A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial. Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: a prospective, randomized trial. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue.
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. 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. 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. The aim of this study was to determine whether or not continuous combined HRT used with GnRH-a for the treatment of endometriosis can prevent hypoestrogenic side effects associated with GnRH-a.
                Forty premenopausal women with laparoscopically proven endometriosis entered the study. The patients were randomized into two groups. Group I (n = 19) received 3.75 mg i.m. leuprolide acetate (LA) every 4 weeks for 24 weeks. Group II (n = 21) received 3.7 mg LA combined with 1.25 mg oral conjugated equine estrogen (CEE) and 5 mg oral medroxyprogesterone acetate (MA).
                Total revised AFS score as well as total pelvic pain scores decreased significantly (P < .001) in both groups. However, a statistically significant difference of hot flushes and sweating was reported by women receiving LA + HRT as compared to those treated with LA alone (P < .001). Furthermore, the bone loss at the lumbar spine was 4.2% in group I compared to 0.9% in group II at the end of the study.
                This study suggests that 1.25 mg CEE + 5 mg MA is effective in preventing hypoestrogenic side effects caused by GnRH-a, while the treatment of endometriosis is not impaired. 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. We sought to evaluate the efficacy of postoperative administration of monophasic, combined, low-dose oral contraceptives on endometrioma recurrence and on persistence-recurrence of associated pain symptoms after laparoscopic treatment of moderate-to-severe endometriosis.
                In a prospective, randomized trial 70 patients who were not attempting to conceive, aged 20 to 35 years, underwent laparoscopic excision of ovarian endometriomas, followed by either postoperative administration of low-dose cyclic oral contraceptives for 6 months or no treatment on the basis of a computer-generated sequence. At 3 and 6 months after surgery and then at 6-month intervals, both groups underwent ultrasonographic examination for possible evidence of endometrioma recurrence and for evaluation of the absence, persistence, or recurrence of pain symptoms.
                Two patients in the oral contraceptive group did not complete the study. After a mean follow-up of 22 months (range, 12-48 months), there were 2 (6.1%) endometrioma recurrences in the 33 patients who received postoperative oral contraceptives versus 1 (2.9%) recurrence in the 35 patients in the control group (not significant). The moderate-to-severe pain recurrence rate was 9.1% in the oral contraceptive group versus 17.1% in the control group (not significant). The mean time to recurrence of either symptoms or endometriomas was 18.2 months in the oral contraceptive group versus 12.7 months in the control group. The 12-month cumulative recurrence rate at life-table analysis was significantly lower for patients receiving oral contraceptives versus control subjects, whereas no significant difference was evident at 24 and 36 months.
                Postoperative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence rate of endometriosis after surgical treatment. A delay in recurrence is evident at life-table analysis. To determine the effect of estrogen replacement therapy (ERT) on recurrence rate and survival in women who have undergone surgery for stage I or II endometrial cancer.
                After surgery, eligible patients were allocated to therapy with ERT or placebo after undergoing hysterectomy with or without pelvic and aortic nodal sampling. Planned duration of hormonal versus placebo treatment was 3 years, with an additional 2 years of follow-up.
                The median follow-up time for all 1,236 eligible and assessable patients was 35.7 months. Stage, grade, histologic subtype, and percentage of patients receiving adjuvant therapy were similarly distributed between the groups. The median age at diagnosis for the 618 patients randomly assigned to ERT was 57 years (range, 26 to 91 years). Two hundred fifty-one patients (41.1%) were compliant with ERT for the entire treatment period. Disease recurrence was experienced in 14 patients (2.3%). Eight patients (1.3%) developed a new malignancy. There were 26 deaths (4.2%), and five deaths (0.8%) were a result of endometrial cancer. The median age at diagnosis for the 618 patients in the placebo group was 57 years (range, 30 to 88 years). Twelve patients (1.9%) experienced disease recurrence. Ten patients (1.6%) developed a new malignancy. There were 9 deaths (3.1%) in the placebo group, and four deaths (0.6%) were a result of endometrial cancer.
                Although this incomplete study cannot conclusively refute or support the safety of exogenous estrogen with regard to risk of endometrial recurrence, it is noteworthy that the absolute recurrence rate (2.1%) and the incidence of new malignancy were low. To determine whether the frequency and severity of dysmenorrhea are reduced in women with symptomatic endometriosis in whom a levonorgestrel-releasing intrauterine device (Lng-IUD) is inserted after operative laparoscopy compared with those treated with surgery only.
                Open-label, parallel-group, randomized, controlled trial.
                A tertiary care and referral center for patients with endometriosis.
                Parous women with moderate or severe dysmenorrhea undergoing first-line operative laparoscopy for symptomatic endometriosis.
                Randomization to immediate Lng-IUD insertion or expectant management after laparoscopic treatment of endometriotic lesions. Proportions of women with recurrence of moderate or severe dysmenorrhea in the two study groups 1 year after surgery and overall degree of satisfaction with treatment. Moderate or severe dysmenorrhea recurred in 2 of 20 (10%) subjects in the postoperative Lng-IUD group and 9/20 (45%) in the surgery-only group. Thus, a medicated device inserted postoperatively will prevent the recurrence of moderate or severe dysmenorrhea in one out of three patients 1 year after surgery. A total of 15/20 (75%) women in the Lng-IUD group and 10/20 (50%) in the expectant management group were satisfied or very satisfied with the treatment received.
                Insertion of an Lng-IUD after laparoscopic surgery for symptomatic endometriosis significantly reduced the medium-term risk of recurrence of moderate or severe dysmenorrhea. 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.
                Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Hormone replacement therapy for women with endometriosis in post-surgical menopause could result in pain and disease recurrence. However, the evidence in the literature is not strong enough to suggest depriving severely symptomatic patients from this treatment. There is a need for more randomised controlled studies.