A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Effects of add-back therapy on bone mineral density and pyridinium crosslinks in patients with endometriosis treated with gonadotropin-releasing hormone agonists. Updating the clinical experience in endometriosis--the European perspective. Pain of endometriosis: effects of nafarelin and danazol therapy. Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis. A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis.
The purpose of this study was to evaluate the efficacy and safety of nafarelin, a gonadotropin-releasing hormone (GnRH) analogue, versus danazol in the treatment of women with endometriosis in Taiwan.
                Fifty-nine women with laparoscopically and pathologically confirmed endometriosis were randomized to receive nafarelin or danazol for 180 days. Efficacy was assessed from mean changes in laparoscopy score (LS) and total symptom severity score (TSSS). Adverse events (AEs) and laboratory parameters, including hematology, hepatic function, blood pressure, and lipid levels, were monitored for safety evaluations.
                All demographic and baseline factors, except body weight, were comparable between the 2 treatment groups. Both nafarelin and danazol satisfactorily resolved pelvic tenderness, induration, pelvic pain, dysmenorrhea and dyspareunia. No significant differences were noted in efficacy endpoints between nafarelin and danazol regarding LS and TSSS at 90 and 180 days of treatment. No significant difference was observed between the 2 groups regarding the overall incidence of AEs, except for laboratory-related AEs. However, nafarelin tended to have less impact than danazol on aspartate transaminase and alanine transaminase, and nafarelin was better tolerated than danazol regarding changes in lipid profiles. Both treatments had little or no effect on hematologic parameters.
                Nafarelin and danazol demonstrated similar clinical efficacy, but nafarelin was associated with fewer laboratory changes and a stable lipid profile, relative to danazol. Moreover, intranasally administered nafarelin is noninvasive, and may be a more comfortable and safer alternative to slow-release injectable GnRH agonists. Based on this study, we suggest that nafarelin, like other GnRH analogues, may be a treatment of choice for Taiwanese women with endometriosis. However, direct comparative studies of nafarelin with slow-release injectable GnRH agonists are now required. A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis. 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. 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. Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRHa) is limited to 6 months because of possible adverse effects on bone metabolism. We designed a randomized, double-blind, placebo-controlled, prospective study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 microg of ethinyl estradiol with 0.15 mg desogestrel) designed to suppress the adverse effects of hypoestrogenism while preserving the efficacy of GnRHa. Both regimens showed significant improvements in endometriosis, dysmenorrhea, and pelvic pain; effects were significantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher loss of lumbar spine bone mineral density (BMD). Urinary levels of pyridinium crosslinks increased significantly in the GnRHa + placebo group, and declined to normal in the GnRHa + add-back group. The add-back therapy protects women taking GnRHas from severe loss of BMD and accelerated bone collagen resorption, but reduces the efficacy of the GnRHa. In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group. To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea, dyspareunia, and pelvic pain associated with endometriosis.
                Prospective, randomized double-blind controlled study. PATIENTS, SETTING, TREATMENTS: Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea, dyspareunia or pelvic pain were randomly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day, or danazol 800 micrograms per day.
                The percentage of patients with dysmenorrhea, dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment. RESULTS [table: see text]
                Nafarelin acetate and danazol both provided significant relief of dysmenorrhea, dyspareunia, and pelvic pain during treatment and for 6 months following treatment in women with endometriosis. Danazol (200 mg three times a day) and medroxyprogesterone acetate (MPA, 100 mg a day) were compared with placebo in the treatment of infertility of patients with endometriosis. Twenty-seven patients had medical therapy alone for 6 months, and 22 patients received it after conservative surgery. The clinical characteristics of the patients in the danazol group (n = 18), the MPA group (n = 17), and the placebo group (n = 14) were comparable to each other. The follow-up time was 30 months. The cumulative pregnancy rates, 33% in the danazol group (n = 6), 42% in the MPA group (n = 7), and 46% in the placebo group (n = 6), did not differ significantly from each other. The time to pregnancy after the start of therapy was 17.7 +/- 8.4 (standard deviation [SD]) months in the danazol group, 18.0 +/- 9.0 months in the MPA group and 10.0 +/- 5.8 months in the placebo group with no significant difference between the groups. The abortion rate was 26%, and there was no significant difference among the groups. Cox multivariant analysis did reveal ovarian endometriosis a prognostically significant negative indicator as regards fecundation in endometriosis (P less than 0.05). In summary, correction of infertility alone does not appear to be an indication for the use of danazol or MPA in the treatment of endometriosis, and ovarian endometriotic lesions but not peritoneal ones do make a worse prognosis as regards fecundation in endometriosis. A prospective, randomized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis. Both regimens induced anovulation and ovarian suppression in all subjects. Mean estradiol (E2) and progesterone (P) levels were suppressed with both regimens, but were lower with leuprolide. There was no difference in cumulative follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, although at times during treatment mean levels of these hormones were lower with leuprolide. Higher P levels in the danazol group, most likely of adrenal origin, indicated a suppressive effect on adrenal steroidogenesis. Symptomatic improvement was significant in both groups. Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups. At 12 months after treatment, cumulative pregnancy and live birth rates were similar in both groups. Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis.
GnRHas appear to be more effective at relieving pain associated with endometriosis than no treatment/placebo. There was no evidence of a difference in pain relief between GnRHas and danazol although more adverse events reported in the GnRHa groups. There was no evidence of a difference in pain relief between GnRHas and levonorgestrel and no studies compared GnRHas with analgesics.