leuprolide and Dyspareunia

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

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

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

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

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

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

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

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

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

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

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

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