A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Pre or post-operative medical treatment with nafarelin in stage III-IV endometriosis: a French multicenter study. Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial. Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: a prospective, randomized trial. Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study. Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial. Comparative study on the efficacy of Yiweining and Gestrinone for post-operational treatment of stage III endometriosis. Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial.
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 investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis.
                Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients).
                Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test).
                Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility. To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial. To determine the effectiveness of a 6-month course of nafarelin in the treatment of stage III-IV endometriosis and to determine if pre-operative use of nafarelin facilitates surgery.
                Prospective, multicenter, clinical trial.
                Eight university hospitals and two private practice institutions in France.
                Fifty-five patients with stage III and IV endometriosis. Two were excluded.
                The severity of endometriosis was assessed at the time of laparoscopy and patients were randomized to have either laparosopic surgery at that time following 6 months of nafarelin therapy (n=28), or laparoscopic surgery following 6 months of nafarelin therapy (n=25). All had 200 microg intranasal nafarelin twice a day for 6 months and a second look laparoscopy.
                Clinical efficacy, tolerance to the treatment.
                Efficacy and tolerance to the treatment were the same in both groups. AFS scores compared on both laparoscopies were significantly better if nafarelin was given prior to surgery (P=0.007).
                This preliminary study shows that in cases of combined medico-surgical treatment for stage III-IV endometriosis, preoperative medical treatment with GnRH-a gives a better AFS score improvement, but no conclusion was possible whether preoperative treatment facilitates surgery. 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. 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. To evaluate the efficacy of the GnRH agonist (GnRH-a) nafarelin compared with placebo administered for 6 months after reductive laparoscopic surgery for symptomatic endometriosis.
                Randomized, prospective, placebo-controlled, multicenter clinical trial.
                Thirteen clinics including private practice and university centers.
                One hundred nine women aged 18-47 with laparoscopically proven endometriosis and pelvic pain who had undergone reductive laparoscopic surgery for endometriosis.
                Patients were randomized to receive either the GnRH-a nafarelin (200 micrograms twice daily) or placebo for 6 months.
                Time to initiation of alternative treatment (the length of time from beginning study medication to receiving alternative therapy or to deeming that the study drug was ineffective) and patient-reported and physician-assessed pelvic pain scores.
                The median time to initiation of alternative treatment was > 24 months in the nafarelin group versus 11.7 months in the placebo group. Fifteen (31%) of 49 nafarelin-treated patients required alternative therapy, compared with 25 (57%) of 44 placebo-treated patients. The patients' pelvic pain scores dropped significantly in the nafarelin and placebo groups after 6 months of treatment. Physician summary ratings showed significant improvement in the nafarelin group and no significant changes in the placebo group after 6 months of treatment.
                Compared with placebo, nafarelin administered after reductive laparoscopic surgery for endometriosis significantly delays the return of endometriosis symptoms requiring further treatment. 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 assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.
                Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).
                Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).
                Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery. The effect of treatment with danazol was evaluated with respect to expectant management after laparoscopic conservative surgery. All patients conservatively operated at laparoscopy for stage III-IV endometriosis from July 1994 to October 1996 were requested to enter the study. Patients who underwent surgery for recurrent endometriosis were excluded from the study, as well as patients who had taken hormonal therapies before laparoscopy. Informed consent was obtained from 77 women who were randomized after surgery to treatment with danazol 600 mg daily for 3 months (n = 36) or to expectant management (n = 41). All patients were regularly followed up every 6 months for evaluation of fertility, recurrence of pain symptoms and disease. During the follow-up, six (55%) of the 11 infertile women allocated to danazol and eight (50%) of the 16 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during follow-up in seven (23%) of the 31 women with pelvic pain allocated to the danazol group and nine (31%) of the 29 allocated to no treatment; the respective cumulative pain recurrence rates at 12 months were 26 and 34% (log rank test, not significant). Three women (8.3%) treated with danazol and six (15%) who received no treatment had disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography (not significant). Our results do not demonstrate a significant advantage of 3 month danazol therapy after laparoscopic surgery for stage III-IV endometriosis with respect to postoperative expectant management. 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. To observe the clinical efficacy and safety of Yiweining (YWN) and gestrinone (GT) in treating post-operational patients of stage III endometriosis (EM-III).
                Fifty-two patients of EM-III after operation were randomly assigned into three groups, the YWN group (20 patients) was treated through oral intake of YWN 200 ml, twice a day; the GT group (19 patients) treated with gestrinone 2.5 mg, twice every week, with the medication starting from the 7th post-operational day and lasting for 6 months. The control group (13 patients) was untreated. Six months was one therapeutic course, and follow-up study was carried out in the 6 - 30 months after the end of the medication.
                The recurrence rate in the YWN group and the GT group were 5.0% and 5.3% respectively, showing insignificant difference between the two groups, but they were lower than that in the control group (30.7%, P < 0.05). Besides, the adverse reaction rate in the YWN group was lower than that in the GT group (10.0% vs 31.6%, P < 0.05).
                Application of YWN to prevent the post-operational recurrence of endometriosis is effective and safe, and its efficacy is similar to that of GT. Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis.
                Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society, revised, classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions. Patients were assigned according to a randomization list to nasal nafarelin, 400 micrograms/day (36 subjects) or placebo nasal spray (39 subjects) for 3 months. Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale.
                No marked differences in pain scores emerged among women allocated to different treatments. The mean reduction of the multidimensional score was 3.6 and 4.0, respectively, in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9. These differences were not statistically significant. Within 1 year from randomization, of the 36 women allocated to nafarelin and the 39 allocated to placebo, seven (19%) and seven (18%), respectively, became pregnant.
                This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis.
There is no evidence of benefit associated with post surgical medical therapy and insufficient evidence to determine whether there is a benefit from pre-surgical medical therapy with regard to the outcomes evaluated.