiomyoma was made on repeat lung biopsy. Treatment with leuprolide acetate decreased pulmonary infiltrates and improved lung function and exercise tolerance.. Accurately diagnosing benign metastasizing leiomyoma has important implications for clinical outcome. Because its clinical presentation may be misleading, immunohistochemical techniques may assist in differentiating benign metastasizing leiomyoma from LAM. This is important because, in benign metastasizing leiomyoma, reduced tumor burden and improved pulmonary function may be achieved by suppressing gonadal steroids.

Topics: Adult; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Female; Humans; Leiomyoma; Leuprolide; Lung Neoplasms; Lymphangioleiomyomatosis; Uterine Neoplasms

Topics: Female; Humans; Leiomyoma; Leuprolide; Menorrhagia; Norpregnadienes; Receptors, Progesterone; Uterine Neoplasms

To determine the direct effect that GnRH analogues leuprolide acetate and cetrorelix acetate have on extracellular matrix in human leiomyoma and patient-matched myometrial cells.. Laboratory study.. University hospital.. None.. Cell culture, proliferation studies, and messenger RNA and protein analysis.. Expression of GnRHR1, COL1A1, fibronectin, and versican variant V0 in treated leiomyoma cells and patient-matched myometrial cells.. Leiomyoma cells were treated with GnRH analogues for 6, 24, and 120 hours. Leuprolide treatment for 6 hours resulted in an increase in expression of GnRHR1 (4.02 ± 0.12-fold), COL1A1 (6.41 ± 0.29-fold), fibronectin (9.69 ± 0.18-fold), and versican variant V0 (7.58 ± 0.43-fold). Leiomyoma cells treated with cetrorelix for 6 hours showed a decreased expression of GnRHR1 (0.5 ± 0.15-fold), COL1A1 (3.79 ± 0.7-fold), fibronectin (0.92 ± 0.09-fold), and versican variant V0 (0.14 ± 0.07-fold). Leuprolide treatment of leiomyoma cells at high concentrations (10(-5) M) did not result in an increase in protein production. Cetrorelix treatment of leiomyoma cells for 6 hours showed an increase in fibronectin protein production (3.14 ± 0.09-fold). Protein production of leiomyoma cells treated with cetrorelix for 120 hours demonstrated a decrease in GnRHR1 (0.51 ± 0.07-fold), COL1A1 (0.35 ± 0.07-fold), fibronectin (1.94 ± 0.08-fold), and versican variant V0 (0.77 ± 0.19-fold).. Our findings demonstrate that GnRH analogue treatment directly regulated COL1A1, fibronectin, and matrix proteoglycan production. The reduction in versican variant V0 gene expression caused by cetrorelix treatment, and its association with the osmotic regulation of leiomyomas, presents a new and innovative approach to therapy for this disease.

Topics: Antineoplastic Agents, Hormonal; Cell Proliferation; Collagen Type I; Collagen Type I, alpha 1 Chain; Dose-Response Relationship, Drug; Extracellular Matrix Proteins; Female; Fibronectins; Gene Expression Regulation, Neoplastic; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leiomyoma; Leuprolide; Receptors, LHRH; RNA, Messenger; Time Factors; Tumor Cells, Cultured; Uterine Neoplasms; Versicans

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

To characterize hyperosmolarity-responsive genes in leiomyoma cells and determine whether gonadotropin-releasing hormone (GnRH) agonist treatment altered their expression.. Laboratory study.. University hospital.. None.. Cell culture under hypertonic conditions and with GnRH agonist treatment, RNA isolation, and real-time reverse-transcriptase polymerase chain reaction (RT-PCR).. Expression of nuclear factor of activated T cells 5 (NFAT5), aldose reductase (AR), and sodium myo-inositol transporter 1 (SMIT) messenger RNA (mRNA) in immortalized leiomyoma and patient-matched myometrial cells.. Leiomyoma cells had increased basal expression of NFAT5 mRNA (1.7±0.08-fold) compared with myometrial cells. The NFAT5 increased further in leiomyoma cells cultured under hyperosmolar conditions (3.0±0.46-fold at 50 mM NaCl and 3.3±0.48-fold at 100 mM NaCl). The NFAT5-regulated mRNA transcripts for AR and SMIT were increased in untreated leiomyoma cells compared with myometrial cells and further increased in leiomyoma cells exposed to osmotic stress. The NFAT5 transcripts were decreased with low-dose GnRH agonist treatment but increased with supraphysiologic doses.. Expression of hyperosmolarity genes was increased in leiomyoma cells relative to myometrial cells. Pharmacologic concentrations of GnRH agonist decreased NFAT5 expression, suggesting that water flows out of leiomyoma cells at pharmacologic doses.

Topics: Aldehyde Reductase; Antineoplastic Agents, Hormonal; Case-Control Studies; Cell Proliferation; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; Gonadotropin-Releasing Hormone; Heat-Shock Proteins; Humans; Leiomyoma; Leuprolide; Osmotic Pressure; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Symporters; Transcription Factors; Tumor Cells, Cultured; Uterine Neoplasms; Water-Electrolyte Balance

To describe a case report of diffuse uterine leiomyomatosis who had successful pregnancy twice following conservative management.. Retrospective report.. Private general hospital.. A nulliparous woman 25 years of age presented with menorrhagia and infertility. She had innumerable small fibroids of 4-42 mm size throughout the myometrium. Size of the symmetrically enlarged uterus was 131×80×60 mm, clinically corresponding to that of 12 weeks of gestation.. She received a GnRH analogue (GnRHa; leuprolide acetate) 3.75 mg per month for 6 months.. Reduction of uterus size, menstrual amount, conception, pregnancy outcome.. Enlarged uterus reduced to almost normal size after 3 doses of GnRHa. She did not experience heavy bleeding during menstruation. She conceived spontaneously in the first cycle after discontinuation of GnRHa. Antenatal course was uneventful. A healthy male baby of 2.5 kg was delivered by cesarean section at 39 weeks. The placenta weighed 330 g. There was no postpartum hemorrhage. She conceived spontaneously for the second time in the first cycle after resumption of menses. Antenatal, intranatal (cesarean section), and postnatal courses of the second pregnancy were uneventful. The second neonate weighed 3.0 kg and the placenta 400 g.. Conservative treatment may help to achieve successful pregnancy in case of diffuse uterine leiomyomatosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Cesarean Section; Female; Gestational Age; Humans; Infant, Newborn; Leiomyomatosis; Leuprolide; Live Birth; Male; Parity; Pregnancy; Treatment Outcome; Ultrasonography, Prenatal; Uterine Neoplasms

We studied morphologic modifications of the endometrium induced by leuprorelin acetate, a gonadotropin-releasing hormone agonist, in women with uterine myomata.. Transmission and scanning electron microscopy observations were performed after 2 or 6 cycles of therapy (every 28 days).. A near-normal endometrium was observed after 2 months of therapy, while treatment with 6 cycles of leuprorelin acetate induced a uniform morphologic regression of the uterine mucosa.. The study demonstrates that leuprorelin acetate induces a unique and time-dependent regression of the endometrial mucous membrane.

Topics: Adult; Antineoplastic Agents, Hormonal; Endometrium; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Uterine Neoplasms

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

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

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Embolization, Therapeutic; Female; Gynecologic Surgical Procedures; Humans; Hysterectomy; Hysteroscopy; Laparoscopy; Leiomyoma; Leuprolide; Menopause; Organ Size; Treatment Outcome; Uterine Neoplasms; Uterus

Gonadotropin-releasing hormone agonist (GnRH-a) therapy is frequently applied to reduce the volume of uterine leiomyomas (UL). In addition, the possible relationship between mast cells (MC) within UL and the development of UL has been suggested, but the role of MC in UL remains to be determined. UL with or without GnRH-a therapy in 121 premenopausal patients were reviewed. The number of MC was evaluated between the two groups, immunohistochemistry was done for insulin-like growth factor-I (IGF-I), and the association between the IGF-I immunoreactivity in UL and the GnRH-a therapy was analyzed. The number of MC significantly increased in UL in GnRH-a therapy, while IGF-I immunoreactivity was significantly reduced in smooth muscle cells of these UL. Furthermore, IGF-I immunoreactivity in MC was inversely correlated with the size reduction rate of UL in GnRH-a therapy. Although GnRH-a therapy is considered to reduce the size of UL transiently, the regression of UL was in part hampered by the increased IGF-I secretion from the increased MC after GnRH-a therapy. Therefore, the more the IGF-I secretion from MC in UL increases, the less effective the GnRH-a therapy is on the size reduction of UL. Thus, the present study may provide an explanation of the possible mechanism of GnRH-a resistance in UL.

Topics: Antineoplastic Agents, Hormonal; Cell Count; Drug Resistance, Neoplasm; Female; Gonadotropin-Releasing Hormone; Humans; Insulin-Like Growth Factor I; Leiomyoma; Leuprolide; Mast Cells; Premenopause; Uterine Neoplasms

GnRH agonist therapy is known to reduce uterine leiomyoma volume, although the molecular mechanisms responsible for this effect remain poorly understood. In this study, we have investigated the molecular mechanisms involved in the anti-proliferative effect of a GnRH agonist, leuprolide acetate (LA), in uterine leiomyomas obtained from six patients treated with LA for 3 months before surgery (group B), compared with tumours from six untreated patients (group A). To this end, we have evaluated the expression and the activity of molecules involved in the regulation of cell survival and proliferation. In group B, the total activity of PI3K was reduced by 60% compared with control samples. Furthermore, LA caused a reduction of PKB activation of approximately 50%, measured as serine 473 phosphorylation. In parallel with PKB reduction in LA samples, we observed a 60% reduction in the phosphorylation of its substrate BAD. While Bcl-xL/BAD association was not significantly modified in LA-treated leiomyomas, BAD/14.3.3 interaction was reduced, due to a 50% decreased 14.3.3 expression. In addition, LA was able to reduce the expression of the antiapoptotic proteins FLIP and PED/PEA15 by 70 and 50% respectively, compared with control samples. We next evaluated the activation of MAP kinases in leiomyomas. Activation of p42 and p44 MAP kinase isoforms was increased by 30% in group B. However, the phosphorylation of the transcription factor Elk1 was not increased in a similar fashion in LA-treated leiomyomas compared with group A. Thus, these data suggest that LA reduction of leiomyoma volume is mediated at least in part by a decreased activation of the PI3K/PKB survival pathway and by the suppression of antiapoptotic factors.

Topics: Apoptosis; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Phosphatidylinositol 3-Kinases; Uterine Neoplasms

Because gonadotropin releasing hormone analogue (GnRHa) therapy often causes leiomyoma regression, in part through alteration of growth factor and receptor expression, we determined whether GnRHa therapy alters the expression of extracellular signal-regulated kinase (ERK) and focal adhesion kinase (FAK), which are linked to intracellular signaling pathways activated by ovarian steroids, growth factors, and adhesion molecules. Leiomyoma and matched unaffected myometrium were collected from women who received GnRHa therapy (n = 5) and untreated women (n = 10). We determined the expression of ERK1, ERK2, FAK, phosphorylated ERK (pERK1/2), and pFAK using Western blotting and immunohistochemical analysis. Leiomyoma and myometrium expressed ERK1 (44 kD), ERK2 (42 kD), and FAK (125 kD) at variable levels with increased ERK2, pERK, and FAK expression in leiomyoma. We found that GnRHa therapy resulted in a noticeable decrease in ERK2 and FAK, with significant reduction in pERK1/2 and low or undetectable levels of pFAK in both leiomyoma and myometrium compared with the untreated group (P <.05). Immunohistochemically ERK1, ERK2, FAK, pERK1/2, and pFAK were localized in smooth muscle cells and connective tissue fibroblasts in GnRHa-treated and untreated leiomyoma and myometrium, with considerable reduction in their intensity as indicated by HScore in GnRHa-treated tissues. The data provide further evidence that leiomyoma regression induced by GnRHa is mediated in part through a mechanism involving suppression of signal transduction pathways involving growth factors or ovarian steroid and adhesion molecules.

Topics: Antineoplastic Agents, Hormonal; Blotting, Western; Female; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Premenopause; Protein-Tyrosine Kinases; Signal Transduction; Uterine Neoplasms

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

This study was undertaken to assess the relationship between insulin-like growth factor (IGF) type I receptor (IGF-I-R) expression in uterine leiomyomas after gonadotropin-releasing hormone (GnRH) analog administration and modifications in uterine size.. Forty-six women with menorrhagia for uterine leiomyomatosis were treated monthly with leuprolide acetate depot 3.75 mg before undergoing surgery. The uterine volume before and after therapy was assessed by transabdominal ultrasonography. Immunohistochemical detection of IGF-I-R was performed on leiomyoma tissue samples. The relationship between IGF-I-R levels and uterine volume changes was analyzed.. Uterine volume decreased after therapy. Patients with a lower immunohistochemical expression of IGF-I-R showed a larger decrease in uterine size.. The shrinkage in uterine volume induced by GnRH analogs seems to be related to the observed reduction in IGF-I-R levels. So, the IGF-I/IGF-I-R system might be involved in leiomyoma growth, and the pharmacologic action of GnRH analogs on uterine leiomyomas might also be related to the effects on IGF-I-R expression.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Receptor, IGF Type 1; Ultrasonography; Uterine Neoplasms; Uterus

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 this study was to elucidate the clinical characteristics of uterine leiomyomas having abnormal chromosome karyotype.. A total of 394 myomas were obtained from 213 patients for cytogenetic analysis. The size (number of nodules=144), histopathology (n=302), and gonadotropin-releasing hormone analogue (GnRHa)-response (n=58) were investigated in relation to chromosome karyotype in myomas.. 302 myomas from 166 patients were successfully karyotyped. A total of 21 myomas from 21 patients showed abnormal chromosome karyotype. The high frequencies of involved chromosomes 12, 14, 1, 7 were observed. The diameters of myomas with abnormal karyotype were significantly larger than those of myomas with normal karyotype. The frequency of the degeneration in myomas with abnormal karyotype was significantly higher than that with normal karyotype. The reduction rate in size of myomas by GnRHa treatments did not differ between the two types (karyotype normal versus abnormal) of nodules.. Chromosomally abnormal myomas were larger in diameter and showed a higher frequency of degeneration, suggesting that the cytogenetic background in uterine leiomyoma affects a tumor's growth potential.

Topics: Adult; Buserelin; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 7; Female; Gonadotropin-Releasing Hormone; Humans; Karyotyping; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Nafarelin; Uterine Neoplasms

This study aimed to examine the activation of poly(ADP-ribose) polymerase (PARP) and the accumulation of its end product, poly(ADP-ribose) (PAR), in uterine leiomyoma specimens obtained from 25 patients receiving Leuplin depot [leuprorelin acetate, depot (LA)] treatment and 46 control patients and explore their correlation with tumor shrinkage and degeneration caused by the therapy. Immunoblotting analysis showed that specimens from LA-treated patients had higher PARP expression. The numbers of both PARP- and PAR-immunolabeled cells were higher in leiomyoma with LA treatment. This was correlated with the clinical response of LA therapy that LA induced more leiomyoma degeneration. The analysis of power Doppler sonography indicated a progressive decrease in blood supply to tumor following LA treatment. In vitro experiments using primarily cultured leiomyoma cells exhibited that the deprivation of serum or ovarian hormones or LA directly failed to induce PARP and PAR production. Our results suggested that reduced blood flow and subsequent ischemic damages in leiomyoma could be responsible for PARP overexpression and PAR accumulation, clinical response, and tumor degeneration caused by LA treatment.

Topics: Antimutagenic Agents; Antineoplastic Agents, Hormonal; Cobalt; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Poly Adenosine Diphosphate Ribose; Poly(ADP-ribose) Polymerases; Tumor Cells, Cultured; Ultrasonography, Doppler, Color; Up-Regulation; Uterine Neoplasms

Topics: Adult; Endothelium, Vascular; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Lymphocytes; Uterine Neoplasms; Vasculitis

GnRH agonist (GnRH-a) therapy is known to shrink uterine leiomyoma, although the molecular mechanisms responsible for this effect remain poorly understood. Conflicting results exist as to whether GnRH-a treatment increases apoptosis in leiomyoma cells. The aim of this study is to investigate the effects of GnRH-a on uterine leiomyomas by profiling the expression levels of apoptosis-related molecules such as Fas/Fas ligand (FasL), caspases 3, 6, 7, 8, 9, and 10, and Bcl-2 from specimens of 20 patients receiving Leuplin Depot (LA), a long-acting GnRH-a, of 3 doses before myomectomy, as well as 24 controls. We found that uterine leiomyomas had up-regulated expressions of FasL and caspase 3 as compared with their homologous normal myometrium control. Both leiomyomas and myometria from LA-treated patients, however, presented a significant decrease in the expressions of FasL and caspase 3 as compared with those from LA-naive control patients. In addition, it was at the posttranscription level that the tumorigenesis of leiomyoma modulated the expressions of FasL and caspase 3 higher, whereas LA suppressed them at gene transcription. Unlike the case of FasL and caspase 3 mentioned above, no significant difference was found between leiomyomas and homologous myometria in the expressions of Fas and caspases 6, 7, 8, 9, and 10. The LA effect made drug-treated leiomyomas produce less Fas and caspases 7, 9, and 10 as compared with nontreated leiomyomas. Immunohistochemical analysis showed that both Fas and FasL were localized predominantly in cytosol. Moreover, leiomyomas had an up-regulated Bcl-2 level, which remained high even in the LA-treated cells. Our findings provide molecular evidence to support our previous observations that GnRH-a therapy fails to increase apoptosis in uterine leiomyomas.

Topics: Adult; Apoptosis; Caspase 3; Caspases; Fas Ligand Protein; fas Receptor; Female; Gene Expression; Humans; Leiomyoma; Leuprolide; Membrane Glycoproteins; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uterine Neoplasms

Specific chromosomal abnormalities, e.g. del(7q), t(12;14), 12 trisomy, and the rearrangement of 6p, are seen in approximately 30% of uterine leiomyomas. We investigated the association between the shrinkage effect of GnRH agonist on uterine leiomyomas and t(12;14), the second most frequent chromosomal abnormality in myomas. This study involved 42 women with uterine leiomyomas treated with a gonadotropin releasing hormone (GnRH) agonist before surgery. The volume of the largest myoma nodule was measured by MRI before and at 12 weeks after the beginning of GnRH agonist treatment, and the percentage change in volume was calculated. A specific chromosomal abnormality, t(12;14), was examined on thin sections of frozen leiomyomas by fluorescence in situ hybridization with chromosome-specific probes. Of the 42 tumors, 8 (19%) showed translocation. The mean (+/- SD) percentages change in volume of the largest myomas without and with translocation were -32+/-24 and 23+/-60%, respectively (p=0.006). The myomas showing translocation had significantly less reduction in size with GnRH treatment than did those without translocation. No myoma with trisomy 12 was found. On the basis of our results, we assumed that uterine leiomyomas showing t(12;14) are not so dependent on ovarian hormones for growth.

Topics: Adult; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 14; Female; Gonadotropin-Releasing Hormone; Humans; In Situ Hybridization, Fluorescence; Interphase; Leiomyoma; Leuprolide; Middle Aged; Translocation, Genetic; Uterine Neoplasms

The skin is a target organ of estrogens. Thus, theoretically, a hypoestrogenic state induced by gonadotropin-releasing hormone analog (GnRHa) treatment may have effects on skin condition. The aim of this study was to evaluate skin condition during GnRHa treatment. Sixteen premenopausal women undergoing GnRHa treatment for 16 weeks, as a presurgical treatment for uterine leiomyomas, were studied. Measurement of serum estradiol levels and epidermal hydration, and evaluation of subjective findings on skin condition using a questionnaire, were performed every 4 weeks during the treatment period. Serum estradiol levels were significantly suppressed at 4 weeks of treatment, and remained low afterwards. Epidermal hydration measured by corneometer did not show any significant difference at any time point examined, compared with that before treatment. No particular subjective findings relating to the skin (dryness, wrinkling, roughness, pigmentation, itching, formication, reaction to cosmetics) were reported during treatment, whereas complaints about hot flushes and sweating were notable. The results of this preliminary study support the notion that GnRHa treatment for 16 weeks is unassociated with apparent changes in skin condition.

Topics: Adult; Body Water; Estradiol; Female; Humans; Leiomyoma; Leuprolide; Middle Aged; Postmenopause; Premedication; Premenopause; Prospective Studies; Skin; Skin Diseases; Surveys and Questionnaires; Uterine Neoplasms

The unopposed estrogen effect is the main cause of leiomyoma growth and is at the basis of the clinical use of gonadotropin-releasing hormone (GnRH) agonists. Platelet-derived growth factor (PDGF) has been indicated as the main growth factor involved, in vitro in the proliferation response of leiomyoma smooth muscle cells to estrogen stimulation. The aim of this article is to evaluate the mitogenic action of PDGF in vivo by studying the relationship between PDGF expression in leiomyomas and post-GnRH analogue treatment changes in uterine volume. Thirty-nine patients suffering from uterine leiomyomas were treated with leuprorelin acetate depot 3.75 mg for three cycles; 31 untreated patients were enrolled as control group. Uterine volume was determined twice by ultrasonography in each patient, the first time at admission and the second time after treatment in the study group and after 3 months in the control group. The change in the uterine volume was then evaluated. Patients underwent surgery, and PDGF immunohistochemical detection was performed on the obtained fibroid samples. Uterine volume decreased significantly after treatment, whereas just a poor modification was found in the controls. The decrease in the uterine volume was found to be statistically related to PDGF expression. Thus PDGF levels decreased in treated patients as compared with controls. The decreased PDGF production in leiomyomas after GnRH analogue treatment and the relationship between decreased PDGF expression and greater shrink age in uterine volume suggest that PDGF might have a mitogenic action on leiomyomas in vivo.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Platelet-Derived Growth Factor; Premenopause; Ultrasonography; Uterine Neoplasms; Uterus

The aim of the present study was to investigate the relationship between the changes in lean and fat mass during gonadotropin-releasing hormone agonist (GnRH agonist) therapy.. Subjects were 24 premenopausal women (mean age, 39.5+/-9.4 years; range, 32-52 years) with uterine leiomyomas. They were given GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Age and height were recorded. Body weight, regional and total body composition, and the ratio of trunk fat mass to leg fat mass (trunk-leg fat ratio) were assessed by whole body scanning with dual-energy X-ray absorptiometry. Changes in these variables were investigated. Relationships between the changes in regional lean and fat mass were investigated using Pearson's correlation test.. Trunk fat mass significantly increased from 8616+/-3538 to 9265+/-3526 g (P<0.01) and trunk-leg fat ratio significantly increased (1.02+/-0.39 to 1.07+/-0.39, P<0.05). Trunk lean mass significantly decreased from 18,509+/-2602 to 17,916+/-2402 g (P<0.01). However, body weight, and lean and fat mass component in the extremities did not change. Change in trunk fat mass was inversely correlated with change in trunk lean mass (r=-0.439, P<0.05), but such relationships were not observed in arm and leg regions.. Inverse relationship between the changes in trunk lean and fat mass is observed during GnRH agonist therapy.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Antineoplastic Agents, Hormonal; Arm; Body Composition; Female; Gonadotropin-Releasing Hormone; Humans; Leg; Leiomyoma; Leuprolide; Middle Aged; Premenopause; Thorax; Treatment Outcome; Ultrasonography; Uterine Neoplasms; Uterus

To examine whether gonadotrophin-releasing hormone agonist or oestradiol can directly affect DNA in leiomyoma cells.. In vitro explant culture of leiomyoma cells.. University research group.. Leiomyoma cells were cultured from the specimens of four premenopausal women at myomectomy.. The presence of gonadotrophin-releasing hormone receptor in leiomyoma cells was determined by reverse transcriptase-olymerase chain reaction. Leiomyoma cells were treated with gonadotrophin-releasing hormone agonist or cultured in different concentrations of oestrogen, progesterone or fetal calf serum for one, four or seven days.. Cell number, expression of proliferating cell nuclear antigen, and DNA damage after one, four or seven days of treatment.. Gonadotrophin-releasing hormone receptor messenger ribonucleic acid was detected on cultured leiomyoma cells. Leiomyoma cell growth was not affected by the addition of gonadotrophin-releasing hormone agonist or progesterone, but increased with oestrogen or fetal calf serum supplementation. Overexpression of proliferating cell nuclear antigen was prevented in cultures added with oestrogen or fetal calf serum, but not related to gonadotrophin-releasing hormone agonist treatment. Significant decreases in DNA damage as indicated by decreased comet number were found in the leiomyoma cultures treated with oestrogen or fetal calf serum for four and seven days but not with gonadotrophin-releasing hormone agonist or progesterone. Furthermore, 5% fetal calf serum supplementation was more growth supporting and more significantly reduced the comet number than 250 pM 17 beta-oestradiol.. Cell growth, proliferating cell nuclear antigen expression and DNA damage are dependent on oestrogen or fetal calf serum, but independent of gonadotrophin-releasing hormone agonist or progesterone. Our findings suggest that gonadotrophin-releasing hormone agonist-induced leiomyoma shrinkage may be due in part to a mechanism involving DNA damage, and support the hypothesis that gonadotrophin-releasing hormone agonist exerts its action indirectly through oestrogen action on the tumour level.

Topics: Antineoplastic Agents, Hormonal; Comet Assay; DNA Damage; DNA, Neoplasm; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Leiomyoma; Leuprolide; Progesterone; Receptors, LHRH; Uterine Neoplasms

To identify the effects of GnRH agonist therapy on body composition (lean and fat mass components) and body fat distribution.. Fifteen women with uterine leiomyomas were given a GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Weight, height, and body mass index (BMI, weight/height) were recorded. Regional and total body composition, trunk-leg fat ratio, bone mineral density of the lumbar spine (L2-L4), and total body were assessed by whole-body scanning with dual-energy x-ray absorptiometry before and after treatment. Uterine volume was measured by transabdominal ultrasonography.. The mean (+/- standard deviation [SD]) lean mass of total body, trunk, and leg decreased significantly (36.3 +/- 4.9 to 35.4 +/- 4.4 kg, P <.01; 18.8 +/- 2.8 to 18.1 +/- 2.8 kg, P <.05; and 11.4 +/- 1.8 to 11.1 +/- 1.6 kg, P <.05; respectively), whereas body fat mass, percentage of body fat, and trunk fat mass increased significantly (20.8 +/- 4.8 to 21.8 +/- 4.6 kg, P <.01; 34.9 +/- 5.9 to 36.5 +/- 5.2%, P <.01; and 8.6 +/- 3.0 to 9.3 +/- 3.0 kg, P <.01; respectively). Trunk-leg fat ratio increased significantly (1.03 +/- 0.32 to 1.12 +/- 0.33, P <.05). Weight, BMI, arm tissue composition (lean and fat mass components), and leg fat mass did not change during 4 months of GnRH agonist therapy. Bone mineral density and uterine volume decreased significantly.. Hypogonadism by GnRH agonist therapy induces lean mass loss, increased adiposity overall, and upper body fat accumulation.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Body Composition; Body Mass Index; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Middle Aged; Premenopause; Ultrasonography; Uterine Neoplasms; Uterus

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

Specific chromosomal abnormalities, such as del(7q), t(12;14), 12 trisomy, or the rearrangement of 6p, are seen in approximately 30% of uterine leiomyomas despite their benign status. We investigated the association between the shrinkage of uterine leiomyomas treated with a GnRH agonist and the interstitial deletion of chromosome 7q, which is one of the most common chromosomal abnormalities in uterine leiomyomas. This study covered 29 women with uterine leiomyomas who were treated with a GnRH agonist before surgery. The volume of the largest myoma nodule was measured by means of MRI before and at 12 weeks after the beginning of GnRH agonist treatment, and the percentage of the reduction in volume was calculated. Genomic DNA was extracted from leiomyoma tissue and peripheral blood, and amplified by PCR using fluorescently-tagged oligonucleotide primers of twelve microsatellite loci on chromosome 7. The PCR products were analyzed for loss of heterozygosity (LOH) using an automated fluorescent DNA sequencer. Of the 29 informative tumors, five (17%) showed LOH with deletion of the common region, D7S491. The mean percentages of the reduction in volume of the largest myomas with LOH or without LOH were 32+/-13 and 18+/-58%, respectively (not significant). One tumor showing interstitial deletion of both alleles (homo-deletion) reduced in volume by 19%. Another tumor showing an extraband increased in volume by 13%. Although tumor specific chromosomal deletion suggested the existence of tumor suppressor genes in this region, there was no significant association between the shrinkage of uterine leiomyomas treated with a GnRH agonist and the interstitial deletion of chromosome 7q.

Topics: Adult; Antineoplastic Agents, Hormonal; Chromosome Deletion; Chromosomes, Human, Pair 7; DNA, Neoplasm; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Loss of Heterozygosity; Microsatellite Repeats; Middle Aged; Polymerase Chain Reaction; Uterine Neoplasms

Uterine leiomyomata of 34 premenopausal women undergoing leiomyomectomy or hysterectomy, and in four cases the corresponding myometrium, were collected at laparotomy or laparoscopy to investigate the ability of these benign smooth muscle cell tumors to express different connexins. Immunohistochemical and Northern blot analyses were performed for the characterization of the expression of connexins Cx43, Cx45, Cx26 and Cx32. Immunofluorescence revealed the presence of Cx43 in most leiomyomata. Only seven leiomyomata lacked Cx43 expression. Cx45 was expressed in 13, a weak Cx26 immunostaining was found in seven cases, whereas Cx32 could not be detected. No correlations between the 17 beta-estradiol or progesterone serum levels and the expression patterns of the connexins Cx43, Cx45 and Cx26 could be observed. Gonadotropin-releasing hormone (GnRH)-agonist or progestin treatment did not influence the connexin expression pattern. Northern blot analyses confirmed these results; however, transcripts of Cx26 were not detectable. Connexin transcripts between myomata and the corresponding myometrium showed no obvious differences. Our data show that uterine leiomyomata are capable of expressing different connexins comparable to the corresponding myometrium, but do not respond to different hormonal conditions. The ability to express the appropriate connexins could explain why these tumors, though developing independently of hormonal levels, are still differentiated benign smooth muscle tumors.

Topics: Blotting, Northern; Connexin 26; Connexin 43; Connexins; Estradiol; Female; Gene Expression; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Progesterone; RNA, Messenger; Uterine Neoplasms

Endocervical epithelium from women treated with gonadotropin releasing hormone agonist (GnRH agonist) were compared with those from untreated women, using metachromatic stain with toluidine blue and immunohistochemistry, for estrogen and progesterone receptors. Smaller endocervical epithelium with lower intraepithelial mucus and more prominent nuclear distribution of estrogen receptors were seen in a woman who was treated for twelve months with GnRH agonists, as compared with those from an untreated premenopausal woman.

Topics: Adult; Antineoplastic Agents, Hormonal; Buserelin; Cervix Uteri; Epithelium; Female; Fluorescent Antibody Technique; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Leuprolide; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Staining and Labeling; Tolonium Chloride; Uterine Neoplasms

We have shown that in situ estrogen synthesized in leiomyoma of the uterus plays a possible role in the promotion of leiomyoma cell growth via an autocrine/paracrine mechanism. In the present study, we demonstrated that leuprorelin acetate, a GnRH agonist widely used for treatment of uterine leiomyoma by down-regulation of pituitary-ovarian function, suppressed the expression of aromatase P450 (an estrogen synthetase) in leiomyoma cells. Given the role of in situ estrogen in leiomyoma cell growth, the inhibition of in situ estrogen synthesis may play a role in GnRH agonist-induced rapid regression of leiomyomas. Quantitative RT-PCR revealed that in women receiving no medication uterine leiomyomas express aromatase P450 mRNA at levels 20 times higher than that in the surrounding myometrium. Leuprorelin acetate treatment (1.88 mg every 4 wk, sc injection) for 12-24 wk reduced the expression of aromatase P450 mRNA in leiomyoma tissue as well as in the myometrium, to approximately one tenth of that in the myometrium of untreated women. Suppression of aromatase P450 expression was also demonstrated by Western blot analysis and aromatase activity assay of microsomal fractions prepared from leiomyomas. On the other hand, no differences in the levels of activity and mRNA of aromatase P450 were observed between leiomyoma cells obtained from women treated with and without leuprorelin acetate injections when cells were cultured ex vivo and stimulated by various combinations of stimulants such as dexamethasone + IL-1beta. The addition of various concentrations of E2 did not affect the aromatase activity of leiomyoma cells, suggesting that deprivation of circulating (ovarian) estrogen is not a cause of decreased expression of aromatase during leuprorelin acetate therapy. On the other hand, 8-d treatment with leuprorelin acetate (100 nmol/liter) reduced dexamethasone + IL-1beta-induced activity and a mRNA level of aromatase by 28% and 42%, respectively. These results indicated that leuprorelin acetate inhibits the expression of aromatase P450 in leiomyoma cells, which contributes to the rapid regression of leiomyoma during leuprorelin acetate therapy.

Topics: Antineoplastic Agents, Hormonal; Aromatase; Blotting, Western; Cell Division; Depression, Chemical; Estradiol; Estrogens; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Leiomyoma; Leuprolide; Menopause; Neoplasm Proteins; RNA, Messenger; Tumor Cells, Cultured; Uterine Neoplasms

We report endometrial adenocarcinoma in two patients shortly after suspending GnRH-agonist treatment for menometrorrhagia and uterine fibromata.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Female; Humans; Injections, Intramuscular; Leiomyoma; Leuprolide; Metrorrhagia; Middle Aged; Myometrium; Neoplasms, Second Primary; Triptorelin Pamoate; Uterine Neoplasms

The aim of this study was to determine which factors in the perioperative period influence the success of endometrial ablation in alleviating menorrhagia.. We performed a retrospective chart review of 120 women aged 27 to 49 years who underwent endometrial ablation after 2 months of preoperative treatment with danazol (Danocrine, 800 mg/d orally) or leuprolide (Lupron, 3.75 mg in one intramuscular injection each month). Patients who required medical management or additional operations to control the vaginal bleeding during follow-up (median follow-up, 37 weeks) were considered to have ablation failures.. Sixty-three percent of patients (76/120) had a successful procedure. The chance of success was greater if a cavity of normal appearance was found (odds ratio, 2.3; P =.04). The finding of an intramural fibroid before the procedure resulted in a reduced trend toward success (odds ratio, 0.4; P =.06). The use of danazol pretreatment improved the rate of success overall (odds ratio, 2.2; P =.05) and especially among women <40 years old (P =.01). Perioperative findings may provide useful information in counseling patients regarding endometrial ablation. Success is greater among patients with a normal intrauterine cavity and after preoperative treatment with danazol.

Topics: Adult; Danazol; Endometrium; Estrogen Antagonists; Female; Humans; Leiomyoma; Leuprolide; Logistic Models; Menorrhagia; Middle Aged; Premedication; Reoperation; Retrospective Studies; Treatment Failure; Treatment Outcome; Uterine Neoplasms

Topics: Female; Humans; Leiomyomatosis; Leuprolide; Mitosis; Uterine Neoplasms

Few studies have been performed on the vascular changes in leiomyomas from patients treated with gonadotropin-releasing hormone agonists (GnRHAs).. To measure luminal diameter and wall thickness of arterioles in uterine leiomyomas using a quantitative stereologic method of analysis.. Thirty leiomyomas from 3 study groups were used: (1) patients treated with GnRHAs (10 patient samples), (2) age-matched controls (10 patient samples), and (3) postmenopausal women (10 patient samples). Measurements of arteriolar luminal diameter and wall thickness were made using a video-based, computerized system attached to the microscope, for which a morphometric ad hoc program was written. Electron micrographs were made of random arterioles from the first 2 groups (GnRHA-treated patients and age-matched controls).. Department of Pathology, Mount Sinai School of Medicine, New York, NY.. A total of 30 patient samples were studied, with 3 groups comprising 10 samples each, including patients treated with GnRHAs, age-matched control patients, and postmenopausal women.. Arterioles in myomas from patients treated with GnRHAs had slightly larger luminal diameters and significantly thicker walls than age-matched controls and resembled arterioles from postmenopausal women. The thickening was due to smooth muscle cell hyperplasia in the muscularis media.. Treatment with GnRHAs causes a thickening of the walls of intramyomatous arterioles, which resemble those of postmenopausal women. This thickening may play a role in the decreased flow of blood reported in GnRHA treatment.

Topics: Adult; Arterioles; Female; Humans; Hyperplasia; Leiomyoma; Leuprolide; Microscopy, Electron; Middle Aged; Muscle, Smooth, Vascular; Nafarelin; Postmenopause; Uterine Neoplasms

The purpose of this report is to estimate the effectiveness of gonadotropin-releasing hormone analogue (Gn-RHa) therapy for peritoneal inclusion cysts.. Patients who had cystic masses that developed after gynecological surgery and were strongly suspected of being peritoneal inclusion cysts based on the results of ultrasound, magnetic resonance imaging (MRI), and tumor marker studies, were treated with a Gn-RHa (buserelin acetate or leuprorelin acetate). Buserelin acetate was administered at a dose of 900 microg/day, and leuprorelin acetate at a dose of 3.75 mg/month. Ultrasonography was performed in the outpatient clinic every 2 weeks after the start of administration to measure the diameter of cysts.. We treated 8 patients with peritoneal inclusion cysts conservatively with a Gn-RHa. The cysts resolved in 7 of the patients. Two of them developed a recurrence, but further Gn-RHa therapy was followed by complete resolution of the cysts in one patient and we resume Gn-RHa therapy to the other patient. The peritoneal inclusion cysts failed to shrink in only one patient.. It is suggested that Gn-RHa therapy is effective in some cases of peritoneal inclusion cysts.

Topics: Adult; Buserelin; Cysts; Female; Genitalia, Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Ovariectomy; Peritoneal Diseases; Postoperative Complications; Recurrence; Treatment Outcome; Ultrasonography; Uterine Neoplasms

A 45-year-old women with chronic idiopathic thrombocytopenic purpura was given monthly injections of the GnRH agonist leuprolide acetate for the treatment of uterine leiomyoma. Two weeks after the fifth injection, she showed mild symptoms of thyrotoxicosis. At that time, serum thyroxin (T4) and triiodothyronine (T3) levels were elevated whereas TSH level was suppressed. Anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies were positive, whereas TSH binding inhibitory immunoglobulin (TBII) was undetectable. Two months later, serum T4 and T3 levels spontaneously decreased below the normal ranges. Five months after the onset of the disease, they returned to normal without any treatment. Anti-TPO and anti-Tg antibodies gradually decreased during the clinical course. Thus, the present case was indicated to be an instance wherein silent thyroiditis developed after leuprolide acetate administration. This is the first report to demonstrate the association of thyroid disorder with leuprolide injection.

Topics: Antineoplastic Agents, Hormonal; Autoantibodies; Female; Humans; Hypothyroidism; Iodide Peroxidase; Leiomyoma; Leuprolide; Middle Aged; Thyroglobulin; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Uterine Neoplasms

In the hormonal treatment of uterine myomas, which are estrogen dependent, GnRH agonist (GnRHa) therapy has become widespread. However, the severe hypo-estrogenic state induced by the GnRHa gives rise to annoying side effects. Although the risk of these side effects may be reportedly modified when GnRHa is combined with estrogen (add-back therapy), it is difficult to target serum estradiol (E2) concentration to stay within the therapeutic window (20 approximately 50 pg/mL) by administering 0.625 mg conjugated equine estrogen (CEE)/day. Also, there is great individual variation in the circulating E2 concentration by administering the same dosage of CEE. Therefore, the use of smaller quantities of CEE in different dosages may approximate more closely to the clinical situation. This article focuses on the methods of administration of CEE combined with GnRHa for women with symptomatic uterine myomas.

Topics: Animals; Antineoplastic Agents, Hormonal; Dose-Response Relationship, Drug; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Horses; Humans; Leuprolide; Myoma; Time Factors; Uterine Neoplasms; Uterus

Since October 1996, at our fibroid center, we have been using the uterine artery embolization (UAE) procedure as a nonsurgical means to treat patients with fibroids and menorrhagia. We have performed this procedure on over 180 patients, 3 of whom experienced vaginal expulsion of submucosal fibroids from two to seven months later.. A 37-year-old woman underwent UAE in November 1997 and expelled five submucosal fibroids two to three months later. A 43-year-old woman underwent UAE in August 1997 and expelled a submucosal fibroid four months later. A 46-year-old woman underwent UAE in April 1997 and expelled a submucosal fibroid seven months later.. The use of UAE to treat patients with fibroids and menorrhagia is relatively new. Our experience has revealed that a significant percentage of patients who have had the embolization procedure will have reduction in menorrhagia and also in the volume of their fibroids. Complications and side effects have been few. Vaginal expulsion of submucosal fibroids can be viewed as a side effect of the procedure, and, to the best of our knowledge, these are the first reported cases of this postembolization occurrence.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Embolization, Therapeutic; Female; Humans; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Treatment Outcome; Uterine Neoplasms

To compare the immunohistochemical expression of Bcl-2 in uterine leiomyomas in patients undergoing myomectomy or hysterectomy with and without preoperative treatment with the gonadotropin-releasing hormone receptor agonist (GnRH-a) leuprolide acetate (LA).. Retrospective case-control study. Seventeen patients with symptomatic uterine leiomyomata were included. Of the 17 patients, 7 were treated with LA (3.75 mg) in three monthly doses prior to myomectomy or hysterectomy. Ten patients who did not receive LA and underwent hysterectomy for leiomyomas served as controls. Formalin-fixed, paraffin-embedded archival tissue from 17 leiomyomas were immunostained with a monoclonal antibody against Bcl-2 protein. Positivity was scored semiquantitatively on a three-tier scale.. Immunostaining for Bcl-2 protein was intense (2-3+) in 7 LA-treated and 10 untreated leiomyomas but was scarce (0-1+) in normal myometrial smooth muscle.. Abundant expression of Bcl-2 protein may be responsible for the growth of leiomyomas by preventing apoptotic cell death. Its increased expression is maintained in GnRH-a-treated leiomyomas.

Topics: Adult; Case-Control Studies; Female; Humans; Hysterectomy; Immunohistochemistry; Leiomyoma; Leuprolide; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Retrospective Studies; Uterine Neoplasms

Topics: Absorption; Antineoplastic Agents, Hormonal; Body Fluids; Endometrium; Female; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

Conservative surgical options for uterine myomata traditionally were abdominal myomectomy, laparoscopic myomectomy, and, more recently, myolysis. Each of these procedures has distinct advantages, but also apparent disadvantages. We attempted to introduce an additional option for conservative surgical treatment of fibroids by freezing the structures, a procedure termed cryomyolysis. In this pilot study, 14 women were pretreated with a gonadotropin-releasing hormone (GnRH) agonist for a minimum of 2 months preoperatively to minimize uterine and myoma size. Cryomyolysis was performed and the GnRH agonist was discontinued. Magnetic resonance imaging scans were performed in 10 of the 14 women after GnRH agonist treatment but before surgery, and 4 months postoperatively. Total uterine volume ranged from 41.3 to 1134.8 ml preoperatively, and 49.5 to 1320 ml postoperatively (mean increase 22% after discontinuation of GnRH agonist). Normal uterine volume ranged from 35.6 to 548.7 ml preoperatively and 45.1 to 729.6 ml postoperatively (mean increase 40%); however, myoma volume showed a mean decrease of 6% (range -87-28%). Analysis of only frozen myomata revealed a mean volume decrease of 10%. Cryomyolysis maintains at or slightly reduces these lesions to post-GnRH agonist size, and all other uterine tissue returns to pretreatment size. We believe cryomyolysis may be an effective conservative surgical approach to uterine fibroids.

Topics: Adult; Antineoplastic Agents, Hormonal; Cryosurgery; Feasibility Studies; Female; Humans; Laparoscopy; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Middle Aged; Pilot Projects; Premedication; Prospective Studies; Uterine Neoplasms; Uterus

Cell proliferation and apoptosis in uterine leiomyoma were investigated during therapy with GnRH agonist (GnRHa). Patients with uterine leiomyomas were injected with 3.75 mg GnRHa (depot leuprolide acetate) at intervals of 4 weeks and underwent hysterectomy or myomectomy at the 2nd, 4th, 8th, 12th, or 16th week of GnRHa therapy. Tissue sections of leiomyomas from these patients and from control patients (control patients received no GnRHa therapy) were stained with the Ki-67 antibody or by an in situ DNA 3'-end labeling method, and numbers of Ki-67 immunostained cells and DNA 3'-end-labeled cells per cm2 were examined as indices of cell proliferation and apoptosis, respectively. The number of Ki-67 immunostained cells/cm2 in leiomyomas at the 2nd week of the GnRHa therapy was comparable with that of control patients. However, it decreased to a level less than one forth that of control patients at the 4th week, and it remained at similar low levels at the 8th, 12th, and 16th week. The number of DNA 3'-end-labeled cells/cm2 in leiomyomas of control patients and in leiomyomas at the 2nd, 8th, 12th, and 16th weeks of GnRHa therapy were at low levels but, at the 4th week, was at an extremely high level (about 5 times more than that of control patients). The present results indicate that GnRHa therapy suppresses cell proliferation and causes a transient increase in apoptosis in uterine leiomyomas.

Topics: Adult; Antineoplastic Agents, Hormonal; Apoptosis; Case-Control Studies; Cell Division; Depression, Chemical; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Leiomyoma; Leuprolide; Middle Aged; Uterine Neoplasms

Gonadotropin-releasing hormone (GnRH) agonists are commonly used in the treatment of uterine leiomyomas, but little is known about their histological and cellular effects on these neoplasms. We examined a cellular proliferation index as determined by the nuclear antigen Ki-67 and proliferating cell nuclear antigen (PCNA) expression, estrogen receptor (ER), and progesterone receptor (PR) expression in 27 leiomyomas from patients treated with the GnRH agonist leuprolide acetate (LA) and compared them with 33 untreated controls. All leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6 months of LA treatment or in the follicular phase of the menstrual cycle in the untreated controls. Histological features examined included cellularity, nuclear atypia, vascular changes (dilated, thickened, or thrombosed vessels), edema, calcification, hemorrhage, necrosis, hyalinization, and mitotic activity. Although no difference was found between GnRH-treated and nontreated groups with respect to most histological features examined, immunohistochemical studies showed a significant decrease in the cellular proliferation index, ER, and PR expression in the LA-treated cases compared with nontreated controls. The cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and 36%, respectively, in the LA-treated group as compared with controls (P < .001). A subset of cases from the LA-treated and nontreated groups were also analyzed with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant difference between the LA-treated and nontreated groups was observed with both groups showing a strong (> 75% of cells) cytoplasmic staining pattern. Results of this study show that LA treatment of leiomyomas results in a decrease in number of cycling cells.

Topics: Adult; Antineoplastic Agents, Hormonal; Cell Division; Female; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Ki-67 Antigen; Leiomyoma; Leuprolide; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Uterine Neoplasms

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Female; Fibrosis; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Menopause; Middle Aged; Uterine Neoplasms

Diverse complications have been reported in association with the growth and medical treatment of uterine leiomyomata. Infarction and necrosis may be common and incite complications from parasitic vascular attachment, pain and thrombosis. The rarity of severe complications in this situation warrants presentation of the following unique association.. A 33-year-old female, gravida 1, para 1, was treated with gonadotropin-releasing hormone agonist (GnRH-a) for three months prior to laparotomy and removal of a solitary, 5,190-g, pedunculated myoma. The mass had secured an additional vascular supply from the transverse colon and omentum. Although the immediate postoperative course was uncomplicated, delayed onset of abdominal pain and fever lead to the diagnosis of superior mesenteric and portal vein thrombosis. Portal vein thrombosis responded to thrombolytic infusion into the superior mesenteric artery. Superior mesenteric vein thrombosis persisted, with evidence of early vascular recanalization. After six weeks of additional anticoagulation, assessment by computed tomographic scan showed complete resolution of all thrombi.. While thrombosis has been reported with GnRH-a therapy in men with prostate cancer, its association with treatment in this benign case may have been a consequence of the massive tumor size. Steroid hormone deprivation potentially contributed to neovascularization and bowel involvement.

Topics: Adult; Anticoagulants; Delayed-Action Preparations; Female; Humans; Leiomyoma; Leuprolide; Mesenteric Veins; Portal Vein; Thrombosis; Uterine Neoplasms

This study examined the histologic changes associated with administration of leuprolide acetate, a gonadotropin-releasing hormone agonist, in leiomyomata. Thirty-seven women treated with leuprolide acetate who subsequently underwent myomectomy or hysterectomy were matched by age (+/- 3 years), race, and uterine size (+/- 2 weeks) with untreated controls. Tissue samples of leiomyomata (four to 10 slides per patient) were examined "blinded" by two pathologists and evaluated for cellularity, edema, myxoid change, hyalinization, fibrosis, inflammation, infarction, and vascular changes (thrombosis, intimal fibrosis, thickening of the vessel wall with narrowing of the lumen, perivascular fibrosis). A matched case-control analysis was conducted for each morphologic characteristic. Cellularity, hyalinization, and fibrosis were graded as 1(+) versus 2(+); all other characteristics were graded as present or absent. The analysis showed that leuprolide acetate-treated leiomyomata had significantly increased hyalinization (p < 0.005) and decreased cellularity (p < 0.10) as compared with controls; there was also thickening of blood vessel walls with narrowing of the lumen (p < 0.01). A subgroup of leuprolide acetate-treated patients categorized as clinical responders (having > 30% reduction in tumor size) more frequently had thickening of vessel walls (p < 0.05) and vascular thrombosis (p < 0.10) than did nonresponders. Our data suggest that a leuprolide acetate-induced hypoestrogenic state may cause vasoconstriction, thickening of blood vessel walls, and thrombosis, leading to ischemia, hyalinization, and atrophy of the leiomyoma.

Topics: Adult; Antineoplastic Agents, Hormonal; Case-Control Studies; Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Middle Aged; Retrospective Studies; Uterine Neoplasms

To define the pathologic changes underlying the mechanism of shrinkage of uterine leiomyomata in patients treated with luprolide acetate.. Retrospective study of pathologic changes seen in leiomyomata removed by hysterectomy or myomectomy in treated and untreated patients, matched by age and size of uteri and leiomyomata.. Gross description and histologic slides of 30 treated and 30 untreated patients.. Histologic examination performed blindly (without knowledge of treatment). Statistical work-up using chi 2 analysis with 1 df.. Degree of hyaline and hydropic degeneration, cellularity, nuclear atypia, necrosis, and obliteration of interface.. Confluent nodular hyaline degeneration representing a scarlike retraction, geographic hydropic degeneration necrosis and obliteration of the interface between myoma and myometrium were found in higher proportions in the treated patients; differences in cellularity, nuclear atypia, and edema were not statistically significant.. The decrease in size of the treated leiomyomata occurs as an accelerated postmenopausal shrinkage because of the antiestrogenic effect of the therapy. Obliterated cleavage planes may explain the difficult enucleation of myomatous nodules in some of the treated patients.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Infant, Newborn; Leiomyoma; Leuprolide; Lymphocytes; Middle Aged; Myometrium; Necrosis; Retrospective Studies; Uterine Neoplasms

Gonadotropin-releasing hormone agonists (GnRH-a) are effective in reducing the pituitary release of gonadotropins, which, in turn, decrease ovarian steroidogenesis. The resulting menopausal state decreases the volume and vascular supply to uterine leiomyomas. Peripheral adipose tissue also contributes significantly to the circulatory estrogen pool, which is formed independent of pituitary function. As such, obesity may interfere with depot leuprolide acetate effects, allowing normal estrogen levels despite gonadotropin suppression.. A premenopausal, morbidly obese woman was referred for treatment of menorrhagia and uterine leiomyomas. Despite administration of depot leuprolide, a GnRH-a, she continued to bleed heavily. Serum estradiol levels remained in the normal range, with suppression of follicle-stimulating hormone (FSH) levels. The desired hypoestrogenic effect from GnRH-a administration was thought to be negated by estradiol levels arising from peripherally derived conversion of adrenal androgens in adipose tissue. A GnRH stimulation test was performed to evaluate the responsiveness of the pituitary to the above therapy. While FSH was suppressed and unresponsive to stimulation, estradiol remained unchanged.. Peripheral production of estrogen appears to be unaffected by leuprolide administration. Consideration should be given to the patient's body habitus when administering a GnRH suppressant. Morbidly obese patients possess an unlimited reservoir for peripheral estrogen synthesis.

Topics: Adipose Tissue; Antineoplastic Agents, Hormonal; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Obesity, Morbid; Uterine Neoplasms

Topics: Blood Loss, Surgical; Female; Gestational Age; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Pregnancy; Preoperative Care; Uterine Neoplasms

We report two cases of leuprolide acetate-treated leiomyomas with striking vascular changes and histologic features of vasculitis and atherosclerosis. These changes may cause ischemic damage if they occur in other organs. We describe the histologic findings and discuss their clinical implications.

Topics: Adult; Arteriosclerosis; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Uterine Neoplasms; Vasculitis

Sixty-five patients with uterine myomas were studied after surgery to investigate the effect of periodic GnRH analog treatment on the prevention of recurrences. A group of patients was treated by leuprolide acetate depot 3 months a year for 3 years. At the end of treatment, these patients showed a significantly reduced uterine volume and myoma recurrence rate as compared to untreated patients. A role of GnRH analogs in the clinical prevention of myoma recurrence could be suggested.

Topics: Adult; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Humans; Incidence; Leiomyoma; Leuprolide; Neoplasm Recurrence, Local; Pilot Projects; Postoperative Care; Ultrasonography; Uterine Neoplasms; Uterus

The aim of this study was to obtain data about the pregnancy rate in patients with uterine leiomyomata after treatment with gonadotropin-releasing hormone (GnRH) agonists followed by myomectomy. Between 1987 and 1993, 61 patients with uterine leiomyomata and sterility underwent 6 months' GnRH agonist treatment, in part with a surgical intervention. Sixty-two per cent of the patients suffered from concomitant endometriosis. After hormonal therapy 41 patients underwent a myomectomy. According to sonographic and clinical criteria, there was no indication for the enucleation of the leiomyomata for the remaining 20 patients. Owing to the combined therapy, consisting of primary treatment of uterine leiomyomata with GnRH agonists, followed by surgical intervention, 25 patients (41%) suffering from long-term sterility (average 4 years) became pregnant. An early abortion occurred in only three cases (12%). No patient who underwent a myomectomy developed new myomata during the following pregnancy. Four patients suffering from a single leiomyoma became pregnant within the first 3 months after myomectomy, all of them conceiving spontaneously. Considering the high rate of spontaneous conceptions and the low abortion and complication rates during pregnancy, the combined therapy of GnRH agonists followed by myomectomy represents a major step forwards in the effective treatment of sterility in patients with uterine leiomyomata.

Topics: Administration, Intranasal; Adult; Antineoplastic Agents, Hormonal; Buserelin; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Infertility, Female; Injections, Intramuscular; Leiomyoma; Leuprolide; Nafarelin; Pregnancy; Pregnancy Rate; Retrospective Studies; Time Factors; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Injections; Leiomyoma; Leuprolide; Lupus Nephritis; Uterine Neoplasms

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

The reported histopathologic findings in leiomyomas treated with leuprolide acetate (LA) differ. We examined 233 myomectomy specimens, including 107 myomas from 30 patients (mean age, 34.7 +/- 4.6 years) treated with LA. Their histopathologic findings were compared with those from a control group of 126 myomas from 30 untreated patients (mean age 32.7 +/- 5.3 years). The LA-treated leiomyomas had myxoid change (n = 2; 1.9%), total necrosis (n=4; 3.7%), focal necrosis (n = 5; 4.7%), calcifications (n = 5; 4.7%), hemorrhage (n = 8, 7.5%), vascular changes (n = 12; 11.2%), hydropic degeneration (n = 22; 20.5%), and hyalinization (n = 61; 57.0%). None of these changes differed significantly from the untreated controls. None of the LA-treated leiomyomas had nuclear atypia, whereas nuclear atypia occurred in four (3.2%) of the untreated leiomyomas; this difference was also not significant. Mitotic figures were present in 8.4% of the LA-treated myomas and 8.5% of untreated controls. The number of mitotic figures per 10 high-power fields was slightly higher in the untreated myomas, but the difference was not statistically significant (range, 0-3 for treated, 0-5 for controls). The degree of cellularity did not differ between the two groups. In conclusion, (a) LA-treated myomas do not significantly differ from untreated myomas with respect to nuclear atypia, calcification, total coagulative necrosis, focal coagulative necrosis, hemorrhage, vascular changes, myxoid change, hydropic degeneration, hyalinization, mitotic activity, or cellularity; and (b) the mechanism leading to a reduction in the size of myomas treated with LA is not apparent from routine histologic examination.

Topics: Adult; Antineoplastic Agents, Hormonal; Cluster Analysis; Female; Humans; Leiomyoma; Leuprolide; Logistic Models; Regression Analysis; Uterine Neoplasms

The objective of the present study was to determine whether GnRH and GnRH receptor are expressed in myometrium and leiomyomata, and if GnRH analogs alone or in the presence of ovarian steroids can modulate the rate of DNA synthesis, proliferation, and transforming growth factor-beta 1 (TGF beta 1) production in myometrial smooth muscle cells in vitro. Reverse transcription-PCR revealed that leiomyomata, unaffected myometrium, and isolated myometrial smooth muscle cells express GnRH and GnRH receptor messenger ribonucleic acid. Furthermore, in a dose-dependent manner, GnRH agonist (leuprolide acetate) inhibited, but GnRH antagonist [D-pGlu1,D-Phe2,D-Trp3.6] (GnRH-Ant1) stimulated, the rate of [3H]thymidine incorporation into myometrial smooth muscle cells (P < 0.05), whereas GnRH-Ant2 (Ac-D-P-Cl-Phe1.2,D-Trp3,D-Arg6,D-Ala10) had no effect. 17 beta-Estradiol (E2) medroxyprogesterone acetate (MPA), and E2 plus MPA (1 micromol/L) stimulated the rate of DNA synthesis by smooth muscle cells (P < 0.05), which was inhibited by GnRH analogs used at 5 micromol/L (P < 0.05). GnRH analogs had no significant effect on myometrial smooth muscle cell proliferation, with the exception of GnRH-Ant1; however, they inhibited the stimulatory action of E2, MPA, and E2 plus MPA in a time-dependent manner (P < 0.05). These cells also synthesized and released approximately 1.32 +/- 0.02 ng/mL total (active plus latent) TGF beta 1, of which 0.73 +/- 0.02 ng/mL was in an active form. E2, MPA, E2 plus MPA, and GnRH analog treatments resulted in an increase in total TGF beta 1 production, whereas GnRH agonist and GnRH-Ant2, but not GnRH-An1, inhibited active TGF beta 1 (P < 0.05). GnRH analogs also inhibited the action of E2 plus MPA on total and active TGF beta 1 production, whereas GnRH-Ant1 further stimulated E2, MPA, or E2 plus MPA action on active TGF beta 1 production (P < 0.05). The data demonstrate for the first time that GnRH and GnRH receptor messenger ribonucleic acid are expressed in myometrium, leiomyomata, and myometrial smooth muscle cells. The local expression of GnRH and receptor along with the direct action of GnRH analogs on the smooth muscle cell DNA synthesis and TGF beta 1 production suggest an autocrine/paracrine role for GnRH in these tissues, a mechanism that may be involved in leiomyomata regression in women receiving GnRH agonist therapy.

Topics: Adult; Amino Acid Sequence; Base Sequence; Cell Division; DNA; Estradiol; Female; Gene Expression; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Medroxyprogesterone Acetate; Molecular Sequence Data; Muscle, Smooth; Myometrium; Receptors, LHRH; Transforming Growth Factor beta; Uterine Neoplasms

The expression and cellular distribution of transforming growth factor-1 (TGF beta 1) through TGF beta 3 and TGF beta type I-III receptor messenger ribonucleic acid (mRNA) and protein were analyzed in leiomyomata from patients receiving GnRH agonist (GnRHa; leuprolide acetate) compared to those in untreated controls. Standard reverse transcription-PCR revealed that the unaffected myometrium and leiomyomata from leuprolide-treated and untreated patients express TGF beta 1-3 and TGF beta type I-III receptor mRNA. The myometrial and leiomyomata smooth muscle cells were the primary site of TGF beta 1-3 and TGF beta type I and II receptor mRNA and protein expression, as determined by in situ hybridization and immunohistochemical localization. These observations indicate that leiomyomata express a higher of level of TGF beta and TGF beta receptor mRNA and protein than unaffected myometrium during the secretory phase of the menstrual cycle, and women who received leuprolide acetate therapy had a substantially lower level of expression than untreated controls. Furthermore, competition-based quantitative reverse transcription-PCR using synthetic internal standards revealed that leiomyomata express a significantly higher number (copies per cell) of TGF beta type II receptor mRNA, followed by TGF beta 1, TGF beta type I receptor, TGF beta 2, and TGF beta 3 (P < 0.05). However, there was a significant decrease in the levels (copies per cell) of TGF beta 1, TGF beta 3, and TGF beta type I and type II receptor mRNA expression in leiomyomata from leuprolide-treated compared to untreated patients (P < 0.05). The data provide further evidence that leiomyomata express mRNA and protein for all components of the TGF beta system, and GnRHa therapy results in down-regulation of their expression. More specifically, these data suggest that TGF beta 1 and TGF beta 3 may play a more important role in leiomyomata growth than TGF beta 2, which leads us to propose that lowering TGF beta and receptor expression may have a direct effect on leiomyomata regression.

Topics: Adult; Female; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Leiomyoma; Leuprolide; Middle Aged; Polymerase Chain Reaction; Receptors, Transforming Growth Factor beta; RNA-Directed DNA Polymerase; RNA, Messenger; Transforming Growth Factor beta; Uterine Neoplasms

Three women experienced bleeding, pain, and pressure symptoms attributable to uterine myomas. Because they were not responsive to conservative therapy, they underwent outpatient laparoscopic myomectomy after 3 months of gonadotropin-releasing hormone agonist administration. The Endo Stitch 10-mm laparoscopic suturing device was used to close the uterus with interrupted and continuous locked sutures. The instrument shortened the operative time by approximately 40 minutes.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Humans; Laparoscopes; Leiomyoma; Leuprolide; Middle Aged; Suture Techniques; Uterine Neoplasms

To evaluate the effectiveness of laparoscopic myomectomy in an ethnic group with a statistically increased frequency of uterine leiomyomata.. Retrospective chart review.. Private practice of one surgeon, and Department of Obstetrics and Gynecology, Rush Medical College, Chicago, Illinois.. Forty-one consecutive African-American women who underwent laparoscopic myomectomy and were followed for 12 to 26 months.. The women received a modified protocol for gonadotropin-releasing hormone agonist treatment before laparoscopic surgery. Laparoscopic myomectomies were performed under general anesthesia using energy sources of monopolar and bipolar electrosurgery and ultrasonic coagulation-cutting (harmonic scalpel).. Seventy percent (70%, 29 women) of procedures were completed on an outpatient basis. Twelve patients were hospitalized for an average of 1.3 days. No significant operative or postoperative complications occurred, and none of the women required blood transfusions or readmission. The conversion rate was zero. Forty patients (91%) reported complete resolution or significant reduction of their symptoms.. Outpatient laparoscopic myomectomy is safe and effective in African-American women with symptomatic uterine leiomyomata of 20 weeks' size or less.

Topics: Adult; Ambulatory Surgical Procedures; Black People; Body Weight; Electrocoagulation; Female; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leiomyoma; Leuprolide; Middle Aged; Retrospective Studies; Treatment Outcome; Uterine Neoplasms

To assess the effectiveness of treating adenomyomata with laparoscopic bipolar coagulation.. Prospective, observational study. Setting. The gynecology department of a community hospital.. Ten women, each with severe dysmenorrhea, chronic menorrhagia, and adenomyomata diagnosed by magnetic resonance imaging.. Laparoscopic bipolar coagulation of adenomyomata.. The mean (+/- SEM) total adenomyoma volume before leuprolide acetate administration was 119 +/- 16 cm3 (range 6-190 cm3); after 3 months of therapy this was reduced to 86 +/- 8 cm3 (range 6-162 cm3, p <0. 0001) a 27.7% reduction. Further reduction occurred 7 to 12 months postoperatively to 31 +/- 3.4 cm3 (range 3-155 cm3, p <0.0001), a 73.9% reduction from baseline. Twelve months postoperatively, seven (70.0%, p <0.05) women had continued resolution or significant reduction of dysmenorrhea and resolution of menorrhagia. One woman (10.0%) with unresolved dysmenorrhea and menorrhagia required hysterectomy, and two (20.0%) with recurrent menorrhagia required resection of the endomyometrium; one continued to have menorrhagia but refused further surgical or medical treatment.. Conservative treatment obviated the need for major surgery in 90% of women with adenomyomata, but further evaluation of this technique is necessary to determine its definitive role.

Topics: Adenomyoma; Adult; Antineoplastic Agents, Hormonal; Dysmenorrhea; Electrocoagulation; Female; Humans; Laparoscopy; Leuprolide; Magnetic Resonance Imaging; Menorrhagia; Middle Aged; Recurrence; Uterine Neoplasms

In a retrospective study, the value of pretreatment with a gonadotropin-releasing-hormone (GnRH) agonist before hysteroscopic myoma resection was assessed in 31 patients suffering from menorrhagia. No difference in operating time, intra-operative fluid deficit, blood loss and postoperative eumenorrhoea rate was found between pretreated and non-pretreated patients with solitary submucous myomas smaller than 4 cm in diameter. Thus, pretreatment with GnRH agonists before the resection of small solitary submucous myomas has no benefit for the patients.

Topics: Antineoplastic Agents, Hormonal; Endoscopy; Female; Humans; Hysteroscopy; Leiomyoma; Leuprolide; Menorrhagia; Premedication; Retrospective Studies; Uterine Neoplasms; Uterus

To examine the effect of equimolar concentrations of hCG and dissociated alpha-subunit on PRL production by leiomyoma and myometrial tissue obtained from different hormonal states and to examine changes in PRL messenger RNA levels as PRL protein levels increased.. Explant cultures of leiomyomas and myometrium were established and cultured for 96 hours. Tissue was studied from normal cycling women, postmenopausal women, pregnant women, and women undergoing GnRH agonist (GnRH-a) therapy. Cultured medium was collected at 24, 48, and 96 hours and assayed for PRL. In selected experiments, tissue was processed at 0 and 96 hours to analyze messenger RNA (mRNA) levels.. Human chorionic gonadotropin and alpha-subunit stimulated PRL secretion in [1] explant cultures of leiomyoma and myometrium from premenopausal women, [2] cultures of tissue treated in vivo with leuprolide acetate for both leiomyoma and myometrium, and [3] myometrium obtained from postmenopausal women. Postmenopausal myometrium was significantly more responsive to stimulation. Prolactin mRNA levels were documented to increase after hormone treatment in postmenopausal myometrium.. Myometrium from postmenopausal women is very responsive to hCG and alpha-subunit. There is a difference in response between tissue obtained from menopausal women and that from women undergoing GnRH-a therapy to achieve a "medical menopause" and reproductive age women. The level of endogenous gonadotropins as well as the steroid milieu may modulate myometrial PRL secretion.

Topics: Antineoplastic Agents, Hormonal; Blotting, Northern; Chorionic Gonadotropin; Culture Techniques; Female; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Myometrium; Postmenopause; Pregnancy; Prolactin; Radioimmunoassay; RNA, Messenger; Time Factors; Uterine Neoplasms

Intravascular leiomyomatosis is an uncommon uterine tumor characterized by grossly visible intravascular proliferation of benign smooth muscle. Based on its role in reducing the size of leiomyomas, leuprolide acetate was given as induction therapy for extensive inoperable intravascular leiomyomatosis.. A 44-year-old woman, gravida 1, para 1-0-0-1, presented in July 1992 with abnormal uterine bleeding. Pelvic examination and ultrasonography revealed the presence of a large irregular pelvic mass. At laparotomy, uterine and bilateral adnexal masses were noted extending up to the pelvic inlet and into the broad and infundibulopelvic ligaments. This tumor was not resectable. Based on histologic and immunoperoxidase studies, the lesion was interpreted as a plexiform epithelioid smooth-muscle tumor of uncertain malignant potential. Leuprolide acetate depot therapy (7.5 mg every 4 weeks) was begun in September 1992 and continued for a total of 20 months. Maximal tumor regression was achieved after 9 months. Subsequent reexploration at 20 months revealed a resectable tumor. Resection was accomplished successfully, leaving no apparent residual disease.. Leuprolide acetate induced tumor regression and rendered debulking surgery feasible in a patient with previously unresectable, widespread, retroperitoneal intravascular leiomyomatosis. Primary hormone therapy may provide alternative therapeutic options for certain cases of intravascular leiomyomatosis.

Topics: Adult; Female; Humans; Leiomyomatosis; Leuprolide; Preoperative Care; Uterine Neoplasms

Thirty-four perimenopausal women with uterine leiomyomas were treated with intramuscular injections of leuprolide acetate depot each 28 days for 6 cycles, and 12 of them after 168 days of no medication underwent a second 6-month therapy cycle. At the end of the observation period the expected improvement during treatment was maintained at cessation of therapy in 15 patients, due to the effect of the natural postmenopausal estrogen deficiency. Only 3 women underwent hysterectomy, due to the regrowth to baseline values of uterine size. It is concluded that the therapy with gonadotropin-releasing hormone analogs in perimenopause offers an effective alternative to surgery in the treatment of uterine leiomyomas.

Topics: Drug Administration Schedule; Estrogens; Female; Humans; Leiomyoma; Leuprolide; Middle Aged; Neoplasm Recurrence, Local; Postmenopause; Premenopause; Treatment Outcome; Uterine Neoplasms

To evaluate the potential savings in cost of care derived from performing vaginal hysterectomies instead of abdominal hysterectomies in selected women with fibroid uteri equivalent in size to a 14-18 week gestation.. Women 35-46 years of age undergoing hysterectomy for fibroid uteri were selected to allow application of conversion rates gained in a separate randomized study using leuprolide acetate depot 3.75 mg. Statewide public data for North Carolina's hospital discharges provided relative rates of hospital charges and leiomyomas for all hysterectomies, by age. Professional charges were omitted from the analysis. Estimated savings were projected to the national level.. During 1992 in North Carolina, 18,110 inpatient hysterectomies were performed for women of all ages; 28.1% of these were for uterine leiomyomas. For women 35-46 years old (12.7% of all hysterectomies), there were 1904 abdominal and 390 vaginal hysterectomies; the mean total charge for abdominal hysterectomy was $5590, and $4732 for the vaginal alternative. These statewide data provide missing elements to allow a national estimate of the potential savings of using GnRH agonist preoperatively. The projected national savings, if 1987 utilization data are used, was $4.6 million, nearly 1.4% of the inpatient charges. The 1992 value of these savings is $6.7 million.. The use of preoperative GnRH agonist therapy before hysterectomy for patients with a uterine size equivalent to a 14-18 week gestation represents a significant cost-saving alternative, increasing the use of vaginal hysterectomy and resulting in potential savings in direct inpatient medical care charges.

Topics: Adult; Cost Savings; Decision Support Techniques; Female; Hospital Charges; Humans; Hysterectomy; Hysterectomy, Vaginal; Leiomyoma; Leuprolide; Middle Aged; North Carolina; Uterine Neoplasms

The objective of this study was to correlate, during 12 weeks of therapy with gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the hemodynamic changes on the uterine artery and the leiomyometrial supplying vessels. Twenty-three premenopausal women with clinically diagnosed uterine leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma volumes and blood flow characteristics of the main uterine artery and leiomyoma supplying vessels-resistance index (RI), pulsatility index (PI) and peak-systolic velocity, obtained by transvaginal color Doppler sonography-were compared with treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy. The first event in the chronological response to the GnRH-a therapy was a statistically significant increase in RI and PI values for major leiomyoma vessels, observed at the end of the 4th week (p < 0.05), which increased significantly after 8 and 12 weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct correlation with a significant decrease of estradiol levels after 4, 8 and 12 weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease of blood flow in the leiomyometrial vessels was followed by a significant decrease of the main uterine artery blood flow after 8 weeks and uterine and leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy. We concluded that a significant increase in leiomyometrial vessels RI and PI values, which was found 4 weeks after the first dose of GnRH-a, but without major leiomyoma volume decrease, emphasizes that the first significant effect of GnRH therapy in the process of uterine and leiomyoma volume shrinkage is the reduction of leiomyometrial rather than uterine blood flow. This effect is followed by a considerable reduction of uterine vascularity and a significant decrease of uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate therapy duration.

Topics: Adult; Estradiol; Female; Hemodynamics; Humans; Leiomyoma; Leuprolide; Middle Aged; Premenopause; Prospective Studies; Ultrasonography, Doppler, Color; Uterine Neoplasms; Vascular Resistance

The steroid receptor concentration and the histological morphology of uterine leiomyomata in premenopausal patients undergoing myomectomy therapy with and without a preoperative GnRH analogue, was analysed to evaluate whether the GnRH analogue therapy leads to important hormonal receptor changes, histomorphological changes and a significant shrinkage of the leiomyomata.. Sixty-one GnRH analogue pretreated leiomyomata and 28 untreated leiomyomata were analysed. To determine the estrogen and progesterone receptor concentrations, immunohistochemical techniques were used and quantified with the immuno-reactive score (IRS-score). The leiomyomata were divided into cellular rich, normal, hyaline or cystic degenerated and necrotic according to their histology.. The GnRH analogue pretreated leiomyomata group showed higher levels of estrogen and progesterone receptors than the untreated group (37.7% of the GnRH analogue group had a high positive and 29.5% a moderate positive estrogen receptor status whereas high levels of estrogen receptor could be found in only 14.3% of the untreated group). The leiomyomata of both groups with the exception of the necrotic ones, were estrogen and progesterone receptor positive.. Our study suggests that pretreatment of uterine leiomyomata leads to a significant increase in the hormonal receptor concentration of these benign tumors. If pretreated leiomyomata are not removed surgically immediately after the therapy, a rapid regrowth can occur and again cause clinical symptoms.

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Uterine Neoplasms

To describe the effectiveness in the clinical use of a new bipolar needle for performing laparoscopic coagulation of symptomatic uterine myomas, and to compare it with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser.. Observational, comparative.. Voluntary community hospital.. Three hundred women, 150 in the Nd:YAG laser group and 150 in the bipolar needle group, who had symptomatic myomas no larger than 10 cm, responded to pretreatment with depot leuprolide, and were no longer interested in childbearing.. Myomas were pierced repeatedly with the bipolar needle to produce numerous cores of coagulation. An average of 30 to 50 passes were made.. Myoma size and location were assessed by endovaginal ultrasound before preoperative treatment with depot leuprolide. The coagulating effect of the bipolar needle devascularized the myomas, and the resulting shrinkage was comparable with that produced by the Nd:YAG laser. Complications were infrequent, with no evidence of myoma regrowth 6 months after the procedure.. The bipolar needle was as effective as the Nd:YAG laser in coagulating symptomatic subserosal and intramural uterine myomas and achieving reduction in size of 50% to 70%, with no regrowth.

Topics: Aluminum Silicates; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Electrocoagulation; Endometrium; Equipment Design; Female; Follow-Up Studies; Humans; Laparoscopes; Laparoscopy; Laser Coagulation; Leiomyoma; Leiomyosarcoma; Leuprolide; Needles; Neodymium; Preoperative Care; Ultrasonography; Uterine Neoplasms; Yttrium

Women with large uterine leiomyomas traditionally have had just one choice for therapy--abdominal hysterectomy. Recently, gonadotropin-releasing hormone (GnRH) agonist therapy has been introduced as an option to shrink tumors before surgery. When administered preoperatively, usually for 2 months, GnRH therapy has been shown to reduce tumor size enough to permit an endoscopic myomectomy or a vaginal hysterectomy. It has also been shown to reduce blood loss associated with the tumors and increase hemoglobin levels. When assessed for its economic impact, preoperative GnRH therapy reduces both direct and indirect costs associated with a hysterectomy.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cost Savings; Drug Costs; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Length of Stay; Leuprolide; Megestrol; Megestrol Acetate; Sick Leave; United States; Uterine Neoplasms

A case of a 34 years old woman with primary sterility secondary to multiple myomatosis, is presented. Any other sterility factor was ruled out. First, she went on laparotomy for multiple myoma resection but two of these were left. The cornual myoma couldn't be removed because the high risk of salpinx damage. The other one was a 3 cm. intracavitary tumor. After four months on leuprolide acetate therapy an hysteroscopic myomectomy was performed. The next menstrual cycle pregnancy was achieved.

Topics: Adult; Female; Humans; Hysteroscopy; Infertility, Female; Leiomyoma; Leuprolide; Pregnancy; Preoperative Care; Time Factors; Ultrasonography; Uterine Neoplasms

Use of leuprolide acetate (Lupron) has been associated with angina in men, but there have been no previous reports of angina or myocardial infarction associated with its use in women. The first case of angina and myocardial infarction occurring in a woman undergoing treatment with leuprolide acetate depot is reported.

Topics: Adult; Angina Pectoris; Female; Humans; Leiomyoma; Leuprolide; Myocardial Infarction; Uterine Neoplasms

During 1992 and 1993, twenty-eight women with uterine leiomyomata received GnRH-agonist (leuprolide acetate) for 3 months before hysterectomy or myomectomy. The decrease in uterine volume and secondary anemia with its collateral effects were assessed, then surgical and post-surgical advantages were assessed too. The real advantages of this treatment are studied and distinguished from theoretic advantages.

Topics: Adult; Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Premedication; Uterine Neoplasms

To determine if short-term, preoperative leuprolide acetate (LA) therapy alters the histologic appearance of uterine leiomyomata.. Retrospective evaluation by a pathologist (who was blinded to patient history) of the histologic features of leiomyomata excised from 36 women, 12 who received preoperative LA and 24 age-matched controls.. Yale-New Haven Hospital, New Haven, Connecticut, from September 1989 to September 1990.. The histologic specimens were evaluated for the presence of mitotic activity, cellular atypia, cellularity, and secondary changes including edema, fibrosis, calcification, hemorrhage, infarction, hyalinization, and vascular appearance.. Of the 12 patients treated with LA, 10 (84%) demonstrated a reduction in uterine volume after 3 to 6 months of LA therapy. There was no difference in any of the histopathologic parameters evaluated between the LA-treated group and the untreated group. Exclusion of leiomyoma, which did not have a reduction in size during LA therapy, did not alter the analysis. Among patients treated with LA, those leiomyoma that did not respond to LA had a greater degree of hyalinization than those that responded.. Reduction in uterine size by short-term LA therapy did not detectably alter histologic appearance of leiomyoma.

Topics: Adult; Female; Humans; Leiomyoma; Leuprolide; Retrospective Studies; Uterine Neoplasms; Uterus

Topics: Delayed-Action Preparations; Female; Humans; Leiomyoma; Leukocyte Count; Leukopenia; Leuprolide; Middle Aged; Uterine Neoplasms

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

Topics: Combined Modality Therapy; Endometrium; Female; Follow-Up Studies; Humans; Hysterectomy; Hysterectomy, Vaginal; Hysteroscopy; Laparoscopy; Leuprolide; Postoperative Complications; Uterine Neoplasms

The use of long acting gonadotropin-releasing hormone (Gn-RH) agonist produces a reversible hypogonadotropic hypogonadism. This effect has been used as presurgical treatment of uterine myomata, resulting in amenorrhea and reduction in uterus and tumour sizes. We describe the case of a 43 year old patient, having a uterine myoma associated with metrorrhagia, admitted to hospital because of extensive deep phlebothrombosis requiring urgent anticoagulation. Because of the risk of exacerbating metrorrhagia and considering the high morbidity associated to emergency hysterectomy, we decided medical treatment with a depot GnRH agonist (leuprolide acetate 3.75 mg IM monthly). Bleeding ceased within 3 days, allowing the maintenance of anticoagulant treatment. A marked reduction in uterine size postponed total hysterectomy to 3 months later. The characteristics of GnRH analogues, their action mechanisms, adverse effects and other clinical indications are discussed.

Topics: Adult; Female; Humans; Hysterectomy; Leiomyoma; Leuprolide; Metrorrhagia; Remission Induction; Uterine Neoplasms

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 case of rapid uterine enlargement and subsequent urinary retention occurring 7 days after GnRH-a administration in a 53-year-old premenopausal woman with myomas is presented. Rapid uterine enlargement was presumed to be caused by hyperestrogenism shortly after GnRH-a administration. The patient was treated with an indwelling Foley catheter for 2 weeks until the uterus decreased to near baseline dimensions. The patient's uterus continued to decrease in size during the 12 weeks she received GnRH-a, and she underwent an uneventful total abdominal hysterectomy and bilateral salpingectomy/oophorectomy after donating 2 units of autologous blood. This case illustrates that adverse effects from GnRH-a treatment may be caused by the transient increase in ovarian steroid secretion shortly after drug administration.

Topics: Acute Disease; Female; Humans; Leiomyoma; Leuprolide; Middle Aged; Urinary Retention; Uterine Neoplasms; Uterus

Three pre-menopausal women with uterine myomas were treated with leuprolide acetate depot and experienced profuse vaginal bleeding 7-11 weeks after initiation of treatment, despite profound oestradiol suppression. In each case, leuprolide therapy was discontinued and the women were treated with combination oral contraceptives and ferrous sulphate. Vaginal bleeding ceased within 24-48 h of oral contraceptive treatment in all women. Haemoglobin concentrations were restored to normal values and all women underwent definitive surgical treatments after 4-6 weeks of oral contraceptive treatment without the need for homologous blood transfusion. The final pathology report revealed focal necrosis of submucous myomas in all cases.

Topics: Adult; Contraceptives, Oral; Delayed-Action Preparations; Drug Therapy, Combination; Estrogens; Female; Ferrous Compounds; Gonadotropin-Releasing Hormone; Hemorrhage; Humans; Leiomyoma; Leuprolide; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms; Vaginal Diseases

A patient with menorrhagia, dysmenorrhea, and an enlarged uterus was treated with a GnRH agonist for leiomyoma volume reduction. A laser-assisted myomectomy yielded five tumors that did not appear to be well demarcated and had a combined weight of only 30 g. Postoperative pathologic evaluation revealed leiomyosarcoma with 22 mitoses per 10 high-power fields. The 8-month delay in therapy was associated with Stage IV, grade 3 disease at diagnosis. In rare cases GnRH agonist therapy may palliate symptoms and delay definitive surgical therapy of leiomyosarcoma, resulting in more advanced disease at diagnosis.

Topics: Adult; Female; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

The Nd:YAG laser dispersion effect, 2-5 mm in diameter, is utilized in a new laparoscopic procedure to coagulate and reduce symptomatic serosal and intramural myomas of moderate size (less than or equal to 10 cm). Depot leuprolide pretreatment for 2-6 months resulted in 40-60% shrinkage. Seventy-five patients 35-50 years old with symptomatic myomas, pain and pressure then underwent Nd:YAG laser coagulation for thorough devascularization of uterine myomas. Postoperative transvaginal ultrasound one, three and six months later showed the myomas reduced an average of 50-70% beyond the effect attributable to leuprolide. In two groups of patients whose myomas measured 5-10 cm and 3-5 cm after leuprolide pretreatment, laser coagulation subsequently reduced the myomas an average of 50%. In patients with postleuprolide myomas of 2-3 cm, virtually no myomas were identified postoperatively. The patients were followed up to 14 months. This laparoscopic procedure can be used in patients approaching menopause who wish to avoid abdominal myomectomy or hysterectomy.

Topics: Adult; Delayed-Action Preparations; Female; Humans; Laparoscopy; Laser Therapy; Leiomyoma; Leuprolide; Middle Aged; Treatment Outcome; Uterine Neoplasms

In 1988 and 1989, 67 women (mean age, 36.7 years) underwent myomectomy to remove uterine fibroids; selection of the procedure was based on the presence of symptoms and the patient's desire to avoid hysterectomy. For 8 weeks before myomectomy, 48 patients with a uterine size greater than or equal to 16 weeks' gestation received the gonadotropin releasing hormone (GnRH) analog leuprolide acetate, 0.5 mg self-administered daily by subcutaneous injection or 3.75 mg as the depot form every 28 days by intramuscular injection; the remaining 19 patients were used for a comparison. In the leuprolide-treated patients, the mean uterine size and mean number of fibroids removed per patient were significantly higher, and the mean postoperative hemoglobin concentration was significantly lower than in the non-leuprolide-treated group. The mean estimated blood loss and mean length of hospital stay were equivalent for the two groups. Eight patients (12%), all but one in the leuprolide-treated group, developed postoperative complications, primarily infections that were treated successfully with antibiotics; one patient, the only one undergoing a repeat myomectomy, experienced pelvic hematoma, infection and pelvic thrombophlebitis. There were no significant adverse reactions attributable to leuprolide administration.

Topics: Adult; Blood Loss, Surgical; Combined Modality Therapy; Female; Humans; Leiomyoma; Length of Stay; Leuprolide; Middle Aged; Postoperative Complications; Premedication; Treatment Outcome; Uterine Neoplasms

The indications for operative laparoscopy have expanded greatly over the past decades, as its many advantages over laparotomy have been recognized. We report our techniques and short-term results concerning myomectomy by laparoscopy. From January 1, 1990 to October 1, 1991, 147 intraperitoneal myomectomies were performed in 70 patients: 46 of 70 were treated preoperatively with a depot gonadotrophin-releasing hormone agonist. No complications were observed. In selected cases, with the advantages of laparoscopic surgery, laparoscopic myomectomy appears to be a safe technique.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leiomyoma; Leuprolide; Premedication; Suture Techniques; Triptorelin Pamoate; Uterine Neoplasms

Twenty-five non-menopausal women with uterine myomas were treated with LHRH-analogues for 3-6 months. An average reduction of 40% in uterine volume was observed. One patient refused to complete her therapy, three had no more menses after the interruption of treatment, nine underwent myomectomy within four weeks of their final administration, while in 12 cases hysterectomy was performed. In all cases the decrease in uterine volume induced by the analogue allowed a more limited intervention and prevented excessive blood loss.

Topics: Administration, Inhalation; Adult; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Chemotherapy, Adjuvant; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Injections, Intramuscular; Leiomyoma; Leuprolide; Luteinizing Hormone; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

Gonadotropin releasing hormone analogs (GnRHa) have been used to induce a reduction in the size of leiomyomas of the uterus after three to six months of therapy. However, none of the studies have noted a significant decrease in size by the first month. Additionally, the results of two reports have suggested long term therapy with GnRHa induced significant aberrations of serum lipoproteins. To evaluate whether or not analog treatment for a short course (two months) would be efficacious, 27 patients with leiomyomas documented by examination of the pelvic area and vaginal ultrasound, who desired to preserve reproductive potential, had myomectomies two and one-half months after commencing depot leuprolide acetate therapy. The reduction in size of the uterus was 35 percent by the first month and the average reduction in the total volume was 44 percent after two months of treatment (474 +/- 364 to 265 +/- 173 milliliters; p less than 0.01). Furthermore, the size of the uterus, determined by examination, decreased significantly from 13.6 +/- 4.0 weeks initially to 10.1 +/- 3.0 weeks preoperatively (p less than 0.0001). Estradiol levels became menopausal by one month of therapy and remained suppressed preoperatively. Menopausal symptoms were well tolerated. Cholesterol, high density lipoprotein, extremely low density lipoprotein and triglyceride levels were not altered by analog treatment, although low density lipoprotein increased from 117 to 130 milligrams per deciliter. A short course of depot leuprolide acetate reduced the size of leiomyomas and surgical tissue planes were preserved, facilitating removal of leiomyomas, and furthermore, there was no significant clinical alteration in lipoprotein or triglyceride levels.

Topics: Adult; Chemotherapy, Adjuvant; Female; Humans; Leiomyoma; Leuprolide; Lipoproteins; Triglycerides; Uterine Neoplasms

The administration of GnRH-a for decreasing the size of uterine leiomyomata is tolerated by most of our patients with a minimum of side effects and difficulty. An unusual case of pseudo-Meigs' syndrome developed after a single dose of depot LA that resulted in an emergent operation in this young woman. The treatment of large leiomyomata uteri with GnRH-a warrants careful clinical surveillance.

Topics: Adult; Ascites; Ascitic Fluid; Female; Humans; Leiomyoma; Leuprolide; Organ Size; Uterine Neoplasms; Uterus

A retrospective analysis of 104 women with leiomyomata uteri treated with LA for at least 12 weeks demonstrated a negative correlation between the percent reduction in uterine volume and serum E2 concentration at treatment week 12. The patient's age, height, or pretreatment uterine volume were not correlated with the degree of uterine shrinkage.

Topics: Adult; Estradiol; Female; Humans; Leiomyoma; Leuprolide; Middle Aged; Uterine Neoplasms; Uterus

Acute vaginal bleeding secondary to uterine myomas can be a devastating event. We report the use of a combined therapeutic approach in a patient who presented with protracted bleeding of a myomatous uterus that was equivalent in size to a 38 week gestation. This patient's course was further complicated by her refusal of blood or blood products.

Topics: Acute Disease; Adult; Anemia; Combined Modality Therapy; Contraceptives, Oral, Synthetic; Drug Therapy, Combination; Estrogens, Conjugated (USP); Female; Hematocrit; Humans; Injections, Subcutaneous; Leiomyoma; Leuprolide; Preoperative Care; Tampons, Surgical; Time Factors; Treatment Refusal; Uterine Hemorrhage; Uterine Neoplasms

The gynecologic resectoscope, recently approved by the Food and Drug Administration for the treatment of abnormal uterine bleeding, was evaluated for its success in the treatment of women with this complaint. Through June 1990, 216 patients were treated with this modality. Ninety were treated with transcervical myomectomy alone since they still desired fertility preservation or wished to avoid hysterectomy. Of the patients treated, 189 (87.5%) had follow-up evaluation for at least three months and some as long as three years. Of the ninety patients treated with resection of a submucous myoma, greater than 90% had a marked improvement in their symptoms, with decreased menstrual bleeding. Of the 96 patients treated with endometrial ablation, 50% were amenorrheic, 26% had hypomenorrhea, 17% had eumenorrhea, and 7% were unimproved. There was only one case of fluid overload, and no patients required a blood transfusion. Complications included two cases of endometritis and one perforation at the time of retrieval of myoma fragments. Four patients required placement of a 30-mL Foley catheter for control of postoperative bleeding. Gynecologic resectoscopy is a safe and effective alternative to major surgery in the management of abnormal uterine bleeding for which conservative measures have not been effective.

Topics: Adult; Aged; Amenorrhea; Antineoplastic Agents; Catheterization; Danazol; Electrocoagulation; Endometrium; Female; Humans; Hysteroscopes; Leiomyoma; Leuprolide; Medroxyprogesterone; Medroxyprogesterone Acetate; Menstruation Disturbances; Middle Aged; Uterine Neoplasms; Uterus

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

Two cases are reported in which MRI was used to monitor the preoperative response of leiomyomata uteri to gonadotropin releasing hormone agonist therapy. The uterus was measured in the cephalocaudad, anterior-posterior, and transverse planes by MRI images. All uterine dimensions decreased in size after leuprolide therapy. One patient ultimately chose leuprolide therapy alone for control of her symptoms while a second patient had four myomas surgically removed after leuprolide therapy. MRI proved to be a good modality to monitor response to leuprolide therapy and assist in the management of these patients.

Topics: Adult; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Uterine Neoplasms; Uterus

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

Recurrence of heavy vaginal bleeding and massive necrosis of a uterine leiomyosarcoma are reported in a 41-year-old female who was being treated with GnRH-a for a presumed uterine fibroid. The pathogenic mechanisms of such an event are reviewed and discussed in light of the available literature on the subject of GnRH-a and the treatment of uterine smooth muscle neoplasms.

Topics: Adult; Female; Humans; Leiomyosarcoma; Leuprolide; Necrosis; Uterine Hemorrhage; 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

Gonadotropin releasing hormone agonists are often used in the management of myomas in an attempt to decrease both the myoma and uterine volume. This therapy in a woman with submucous myomas resulted in profuse vaginal bleeding requiring a transfusion and myomectomy.

Topics: Adult; Blood Transfusion; Female; Humans; Leiomyoma; Leuprolide; Uterine Hemorrhage; Uterine Neoplasms

We present a case of a 46-year-old woman evaluated for abnormal uterine bleeding and an enlarged uterus, with normal endometrial sampling. Three months of leuprolide acetate injections resulted in a nonenlarging uterus and resolution of iron deficiency anemia and menorrhagia. Intraoperative examination suggested leiomyosarcoma, which was confirmed by postoperative permanent histologic sections. Residual uterine sarcomatous disease was confirmed on reexploration. Similar cases will continue to raise arguments against conservative hormonal intervention in the perimenopausal woman with an enlarged uterus. As the gynecologist gains familiarity with the use of gonadotropin-releasing hormone analogue therapy in the treatment of myomatous uteri, the criteria for hysterectomy will become less rigid and the potential for delay in the diagnosis and treatment of sarcomatous disease will become more common. Physicians must be cognizant of this potential complication of conservative therapy of leiomyomata uteri.

Topics: Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyosarcoma; Leuprolide; Middle Aged; Uterine Neoplasms

Topics: Female; Gonadotropin-Releasing Hormone; Hemorrhage; Humans; Leuprolide; Myoma; Uterine Neoplasms

Several studies have shown a decrease in uterine and/or leiomyoma volume when treated with leuprolide acetate (LA), a widely used gonadotropin-releasing hormone agonist. The mechanism by which these changes occur is unknown. In this study, the histopathological slides of 31 women of reproductive age who underwent hysterectomy or myomectomy were blindly reviewed by a pathologist. Seventeen women underwent myomectomy. Among those, 10 were treated with LA. The tumors in all of these patients were reduced in size after therapy. Histopathologically, the LA treatment correlated with a significant reduction in cellularity. No significant change in fibrosis, edema, or mitotic activity was seen.

Topics: Adult; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leiomyoma; Leuprolide; Magnetic Resonance Imaging; Muscle, Smooth; Retrospective Studies; Uterine Neoplasms

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

Topics: Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms

Topics: Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Uterine Neoplasms; Uterus

Three cases of heavy vaginal bleeding during leuprolide acetate therapy for leiomyomata are reported. In all cases, acute anemia developed, necessitating blood transfusions and emergency myomectomies. Pathologic diagnoses demonstrated hyaline degeneration of submucous fibroids in each instance.

Topics: Adult; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Menorrhagia; Uterine Neoplasms

Five premenopausal women with leiomyomata uteri were treated with leuprolide for 3 months and demonstrated a reduction in mean uterine volume of 49%. Cyclic conjugated equine estrogens and MPA were added to leuprolide therapy during the ensuing 24 months, with no significant changes in mean uterine volume or peripheral bone density.

Topics: Bone and Bones; Climacteric; Drug Administration Schedule; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Pilot Projects; Ultrasonography; Uterine Neoplasms; Uterus