goserelin and Endometriosis

Goserelin acetate is a gonadotropin-releasing hormone analog that is commonly used in patients with prostate cancer, endometriosis, and precocious puberty. The side effects of the drug include allergic rash, flushing, excessive sweating, skin swelling at the injection site, sexual dysfunction, erectile dysfunction, and menopausal symptoms. However, erythema nodosum has so far not been reported. In this paper, we have presented the case of erythema nodosum caused by goserelin acetate and a review of the literature on its adverse effects, thus providing useful insights into clinical management and medication safety.

Topics: Delayed-Action Preparations; Endometriosis; Erythema Nodosum; Female; Goserelin; Humans; Male

Endometriosis is associated with pain and infertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy.. To assess the effectiveness and safety of laparoscopic surgery in the treatment of pain and infertility associated with endometriosis.. This review has drawn on the search strategy developed by the Cochrane Gynaecology and Fertility Group including searching the Cochrane Gynaecology and Fertility Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, reference lists for relevant trials, and trial registries from inception to April 2020.. We selected randomised controlled trials (RCTs) that compared the effectiveness and safety of laparoscopic surgery with any other laparoscopic or robotic intervention, holistic or medical treatment, or diagnostic laparoscopy only.. Two review authors independently performed selection of studies, assessment of trial quality and extraction of relevant data with disagreements resolved by a third review author. We collected data for the core outcome set for endometriosis. Primary outcomes included overall pain and live birth. We evaluated the quality of evidence using GRADE methods.. We included 14 RCTs. The studies randomised 1563 women with endometriosis. Four RCTs compared laparoscopic ablation or excision with diagnostic laparoscopy only. Two RCTs compared laparoscopic excision with diagnostic laparoscopy only. One RCT compared laparoscopic ablation or excision with laparoscopic ablation or excision and uterine suspension. Two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only. One RCT compared laparoscopic ablation with diagnostic laparoscopy and gonadotropin-releasing hormone (GnRH) analogues. Two RCTs compared laparoscopic ablation with laparoscopic excision. One RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy. One RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep endometriosis infiltrating the rectum. Common limitations in the primary studies included lack of clearly described blinding, failure to fully describe methods of randomisation and allocation concealment, and poor reporting of outcome data. Laparoscopic treatment versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic treatment on overall pain scores compared to diagnostic laparoscopy only at six months (mean difference (MD) 0.90, 95% confidence interval (CI) 0.31 to 1.49; 1 RCT, 16 participants; very low quality evidence) and at 12 months (MD 1.65, 95% CI 1.11 to 2.19; 1 RCT, 16 participants; very low quality evidence), where a positive value means pain relief (the higher the score, the more pain relief) and a negative value reflects pain increase (the lower the score, the worse the increase in pain). No studies looked at live birth. We are uncertain of the effect of laparoscopic treatment on quality of life compared to diagnostic laparoscopy only: EuroQol-5D index summary at six months (MD 0.03, 95% CI -0.12 to 0.18; 1 RCT, 39 participants; low quality evidence), 12-item Short Form (SF-12) mental health component (MD 2.30, 95% CI -4.50 to 9.10; 1 RCT, 39 participants; low quality evidence) and SF-12 physical health component (MD 2.70, 95% CI -2.90 to 8.30; 1 RCT, 39 participants; low quality evidence). Laparoscopic treatment probably improves viable intrauterine pregnancy rate compared to diagnostic laparoscopy only (odds ratio (OR) 1.89, 95% CI 1.25 to 2.86; 3 RCTs, 528 participants; I. Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. No data were reported on live birth. There is moderate quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only. No studies were found that looked at live birth for any of the comparisons. Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

Topics: Antineoplastic Agents, Hormonal; Denervation; Electrocoagulation; Endometriosis; Female; Goserelin; Helium; Humans; Infertility, Female; Laparoscopy; Pelvic Pain; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Uterus

Endometriosis is a common gynaecological condition which affects many women of reproductive age worldwide and is a major cause of pain and infertility. The combined oral contraceptive pill (COCP) is widely used to treat pain occurring as a result of endometriosis, although the evidence for its efficacy is limited.. To determine the effectiveness, safety and cost-effectiveness of oral contraceptive preparations in the treatment of painful symptoms ascribed to the diagnosis of laparoscopically proven endometriosis.. We searched the following from inception to 19 October 2017: the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane CENTRAL Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial registers ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform (WHO ICTRP). We also handsearched reference lists of relevant trials and systematic reviews retrieved by the search.. We included randomised controlled trials (RCT) of the use of COCPs in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis that had been made visually at a surgical procedure.. Two review authors independently assessed study quality and extracted data. One review author was an expert in the content matter. We contacted study authors for additional information. The primary outcome was self-reported pain (dysmenorrhoea) at the end of treatment.. Five trials (612 women) met the inclusion criteria. Only three trials (404 women) provided data that were suitable for analysis.Combined oral contraceptive pill versus placeboTwo trials compared COCP with a placebo. These studies were at high risk of bias. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence very low. Evidence was downgraded for imprecision as it was based on a single, small trial and for the visual analogue scale data there were wide confidence intervals (CIs). There appeared to have been substantial involvement of the pharmaceutical company funding the trials.Treatment with the COCP was associated with an improvement in self-reported pain at the end of treatment as evidenced by a lower score on the Dysmenorrhoea verbal rating scale (scale 0 to 3) compared with placebo (mean difference (MD) -1.30 points, 95% CI -1.84 to -0.76; 1 RCT, 96 women; very low quality evidence), a lower score on the Dysmenorrhoea visual analogue scale (no details of scale) compared with placebo (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women; very low quality evidence) and a reduction in menstrual pain from baseline to the end of treatment (MD 2.10 points, 95% CI 1.38 to 2.82; 1 RCT, 169 women; very low quality evidence).Combined oral contraceptive pill versus medical therapiesOne underpowered trial compared the COCP with another medical treatment (goserelin). The study was at high risk of bias; the trial was unblinded and there was insufficient detail to judge allocation concealment and randomisation. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence ranged from low to very low.At the end of treatment, the women in the goserelin group were amenorrhoeic and therefore no comparisons could be made between the groups for the primary outcome. At six months' follow-up, there was no clear evidence of a difference between women treated with the COCP and women treated with goserelin for measures of dysmenorrhoea on a visual analogue scale (scale 1 to 10) (MD -0.10, 95% CI -1.28 to 1.08; 1 RCT, 50 women; very low quality evidence) or a verbal rating scale (scale 0 to 3) (MD -0.10, 95% CI -0.99 to 0.79; 1 RCT, 50 women; very low quality evidence). At six months' follow-up, there was no clear evidence of a difference between the COCP and goserelin groups for reporting complete absence of pain as measured by the visual analogue scale (risk ratio (. Based on the limited evidence from two trials at high risk of bias and limited data for the prespecified outcomes for this review, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with placebo and the findings cannot be generalised.Based on the limited evidence from one small trial that was at high risk of bias, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with other medical treatments. Only one comparison was possible, with the medical intervention being goserelin, and the findings cannot be generalised.Further research is needed to fully evaluate the role of COCPs in managing pain-related symptoms associated with endometriosis. There are other formulations of the combined hormonal contraception such as the transdermal patch, vaginal ring or combined injectable contraceptives which this review did not cover but should be considered in future updates.

Topics: Contraceptives, Oral; Dysmenorrhea; Endometriosis; Female; Goserelin; Humans; Pelvic Pain; Randomized Controlled Trials as Topic

Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity and is associated with pain and subfertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy.. To assess the effectiveness and safety of laparoscopic surgery in the treatment of painful symptoms and subfertility associated with endometriosis.. This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group including searching CENTRAL, MEDLINE, EMBASE, PsycINFO, and trial registries from inception to July 2013.. Randomised controlled trials (RCTs) were selected in which the effectiveness and safety of laparoscopic surgery used to treat pain or subfertility associated with endometriosis was compared with any other laparoscopic or robotic intervention, holistic or medical treatment or diagnostic laparoscopy only.. Selection of studies, assessment of trial quality and extraction of relevant data were performed independently by two review authors with disagreements resolved by a third review author. The quality of evidence was evaluated using GRADE methods.. Ten RCTs were included in the review. The studies randomised 973 participants experiencing pain or subfertility associated with endometriosis. Five RCTs compared laparoscopic ablation or excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus ablation. One RCT compared laparoscopic ablation versus diagnostic laparoscopy and injectable gonadotropin-releasing hormone analogue (GnRHa) (goserelin) with add-back therapy. Common limitations in the primary studies included lack of clearly-described blinding, failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias.Laparoscopic surgery was associated with decreased overall pain (measured as 'pain better or improved') compared with diagnostic laparoscopy, both at six months (odds ratio (OR) 6.58, 95% CI 3.31 to 13.10, 3 RCTs, 171 participants, I(2) = 0%, moderate quality evidence) and at 12 months (OR 10.00, 95% CI 3.21 to 31.17, 1 RCT, 69 participants, low quality evidence). Compared with diagnostic laparoscopy, laparoscopic surgery was also associated with an increased live birth or ongoing pregnancy rate (OR 1.94, 95% CI 1.20 to 3.16, P = 0.007, 2 RCTs, 382 participants, I(2) = 0%, moderate quality evidence) and increased clinical pregnancy rate (OR 1.89, 95% CI 1.25 to 2.86, P = 0.003, 3 RCTs, 528 participants, I(2) = 0%, moderate quality evidence). Two studies collected data on adverse events (including infection, vascular and visceral injury and conversion to laparotomy) and reported no events in either arm. Other studies did not report this outcome. The similar effect of laparoscopic surgery and diagnostic laparotomy on the rate of miscarriage per pregnancy was imprecise (OR 0.94, 95% CI 0.35 to 2.54, 2 studies, 112 women, moderate quality evidence).When laparoscopic ablation was compared with diagnostic laparoscopy plus medical therapy (GnRHa plus add-back therapy), more women in the ablation group reported that they were pain free at 12 months (OR 5.63, 95% CI 1.18 to 26.85, 1 RCT, 35 participants, low quality evidence).The difference between laparoscopic ablation and laparoscopic excision in the proportion of women reporting overall pain relief at 12 months on a VAS 0 to 10 pain scale was 0 (95% CI -1.22 to 1.22, P = 1.00, 1 RCT, 103 participants, low quality evidence).. There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis reduces overall pain and increases live birth or ongoing pregnancy rates. There is low quality evidence that laparoscopic excision and ablation were similarly effective in relieving pain, although there was only one relevant study. More research is needed considering severe endometriosis, different types of pain associated with endometriosis (for example dysmenorrhoea (pain with menstruation)) and comparing laparoscopic interventions with holistic and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

Topics: Antineoplastic Agents, Hormonal; Endometriosis; Female; Goserelin; Humans; Infertility, Female; Laparoscopy; Pelvic Pain; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic

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

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

Topics: Adjuvants, Pharmaceutic; Adult; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Premenstrual Syndrome; Uterine Hemorrhage

To review the evidence that add-back hormone replacement therapy (HRT) can ameliorate the metabolic consequences of gonadotropin-releasing hormone (GnRH) agonist treatment in women with symptomatic endometriosis.. A review of relevant literature.. Early studies suggested that add-back HRT maintained bone mineral density (BMD) without reducing the symptomatic benefit of GnRH treatment. Both high-dose progestogen and low dose progestogen plus cyclical etidronate are effective in maintaining BMD. Standard and low dose HRT add-back may be more effective in relieving the hypo-estrogenic side-effects of GnRH agonist therapy. Randomized controlled studies have shown that both low-dose and standard-dose add-back HRT reduce the side-effects of GnRH agonist therapy, and that this benefit extends to 12 months of treatment.. GnRH agonist treatment with add-back HRT seems to offer the hope of improved treatment for women with endometriosis, but the optimum treatment duration and time to start HRT have yet to be defined.

Topics: Bone Density; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormone Replacement Therapy; Humans

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

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

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

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

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

Topics: Danazol; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The management of women with endometriosis is complex and necessitates individualization of patient care. The most commonly used medical therapies are danazol, GnRH agonists, medroxyprogesterone acetate and gestrinone. Studies to date have shown these drugs to have equal efficacy in terms of reduction in laparoscopic score and relief of symptoms. However, their side-effects make them unsuitable for long-term use. The addition of low dose hormone replacement therapy to GnRH agonist regimens may allow prolonged use but the current cost of these agents is high. Low dose oral contraceptive pills deserve further investigation. The role of medical treatment for women with endometriosis and infertility is controversial. There is no place for hormonal therapy in such women with stage I or II disease. When expectant management fails, gamete intrafallopian transfer offers excellent results. For those with stage III or IV disease, surgery is preferable with adjunctive medical therapy in selected cases. If pregnancy does not ensue, in vitro fertilization and embryo transfer are the next line of management, and results are optimized by prior medical therapy and aspiration of endometriomas. Major advances have been made in the medical management of endometriosis. However, current treatment strategies are ineffective in eliminating the disease in most women. New approaches are required in both basic and clinical research in order to finally eradicate this often devastating disease.

Topics: Danazol; Endometriosis; Estrogens; Female; Gestrinone; Goserelin; Humans; Infertility, Female; Laparoscopy; Medroxyprogesterone Acetate; Menopause; Pelvic Pain; Pregnancy; Pregnancy Outcome; Reproductive Techniques; Severity of Illness Index; Treatment Outcome

Topics: Buserelin; Endometriosis; Female; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.

Topics: Animals; Breast Neoplasms; Buserelin; Drug Evaluation; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Goserelin; Humans; Leiomyoma; Male; Menstruation Disturbances; Polycystic Ovary Syndrome; Prostatic Neoplasms; Uterine Neoplasms

Although there are various hormone therapies, including gonadotropin-releasing hormone agonist, danazol, levonorgestrel-releasing intrauterine system, dienogest, and low-dose estrogen progestin, no consensus opinion has been reached in terms of which medication should be used and for how long it should be administered. We aimed to determine whether dienogest or goserelin is the better postoperative therapy to prevent recurrence of endometriosis.. A prospective cohort randomized study were conducted, including 198 patients diagnosed as having endometriosis. A total of 111 patients were randomly assigned into two groups: the dienogest-administered group (n = 56) and the goserelin-administered group (n = 55). Patients were followed for 24 months after laparoscopic surgery. Those who gave consent but desired no postoperative therapy were assigned to the non-treatment group (n = 79). Recurrence, side-effects, degrees of menstrual pain and chronic pelvic pain measured by the Visual Analogue Scale were compared among the three groups: the dienogest, goserelin, and non-treatment groups.. No significant difference was observed in the postoperative recurrence rate between the dienogest and goserelin groups. No significant difference was found in the recurrence rate between the goserelin group and non-treatment group; however, a significant difference was found in the recurrence rate between the dienogest group and the non-treatment group (P = 0.027). Menstrual pain and chronic pelvic pain were significantly improved in both treatment groups. Side-effects were markedly observed in the goserelin group as compared with the dienogest group.. Dienogest is available for prolonged administration of more than 6 months, so it is more useful than goserelin, which is available only for short-term administration.

Topics: Adult; Conservative Treatment; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormone Antagonists; Humans; Nandrolone; Pain; Postoperative Care; Prospective Studies; Recurrence; Secondary Prevention

As a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment.. Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded.. (1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4 th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8 th and 12 th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05). (4) The posttherapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly in all the three groups (P < 0.05). After therapy, serum E2 level in Tibolone group was obviously higher than the other two groups (P < 0.05), while FSH and LH levels were obviously lower (P < 0.05). (5) The incidence of vaginal bleeding, breast distending pain in Tibolne group was obviously higher than Kuntai group (P < 0. 05).. Kuntai capsule is effective on the peri-menopausal symptoms induced by postoperative GnRH-a administration to EMS patients, although its clinical effect might be a few weeks later than Tibolone. Kuntai capsule might be a little safer than Tibolone tablet.

Topics: Adult; Double-Blind Method; Drugs, Chinese Herbal; Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Norpregnenes; Young Adult

Seventy patients with stage III or IV endometriosis were randomly assigned to 2 groups after conservative surgery. Group O (n = 35) received 3 cycles of a 28-day gonadotropin-releasing hormone agonist (GnRH-a) treatment (goserelin, 3.6 mg) starting 3-5 days postoperatively. Group M (n = 35) received the same treatment starting on days 1-5 of menstruation. Groups were further subdivided according to add-back treatment. Pre- and posttreated levels of estradiol (E2 ), follicle stimulating hormone (FSH), and luteinizing hormone (LH) and visual analog scale (VAS), Kupperman menopausal index (KMI), and bone mineral density (BMD) scores were recorded. The incidence of uterine bleeding was assessed. In both groups, serum levels of E2 , FSH, and LH and VAS scores decreased significantly after treatment. Spotting was the most frequent bleeding pattern. During cycle 1, the bleeding time in group M was much longer that than that in group O (P =.001), and the bleeding rate in group M was significantly higher than that in group O (P =.024, RR = 1.185). In patients with stage III or IV endometriosis, the efficacy of GnRH-a initiated 3-5 days postoperatively was equivalent to that of GnRH-a initiated on days 1-5 of menstruation. Female patients who initiated GnRH-a treatment 3-5 days postoperatively experienced less uterine bleeding during the first cycle of treatment.

Topics: Adult; Drug Administration Schedule; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Menstruation; Middle Aged; Postoperative Period; Uterine Hemorrhage; Young Adult

The testing represented a prospective study that was performed at the Gynaecology and Obstetrics Clinic "Narodni Front" in Belgrade during a two-year period. The study encompassed female patients with ovarian endometrioma operated with laparoscopic surgery. The research objective was to determine the percentage of occurrence of relapses in patients operated for endometriosis of the ovary in relation to the stage of the disease and the type of performed operation, and which were receiving suppressive therapy with gonadotropin-releasing hormone (GnRH) analogues after the surgery compared to those who were not receiving suppressive therapy after the operation.. The recurrence of endometriosis on the ovary of the test and control groups was monitored during the first year after surgery. In all patients ultrasound checks were done every month during the first six months after surgery, and then every three months for the next six months. In all patients in whom the recurrence, i.e. endometrioma on the ovary larger than three cm was revealed postoperatively by ultrasound, the laparoscopic removal of the endometrioma was performed again as well as the histopathological examination of the material.. There was no statistically significant difference in the distribution of recurrence of endometriosis between the groups formed according to the type of surgical technique (cystectomy or cystotomy). The recurrence of endometriosis occurred later in the group of patients in which the treatment GnRH analogues was applied after the surgical treatment. The recurrence of endometriosis in more severe stages (Stage III and IV) occurs later in the group of patients in which the treatment GnRH analogues is applied after the surgical treatment.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Gynecologic Surgical Procedures; Humans; Laparoscopy; Middle Aged; Ovarian Diseases; Ovary; Pregnancy; Prospective Studies; Recurrence; Treatment Outcome; Triptorelin Pamoate; Young Adult

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

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

To compare the efficacy of aromatase inhibitor vs. gonadotrophin-releasing hormone agonists in treating premenopausal women with uterine adenomyosis.. A prospective randomized controlled study.. A university hospital and a private practice setting.. Thirty-two patients with uterine adenomyosis.. Patients were randomly allocated to receive oral letrozole (2.5 mg/day) or a subcutaneous gonadotropin-releasing hormone agonist (goserelin, 3.6 mg) for 12 weeks. Uterine and adenomyoma volumes were determined at baseline and during treatment at four, eight and 12 weeks.. Measurements were performed at baseline and during treatment at four, eight 8 and 12 weeks, and mean values were calculated. Symptoms at the start and after 12 weeks were evaluated.. No significant differences in the total uterine size between the post treatment uterine volumes in the two groups (20.1, 15.4 and 13.0 cm(3) vs. 21.7, 15.1 and 11.7 cm(3) , at four, eight and 12 weeks, respectively). Total adenomyoma volume decreased by 8.6, 29.7 and 40.9% vs. 5.7, 34.6 and 49.1% after four, eight and 12 weeks of treatment, in group A and B, respectively. Two patients became pregnant in group A during treatment.. Aromatase inhibitors are as effective as gonadotropin-releasing hormone agonists in reducing adenomyoma volume and improving symptoms.

Topics: Administration, Oral; Adolescent; Adult; Aromatase Inhibitors; Drug Administration Schedule; Endometriosis; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Subcutaneous; Letrozole; Nitriles; Premenopause; Single-Blind Method; Treatment Outcome; Triazoles; Uterine Diseases; Young Adult

To compare efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena) with depot GnRH analogue (GnRH-a; gosareline acetate; Zoladex) on endometriosis-related chronic pelvic pain (CPP) in patients with severe endometriosis during 12 months.. Prospective, randomized, controlled study.. The reproductive endocrinology unit of a tertiary, research and education hospital.. Forty women with severe endometriosis (revised The American Fertility Society [AFS] classification >40) and endometriosis-related CPP and control groups were enrolled in the study.. The patients were treated with either LNG-IUS (n = 20) or GnRH-a (n = 20). The GnRH-a dose was repeated every 4 weeks for 24 weeks.. Scores of CPP were evaluated using a visual analogue scale (VAS) and total endometriosis severity profile (TESP).. The TESP score decreased in the LNG-IUS group at first, third, and sixth month follow-up visits, whereas at the 12th month follow-up visit, the TESP scores were increased to values similar to pretreatment values. Although the VAS score had no significant alteration during the follow-up period in the LNG-IUS group, the GnRH-a group showed a significant decrease in the VAS score and TESP score at the end of 1 year. The LNG-IUS treatment showed a lower patient satisfaction.. Both treatment modalities showed comparable effectiveness in the treatment of CPP-related endometriosis.

Topics: Adult; Chronic Disease; Delayed-Action Preparations; Endometriosis; Female; Fertility Agents, Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Gynecologic Surgical Procedures; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Pain, Postoperative; Pelvic Pain; Treatment Outcome; Uterine Diseases

To compare clinical effect of gonadotropin releasing hormone agonist (GnRH-a) alone and GnRH-a combined with low-dose dydrogesteronea and estradiol valerate on sex hormone, hypoestrogenic symptoms, quality of life and bone mineral density (BMD) in treatment of endometriosis.. Seventy patients with moderate or severe endometriosis, who were diagnosed by laparotomy or laparoscopic surgery within two months, were randomly assigned into two groups. 35 patients in GnRH-a group were treated by goserelin (3.6 mg) for three months, and 35 patients in add-back group were treated by goserelin (3.6 mg) combined with estradiol valerate 0.5 mg and dydrogesteronea 5 mg daily. Before and after the treatment, clinical parameters were recorded and analyzed, including visual analog scale (VAS), medical outcomes survey short form 36 (SF-36), Kupperman menopausal index (KMI), BMD, the serum level of follicle stimulating hormone (FSH), estradiol (E2) and bone gla-protein (BGP). The first menstruation and VAS were also followed up after treatment.. Every 3 cases in two groups lost follow-up. (1) Reproductive hormone: the level of E2 in add-back group [(94+/-71) pmol/L] was significantly higher than (54+/-52) pmol/L in GnRH-a group (P<0.01). The level of FSH in add-back group [(3.0+/-1.9) U/L] was significantly lower than (5.7+/-2.9) U/L in GnRH-a group (P<0.05). (2) VAS: after treatment, VAS in both group decreased significantly when compared with that before treatment (P<0.05), and remained until menstruated. (3) KMI: KMI in add back-group (10+/-8)was significantly lower than (14+/-6) in GnRH-a group (P<0.05). (4) BMD: compared with that before treatment, BMD decreased significantly after treatment in GnRH-a group (P<0.05), no remarkable difference of BMD was observed before and after treatment in add-back group. Before treatment, serum BGP in both groups did not show statistical difference. After treatment, the level of BGP in GnRH-a group [(7932+/-5206) ng/L] was significantly higher than (5419+/-2917) ng/L in add-back group (P<0.05).. GnRH-a combined with estrogen-progesterone regimen could relieve pain from endometriosis as effectively as GnRH-a alone and reduce hypoestrogenic symptoms and bone loss. Therefore, it is a safe and effective treatment.

Topics: Adolescent; Adult; Bone Density; Drug Administration Schedule; Dydrogesterone; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Osteocalcin; Pain; Quality of Life; Severity of Illness Index; Treatment Outcome; Young Adult

The key enzyme in the biosynthesis of estradiol, aromatase, has been demonstrated within endometriosis. Combined administration of aromatase inhibitor and GnRH-agonist may efficiently suppress estrogen biosynthesis through a combined pituitary, ovarian, peripheral and "in situ" action. The aim of this study was to test the concept of combined down-regulation prior to IVF in patients with endometriomas.. Prospective pilot study in a university-based tertiary fertility clinic including 20 infertile patients with endometriomas undergoing IVF/ICSI. The patients received goserelin 3.6mg sc on treatment Days 1, 28 and 56, and one daily tablet of anastrozole 1mg from Day 1 to Day 69. Controlled ovarian stimulation was initiated from Day 70. Outcome measures were change in endometriomal volume and serum CA125 during down-regulation, standard IVF parameters including pregnancy and delivery rate, and endocrine response. The paired T test and Wilcoxon Signed Rank test were used to analyse paired differences.. During the combined down-regulation, the endometriomal volume and the serum CA125 level decreased by 29% (3-39%) and 61% (21-74%), respectively (median (95%CI), P=0.007 and P=0.001). In the IVF/ICSI cycle, the number of oocytes retrieved was 7.5 (6.0-10.0) and the fertilization rate was 0.78 (0.38-1.0). Nine patients (45%) conceived, five (25%) had a clinical pregnancy, and three (15%) delivered healthy children (two singletons and one twin).. Prolonged combined anastrozole and goserelin down-regulation significantly reduces endometriomal volume and serum CA125, and is compatible with IVF pregnancy and delivery. However, a high pregnancy loss was noted.

Topics: Adult; Anastrozole; Aromatase Inhibitors; CA-125 Antigen; Down-Regulation; Drug Therapy, Combination; Endometriosis; Estrogens; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Goserelin; Humans; Nitriles; Pilot Projects; Pregnancy; Pregnancy Outcome; Prospective Studies; Triazoles; Uterine Diseases

To evaluate effects and safety of gonadotrophin-releasing hormone agonist (GnRH-a) combined with transdermal estradiol and medroxyprogesterone acetate in the treatment of endometriosis.. From January 1st, 2007 to July 31st, 2007, 28 endometriosis patients underwent laparoscopic or transabdominal surgery in Obstetrics and Gynecology Hospital affiliated to Fudan University were randomly divided into group A and group B. 14 patients in group A received 3.6 mg goserelin once every 4 weeks, 12 weeks in all. 14 patients in group B received goserelin and added 1/2 piece of half-hydrate estradiol every week and 6 mg oral medroxyprogesterone acetate per day, 12 weeks in all. Serum estradiol (E2), follicle stimulating hormone (FSH), bone gla protein levels, visual analogue scale (VAS) of pain, bone mineral density of lumbar spine, vaginal exfoliate cell spurs and the form of Kupperman were compared in patients before and after treatment.. (1) After treatment, the level of FSH and E2 levels were (5.0 +/- 2.6) U/L and (29 +/- 17) pmol/L in group A and (3.0 +/- 1.5) U/L, and (87 +/- 53) pmol/L in group B, which were significantly lower than those before treatment [FSH (17.0 +/- 12.2) U/L, and E2 (184 +/- 194) pmol/L in group A and FSH: (15.3 +/- 13.6) U/L and E2: (281 +/- 242) pmol/L in group B, P < 0.01]. On the seventh day after three-month GnRH-a treatment, it was observed that the level of E2 was higher and FSH was lower in group B than the level of E2 and FSH of group A (P < 0.01). (2) After treatment, the basal vaginal exfoliate cell proportion in group A [(66.2 +/- 29.0)%] was significantly lower than that in group B [(11.8 +/- 28.0)%, P < 0.01]; while patients in group A owned a lower proportion of the middle [(29.1 +/- 23.1)%], superficial layers [(4.0 +/- 5.5)%] and esinophilic cells [(2.3 +/- 2.6)%] than patients group B [middle layer: (73.0 +/- 25.2)%; superficial layer: (15.2 +/- 10.9)%; esinophilic cells: (10.8 +/- 7.9)%; P < 0.01. (3) Before the treatment, patients'VAS scores of total, pelvic pain, dysmenorrheal and dyspareunia were 7.43 +/- 3.20, 2.35 +/- 1.82, 4.93 +/- 1.98 and 0.14 +/- 0.53 in group A and were 7.71 +/- 2.02, 2.57 +/- 1.60, 4.86 +/- 1.56 and 0.29 +/- 1.07 in group B; after treatment, the scores above were changed to 0. 14 +/- 0.36, 0.07 +/- 0.27, 0.07 +/- 0.27 and 0 in group A and 0.36 +/- 0.50, 0.29 +/- 0.47, 0.07 +/- 0.27 and 0 in group B, which were all significantly lower than those before treatment separately (P < 0.01). When menstruation recovered, the scores were 0.21 +/- 0.43, 0.07 +/- 0.27, 0.14 +/- 0.36, and 0 in group A and 0.50 +/- 0.65, 0.29 +/- 0.47, 0.21 +/- 0.43 and 0 in group B, which were also significantly lower than those before treatment (P < 0.01), however, no statistical difference was found between groups at any time spot (P > 0.05). (4) In group A, the bone density after treatment [(0.96 +/- 0.06) g/cm2] was lower than that before treatment [(0.99 +/- 0.06) g/cm2, P < 0.01)]. In group B, the index was (0.98 +/- 0.09) g/cm2, which was lower than that before treatment [(0.99 +/- 0.10) g/cm2, P = 0. 201]. No statistical difference was found between groups (P > 0.05). The bone loss rate were (-2.77 +/- 1.97)% in group A and (-0.93 +/- 2.86)% in group B (P = 0.058). Before treatment, the bone gla protein was (13 +/- 3) microg/L in group A and (13 +/- 6) microg/L in group B. After treatment, the bone gla protein levels was (17 +/- 6) microg. The add-back therapy that consists of an estradiol patch and oral medroxyprogesterone acetate is effective and safe treatment for endometriosis.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Calcitonin; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Medroxyprogesterone Acetate; Menstrual Cycle; Pain; Treatment Outcome

The study is prospective and involves 112 patients suffering from pelvic endometriosis aging from 19-38 years. (28.6 average age). The disease was diagnosed via laparoscopy and the stage was determined using the revised AFS classification. Zoladex (Goserelin depot--3.6 mg) is being applied every 28 days for 6 months in the hypodermic tissue of the front abdomen wall. All patients are being examined monthly after every Zoladex application (for subjective complaints--dysmenorrheal, dyspareunea, pelvic pain; serum estradyol-E2; amenorrhea; side effects) and every 24 months (recuperation of the menstrual cycle, pregnancy).. In 88% of the patients amenohrea is obsereved in the first eight weeks of therapy. The menstrual cycle takes an avarege of 68 (31-139) after the last Zoladex application to reappear. At the end of the first month after the first application the serum level of estradyol E2 is lowered to a menopause level (from 750-800 to 120-130 Pmol/L) and it remains as low till the end of the treatment. Eight weeks after the completion of the therapy it goes back to its normal values. During the course of the first month of amenorrhea condition a 38% fall in the level of complaints (dysmenorrheal, dyspareunea, pelvic pain) is observed. After the 6th month 88% of the patients have no complaints. Side effects observed during the course of treatment include warm waves, sweating, vaginal dehydration (60-80%) which do not in any way disturb the patients to the point of quitting the therapy and do disappear with its end. The focus group contains 54 infertile patients with endometrioses willing to get pregnant. In 12 months after the completion of the treatment 16 of the patients become pregnant, followed by 12 more in the next one year.. Zoladex causes amenorrhea, which lasts till the end of the treatement. It causes a rapid drop of the serum consentration to a menopause level. Causes a strong and durable treatment of the symptoms of endometriosis. The side effects disappear with the end of the therapy. The treatment is easy to go through and there no cases of a quitting patient. The treatment has a curable effect over the endometriosys and in cases of infertility provides a possibility for pregnancy.

Topics: Adult; Amenorrhea; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menstrual Cycle; Pelvic Inflammatory Disease; Pregnancy; Prospective Studies; Treatment Outcome

The size of the pool of growing follicles was normal after prolonged down-regulation, as indicated by normal AMH levels 4 and 8 weeks after goserelin administration. However, there was a profound down-regulation of LH levels; therefore we suggest administration of exogenous LH to proceed to IVF or alternatively stimulation of endogenous LH secretion with daily administration of GnRH agonist. These need to be assessed prospectively.

Topics: Anti-Mullerian Hormone; Down-Regulation; Endometriosis; Female; Follicle Stimulating Hormone; Glycoproteins; Goserelin; Humans; Luteinizing Hormone; Pilot Projects; Pituitary Gland; Testicular Hormones

The effect of physical training on bone mineral density (BMD) in women with endometriosis treated with gonadotropin-releasing hormone (GnRH) analogs was studied.. Nineteen Caucasian premenopausal women aged 23-38 years were included in the study. The subjects were all treated with 21.6 mg goserelin during 6 months. The patients were randomized to physical training n=8 or to a control group n=11. The total period of training was 12 months, whereas GnRH treatment was terminated after 6 months. BMD was measured in the femoral neck area and the lumbar spine using dual X-ray absorptiometry (DEXA). This was performed just before treatment, after 6 months and after 12 months. Six women fulfilled the training during 12 months of observation. In the control group 10 women were followed up for 12 months.. After 6 months the women in the physical training group were 2.1% below baseline. Six months later these women had gained BMD in the femoral neck and were 0.6% below baseline. Those in the control group lost 2.8% after 6 months and were 3.6% below baseline after 12 months. The difference in loss of BMD after 12 months between the groups was significant 0.029. In the spine there was no significant difference between the two groups.. Physical training in women with endometriosis was found to rebuild bone after treatment with GnRH analogs when compared to a control group. This effect could be demonstrated 6 months after cessation of GnRH treatment.

Topics: Absorptiometry, Photon; Adult; Antineoplastic Agents, Hormonal; Bone Density; Endometriosis; Exercise; Female; Femur Neck; Follow-Up Studies; Goserelin; Humans; Pilot Projects; Uterine Diseases

Among patients using GnRH analogues for endometriosis it has been postulated that peripheral and inflammation-induced in-situ aromatization of adrenal androgens are probably the main reasons for the high rates of failure during follow-up. We hypothesized that in cases with premenopausal severe endometriosis, use of a combination of anastrozole and goserelin to achieve almost maximal endocrine blockade of estrogen synthesis after conservative surgery may increase the pain-free interval and reduce the recurrence rates as compared to goserelin alone.. In a prospective randomized trial, we evaluated the efficacy of using either a combination of anastrozole and goserelin for 6 months or goserelin alone for 6 months after conservative surgery for severe endometriosis. The primary outcome measures were the symptom recurrence rates and the impact of treatment on endometriosis-related multidimensional score. The secondary outcome measures were the impact of allocated treatment regimens on menopausal quality of life and on lumbar spine bone mineral density (BMD).. When we analyzed the Kaplan-Meier survival curves, we detected a statistically significant advantage of goserelin plus anastrozole as compared to goserelin only, in terms of the median time to detect symptom recurrence (>2.4 versus 1.7 months; log-rank test; P=0.0089). This statistically significant advantage occurred with a relative risk of 4.3 [95% confidence interval (CI) 1.3-9.8]. Three cases out of 40 recurred in the goserelin plus anastrozole arm (7.5%), whereas we detected recurrences in 14 cases out of 40 cases in the goserelin-only arm (35%) during the follow-up period of 24 months. Based on these data, the interpretation of Kaplan-Meier curves indicates that at the end of follow-up, 54.7 versus 10.4%, respectively, of the patients were free of recurrence. The mean of the differences in terms of Deltabaseline-24 months post-medical therapy multidimensional score were statistically significant in favour of goserelin and anastrozole (9.2 +/- 2.1 versus 6.7 +/- 2.8; paired t-test; P<0.0001; 95% CI 1.5-4.0). We observed a statistically significant difference in suppression of estradiol concentrations and a significantly greater BMD loss at the end of treatment in the goserelin and anastrozole arm as compared to goserelin-only arm. However, this did not elicit deterioration in menopausal quality of life and the observed bone loss was not significant in terms of DeltaBMD between the groups at 2 years of treatment withdrawal.. Six months of treatment with anastrozole and goserelin as compared to goserelin alone increased the pain-free interval and decreased symptom recurrence rates in patients following surgery for severe endometriosis. Furthermore, menopausal quality of life and BMD at 2 years after medical therapy remained unaffected.

Topics: Adult; Anastrozole; Aromatase Inhibitors; Bone Density; Drug Administration Schedule; Drug Therapy, Combination; Endometriosis; Enzyme Inhibitors; Estradiol; Female; Goserelin; Humans; Menopause; Nitriles; Palliative Care; Patient Selection; Postoperative Care; Quality of Life; Secondary Prevention; Severity of Illness Index; Survival Analysis; Treatment Outcome; Triazoles

To examine whether ultralong GnRH analog (GnRH-a) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate.. Prospective, randomized, controlled study.. University clinic for reproductive medicine and gynecologic endocrinology.. One hundred ten patients with stage II to IV endometriosis according to ASRM criteria.. Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART, and 55 patients received 3 cycles of ART alone immediately after surgery.. Clinical pregnancy rates.. The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a. The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI.. Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis.

Topics: Adult; Endometriosis; Female; Fertilization in Vitro; Goserelin; Humans; Insemination, Artificial, Homologous; Postoperative Period; Pregnancy; Prospective Studies; Sperm Injections, Intracytoplasmic; Time Factors; Treatment Outcome

The medical treatment of the pelvic endometriosis includes the hormonal therapy that attacks directly to the endometriosis lesions or indirectly it inhibits the endometrial proliferation and it induces atrophy through the estrogenic deprivation, or to inclination of a combination of these effects. The objective of the present study was to evaluate the effects of two gonadotrophin release analogs in the treatment of the endometriosis. 15 patients were studied in who the diagnosis settled down of endometriosis by means of laparoscope; these were formed two groups in aleatory form and there were administered to each one them nafarelin acetate in dose of 200 or 400 micrograms each 12 hours or goserelin acetate in dose of 3.6 mg every 21 days; the serum levels of the stimulating follicle, luteinizing, estradiol and prolactin hormones were determined at intervals of four weeks and the secondary effects of these drugs were reported. There were carried out a second look laparoscope in 10 patients. The statistical analysis was carried out by means of the test of hypothesis of Wilcoxon and X2. Inside those results were found that as much the nafarelin as the Goserelin are able to diminish the gonadotropins and estradiol serum levels. Both analogs are effective for the control of the endometriotic lesions. The secondary symptoms are smaller and better supported by the patients using nafarelin. In conclusion as much the nafarelin as the goserelin are appropriate medications for the treatment of the pelvic endometriosis and the election between one or another one can settle down for the comfort of application, secondary effects and cost.

Topics: Antineoplastic Agents, Hormonal; Endometriosis; Goserelin; Hormones; Humans; Nafarelin

To assess the effect of add-back therapy with continuous combined estrogen-progestin on the GnRH agonist-induced hypoestrogenic state and its effectiveness in healing of endometriotic lesions.. A prospective, randomized, placebo-controlled, double-blind trial.. Multiple centers in The Netherlands.. 41 premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Society scores >/=2).. Patients were randomly assigned to receive a subcutaneous depot formulation of goserelin, 3. 6 mg, every 4 weeks, plus oral placebo or oral continuous combined estradiol-norethisterone acetate add-back therapy daily for 24 weeks.. Endometriosis response, bone mineral density, transvaginal ultrasonographic changes, endocrinologic effects, and subjective side effects.. The number of endometriotic implants was significantly reduced in both groups. In the group that received GnRH agonist plus placebo, bone mineral density of the lumbar spine decreased by 5.02%.. The effectiveness of GnRH agonist treatment for endometriosis was not decreased by the addition of add-back continuous combined hormone replacement therapy. Bone mineral density of the lumbar spine was maintained and subjective side effects were diminished.

Topics: Adult; Bone Density; Double-Blind Method; Endometriosis; Estradiol; Estrogens; Female; Follicle Stimulating Hormone; Goserelin; Hormone Replacement Therapy; Humans; Netherlands; Progestins; Prospective Studies; Ultrasonography; Uterus

To identify the effects of long-term GnRH agonist use (6-24 months), with and without add-back therapy, and spontaneous reversibility of bone mass density (BMD) up to 6 years after treatment.. A prospective, randomized, long-term follow-up study.. Obstetrics and gynecology department in a university hospital in the United Kingdom.. Forty-nine symptomatic women with a laparoscopic diagnosis of endometriosis who had been identified for treatment with long-acting GnRH agonist and volunteered to participate in the study.. Women were randomly allocated to receive hormone replacement therapy (HRT) as a daily oral dose of estradiol, 2 mg, and norethisterone acetate, 1 mg, or no treatment in addition to monthly subcutaneous implants of goserelin acetate for up to 2 years, until cessation of symptoms. Bone mineral density (BMD) at the lumbar spine (C2-C4) and hip (Ward triangle) was measured every 6 months.. BMD changes in both groups.. 45 women were followed up for 6 years, at the end of which the groups did not differ significantly in the reduction in mean BMD at the lumbar spine or hip.. BMD reduction occurs during long-term GnRH agonist use and is not fully recovered by up to 6 years after treatment. Use of HRT does not affect this process.

Topics: Adult; Bone Density; Drug Implants; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Hip Joint; Hormone Replacement Therapy; Humans; Longitudinal Studies; Lumbosacral Region; Middle Aged; Norethindrone; Norethindrone Acetate; Prospective Studies; Spine

The effects of goserelin and nafarelin were compared in a prospective, randomized, open, parallel study of 6 months' treatment of 252 women with symptomatic, laparoscopically proven endometriosis. Twenty-eight departments of obstetrics and gynecology in Sweden, Norway, Denmark and Finland were included. Evaluations were made every 3 months for quantification of pain, bleeding and adverse events and convenience of treatment, and at 3 months after the end of treatment, when a control laparoscopy was performed for evaluation of changes in endometriotic lesion size, color and location. Thirty-nine patients withdrew and 113 women given goserelin and 100 women given nafarelin completed the study. There were no statistically significant differences between the groups, either in adverse events or in bleeding. There were no correlations between location, lesion size or type of lesion, and symptom score in either group, or between treatments with regard to change in endometriosis score. In both groups, the percentage of red and black lesions was reduced while the proportion of white lesions increased. The pain score was significantly reduced in both groups. Local irritation in the nasal mucosa was reported in both groups, mostly in the nafarelin-treated group. The goserelin-treated group also reported local symptoms at the injection site. We conclude that there is no statistically significant difference in treatment results or side-effects between goserelin and nafarelin when used for the treatment of endometriosis.

Topics: Administration, Intranasal; Adolescent; Adult; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Hormones; Humans; Injections, Subcutaneous; Luteinizing Hormone; Middle Aged; Nafarelin; Nasal Mucosa; Pain Measurement; Patient Satisfaction; Prospective Studies

Endometriosis is one of the most common benign gynecological diseases, affecting an estimated 10-15% of all premenopausal women. In this open multicentric prospective study, we investigated the effectiveness and tolerance of a gonadotropin releasing hormone agonist (goserelin) for the treatment of symptomatic endometriosis. One hundred and thirteen patients were included in the study. During the treatment, we documented a relevant reduction in the rAFS score and in the additive diameter of the implants. In addition, we noted a reduction in pelvic pain and an improvement of symptoms on pelvic examination. These effects were also reported during the follow up visits (24 weeks). Only 12 patients had intolerable side effects (hot flushes, sweating during the night, vaginal dryness, depression), which could be managed with transdermal 17 beta estradiol, without reducing therapeutic effectiveness. In conclusion, gonadotropin releasing hormone analogs proved to be an excellent treatment for symptomatic endometriosis and are generally well tolerated.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Follow-Up Studies; Goserelin; Humans; Middle Aged; Prospective Studies; Treatment Outcome

To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post-operative hormonal therapy compared with women treated with surgery only. Pregnancy rates and time to conception in women wanting children were also evaluated.. A multicentre, prospective, randomised controlled study.. Nineteen Italian academic departments and teaching hospitals specialising in reparative and reconstructive surgery.. A total of 269 women undergoing conservative surgery for mild to severe symptomatic endometriosis.. After surgery the women were assigned to treatment with subcutaneous goserelin depot injections for six months or to expectant management. Dysmenorrhoea, deep dyspareunia, nonmenstrual pain and general discomfort were graded according to a verbal rating scale from 0 (absent) to 3 (severe) and the scores summed to give a total symptoms score. Only patients with at least one preoperative moderate or severe symptom were enrolled. The women were evaluated regularly for two years.. Post-operative pain recurrences (total symptoms scores > or = 5), time to recurrence, pregnancy rates and time to conception in the two study groups.. At one- and two-year follow up visits, 14/107 (13.1%) and 19/81 (23.5%) patients had moderate or severe symptoms recurrence in the goserelin group compared with, respectively, 22/103 (21.4%) and 27/74 (36.5%) in the expectant management group (P = 0.143 at 1 year and 0.082 at 2 years). Time to symptoms recurrence was significantly longer in the goserelin group according to survival analysis (Wilcoxon test, P = 0.041). Among women wanting children, few conceptions occurred in both the goserelin (8/69, 11.6%) and the expectant management group (14/76, 18.4%). There was no significant difference at survival analysis (Wilcoxon test, P = 0.427).. Post-operative treatment with goserelin significantly prolonged the pain-free interval after conservative surgery for symptomatic endometriosis and did not influence reproductive prognosis.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pain, Postoperative; Pelvic Pain; Postoperative Care; Prospective Studies; Recurrence

To investigate the effect of medrogestone on bone mineral density (BMD) and bone turnover under conditions of estrogen withdrawal, premenopausal women with endometriosis were treated with goserelin (Zoladex), combined with either placebo (group A, n = 12) or 10 mg medrogestone (Prothil, group B, n = 11) for six months, and followed for an additional six months. Lumbar spine BMD was measured at 0 and 6 month. Markers of bone turnover were serum bone alkaline phosphatase (sBAP) and osteocalcin (sOC) by ELISA, and urinary total pyridinoline (uPYD) and deoxypyridinoline crosslinks (uDPD) by HPLC. Patients in both groups had a similar and significant decrease in BMD after 6 months (4%, p < 0.01). The time course of changes in bone turnover, in contrast, was different in both groups. In group A, crosslink excretion increased from one month onwards, while no changes were seen in group B. In group A, sBAP levels rose during treatment, while in group B, this rise was delayed until treatment was terminated. Additionally, group B showed an initial suppression of sBAP and sOC. In both groups, sOC increased after treatment was discontinued. Medrogestone at 10 mg/d does not prevent lumbar bone loss in premenopausal women under estrogen deprivation. In the medrogestone add back group, the changes in bone turnover are compatible with low turnover bone loss,as ooposed to a state of high turnover seen in the unopposed goserelin group. This effect may be due to glucocorticoid receptor mediated actions of medrogestone on bone.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Bone and Bones; Bone Density; Bone Remodeling; Double-Blind Method; Endometriosis; Female; Goserelin; Humans; Kinetics; Medrogestone; Osteocalcin; Osteoporosis; Placebos; Premenopause; Progesterone Congeners

To determine whether hormone replacement therapy (HRT) plus goserelin (Zoladex) is as effective as goserelin alone for the relief of pelvic symptoms of endometriosis and to determine whether it reduces both the loss of bone mineral density (BMD) and the physiologic side effects associated with goserelin therapy.. Prospective, placebo-controlled study, open label for goserelin therapy and double-blind for HRT.. Forty-two teaching or community hospitals.. Premenopausal women with symptomatic endometriosis.. Statistically significant mean decreases from baseline in the total pelvic symptom score and total subjective score were observed by week 24 for all three groups. There were no statistically significant treatment differences for change in total symptom score. Some degree of BMD loss occurred in the three groups; however, the percentage loss was consistently greater in the HRT0 group than in the HRT1 or HRT2 groups. When analyzed separately, no overall age effect on BMD change was seen in women >30 years of age versus women < or = 30 years. The HRT1 and HRT2 groups had fewer occurrences of hot flushes and vaginal dryness than did the HRT0 group.. Goserelin plus HRT is as effective as goserelin alone in relieving pelvic symptoms of endometriosis and attenuates both the loss of BMD and the physiologic side effects of hot flushes and vaginal dryness associated with goserelin therapy.

Topics: Adolescent; Adult; Bone Density; Double-Blind Method; Endometriosis; Estrogen Replacement Therapy; Female; Goserelin; Humans; Menstrual Cycle; Middle Aged; Pelvis; Prospective Studies

To investigate the efficacy and safety of tibolone on hypoestrogenic vasomotor symptoms and bone parameters in patients treated with goserelin acetate.. Prospective, randomized placebo controlled double-blind study.. Human volunteers in a university-based fertility clinic.. Twenty-nine women of mean age 29.2 +/- 4.8 years with mild to severe endometriosis undergoing 6 months of treatment with 3.6 mg goserelin acetate in an SC depot formulation were studied.. The patients were allocated randomly to either 2.5 mg/d tibolone (n = 15) or an iron pill (n = 14) in a double-blinded fashion beginning in the third cycle.. Frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were assessed by the patients using 0 to 6 point scoring system and compared. Samples of urine were obtained for calcium and creatinine (Ca:Cr) ratios at the start of treatment and monthly there after. The vasomotor scoring for each symptom and Ca:Cr ratios before the treatment and at the end of 6th month were analyzed by parametric and nonparametric tests.. The mean age, weight, vasomotor scores, pelvic scores, and urine Ca:Cr ratios were similar in both placebo and tibolone group (28.7 +/- 4.8 versus 27.6 +/- 6.3 years, 50.9 +/- 5.3 versus 53.1 +/- 7.1 kg, 4.7 +/- 1.1 versus 4.2 +/- 0.8, and 0.056 +/- 0.008 versus 0.059 +/- 0.006, respectively). The decreases in vasomotor scoring as regards to hot flushing, sweating, and other associated symptoms were statistically significant in tibolone group compared with placebo (10.4 +/- 1.6 versus 24.6 +/- 4.9). During the study significant reductions in urine Ca:Cr ratio was obtained in the tibolone patients compared with placebo (0.031 +/- 0.006 versus 0.0055 +/- 0.007). The incidence of side effects (weight change, vaginal bleeding) was low and did not differ from the placebo group.. Considering the beneficial effects of tibolone on vasomotor symptoms and bone loss, our data suggest that this synthetic steroid is an effective and safe option in relieving symptoms induced by GnRH-analogue.

Topics: Adult; Anabolic Agents; Double-Blind Method; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Norpregnenes; Osteoporosis; Prospective Studies

To examine the effects of concomitant use of goserelin and medroxyprogesterone acetate (MPA) in the treatment of endometriosis.. Thirty-eight women with laparoscopically confirmed endometriosis were treated with once-a-month s.c. injections of goserelin acetate 3.6 mg (Zoladex depot; Zeneca Pharmaceutics, Cheshire, United Kingdom) randomly combined with either MPA (100 mg daily; n = 19) or a placebo (one tablet daily; n = 19) in a double-blind trial. Symptoms and side effects were monitored for a treatment period of 6 months and a follow-up period of 6 months. Blood and urine samples were collected for the assessment of endocrine and biochemical parameters. A second-look laparoscopy was performed 6 months after the treatment in 29 women.. The extent of endometriosis was diminished similarly in both treatment groups, as were pelvic symptoms. Fewer women in the MPA group had hot flushes and sweating at 3 and 6 months of treatment. Sex hormone-binding globulin decreased in the MPA group but not in the placebo group. Consequently, the E2 index (E2/SHBG X 100), reflecting the free fraction of E2, fell more in the placebo group than it did in the MPA group. The increased urinary excretion of calcium observed during placebo treatment was prevented by MPA.. High-dose MPA combined with a GnRH agonist (GnRH-A) diminished some antiestrogenic effects of the agonist. A reduction in hypoestrogenic side effects and a possible bone-sparing effect can be regarded as beneficial, especially as the good effect of the GnRH-a on endometriotic implants and pelvic symptoms prevailed.

Topics: Adult; Double-Blind Method; Drug Therapy, Combination; Endometriosis; Estrogen Antagonists; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Sex Hormone-Binding Globulin

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

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

To determine the safety and effectiveness of ZOLADEX depot (goserelin) in the therapy of endometriosis (study No. 9393CZ/0001).. A multicentric prospective open study of 60 women with endometriosis. R-AFS score of pelvic endomemtriosis was established in patients suffering from pelvalgia, dyspareunia and dysmenorrhoea during pre-treatment laparoscopy. The effect of Zoladex depot applied subcutaneously were evaluated by gynaecological and laboratory examinations, including assessment of subjective complaints every four weeks in the course of six months. Laparoscopic check-up was carried out immediately after terminating the therapy.. (1) The average total score of subjective complaints decreased by 90% after 24 weeks of treatment. (2) Treatment was successful in 67% patients, i.e. laparoscopic examination showed a decrease of the R-AFS score by at least 50%. In 28% treated women visible endometrial foci disappeared completely. (3) The most frequent side-effects of therapy are associated with hypoestrogenic effects of GnRH agonists. Vasomotor instability, flushes and night hyperidrosis occurred in 93% and 90% treated women, respectively.. Goserelin acetate is a synthetic GnRH agonist suitable for safe and effective therapy of pelvic endometriosis. The administration of 3.6 mg goserelin every day for 24 weeks reduced markedly the size of endomerial foci and painful symptoms.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Prospective Studies

To verify if a 6-month period of hypoestrogenism due to chronic treatment with GnRH analogue (GnRH-a) causes irreversible bone loss in young women.. Controlled clinical study in volunteer women.. Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy.. Twenty-eight women (mean age +/- SE 81.1 +/- 0.99 years) with endometriosis diagnosed by laparoscopy and 25 healthy, normally cycling women of the same age (28.3 +/- 1.14 years).. In women with endometriosis, six SC implants of the GnRH-a compound, 3.6 mg goserelin acetate depot, were administered every 28 days starting within 15 days of laparoscopy. Compounds interfering with bone metabolism or hormonal formulations were not taken by control women during the entire period of the study.. Evaluation of lumbar bone mineral density at the start of the study and 6, 12, and 30 months later.. At the onset of the study, lumbar bone mineral density did not differ in women with endometriosis and control women. Lumbar bone mineral density values significantly decreased after 6 months of GnRH-a treatment. This reduction was still evident 6 months after GnRH-a interruption. However, 24 months after treatment withdrawal, bone mineral density reduction disappeared and bone mineral density values were completely superimposable (+/- O.4 percent) to those observed before treatment. In contrast, control women lumbar bone mineral density values did not change during the entire period of observation.. These data suggest that GnRH-a treatment for 6 months is not associated with long-term effects on lumbar bone density.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Drug Implants; Endometriosis; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Osteoporosis; Time Factors

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

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

A multicentre, open, randomized comparison of depot goserelin versus danazol to treat endometriosis was undertaken in 9 Australian/New Zealand centres. The study compared the effects of the 2 drugs on subjective and objective parameters in women with symptomatic and/or infertility associated endometriosis. The duration of treatment was 24 weeks with either depot goserelin acetate, 3.6 mg, subcutaneously at 4-weekly intervals or danazol, 600 mg/day. As shown in previous studies, depot goserelin and danazol were equally effective in reducing endometriosis scores and pain. Patients in our study showed considerably more intolerance of study drugs, particularly danazol, than women in American and European reports: 19 of 36 women randomized to danazol in our study failed to complete 6 months therapy, because of adverse events (9/36) or because of unwillingness to continue with therapy (8/36). Consumer satisfaction with medical treatment for endometriosis was an important issue in this study.

Topics: Adult; Antineoplastic Agents, Hormonal; Danazol; Delayed-Action Preparations; Endometriosis; Estrogen Antagonists; Female; Goserelin; Humans; Prospective Studies; Treatment Outcome

The usefulness of the gonadotrophin-releasing hormone (GnRH) agonists in treating benign chronic gynaecological disorders, such as endometriosis and uterine fibroids, or pre-menstrual syndrome (PMS), is limited by their hypo-oestrogenic side effects, including bone demineralisation and vasomotor symptoms. Studies in patients receiving GnRH agonists and hormone replacement therapy (HRT) show that whilst the efficacy of GnRH agonist monotherapy in treating endometriosis and fibroids is maintained, the concomitant add-back HRT can prevent the bone loss and reduce the incidence and severity of vasomotor symptoms. However, in a study of add-back HRT (an oestrogenic plus a progestogenic agent) in severe PMS, although the efficacy of Zoladex (goserelin acetate) against oestrogen-responsive symptoms, such as mood, was still evident, progestogenic side effects still occurred. It is likely that add-back HRT may need to be tailored to individual indications.

Topics: Adult; Bone Density; Double-Blind Method; Endometriosis; Estrogen Replacement Therapy; Female; Goserelin; Humans; Middle Aged; Premenstrual Syndrome; Treatment Outcome

Add-back hormone replacement therapy (HRT) can alleviate the undesirable hypo-oestrogenic effects of the gonadotrophin-releasing hormone (GnRH) agonists, including loss in bone mineral content. However, this approach presents a dilemma in patients with endometriosis as the re-introduction of oestrogen could re-stimulate the endometriotic process. There have been three recently published European studies investigating the combination of GnRH agonist plus add-back HRT in the treatment of endometriosis. The loss of bone mineral density was significantly diminished in a study using 25 micrograms oestradiol patches combined with continuous medroxyprogesterone acetate (5 mg). Neither this low oestrogen dose nor a full bone-sparing dose of oral oestradiol (2 mg daily) reduced the efficacy of Zoladex (goserelin acetate) in patients with endometriosis. Furthermore, in a small open study the gonadomimetic tibolone totally prevented the loss of bone structure during GnRH agonist therapy. If a GnRH agonist is considered the treatment of choice, then HRT should be used in combination.

Topics: Administration, Cutaneous; Bone Density; Double-Blind Method; Drug Combinations; Endometriosis; Estradiol; Estrogen Replacement Therapy; Female; Goserelin; Humans; Injections; Luteinizing Hormone; Medroxyprogesterone Acetate; Norethindrone; Norethindrone Acetate; Treatment Outcome

Topics: Administration, Oral; Bone Density; Double-Blind Method; Endometriosis; Estrogen Replacement Therapy; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Osteoporosis; Prospective Studies

Add-back hormone replacement therapy has been shown to alleviate some of the hypo-oestrogenic side effects associated with gonadotrophin-releasing hormone agonists, including demineralisation of bone. Studies on patients with uterine fibroids have shown that concomitant add-back therapy reduced the efficacy of these agents, but that deferred administration was less detrimental. This trial set out to investigate if deferred add-back therapy could offer any advantages to patients with endometriosis compared with immediate therapy. Zoladex [goserelin acetate (3.6 mg every 4 weeks)] was given for 24 weeks either with placebo, with medrogestone (10 mg/day) for 24 weeks (immediate add-back therapy), or with placebo for 12 weeks followed by medrogestone (10 mg/day) for 12 weeks (deferred add-back therapy) to 123 patients. The number of responders measured using the Revised American Fertility Society score (decrease in this score of > or = 50%) was greatest in the immediate add-back therapy group, although there were no significant differences between groups. All three treatment groups showed significant decreases in bone mineral density compared with baseline but smaller losses were generally observed in the add-back groups. A significantly smaller number of patients in the immediate add-back group reported hot flushes during the first 12 weeks of treatment compared with the deferred add-back group. In conclusion, it appears that there is no extra advantage to patients with endometriosis being treated with goserelin in delaying the start of add-back therapy.

Topics: Bone Density; Double-Blind Method; Drug Therapy, Combination; Endometriosis; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Premenopause; Prospective Studies

To investigate whether the addition of low-dose estrogen-P combination hormone replacement therapy (HRT) to GnRH agonist (GnRH-a) treatment for endometriosis reduces the pharmacologic side effects of such treatment without reducing efficacy and to determine the endocrinologic changes during treatment.. Prospective, randomized, double-blind, placebo-controlled, comparative study of two drug regimens: 3.6 mg goserelin acetate in a 28-day SC depot formulation once monthly for 6 months plus either a combination of 2 mg 17 beta-E2 and 1 mg norethisterone acetate (NET) 1 mg or matching placebo tablets once daily for 6 months.. Multicenter study in three tertiary referral centers at university teaching hospitals and two central hospitals.. Women with laparoscopically confirmed symptomatic endometriosis were included in the study.. Of the total of 109 patients screened, 93 were recruited and 88 patients were randomized to either the HRT or the placebo group. Four women were withdrawn because of various medical reasons, and 76 patients were followed-up for a total of 12 months. In terms of efficacy, there was no difference between the two drug regimens for objective or subjective response. There were significantly less postmenopausal symptoms in the patients treated with goserelin plus HRT compared with those treated with goserelin plus placebo.. Goserelin diminished significantly the symptoms and laparoscopic scores of endometriosis. The addition of HRT did not reduce the efficacy of goserelin but diminished the postmenopausal symptoms during treatment.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Endometriosis; Estradiol; Estrogen Replacement Therapy; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Laparoscopy; Middle Aged; Norethindrone; Norethindrone Acetate; Progesterone Congeners; Prospective Studies

To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis.. Randomized controlled trial.. Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain.. Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection.. There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely.. The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished.

Topics: Adult; Bone Density; Endometriosis; Estradiol; Estrogen Replacement Therapy; Female; Follicle Stimulating Hormone; Goserelin; Humans; Lipids; Luteinizing Hormone; Medroxyprogesterone Acetate; Premenopause; Prospective Studies

The administration of gonadotrophin-releasing hormone (GnRH) analogs to premenopausal women causes hypoestrogenism and bone loss, but the effects on cancellous microstructure have not been determined. In this study we have assessed bone structure in transiliac biopsies obtained from women before and after treatment for endometriosis with GnRH analogs. Twenty-one premenopausal women were studied, paired biopsies being obtained in 13; five women received both GnRH analogs and Org OD 14 (Tibolone, Livial). Comparison of pre- and post-treatment biopsies in women treated only with GnRH analogs showed a reduction in indices related to connectivity (node-to-terminus ratio, node-to-loop strut length, p < 0.02) and increase in inversely related indices (terminus-to-terminus and node-to-terminus strut length, p < 0.03). No significant changes were seen in any of the structural indices in women receiving both GnRH and Org OD 14 therapy. Activation frequency and bone formation rate at tissue level increased in women treated with GnRH agonists alone, although this change was not statistically significant. Our results suggest that bone loss induced by GnRH analogs may be associated with adverse effects on cancellous microstructure which are unlikely to be reversed following cessation of therapy. Concurrent treatment with Org OD 14 appears to prevent these changes.

Topics: Adult; Anabolic Agents; Biopsy; Bone Density; Bone Resorption; Drug Therapy, Combination; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ilium; Norpregnenes; Osteoporosis, Postmenopausal; Premenopause; Triptorelin Pamoate

GnRH analogues are being used increasingly for a number of oestrogen dependent conditions in women. The resultant profound hypo-oestrogenism is a disadvantage, however, but the preservation of pituitary sensitivity to negative feedback by oestradiol is not well defined. We have determined the effect on gonadotrophins and inhibin of GnRH analogue plus low-dose continuous combined hormone replacement therapy in comparison with GnRH analogue therapy alone.. Randomized controlled trial.. Fifty premenopausal women with endometriosis randomized to treatment with goserelin alone (Group 1) or goserelin plus 17 beta-oestradiol and medroxyprogesterone acetate (Group 2).. FSH, LH, oestradiol, oestrone, inhibin before and during treatment.. Oestradiol and oestrone were suppressed in both groups, but Group 2 had significantly higher oestradiol during the hormone replacement therapy period. LH was suppressed in both groups. In Group 1, FSH levels recovered during treatment but, in contrast, in Group 2, FSH levels remained suppressed throughout treatment. Inhibin was significantly lower in Group 2, but not in Group 1, during treatment compared to pretreatment.. Pituitary secretion of FSH appears to remain responsive to feedback control by oestradiol during GnRH analogue therapy and is incompletely suppressed, unlike LH which remains completely suppressed. The possible mechanisms for this are discussed.

Topics: Adult; Antineoplastic Agents, Hormonal; Endometriosis; Estradiol; Estrogen Replacement Therapy; Estrone; Feedback; Female; Follicle Stimulating Hormone; Goserelin; Humans; Inhibins; Luteinizing Hormone; Medroxyprogesterone Acetate; Prospective Studies

To evaluate the role of GnRH agonist (GnRH-a) and/or drainage in the management of large endometriomas.. This prospective clinical study was conducted in a parallel and randomized design.. Department of Gynecology, Cliniques Universitaires St. Luc, Brussels, Belgium.. Eight infertile women with laparoscopically confirmed ovarian endometriotic cysts. After laparoscopic drainage of the ovarian cyst, patients were randomized. Patients in group I (n = 40) received no therapy. Patients in group II (n = 40) received GnRH-a therapy for 12 weeks. A second-look laparoscopy was performed after 12 weeks in each woman.. After drainage, a quick recurrence of the endometrial cyst was observed in only group I. Indeed, the score and the cyst size were similar to the values observed before the first laparoscopy. In group II, a significant decrease in score and cyst diameter was observed. Ovarian biopsies revealed significant reduction in the stromal vascularization and a significant reduction in the mitotic activity in the group of women treated with GnRH-a.. The quick recurrence of the ovarian cyst after drainage proved that drainage alone is ineffective. Drainage followed by GnRH-a was effective in the reduction of cyst size and the glandular mitotic activity.

Topics: Adult; Biopsy; Drainage; Endometriosis; Female; Goserelin; Humans; Laparoscopy; Ovarian Cysts; Ovarian Diseases; Ovary; Prospective Studies

Topics: Bone Density; Endometriosis; Estradiol; Estrogen Replacement Therapy; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Treatment Outcome

Uterine myomas and endometriosis are benign pathologies frequently encountered in women. Myomas are often associated with infertility and/or menorrhagia particularly if they are sub-mucosal. Endometriosis is diagnosed in more than 35% of infertile patients. These two common pathologies are oestrogen-dependent and the administration of a GnRH agonist has been proposed as a non-surgical approach to the treatment of myomas and endometriosis. GnRH agonists cannot, however, be considered as definitive medical therapy because most myomas and endometriotic cysts return to their initial size within 4 months following the cessation of treatment. Moreover, because of the menopausal-like state that they induce, GnRH agonists provoke bone demineralization and for this reason, their long-term use is not recommended. These agents should, therefore, be considered as an adjuvant preoperative therapy. The aim is, above all, to achieve a preoperative reduction of tumour size, thus facilitating the endoscopic surgery: either hysteroscopic resection in the case of sub-mucosal myomas, or vaporization of ovarian cysts in the case of cystic endometriotic lesions.

Topics: Adult; Biopsy; Combined Modality Therapy; Endometriosis; Female; Goserelin; Humans; Hysteroscopy; Infertility, Female; Laparoscopy; Leiomyoma; Menorrhagia; Ovarian Cysts; Preoperative Care; Prospective Studies; Treatment Outcome; Uterine Neoplasms

Eighteen patients affected by laparoscopically confirmed endometriosis were randomly assigned to three different schedules of treatment with gonadotropin-releasing hormone agonist (GnRH-a) (goserelin depot formulation 3.6 mg) every 28 days for 6 months. Six women received the first implant in early follicular phase, 4 in late luteal phase and 8 in 3rd and 17th day from onset of menses. Pretreatment and posttreatment laparoscopic score, performed according to the American Fertility Society scoring system, were compared; a significant reduction in the extent of disease was observed in each group investigated (A and C: p < 0.01; B: p < 0.05). In each treatment group after the second GnRH-a implant the mean levels of estrone-3-glucuronide (E1-3G), daily measured in early morning urine specimens during the control cycle and the first three months of therapy, were suppressed to menopausal women range. In group B during the 2nd and 3rd month of therapy, the urinary mean levels of E1-3G were significantly lower than in group A and C. In conclusion the different goserelin depot administration schedules gave similar laparoscopic improvement, in spite of the first GnRH-a administration in luteal phase allowed a more marked estrogenic suppression.

Topics: Adult; Delayed-Action Preparations; Endometriosis; Estrogen Antagonists; Estrone; Female; Follicular Phase; Goserelin; Humans; Laparoscopy; Luteal Phase; Luteinizing Hormone; Ovarian Function Tests; Pregnanediol

To compare the efficacy, endocrine effects, and safety of Zoladex (goserelin acetate) and danazol in the treatment of premenopausal women with endometriosis in a multicenter, randomized, open study.. Three hundred fifteen patients with stages I-IV endometriosis (revised American Fertility Society [AFS] classification) were treated with Zoladex, 3.6 mg every 28 days by subcutaneous injection, or danazol, 400 mg orally twice daily for 24 weeks. Efficacy was assessed by determination of pelvic signs and symptoms scores and revised AFS endometriosis scores. Endocrine effects were determined by measurements of hormone levels. Safety was evaluated by physical examination, laboratory indices, occurrence of adverse events, and bone mineral density changes.. Both treatments significantly (P < .0001) reduced mean subjective signs and symptoms scores both during and after therapy. The mean percent reduction in the revised AFS endometriosis score after 24 weeks of treatment was 53% for Zoladex and 33% for danazol, and reduction in the endometrial implants score was 56% for Zoladex and 46% for danazol. Serum estradiol levels decreased to the postmenopausal range in the Zoladex group and to the early follicular phase range in the danazol group. Hypoestrogenic effects occurred more frequently with Zoladex, whereas androgenic side effects were more common with danazol. There was a higher percentage of withdrawals due to adverse events with danazol than with Zoladex. Mean bone mineral density decreased from baseline by 5.4% in the Zoladex group and increased by 1.0% in the danazol group at the end of treatment.. Zoladex is as well tolerated and as effective as danazol in the treatment of premenopausal women with endometriosis.

Topics: Administration, Oral; Adult; Danazol; Drug Implants; Endometriosis; Estradiol; Female; Goserelin; Humans; Pelvic Neoplasms

To determine the long-term recurrence rate of endometriosis after treatment with gonadotropin-releasing hormone analogues (GnRH-a).. A historical prospective study.. Royal Free Hospital, London, a tertiary referral center for the treatment of endometriosis.. One hundred thirty patients with endometriosis had treatment with GnRH-a buserelin acetate, goserelin, and nafarelin acetate between the years 1985 and 1987. Patients no longer being followed in the gynecology clinic were sent a questionnaire to determine their state of health. Information was also requested from the patient's general practitioner.. The cumulative recurrence rate for the fifth year after treatment ended was 53.4%.. Patients with a higher disease stage at the outset were more likely to experience recurrence and experience it earlier than patients with minimal disease. Fifth-year recurrence rates were 36.9% for minimal disease and 74.4% for severe disease. The change in endometriosis stage classification scores at second-look laparoscopy for those patients whose disease recurred after treatment was not significantly different from those whose disease did not recur during the study period.. Patients with endometriosis treated with GnRH-a are highly likely to suffer a recurrence of their disease, particularly if their disease is severe at the outset.

Topics: Adolescent; Adult; Buserelin; Endometriosis; Female; Follow-Up Studies; Goserelin; Humans; Middle Aged; Nafarelin; Prospective Studies; Recurrence

To evaluate the efficacy of goserelin versus a low-dose cyclic oral contraceptive (OC) in improving pelvic pain in women with endometriosis and to compare recurrence of symptoms during follow-up.. Open-label, randomized trial.. University hospital endometriosis center.. Fifty-seven women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis.. Six-month treatment with goserelin depot (n = 29) or a low-dose cyclic OC (n = 28) followed by 6-month follow-up.. Variation in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale.. At 6 months of treatment, a significant reduction in deep dyspareunia was observed in both groups, with goserelin superior to the OC at linear analog scale assessment. Nonmenstrual pain was diminished on both scales without differences between treatments. Women taking the OC experienced a significant reduction in dysmenorrhea. At the end of follow-up, symptoms reappeared without differences in severity between the groups.. Low-dose cyclic OCs may be a valuable alternative for the treatment of dysmenorrhea and nonmenstrual pain associated with endometriosis. Symptoms recurred in most subjects 6 months after drug withdrawal.. Physicians at the University of Milan in Italy compared data on 29 endometrial patients who received 3.6 mg goserelin in a 28-day subcutaneous depot formulation for 6 months to treat nonmenstrual pelvic pain, dysmenorrhea, and pain during coitus (dyspareunia) with data on 28 other endometrial patients treated with a low-dose monophasic oral contraceptive (OC) (.02 mg ethinyl estradiol and 0.15 mg desogestrel) for 6 months. They followed the women for 6 months after treatment ended. The physicians wanted to determine the efficacy of goserelin, a gonadotropin-releasing hormone (GnRH) agonist, versus a low dose OC to relieve pelvic pain in patients with endometriosis and to compare pain recurrence after drug withdrawal. (GnRH agonists are current medical treatments for pelvic pain, but they have several side effects and are expensive; and therefore their use is restricted.) At the end of treatment, both goserelin and the low-dose OC significantly reduced dyspareunia (p .01), especially goserelin according to the linear analog scale (pain symptom score, 1.8 points lower). Both treatments improved nonmenstrual pain equally at the end of treatment (p .01). The low-dose OC reduced dysmenorrhea greatly at the end of treatment (p .01). The researchers could not evaluate dysmenorrhea in goserelin cases, since these patients experienced amenorrhea. The only persistent significant reduction at the end of follow-up occurred with dyspareunia in goserelin patients (p .05). In the other patients, pelvic pain returned to baseline levels 6 months after treatment ended. The severity of pelvic pain did not differ between groups 6 months after follow-up. These results suggested that low-dose OCs may be an effective alternative treatment for dysmenorrhea and nonmenstrual pelvic pain linked to endometriosis.

Topics: Adolescent; Adult; Contraceptives, Oral; Dysmenorrhea; Dyspareunia; Endometriosis; Female; Follow-Up Studies; Goserelin; Humans; Pain; Recurrence

To compare the efficacy and safety of goserelin depot and danazol for endometriosis.. Open, randomized comparative trial.. Multicenter European academic clinical institutions.. A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy.. A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks.. Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures.. There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol.. The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d.

Topics: Adolescent; Adult; Buserelin; Danazol; Delayed-Action Preparations; Endometriosis; Female; Goserelin; Humans; Menstruation; Pregnancy

Hot flushes are the commonest symptom induced by gonadotropin-releasing hormone agonists (GnRHa). We performed an open observational trial to evaluate the efficacy of veralipride, an antidopaminergic drug, in reducing hot flushes in 25 premenopausal women treated with a GnRHa for endometriosis (8 subjects) or menorrhagia (17 subjects). The patients received goserelin depot for 6 months and veralipride was added for the third month. Hot flushes, severe in all women at 2 months, improved in both frequency and intensity in 92% of the subjects during veralipride administration. The benefit obtained persisted until the end of the GnRHa treatment.

Topics: Adult; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Flushing; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Menorrhagia; Middle Aged; Prolactin; Sulpiride

The evaluation of cholesterol fractions and apoproteins during ovarian suppression by a GnRH agonist implant vs danazol in the treatment of endometriosis.. A randomized study in 33 patients comparing goserelin (3.6 mg/4 weeks s.c., n = 20) with danazol (2 x 400 mg/day p.o., n = 13) in patients with a laparoscopic diagnosis of endometriosis and treated for 6 months.. Triglycerides, cholesterol (C), LDL-C, HDL-C subfractions and apoproteins A-1 and B were measured at admission, at months 2, 4 and 6 of treatment and at month 2 post-treatment.. After 1 month of therapy, serum oestradiol levels were maintained in the menopausal range with goserelin and in the early follicular phase range with danazol. Goserelin induced a significant elevation in HDL-C (by 31.4%), in HDL2-C (24.6%) and in HDL3-C (45.7%) but no significant change in LDL-C or in ApoA-1 and ApoB. By contrast, danazol caused significant diminutions in HDL-C (23.9%), HDL2-C (56.6%) and ApoA-1 (35.6%). Moreover, danazol increased LDL-C (10.5%) and ApoB (29.0%, P less than 0.05). The lipoprotein changes during goserelin had a favourable effect on the atherogenic index (cholesterol/HDL-C) and ApoA-1/ApoB ratio whereas those of danazol had opposite effects. These changes reverted 2 months after danazol while HDL was still elevated after goserelin.. In relation to cholesterol, goserelin is a safe medication. The significance of temporary adverse changes in cholesterol fractions due to danazol is still unknown.

Topics: Adult; Apolipoproteins; Buserelin; Cholesterol, HDL; Cholesterol, LDL; Danazol; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans

In summary then, Zoladex depot (Goserelin 3.6 mg) administered monthly for a period of six months proved highly efficacious in achieving endocrine parameters of pituitary desensitization and hypo-oestrogenism. Initial studies treating symptomatic patients with endometriosis shows satisfactory relief of symptoms and significant impact on the disease process as shown by resolution or reduction in number and size of disease deposits. The depot can be given as a subcutaneous injection without the need of local anaesthesia and its duration of action is 28 days. Zoladex depot should offer a suitable, acceptable form of treatment for patients with endometriosis.

Topics: Buserelin; Chemistry, Pharmaceutical; Delayed-Action Preparations; Endocrine Glands; Endometriosis; Female; Goserelin; Humans; Multicenter Studies as Topic; Safety

In an attempt to determine whether the suppression in oestradiol levels caused by danazol is due to an effect on the hypothalamic-pituitary axis, we compared the endocrine effects of danazol with those of the LHRH (GnRH) agonist analogue goserelin. Serum levels of immunoreactive LH (I-LH), FSH, 17 beta-oestradiol (E2) and bioactive LH (B-LH) (using a mouse Leydig cell bioassay), were measured in ten and 20 women with endometriosis treated with danazol and goserelin, respectively. I-LH was measured both by radioimmunoassay (RIA) and immunoradiometric assay (IRMA). During 6 months of treatment with 600 mg of danazol daily, mean serum E2 decreased (P less than 0.05) to levels near the upper limit of the post-menopausal range (to a mean (and 95% confidence interval of the mean) of 117 (65-169) pmol/l) whereas FSH, I-LH (both by RIA and IRMA) and B-LH levels were not significantly altered. During 6 months of treatment with monthly depot injections of 3.6 mg goserelin, mean serum E2 decreased (P less than 0.001) to well within the post-menopausal range (to 23 (18-28) pmol/l). The mean FSH, I-LH and B-LH levels also decreased (P less than 0.05) during therapy with goserelin (from 3.9 (3.1-4.7) to 2.0 (1.6-2.4) IU/l for FSH, from 5.3 (4.5-6.1) to 1.9 (1.7-2.1) IU/l for RIA-LH, from 2.9 (2.5-3.3) to less than 0.5 (less than 0.5) IU/l for IRMA-LH and from 9.1 (7.1-11.1) to 2.9 (2.6-3.2) IU/l for B-LH).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Buserelin; Danazol; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone

To investigate the effects of medical treatment of endometriosis on concentrations of insulin and glucagon in comparison with those of androgens, 12 non-obese women with minimal endometriosis were randomly allocated to receive treatment with either danazol or the gonadotropin-releasing hormone analogue, goserelin. In subjects treated with danazol, mean (SD) summed serum insulin (1.08 (0.22) nmol/l pretreatment; 3.00 (1.50) nmol/l after treatment, p less than 0.05) and summed plasma glucagon (94 (21) pmol/l pretreatment; 238 (113) pmol/l after treatment, p less than 0.05) responses to oral glucose administration increased significantly, but remained unchanged in subjects treated with goserelin. In the danazol-treated group, the mean free testosterone index increased from 3.3 (1.6) to 13.3 (4.2) (p less than 0.01), but there was no correlation between either glucagon or insulin and free testosterone index. In the goserelin-treated subjects, however, there was no change in mean free testosterone indices (pretreatment 3.6 (1.0), post-treatment 3.9 (1.8). Thus, the increase in free testosterone index induced by danazol treatment is not responsible for the concomitant development of hyperinsulinaemia and hyperglucagonaemia.

Topics: Adult; Androgens; Blood Glucose; Buserelin; C-Peptide; Danazol; Endometriosis; Female; Follicle Stimulating Hormone; Glucagon; Glucose Tolerance Test; Goserelin; Humans; Insulin; Luteinizing Hormone; Testosterone

Topics: Buserelin; Danazol; Delayed-Action Preparations; Endometriosis; Female; Goserelin; Humans

Endometriosis is a chronic inflammatory gynaecological disease characterized by the growth of endometrial tissue outside the uterine cavity. There are currently no definitive non-invasive diagnostic tools. Glycosylation is the most common posttranslational modification of proteins and altered glycosylation has been found in many diseases, including chronic inflammatory conditions and cancer. Sialylation and galactosylation on serum IgG have previously been found to be altered in endometriosis and serum sialylation changed after Zoladex (Goserelin Acetate) therapy. Using IgG and whole serum glycoproteins, we investigated N-glycosylation in two clinical cohorts of women with and without endometriosis. PNGase F-digested serum samples were fluorescently labelled and N-glycans were profiled by ultra-performance liquid chromatography. Clinical data was collected to link glycomic findings with metabolic and hormonal profiles. Total serum glycoprotein and IgG glycosylation differed in patients with endometriosis compared to control cases. The most significantly altered was glycan peak 3 from IgG, containing bisected biantennary glycans, which was decreased in the endometriosis cohorts (p = 0.0000005-0.018). In conclusion, this is the first pilot study to identify changes in N-glycans from whole serum glycoproteins associated with endometriosis. A larger validation study is now warranted and such studies should include the follow-up of surgically and pharmacologically treated patients.

Topics: Endometriosis; Female; Glycoproteins; Goserelin; Humans; Immunoglobulin G; Pilot Projects; Polysaccharides

Endometriosis is recognized as an estrogen-dependent inflammation disorder, estimated to affect 8%-15% of women of childbearing age. Currently, the etiology and pathogenesis of endometriosis are not completely clear. Underlying mechanism for endometriosis is still under debate and needs further exploration. The involvement of transcription factors and immune mediations may be involved in the pathophysiological process of endometriosis, but the specific mechanism remains to be explored. This study aims to investigate the underlying molecular mechanisms in endometriosis.. The gene expression profile of endometriosis was obtained from the gene expression omnibus (GEO) database. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were applied to the endometriosis GSE7305 datasets. Cibersort and MCP-counter were used to explore the immune response gene sets, immune response pathway, and immune environment. Differentially expressed genes (DEGs) were identified and screened. Common biological pathways were being investigated using the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Transcription factors were from The Human Transcription Factors. The least absolute shrinkage and selection operator (Lasso) model identified four differential expressions of transcription factors (AEBP1, HOXB6, KLF2, and RORB). Their diagnostic value was calculated by receiver operating characteristic (ROC) curve analysis and validated in the validation cohort (GSE11691, GSE23339). By constructing the interaction network of crucial transcription factors, weighted gene coexpression network analysis (WGCNA) was used to search for key module genes. Metascape was used for enrichment analysis of essential module genes and obtained HOXB6, KLF2. The HOXB6 and KLF2 were further verified as the only two intersection genes according to Support Vector Machine Recursive Feature Elimination (SVM-RFE) and random forest models. We constructed ceRNA (lncRNA-miRNA-mRNA) networks with four potential transcription factors. Finally, we performed molecular docking for goserelin and dienogest with four transcription factors (AEBP1, HOXB6, KLF2, and RORB) to screen potential drug targets.. Immune and metabolic pathways were enriched in GSVA and GSEA. In single sample gene set enrichment analysis (ssGSEA), most immune infiltrating cells, immune response gene sets, and immune response pathways are differentially expressed between endometriosis and non-endometriosis. Twenty-seven transcription factors were screened from differentially expressed genes. Most of the twenty-seven transcription factors were correlated with immune infiltrating cells, immune response gene sets and immune response pathways. Furthermore, Adipocyte enhancer binding protein 1 (AEBP1), Homeobox B6 (HOXB6), Kruppel Like Factor 2 (KLF2) and RAR Related Orphan Receptor B (RORB) were selected out from twenty-seven transcription factors. ROC analysis showed that the four genes had a high diagnostic value for endometriosis. In addition, KLF2 and HOXB6 were found to play particularly important roles in multiple modules (String, WGCNA, SVM-RFE, random forest) on the gene interaction network. Using the ceRNA network, we found that NEAT1 may regulate the expressions of AEBP1, HOXB6 and RORB, while X Inactive Specific Transcript (XIST) may control the expressions of HOXB6, RORB and KLF2. Finally, we found that goserelin and dienogest may be potential drugs to regulate AEBP1, HOXB6, KLF2 and RORB through molecular docking.. AEBP1, HOXB6, KLF2, and RORB may be potential biomarkers for endometriosis. Two of them, KLF2 and HOXB6, are critical molecules in the gene interaction network of endometriosis. Discovered by molecular docking, AEBP1, HOXB6, KLF2, and RORB are targets for goserelin and dienogest.

Topics: Carboxypeptidases; Endometriosis; Female; Gene Expression Profiling; Goserelin; Humans; Molecular Docking Simulation; Repressor Proteins; RNA, Long Noncoding; Transcription Factors

Topics: Antineoplastic Agents, Hormonal; Endometriosis; Female; Goserelin; Hemopneumothorax; Humans; Magnetic Resonance Imaging; Middle Aged; Single Photon Emission Computed Tomography Computed Tomography; Thoracic Diseases

To evaluate the effects of combined treatment approaches on endometriosis-associated infertility in different stages of endometriosis using laparoscopy, gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and in vitro fertilization (IVF).. This retrospective study was carried out on 179 women with surgically confirmed endometriosis. Patients were divided into subgroups: group 1 (stage I-II, n = 121) and group 2 (stage III-IV, n = 58). Patients eligible for IVF, who were found to have adenomyosis or moderate to severe endometriosis, were also given postoperative GnRHa. Pregnancy and delivery rates were cumulatively calculated during 5 years according to the severity of the disease.. The overall pregnancy, delivery and miscarriage rates were 66.5, 56.4 and 15.1%, respectively, for all patients following spontaneous and assisted conception. There were no significant differences in reproductive outcomes between the study groups. The pregnancy and delivery rates were also comparable within group 1 between the patients with and without GnRHa treatment.. Pregnancy and delivery rates at different stages of endometriosis were not affected by the different approaches used for infertility treatment, with >60 and >50% of patients having conceived and delivered a baby, respectively, in both groups. The usefulness of GnRHa treatment for endometriosis patients with minimal to mild forms is questionable and deserves further studies.

Topics: Abortion, Spontaneous; Adult; Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Laparoscopy; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Rate; Retrospective Studies

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

To investigate clinicopathological features of abdominal wall endometriosis (AWE).. A retrospective study was conducted on 151 consecutive AWE patients undergoing treatment in Affiliated Obstetrics and Gynecology Hospital, Fudan University from January 2003 to December 2010. The period of following up was at range of 16 to 97 months.. (1) The incidence of AWE was 1.96% (166/8469). All 151 AWE cases followed up had previous cesarean sections. The period between the previous cesarean section (CS) and the onset of symptoms of AWE was 24 months (3 - 192 months). However, the latency was not associated with the age at CS, incision site, gestational week at CS, duration of lactation, postpartum menstruation recovery, the choice of contraceptives and size of AWE (P > 0.05). The duration of disease, defined to be the time interval between the onset of symptoms and surgery, was 26 months (2 - 168 months), which was negatively correlated with the latent period (r = -0.267, P < 0.05) and was positively with size of AWE (patients with large-scar endometrioma with diameter of lesions ≥ 3 cm had longer disease duration than those with small-scar endometriomas < 3 cm, r = 0.326, P < 0.05). (2) The rate of pre-operational ultrasonography detection was 97.4% (147/151). The lesion size detected by pre-operative ultrasonography was significantly smaller than that measured intraoperatively by palpation (20 mm versus 35 mm, P < 0.05). Moreover, only 26.5% (40/151) of AWE patients were found to have deep infiltration by pre-operative ultrasonography. (3) All patients were managed by surgical treatment to completely excise lesions on the abdominal wall. Of all 34 patients (22.5%, 34/151) took medicine pre-operatively while 57 patients (37.7%, 57/151) taking medicine post-operatively. The rate of recurrence was 3.1% (3/96) of cases with lesions ≥ 3 cm, which was significantly lower than 17.8% (8/45) in cases with lesion < 3 cm (P < 0.05). (4) After surgery, the symptoms were found to be relieved in 93.4% (141/151) of patients. The recurrence rate was 7.8% (11/141) while the average recurrent time was (20 ± 16) months.. Surgery is the main management on AWE. The risk factors associated with recurrence were size of lesion and postoperative medication.

Topics: Abdominal Pain; Abdominal Wall; Adult; Cesarean Section; Endometriosis; Female; Gestrinone; Goserelin; Humans; Hysterectomy; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Time Factors

To investigate the effect of gonadotropin-releasing hormone analogues (GnRHa) on the peritoneal fluid microenvironment in women with endometriosis.. Peritoneal fluid was collected from 85 women with severe endometriosis (rAFS stage III and IV) during laparoscopic surgery during the proliferative phase. Prior to surgery clinical data were collected. The concentrations of specific markers for endometriosis in the peritoneal fluid were determined using an ELISA and a comparison between peritoneal fluid markers in women using GnRHa and no hormonal treatment was performed using a non-parametric Mann-Whitney U test.. The study included peritoneal fluid from 39 patients who had been administered GnRHa (Zoladex(®)) in the three months prior to surgery and 46 from women with no hormonal treatment in this period. Concentrations of IL-8, PAPP-A, glycodelin-A and midkine were significantly reduced in the GnRHa treatment group compared to women receiving no hormonal treatment. RANTES, MCP-1, ENA-78, TNF-α, OPG, IP-10 and defensin showed no significant change between the two groups.. GnRHa mediate a significant regression in the inflammatory nature of the peritoneal microenvironment in women with endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Ascitic Fluid; Case-Control Studies; Cytokines; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Inflammation; Up-Regulation

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

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

To evaluate the short-term and long-term efficacy of conservative laparoscopic surgery combine with goserelin in treatment of severe ovarian endometriosis.. From January 2004 to December 2008, 206 patients with severe ovarian endometriosis underwent laparoscopy surgery in Nanjing Drum Tower Hospital, Affiliated Nanjing University Medical School were enrolled in this retrospective study. According to the revised classification American Fertility Society (r-AFS), 123 (123/206, 59.7%) cases were at stage III and 83 (83/206, 40.3%) patients were at stage IV. Among 138 cases presented pelvic pain. All the patients underwent laparoscopic cystectomy, of which 117 patients with childbearing preserving underwent hysteroscopy and hydrotubation examination, including 7 cases with bilateral salpingectomy, 2 cases with bilateral tubal obstruction and 108 cases with normal reproduction. After surgery, all cases were administered by goserelin treatment at dose of 3.6 mg per 28 days for 3 to 6 months. At 1 to 5 years following up, pelvic pain, pregnancy and recurrence were observed, those factors associated with pregnancy rate and endometriosis recurrence were analyzed.. (1) Pelvic pain: complete remission rate of pelvic pain was 76.1% (105/138) at 1 to 5 years after surgery. (2) Pregnancy: total pregnancy rate was 70.4% (76/108), spontaneous pregnancy rate was 68.8% (66/96) and pregnant rate of in vitro fertilization and embryo transfer (IVF-ET) was 10/12. Pregnancy rate at 1 year was 57.3% (55/96) and accounting for 83.3% (55/66) in all pregnant women. Live birth rates of spontaneous pregnant and IVF-ET were 86.4% (57/66) and 9/10, respectively. (3) Recurrence: the total recurrence rate was 8.3% (17/206) at 1 to 5 years. The recurrence rates and the cumulative recurrence rates were 3.9% (8/206) and 3.9% (8/206) at the first year after operation, 2.0% (3/149) and 6.7% (10/149) at the second year, 1.0% (1/99) and 8.0% (8/99) at the third year, 10.9% (5/46) and 17.4% (8/46) at the fourth year, 0 and 2/18 at the fifth year, respectively.. It was suggested that conservative laparoscopic surgery combined with goserelin in treatment of stage III or IV ovarian endometriosis could reduce the recurrence risk of severe ovarian endometriosis and improve the pregnant rate of endometriosis-associated infertility.

Topics: Adult; Endometriosis; Female; Follow-Up Studies; Goserelin; Humans; Laparoscopy; Pelvic Pain; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Recurrence; Severity of Illness Index; Treatment Outcome; Young Adult

Endometriosis no ectopic endometrial stroma and glands. Have different risk factors. Four theories explain it: the theory of coelomic metaplasia, embryonic cell debris, deployment and immunological. Clinical data are pain and infertility. For the American Fertility Society (AFS) is divided into minimal, mild, moderate and severe. Diagnostic studies are antigen Ca 125, Magnetic Resonance, and abdominal ultrasound. The ideal method is direct visualization with histological confirmation. The medical and surgical treatment.. To determine the risk factors, diagnosis of Endometriosis and effectiveness of treatments used in clinical Endometriosis Gynecology Unit at the General Hospital of Mexico OD.. A descriptive, longitudinal and retrospective duration of 2 years 6 months in 30 patients diagnosed with endometriosis in the clinical treatment of Endometriosis General Hospital of Mexico OD.. The most affected age group was 21 to 25 years, the risk factors are Gesta 1, a resident of Mexico, Mullerian malformation. The symptom was dysmenorrhea. In 16 were diagnosed as a surgical finding and laparoscopically diagnosed.. It is important to study the risk factors. The diagnosis is made using clinical data, quantification of CA125 antigen and imaging studies. Medical treatment is indicated both in the preoperative as well as postoperative surgical treatment and seeks to eradicate the lesions.

Topics: Adolescent; Adult; CA-125 Antigen; Comorbidity; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Danazol; Diagnostic Imaging; Endometriosis; Female; Genital Neoplasms, Female; Goserelin; Gynecologic Surgical Procedures; Gynecological Examination; Hospitals, General; Humans; Mexico; Middle Aged; Obstetrics and Gynecology Department, Hospital; Reproductive History; Retrospective Studies; Risk Factors; Young Adult

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

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

Four women, who previously had undergone multiple unsuccessful in vitro fertilisation (IVF) cycles because of failure of implantation of good quality embryos, were identified as having coexisting uterine adenomyosis. Endometrial biopsies showed that adenomyosis was associated with a prominent aggregation of macrophages within the superficial endometrial glands, potentially interfering with embryo implantation. The inactivation of adenomyosis by an ultra-long pituitary downregulation regime promptly resulted in successful pregnancy for all women in this case series.

Topics: Adult; Anti-Inflammatory Agents; Embryo Implantation; Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Goserelin; Humans; Macrophages; Prednisolone; Pregnancy; Pregnancy Rate; Progesterone

To evaluate follicle loss and its associated factors during laparoscopic cystectomy for ovarian endometrioma.. Between October 2008 and December 2009, 140 patients with ovarian cysts undergoing laparoscopic cystectomy at Peking Union Medical Hospital were enrolled: 74 had ovarian endometrioma with no preoperative hormonal therapy (group A), 40 had ovarian endometrioma pretreated with GnRHa (group B), and 26 had non-endometriotic cysts (group C). Pre-, peri- , and postoperative clinical data were collected, and cyst specimens were evaluated histologically.. The number of capsules showing follicles and the mean number of follicles per capsule were lower in group C than in group A or B (P<0.05). Fewer type IIC than type IIB endometriomas showed follicles (P<0.05). The number of follicles per cyst was related negatively to disease duration but positively to pain severity. Women in group A with unilateral endometrioma had a lower mean dysmenorrhea score after the surgery (P<0.05), but no change in basal follicle-stimulating hormone (FSH).. The type of cyst, disease duration, and severity of dysmenorrhea were associated with ovarian follicle loss during laparoscopic excision of endometrioma. Laparoscopic unilateral cystectomy for endometrioma was effective in relieving pain but had little effect on serum FSH, which might reflect the remaining ovarian reserve.

Topics: Adolescent; Adult; China; Dysmenorrhea; Endometriosis; Female; Follicle Stimulating Hormone; Follow-Up Studies; Goserelin; Humans; Laparoscopy; Middle Aged; Ovarian Cysts; Ovarian Follicle; Pain; Retrospective Studies; Severity of Illness Index; Time Factors; Young Adult

To determine the effect of GnRH I and GnRH II on the secretion of VEGF by eutopic and ectopic endometrial stromal cells cultured in vitro, and to provide theoretical basis for exploring new treatments for endometriosis (EMs).. Eutopic and ectopic endometrium stromal cells cultured in vitro were treated with different concentrations of GnRH II and a GnRH I (goserelin), and a control group was not treated by GnRH II and GnRH I. Enzyme linked immunosorbent assay (ELISA) was used to measure the content of vascular endothelial growth factor (VEGF) protein in the medium of the above 2 groups.. (1) There was no difference in the VEGF protein secreted by eutopic and ectopic stromal cells in the medium after being cultured in vitro for 48 h (P>0.05). (2) 10(-10), 10(-8), and 10(-6) mol/L GnRH II dose-dependently reduced VEGF protein secreted by endometrial stromal cells (P<0.05),and the inhibition effect was stronger than that of GnRH I (P<0.05).(3)The inhibition effect of GnRH II on VEGF in ectopic stromal cells was stronger than that of eutopic stromal cells (P<0.05).. (1) Ectopic stromal cells cultured in vitro can secrete VEGF,which has no difference from the eutopic stromal cells, and which may play an important role in the formation and development of EMs. (2) GnRH II can dose-dependently reduce VEGF protein secreted by ectopic and eutopic endometrial stromal cells cultured in vitro,and the inhibition effect is stronger than that of GnRH I, providing theoretical basis for exploring new treatments for EMs.

Topics: Adult; Cells, Cultured; Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Stromal Cells; Vascular Endothelial Growth Factor A; Young Adult

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

Catamenial pneumothorax is defined as spontaneous pneumothoraces occurring within 72 h before or after onset of menstruation. It is rare but clinical index of suspicion should be high in ovulating women with spontaneous pneumothoraces. The mechanism is unclear but is thought to involve pre-existing or acquired diaphragmatic defects and endometrial implants. Traditional therapy involving hormonal treatment or surgical pleurodesis alone is associated with high rates of recurrence. A series of four patients with catamenial pneumothorax managed at our institution is presented to highlight the condition to various surgical specialties to whom it may present, and to emphasise the importance of both surgical and hormonal interventions in preventing recurrence. Each patient underwent video-assisted thoracoscopic inspection of the diaphragm, mechanical pleurodesis and, most importantly, repair of diaphragmatic defects with an artificial mesh. Surgical treatment was strictly followed by a course of gonadotrophin-releasing hormone analogue therapy in three patients, with no recurrence to date (longest follow-up 45 months). The fourth patient suffered a postoperative recurrence when hormonal treatment was delayed for 6 weeks, stressing the importance of hormonal treatment in conjunction with surgery.

Topics: Adult; Diaphragm; Endometriosis; Female; Goserelin; Humans; Menstruation Disturbances; Ovulation; Pneumothorax; Secondary Prevention; Surgical Mesh

The authors presented the importance of the gynecological laparoscopy for diagnosis of the external genital endometriosis in its different forms. In the last 20 years, it was seen that laparoscopy is not only the basic method for diagnostics but also for the surgical treatment of the endometriosis. Thirty to fifty percent of the females with endometriosis in reproductive age have available sterility. The authors presented the cases, which have been laparoscopically proven for endometriosis and sterility for 7 years' period in Gynecological clinic in MBAL-Pleven and the results from the treatment with analog of the Gonadoliberins (Zoladex).

Topics: Bulgaria; Endometriosis; Female; Goserelin; Humans; Infertility, Female; Laparoscopy; Retrospective Studies; Treatment Outcome

A very rare--casuistic--case of endometriosis is presented, which appeared ten years after surgical menopause (hysterectomy and ovariectomy) without concomitant use of hormone replacement therapy or phytoestrogens. The possibilities of endogenous production and exogenous supply of estrogens in the female organism are discussed as well as the possible causes of proliferation of endometrial lesions during postmenopausal period. When menopause is induced by surgery (a stress for the organism) without exogenous supply of estrogens (HRT, phytoestrogens, xenoestrogens) the production of suprarenal hormones, including androgens, increases. The peripheral conversion of androgens into estrogens in fat tissue is increased and implanted during hysterectomy endometrial lesions in vagina walls are stimulated.

Topics: Aged; Diagnosis, Differential; Endometriosis; Estradiol; Female; Goserelin; Hemorrhage; Humans; Hysterectomy; Ovariectomy; Polyps; Postmenopause; Testosterone; Vaginal Diseases

To evaluate the usefulness of the histological classification of endometriosis in predicting responses to treatment.. We evaluated 412 biopsy specimens from 241 patients with pelvic endometriosis. Pain and infertility were evaluated before surgery. Disease location and stage of development were analyzed according to the 1985 American Society of Reproductive Medicine (ASRM) classification. Histological findings were classified as stromal, well-differentiated, undifferentiated, and mixed endometriosis. Clinical response to pain or infertility was evaluated.. Histological findings, disease location and stage of development, and response to treatment were compared. Undifferentiated endometriosis was more frequently associated with stages III/IV than the well-differentiated and stromal histological types. Pure or mixed undifferentiated patterns were more frequently associated with rectovaginal endometriosis. When considering pain symptoms, patients presenting well-differentiated or stromal histological patterns responded better to therapeutic treatment than those who presented undifferentiated histological patterns. There were no significant differences in cases related to sterility.. The histological categorization of endometriosis can help predict the behavioral patterns of the disease.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Endometriosis; Female; Goserelin; Gynecologic Surgical Procedures; Humans; Infertility, Female; Pain; Pain Management; Predictive Value of Tests; Treatment Outcome

Endometriosis, uncontrolled proliferation of ectopic and eutopic endometriotic tissues, is common in women at reproductive age, and may affect fertility. The role of macrophages in the pathogenesis is well proved, but engagement of T cells in the pathogenesis of endometriosis is a matter of controversy.. T-cell involvement in the pathogenesis of endometriosis was the objective of our study performed on women aged 24-46 years with diagnosed endometriosis. All the patients that were studied underwent diagnostic laparoscopy.. We evaluated the distribution of T-lymphocyte subpopulations in peripheral blood (PB), peritoneal fluid (PF) and in endometriotic tissues (ET), as well as cytokines [interleukin (IL)-2, IL-4, IL-10, IL-12, interferon (IFN)-gamma] production by peripheral blood lymphocytes. IFN-gamma, tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 were investigated for their intracellular presence. The experiments were carried out before and after 6 months treatment with the GnRH-Analogous Goserelin (Zeneca Pharmaceuticals). The number of performed investigations is presented. Statistical analysis was performed using Statistica/Win 5.0 software and Student's t-test, the paired Student t-test and Fisher's exact test when appropriate.. We have compared the lymphocyte subset re-distribution with regard to the American Fertility Society (AFS) stages and scores, but no differences were observed. The significant increase in CD4:CD8 ratio, the decrease in the number of natural killer (NK) cells in PB and the decrease in CD4:CD8 ratio in PF and ET of women with endometriosis was noted. The diminished IFN-gamma secretion by phytohemagglutinim (PHA)-stimulated lymphocytes in vitro derived from women with endometriosis and increased IL-4 production may be responsible for defective immunosurveillance against overgrowth of endometriotic tissues. The diminished NK cells number in PB of women with endometriosis argues for such a hypothesis. The increased deposits of proinflammatory IL-6 and TNF-alpha in the T lymphocytes of women with endometriosis may be related to T-regulatory lymphocyte function and their inability to suppress cell proliferation in endometriosis. GnRH-Analogous Goserelin treatment normalises cytokine production and induces patient recovery.. The significant functional and phenotypic differences between the lymphocytes from healthy women and women with endometriosis were noted. The diminished IFN-gamma production in relation to decreased NK cells number and the increased IL-4 production before the treatment and normalisation after the treatment suggest the involvement of the deregulated T-cell system in the growth stimulation and recruitment of endometriotic cells. The increased CD4:CD8 ratio, IL-6, TNF-alpha deposits and diminished anti-inflammatory IL-10 production by lymphocytes may participate in the pathogenesis of endometriosis, and may secondarily affect the monocyte/macrophage function.

Topics: Adult; Ascitic Fluid; CD4-CD8 Ratio; Cytokines; Endometriosis; Endometrium; Female; Goserelin; Humans; Inflammation Mediators; Interferon-gamma; Interleukin-4; Killer Cells, Natural; Laparoscopy; Lymphocyte Count; Middle Aged; T-Lymphocytes

Endometriosis is a disease causing the growth of endometrial tissue outside its proper localisation. The frequency of this disease occurrence is estimated for about 10% of women at reproductive age. More and more often scientific studies reveal the key role of immunological disorders as the factor contributing to the development of endometriosis. Investigators pay their attention not only on the composition of immunological cells, but on the amount and proportion of their products, including cytokines, as well. Aim of the study was the evaluation of cytokine generation by peripheral blood lymphocytes derived from women with endometriosis, as well as the estimation of combined surgical and pharmacological treatment influence on this production.. The study group consisted of 72 patients treated in Surgical Gynecology Department of Polish Mother Health Centre Research Institute in Lodz, in years 1998-2002. Endometriosis was diagnosed during laparoscopy or laparotomy in 60 of them. The diagnosis was confirmed in histopathological examination. 14 of those patients were qualified to 6 months long Zoladex therapy (AstraZeneca), following the operation. Zoladex was used in a dose of 3.6 mg per month. Evaluation of the cytokine generation was performed before the treatment and repeated after the full therapy. 12 women with no signs of endometriosis lesions existence were the comparison group. Immunofluorescence method ELISA and ENDOGEN commercial kits were used for evaluating the cytokine concentration levels.. Significant decrease in IFN-gamma generation (p < 0.05) by peripheral blood lymphocytes was noted in women with endometriosis before the treatment as compared to women without this disease. Therapy caused its increase and the difference was statistically significant. Significantly higher levels of the IL-4 generation after PHA stimulation were also observed in women with endometriosis then in women from the comparative group. The therapy of endometriosis caused the decrease in IL-4 production, but the differences were not statistically significant (p < 0.05). Significant differences in IL-4 generation after the treatment as compared to the values noted before the treatment were observed only after using conkanavaline A as the lymphocyte stimulator. Generation levels of IL-2, IL-10 and IL-12 did not vary significantly after the combined surgical and pharmacological treatment of endometriosis.. 1. Significant decrease in IFN-gamma concentration was shown in patients with endometriosis, which proves the role of this cytokine in the pathogenesis of this disease. 2. Combined surgical and pharmacological treatment causes the increase in IFN-gamma production by peripheral blood lymphocytes.

Topics: Adult; Antineoplastic Agents, Hormonal; Case-Control Studies; Cytokines; Endometriosis; Enzyme-Linked Immunosorbent Assay; Female; Goserelin; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-2; Interleukin-4; Time Factors; Treatment Outcome

Cutaneous and subcutaneous endometriosis occurs most commonly as a secondary process in scars after abdominal or pelvic surgical procedures including hysterectomy, cesarean sections and episiotomy. Simple excision is the recommended management and local recurrence after adequate excision is uncommon. A 32-year-old woman presented with a 5-cm firm tumor on the right perineum. There was cyclical bleeding and fluctuation in size. She was initially treated with subcutaneous goserelin acetate. The lesion decreased in size and was then successfully excised 4 months later.

Topics: Adult; Antineoplastic Agents, Hormonal; Cicatrix; Endometriosis; Episiotomy; Female; Goserelin; Humans; Perineum; Skin Diseases

We report the case of a 30-year-old patient who underwent a segmental ureteral resection with ureteroureterostomy because of the presence of a left ureterohydronephrosis caused by an intrinsic ureteral endometriotic lesion. Preoperatively, the patient received a 3 months course of GNRH agonists. The serum estradiol level was at 12 pg/ml at the moment of surgery. Histology and immunohistochemistry performed on the resected specimen showed the presence of numerous large haemorrhagic endometriotic foci containing very high levels of alpha-estrogen and progesterone nuclear receptors, a high Ki-67 labeling index and a strong positivity for EGF-receptor. This is the first report of immunohistochemical study performed on ureteral endometriosis preoperatively treated with GNRH agonists. Because hormonal treatments are often prescribed in the treatment of ureteral endometriosis, clinicians should be aware of the possibility of persisting very active and proliferative ureteral endometriotic lesions even under treatment with GNRH agonists and very low levels of circulating estradiol.

Topics: Adult; Endometriosis; ErbB Receptors; Estradiol; Estrogen Receptor alpha; Female; Goserelin; Humans; Hydronephrosis; Immunohistochemistry; Ki-67 Antigen; Premedication; Receptors, Estrogen; Receptors, Progesterone; Ureteral Diseases; Ureterostomy; Urography

Pulmonary lesions and ureter involvement are rare complications of endometriosis. We describe the first case with an involvement of both sites in this condition. The radiographs showed "pulmonary metastases" together with clinical findings of a hydronephrosis, mimicing a malignant metastatic gynecologic tumor of unknown primary. A laparoscopy showed severe endometriotic lesions; therefore the findings were most likely related to the condition of endometriosis. The patient was treated with gosereline acetate for six months (Zoladex). Control radiographs showed complete regression of the pulmonary lesions and the patient is symptom free at 36 months after diagnosis.

Topics: Adult; Endometriosis; Female; Goserelin; Humans; Lung Diseases; Tomography, X-Ray Computed; Ureter

Topics: Adult; Combined Modality Therapy; Endometriosis; Female; Fertility Agents, Female; Goserelin; Humans; Infertility, Female; Microsurgery; Pregnancy

To study the role and value of gonadotropin-releasing hormone agonists (GnRH-a) and laparoscopy for the treatment of adenomyosis with infertility.. Four cases were seen with adenomyosis and infertility, 3 of these cases also presented local adenomyomata in the posterior uterine wall. GnRH-a Triptorelin (decapeptyl) or Goserelin (Zoladex) therapy was instituted for six months before laparoscopic surgery for coexisting pelvic pathologic infertility factors in one case and after laparoscopic surgery in three cases.. All cases remained amenorrheic during GnRH-a therapy. After the GnRH-a therapy, all enlarged uterus (7-10 weeks gestation size) all decreased to normal or near normal size; menstruation returned in 80-90 days and three cases conceived within four menstrual periods after cessation of treatment. In the 4 cases one pregnancy resulted in the birth of a healthy 3150 g male newborn at 38 weeks gestation by cesarean section; one pregnancy was terminated after adenomyomectomy by emergency cesarean section at 30 weeks gestation because of threatened rupture of uterus; one case was then normal at 28 weeks pregnancy; the last case had 2 resumptive menstrual periods and was still being followed up.. GnRH-a is markedly efficient in reducing adenomyotic uterine size, facilitates uterine or endometrial receptivity for embryos and enhances uterine ability to maintain pregnancy. For adenomyomata associated with infertility, GnRH-a instead of surgical removal of lesions, which are deep in the myometrium, may avoid uterine rupture when pregnancy occurs. For infertility, GnRH-a treatment before laparoscopic surgery greatly decreases surgical difficulties and blood loss in certain cases.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Laparoscopy; Triptorelin Pamoate

To Study the role of gonadotropin releasing hormone agonists (GnRH-alpha) in the treatment of adenomyosis with infertility.. Adenomyosis was diagnosed under lapososcopy in 4 infertile cases. Meanwhile coexsting endometriosis, pelvic adhesion and adenomyoma were treated by surgery and endocoagulator in 4 and 2 cases respectively. GnRH-alpha (triptorelin or goserelin) therapy was given for six months before laparoscopic surgery in 1 case and after laparoscopic surgery in 3 cases. Their fecundity outcome were followed-up after cessation of GnRH-alpha treatment.. All cases became amenorrheic during GnRH-alpha therapy. The enlarged uteri all decreased to normal or near normal size. Menstruation returned in 80-90 days after cessation of treatment. Three cases conceived within four menstrual periods. One of them resulted in the birth of a healthy 3 150 g male at 38 weeks gestation by cesarean section. The second pregnancy resulting after adenomyomectomy was terminated by emergent cesarean section at 30 weeks gestation because of threatened rupture of uterus. The third is now normal at 28 weeks pregnancy. The fourth has had 2 menstrual periods and is still being followed up.. (1) GnRH-alpha thus used is efficient in reducing the adenomyotic uterine size, and may facilitate fertility. (2) For ademyomata associated with infertility, GnRH-alpha therapy may avoid the risk of rupture of uterus which may occur after adenomyomectomy pregnancy. (3) For infertility, GnRH-alpha treatment before laparoscopic surgery greatly decreases surgical difficulties and blood loss in certain cases.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Triptorelin Pamoate; Uterine Diseases

To evaluate the clinical utility of recently developed biochemical markers in the assessment of bone metabolism during GnRH agonist (GnRHa) treatment, we compared five bone resorption markers [C-telopeptide (CTX) and N-telopeptide (NTX) of type I collagen, hydroxyproline (Hpr), pyridinoline (Pyr), and deoxypyridinoline (Dpyr)] and two bone formation markers [total alkaline phosphatase (Alp) and osteocalcin (OC)]. Sixty-eight normally menstruating women were injected with a long-acting GnRHa once a month for 24 weeks for the treatment of endometriosis or leiomyoma. The mean percentage bone loss at the lumbar spine was 3.79% at the end of treatment. Although levels of all markers increased significantly as the treatment progressed, CTX and NTX exhibited the highest correlation coefficients between bone loss at 24 weeks and the seven markers measured at 0, 4, 12, 16, and 24 weeks of treatment. Serum estradiol levels were similarly suppressed during the treatment in both fast losers (whose bone loss was more than the mean) and slow losers (whose bone loss was less than the mean). However, significantly higher z-scores of bone resorption markers, but not of bone formation markers, were observed in the fast losers at 24 weeks of treatment, suggesting a more accelerated bone resorption in this group. Whereas the three highest z-scores at 24 weeks of treatment were CTX, NTX, and Dpyr (in that order), the highest z-score (P < 0.05) was observed for CTX in the fast losers. The subjects in the highest quartile of CTX, the highest, and second highest quartiles of NTX at 24 weeks of treatment experienced 2.1, 2.2, and 1.7 times more bone loss (P < 0.001), respectively, than those in the lowest quartiles. Furthermore, the subjects in the highest quartile of both CTX and NTX experienced 3.6 times more bone loss (P < 0.001) than those in the lowest quartile of both markers. These results indicate that both CTX and NTX are useful and sensitive markers for bone resorption in a hypoestrogenic state induced by GnRHa.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Antineoplastic Agents, Hormonal; Biomarkers; Bone Remodeling; Buserelin; Collagen; Collagen Type I; Endometriosis; Estradiol; Female; Goserelin; Humans; Hydroxyproline; Leiomyoma; Osteocalcin; Peptides; Retrospective Studies

The effects of estrogen suppression on bone mineralization in young women were studied by quantitative backscattered electron (BSE) imaging of transiliac biopsies taken before and after treatment for endometriosis. Treatment (6 months) was with analogs of gonadotrophin releasing hormone (GnRH) given either alone (six paired biopsies), which resulted in a marked reduction in the levels of circulating estrogen, or in conjunction with tibolone, a synthetic steroid with estrogenic, progestrogenic, and androgenic properties (four paired biopsies). Estrogen withdrawal increased (p < 0.01) and concomitant tibolone treatment decreased (p < 0.05) the overall mean bone density. Estrogen withdrawal increased the fraction of bone with a high mineralization density [pretreatment: 0.236+/-0.007; GnRH: 0.279+/-0.009, mean +/- standard error of the mean (SEM); p < 0.01]. The concomitant addition of tibolone reversed these effects and increased the proportion of bone with a low mineralization density (pretreatment: 0.198 +/- 0.005; tibolone: 0.230 +/-0.008, p < 0.01). Using previously published data, the mean bone density was inversely correlated with mean wall thickness in cancellous bone (p = 0.030) and with the percentage of active osteons (p = 0.023) in cortical bone. Although treatment had similar effects on the mean bone mineralization density of cortical and cancellous bone, there were different distributions of mineralization between the two sites, with cancellous bone having more skewed and kurtotic distributions both before and after estrogen withdrawal. This study indicates that a short-term estrogen suppression results in the accumulation of bone with a higher mineralization density. As bone with a high mineral content has a decreased impact resistance, this might increase fracture risk. Understanding the cellular and biochemical mechanisms responsible for the local distribution of bone mineral when estrogen is withdrawn may allow the development of new strategies for maintaining bone quality after menopause.

Topics: Adult; Antineoplastic Agents, Hormonal; Biopsy; Bone Density; Calcification, Physiologic; Drug Therapy, Combination; Endometriosis; Estrogens; Female; Goserelin; Humans; Ilium; Microscopy, Electron, Scanning; Norpregnenes; Triptorelin Pamoate

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ovarian Diseases; Pregnancy

We have studied epidermal growth factor (EGF) receptor expression in endometrium and in endometriotic implants, testing a group of 36 women before and after a 4-month gonadotropin-releasing hormone (GnRH) analog (GnRH-a) goserelin depot treatment. Each woman underwent laparoscopy twice. At the initial laparoscopy, before starting treatment, the disease was staged according to the American Fertility Society (AFS) classification and biopsies of endometriotic implants were undertaken. The follow-up laparoscopy was performed within 5 weeks of the last GnRH-a administration. Biopsies were taken from areas of previously noted disease, both visually persistent and visually free of disease. At the time of each laparoscopy, photographs of all areas of disease were taken. Specimens of eutopic endometrium were collected from each patient at the time of laparoscopy by a Novak curette. Endometrial and endometriotic samples were processed for immunohistochemical detection of EGF receptor, using anti-EGF receptor monoclonal antibody Ab-3. After treatment, the marked improvement of AFS score was associated with a dramatic reduction of EGF receptor immunostaining, but the exact meaning of this finding is still not completely understood. The dramatic reduction of EGF receptor expression in eutopic and ectopic endometrium samples after treatment is not obviously related to the hypoestrogenism induced by the drug. It has been suggested that steroid hormones and EGF play a role in regulation of EGF receptor expression, so that drugs such as goserelin depot could act directly at local peripheral level influencing the EGF receptor expression via the production of its ligand.

Topics: Adult; Antibodies, Monoclonal; Delayed-Action Preparations; Endometriosis; ErbB Receptors; Female; Goserelin; Humans; Immunohistochemistry; Laparoscopy; Pelvis

The effects of estrogen suppression on osteonal remodeling in young women was investigated using transiliac biopsies (eight paired biopsies + four single pre; three single post biopsies) taken before and after treatment for endometriosis (6 months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen withdrawal increased the proportion of Haversian canals with an eroded surface (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002), and alkaline phosphatase (ALP) 116%, p = 0.043) but not those showing tartrate-resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p = 0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in canals with diameters greater than 50 microns (p = 0.0089) and also the number of osteons with diameters over 250 microns (p = 0.049). ALP activity in individual osteoblasts was increased but not significantly following treatment (p = 0.051). Wall thickness was significantly correlated with osteon diameter (p < 0.001). In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption. Enzyme activities and numbers of active canals were also not increased with the concurrent treatment, but there was still an increase in the osteon diameter. As previously shown for cancellous bone, estrogen withdrawal increased cortical bone turnover. We have now shown that resorption depth within Haversian systems was also increased with treatment. The enhanced TRAP activity in individual osteoclasts supports the concept that osteoclasts are more active following estrogen withdrawal in agreement with theoretical arguments advanced previously. Understanding the cellular and biochemical mechanisms responsible for increased depth of osteoclast resorption when estrogen is withdrawn may allow the development of new strategies for preventing postmenopausal bone loss.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Biopsy; Bone Density; Bone Remodeling; Drug Therapy, Combination; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ilium; Isoenzymes; Norpregnenes; Osteoclasts; Osteoporosis, Postmenopausal; Software; Tartrate-Resistant Acid Phosphatase; Triptorelin Pamoate

The management of large endometriomas was described in a series of 814 patients. Combined therapy using gonadotrophin-releasing hormone agonist (GnRHa) and carbon dioxide laser laparoscopy was proposed. Drainage and GnRHa for 12 weeks provoked a reduction of the endometrioma size up to 50% of the initial value. After vaporization of the internal wall, a cumulative pregnancy of 51% after 1 year was achieved. A recurrence rate of 8% was observed for a follow-up of 2-11 years. Histological data demonstrated that the epithelium covering the ovary which is the mesothelium can invaginate in the ovarian cortex. Some of the invaginations were seen to be continuous with endometrial tissue, strongly suggesting the metaplasia theory in the pathogenesis of ovarian endometrioma.

Topics: Combined Modality Therapy; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Laser Therapy; Metaplasia; Ovarian Cysts; Ovarian Diseases; Pregnancy; Recurrence

Topics: Adult; Autoantibodies; Cardiolipins; Endometriosis; Female; Fertilization in Vitro; Goserelin; Histones; Humans

A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. We postulate that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. We believe this is the first report of this complication following use of GnRH analogue.

Topics: Adult; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Polyps; Substance Withdrawal Syndrome

Topics: Endometriosis; Female; Goserelin; Humans

Women suffering from endometriosis are treated with long-acting analogues of gonadotropin-releasing hormone (GnRH). This is a case of hypersensitivity reaction to a goserelin acetate implant that manifested as an anaphylactic reaction. This is the first report of a hypersensitivity reaction to the GnRH analogue, goserelin acetate (Zoladex, Zeneca Pharmaceuticals, Wilmington, DE).

Topics: Adult; Antineoplastic Agents, Hormonal; Drug Hypersensitivity; Endometriosis; Female; Goserelin; Humans

Clinical and pathological changes of the mammary gland have been studied in 64 women affected by symptomatic Benign Breast Disease (BBD) coexisting with endometriosis or uterine leiomyomata. These patients were rendered hypoestrogenic by subcutaneous administration of the LH-RH analogue Goserelin depot [D-ser (tBu)6 Aza-Gly10-GnRH (ICI118630)] performed every 28 days, for six months. They were evaluated clinically and ultrasonographically before and after treatment to find possible changes of BBD as well as of endometriosis or uterine leiomyomata. Mammary biopsies were performed before and after treatment in all the patients to study the changes of EGF-R expression. Results showed that clinical improvement is accompanied with a reduction of EGF-R expression.

Topics: Antineoplastic Agents, Hormonal; Endometriosis; ErbB Receptors; Female; Goserelin; Humans; Leiomyomatosis; Uterine Diseases; Uterine Neoplasms

Topics: Adult; Antineoplastic Agents, Hormonal; Endometriosis; Female; Goserelin; Humans; Leiomyomatosis; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Uterine Neoplasms

Endometriosis is one of the main causes of female sterility, leading not only to subjective complaints, such as anovulatory menstrual cycles and LUF syndrome, but also to appearance of antisperm antibodies due to the increased number of macrophages, We present our experience in the treatment of endometriosis with the GnRH analogue Zoladex, product of Zeneca, as well as in the treatment of antisperm antibodies with methyiprednizolon acetate, Depomedrol of Upjohn.

Topics: Adult; Delayed-Action Preparations; Drug Therapy, Combination; Endometriosis; Female; Goserelin; Humans; Immunosuppressive Agents; Infertility, Female; Methylprednisolone; Methylprednisolone Acetate; Tablets; Uterine Diseases

In the design of clinical trials, sample size determination is usually undertaken by statisticians and clinicians. It is rare for health economists to be involved in this aspect of trial design. However, there are a number of outcome changes that are of 'economic significance', and it is important for trial designers and funders to be aware of these before planning, funding and mounting a trial. In this paper we demonstrate through the use of three examples (prevention of osteoporosis, management of infertility, and endometriosis) how economics can be used to influence the size of a clinical trial. Trials that are too small or too large waste research resources; health economics can lead to more efficient trial designs.

Topics: Adult; Aged; Clinical Trials as Topic; Cost-Benefit Analysis; Danazol; Endometriosis; Female; Goserelin; Humans; Hydrochlorothiazide; Infertility, Female; Osteoporosis; Research Design; Sample Size; Treatment Outcome

Topics: Adnexal Diseases; Adolescent; Adult; Endometriosis; Female; Genital Diseases, Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Uterine Diseases

Topics: Adnexal Diseases; Adult; Endometriosis; Female; Goserelin; Humans; Pregnancy; Pregnancy, Multiple

Topics: Danazol; Endometriosis; Endometrium; Female; Follow-Up Studies; Goserelin; Hemostasis, Endoscopic; Humans; Hysteroscopy; Laser Therapy; Leiomyoma; Menorrhagia; Preoperative Care; Treatment Outcome; Uterine Neoplasms

Topics: Drug Implants; Endometriosis; Female; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Uterine Diseases

Topics: Adult; Buserelin; Drug Therapy, Combination; Endometriosis; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Goserelin; Humans; Medroxyprogesterone; Pelvic Neoplasms

In the period 1988-1990 this prospective study of 33 women with moderate or severe endometriosis who underwent laparoscopy for infertility and/or chronic pelvic pain, was conducted to evaluate the efficacy of aspirating endometriotic cysts followed by administration of a gonadotropin releasing hormone (GnRH) agonist in reducing the size of ovarian endometriomas. The cysts (mean diameter, 4.5 cm; range, 2-7; unilateral, 21 cases; bilateral, 12 cases) were punctured, aspirated, washed and emptied completely. After laparoscopy, 15 subjects received goserelin administered as a 28-day subcutaneous depot for three months, whereas 18 patients undergoing simple observation constituted internal controls. Ultrasound scans were performed before and at one, three and six months after laparoscopy. One case and three controls requested surgery between the four- and five-month follow-up scans and did not complete the study. All the other women had recurrent cysts at the six-month scan. There were no significant differences in mean endometrioma diameter between the two groups at any observation time nor between prelaparoscopic and six-month ultrasound examinations within each treatment group. We conclude that aspiration and washing of endometriotic cysts, combined with postoperative administration of GnRH agonists or not, is ineffective.

Topics: Adult; Analysis of Variance; Biopsy, Needle; Buserelin; Endometriosis; Female; Goserelin; Humans; Laparoscopy; Ovarian Neoplasms; Prospective Studies; Suction; Ultrasonography

Topics: Adult; Buserelin; Combined Modality Therapy; Endometriosis; Female; Goserelin; Humans; Hysteroscopy; Leiomyoma; Myometrium; Ovarian Neoplasms; Prospective Studies; Uterine Neoplasms

To evaluate the safety and efficacy of Goserelin (Zoladex depot; ICI Pharmaceuticals, Macclesfield, Cheshire, United Kingdom) in the treatment of endometriosis.. Open study.. Eleven centers in Germany and 1 center in Austria.. One hundred forty-six patients with pelvic endometriosis.. Goserelin (Zoladex depot) therapy, one depot (3.6 mg) subcutaneously every 4 weeks for 6 months.. Total subjective score and total pelvic symptom score showed a reduction by 86% and 93%, respectively, at the end of the treatment and did not exceed one fifth of the pretreatment value throughout the follow-up period of 48 weeks. One hundred seven women underwent a second laparoscopy at the end of the therapy for determination of objective efficacy: 54% of the patients showed a reduction of implants and adhesions by at least 50% or more, and 31.5% had a complete resolution of visible deposits. The mean reduction of implants and adhesions was 50%, and the mean reduction of implants 72%. Twenty of 64 (31.3%) previously infertile patients successfully conceived within 12 months after discontinuation of the therapy. Goserelin led to a down regulation of the pituitary ovarian axis and as a pharmacological effect of this hypoestrogenism most patients had hot flushes and vaginal dryness.. Zoladex depot therapy proved to be safe and effective in the medical treatment of endometriosis.

Topics: Adult; Buserelin; Delayed-Action Preparations; Endometriosis; Female; Gonadal Steroid Hormones; Goserelin; Humans; Pregnancy; Uterine Hemorrhage

Before treatment, the trabecular bone mineral content of the lumbar spine and femoral neck was not significantly different between endometriosis patients and age-matched controls (N = 26). In 17 subjects treated with a monthly goserelin implant, serum estradiol (E2) levels were suppressed into the menopausal range. Mean decreases from pre-treatment values in the lumbar spine and femoral neck were -5.7 and -3.8% at 3 months and -8.2 and -7.7% at 6 months of treatment, respectively; lumbar spine values were significantly different (P less than .05) from those of the control group, whose values changed little during the same period. Significant increases over baseline values were also observed in urinary calcium-creatinine ratio and serum alkaline phosphatase. In nine danazol-treated subjects, serum E2 levels were generally within the early follicular-phase range. There were no significant changes in bone assessments. Normal menses returned within 2 months after cessation of either medication. Six months after goserelin treatment, the lumbar spine and femoral neck bone mineral content was still reduced but to values not significantly different from the pre-treatment and control values; urinary calcium-creatinine ratio was decreased, whereas serum alkaline phosphatase was still elevated. The rapid and deep suppression of ovarian steroidogenesis by a monthly goserelin implant induced significant bone loss compared with the control and danazol groups. This loss was not reversed completely 6 months after cessation of treatment, but bone densities at that time were not different from those of controls. Studies of larger numbers of patients followed for longer periods will be required to resolve the question of complete reversibility.

Topics: Adult; Alkaline Phosphatase; Bone Density; Buserelin; Danazol; Drug Implants; Endometriosis; Estradiol; Female; Femur Neck; Follow-Up Studies; Genital Neoplasms, Female; Goserelin; Humans; Random Allocation; Spine

We report a case of recurring catamenial pneumothorax with concurrent pelvic endometriosis. Thoracoscopy revealed a blue-like lesion on top of the dome of the right hemidiaphragm. Microscopic examination of biopsy specimens showed endometriosis. The patient was treated with a Gn-RH analogue and remains well without further evidence of pneumothorax after six months.

Topics: Adult; Buserelin; Endometriosis; Female; Goserelin; Humans; Menstruation; Pleural Neoplasms; Pneumothorax; Recurrence

Fourteen patients affected by endometriosis were treated by Danazol and by Goserelin. The two treatments were compared. From the study it emerged that both treatments were equally effective; however, the analogs gave a more favourable therapeutic profile.

Topics: Bone Density; Buserelin; Danazol; Endometriosis; Female; Goserelin; Humans; Pelvic Neoplasms

Eighty patients with different stages of genital endometriosis were treated with Zoladex, a gonadotrophin-releasing hormone analogue in a depot formulation, injected subcutaneously every 4 weeks. The stages of endometriosis (I-IV) were classified according to the revised American Fertility Society recommendations (AFS criteria) via pelviscopy before and after 6 months of treatment. Fifty-eight second-look pelviscopies were performed with the following objective changes after (before) treatment: Stage IV 0 (3); Stage III, 2 (13); Stage II, 12 (30); Stage I, 19 (12). Twenty-five patients presented with Stage 0 after therapy and were healed. All 57 symptomatic patients showed a subjective response to Zoladex therapy with a significant decrease of the total pelvic symptom score. Thirty-eight patients with infertility wished to become pregnant and so far 16 (40%) have conceived. During therapy, the serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol and progesterone were significantly suppressed. All patients were amenorrhoeic after 1-2 injections. Restoration of ovarian function with resumption of menstruation occurred within 57-92 days after the last injection of Zoladex (1-2 months after end of treatment). Side-effects were minimal and were those expected of the hypo-oestrogenic state, such as hot flushes, vaginal dryness and decrease of libido.

Topics: Adult; Buserelin; Delayed-Action Preparations; Endometriosis; Estradiol; Female; Goserelin; Humans; Luteinizing Hormone; Pregnancy; Pregnancy Outcome; Progesterone; Prolactin; Testosterone

Topics: Adult; Androgens; Antineoplastic Agents; Buserelin; Drug Implants; Endometriosis; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intramuscular; Leiomyoma; Luteinizing Hormone; Triptorelin Pamoate; Uterine Neoplasms

Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 +/- 0.21 to 3.71 +/- 0.36 (mean +/- SEM) at 120 min (P less than 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women (n = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 +/- 0.22 to 2.59 +/- 0.24, and the B/F ratio from 1.78 +/- 0.22 to 2.90 +/- 0.30 (P less than 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (less than 0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of +/- SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 +/- 0.5 to 0.14 +/- 0.03 (P less than 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 +/- 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 +/- 0.49, and the B/F ratio was 3.53 +/- 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P less than 0.01 for all).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aged; Biological Assay; Buserelin; Endometriosis; Female; Fluorescent Antibody Technique; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Menopause; Middle Aged; Nafarelin; Orchiectomy; Ovarian Neoplasms; Ovariectomy; Prostatic Neoplasms; Radioimmunoassay; Uterine Neoplasms

Thirty-two patients with laparoscopic diagnosis of endometriosis were treated for 6 months with the gonadotropin-releasing hormone agonist goserelin depot. Hormonal and clinical evaluations were conducted during treatment and for a 6-month follow-up period. Serum 17 beta-estradiol levels were sharply suppressed. Luteinizing hormone was also decreased, whereas follicle-stimulating hormone, after an initial fall, gradually rose to pretreatment levels. Ovarian androgenic production was less inhibited, total testosterone being the only significantly suppressed hormone. There was a marked improvement of signs and symptoms of endometriosis and a 47.3% reduction of laparoscopic score. The results of this study suggest that goserelin depot provides a very good suppression of ovarian estrogen production and is highly effective in decreasing the symptoms of endometriosis with an acceptable compliance by the patient.

Topics: Adult; Buserelin; Delayed-Action Preparations; Endocrine Glands; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menstrual Cycle; Prolactin

In addition to surgery, several hormonal treatments are available for endometriosis. Although efficacious, drug treatment is limited by side effects. Recent work with LHRH analogues as a potential treatment for endometriosis has shown promising results.

Topics: Buserelin; Danazol; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Nafarelin

Plasma lipid risk markers for coronary heart disease (CHD) are influenced by sex steroid concentrations. Therapies that alter sex hormone levels have the potential to affect CHD risk. Zoladex had no effect on plasma lipids, but increased high density lipoprotein (HDL) subfraction 3, a lipoprotein of uncertain clinical significance. Danazol increased low density lipoprotein and decreased HDL concentrations to give a lipid profile associated with increased risk of CHD.

Topics: Buserelin; Cholesterol; Danazol; Endometriosis; Female; Goserelin; Humans; Lipoproteins; Pelvic Neoplasms; Pregnadienes; Risk Factors; Triglycerides

The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.

Topics: Adult; Bone Density; Buserelin; Danazol; Endometriosis; Female; Goserelin; Humans; Osteoporosis; Pregnadienes

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

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

Topics: Administration, Cutaneous; Buserelin; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Endometriosis; Estradiol; Female; Goserelin; Humans

We know that there is a wide range of clinical applications for GnRH analogues in the field of benign gynaecological disorders. As we understand more of the physiology and mechanism of these GnRH agonists, and there appear more varied and perhaps efficient delivery systems, and antagonists become available, it may be possible to develop a graded approach in suppression of the hypothalamic pituitary axis. The true potential of these agents is then yet to be fully realized. There can be no doubt they are going to influence practice dramatically over the next decade. The potency of these agents, perhaps specifically their effects of oestrogen deficiency and calcium bone metabolism, suggests that limitation of duration of use and timing of recurrent administration to individuals is likely to be necessary.

Topics: Buserelin; Danazol; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Nafarelin; Osteolysis; Polycystic Ovary Syndrome; Uterine Neoplasms

Topics: Buserelin; Delayed-Action Preparations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Uterine Neoplasms