Is danazol a useful treatment in unexplained primary infertility? The "treatment" of unexplained infertility with danazol. Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis. Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study. Side effects of danazol compared with an ethinyloestradiol/norgestrel combination when used for postcoital contraception. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study. Buserelin versus danazol in the treatment of endometriosis-associated infertility. A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis.
39 patients with primary unexplained infertility were treated in a double-blind placebo-controlled study of danazol. 14 patients completed a treatment course of danazol and 17 of placebo. One patient in the placebo group conceived during the 12 months follow-up period, and none in the danazol group. Danazol does not seem to be an effective treatment for unexplained primary infertility. In order to investigate the possible stimulating effect of danazol on fertility, a randomized clinical trial was performed on 40 women with unexplained infertility. Of these 40 women, 21 received 200 mg of danazol daily for 100 days and 19 received a placebo treatment during the same period. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, estrone, estradiol, progesterone, and testosterone were followed before, during, and after treatment. Danazol administration induced anovulation in all women, with prompt resumption of normal ovulatory function after discontinuation of the drug. No influence was seen on serum LH, FSH, and testosterone levels, but serum estrone, estradiol, and progesterone levels decreased significantly during treatment. Serum prolactin levels also decreased, but not significantly. No pregnancies occurred in the placebo group during a 6-month follow-up period. In the danazol group, five pregnancies occurred, of which two were ectopic and three went to term. The difference in pregnancy rate between both groups was statistically significant (P less than 0.05). 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. We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis. A postcoital contraceptive with a lower incidence of nausea and vomiting than oestrogen-progestogen combinations would be a significant advance. During a nine-month period, 101 women were treated at the Margaret Pyke Centre in London with either an oestrogen-progestogen combination or with danazol. A comparison of the side effects of each drug is reported. Those treated with danazol were six times less likely to experience nausea and none vomited. With the exception of breast symptoms, other side effects were five times less common in women receiving danazol. These differences give danazol a clear advantage in terms of patient acceptability. Further experience will enable the efficacy of danazol to be evaluated and so determine whether this drug should become the preferred hormonal postcoital treatment. A double-blind, randomized, prospective therapeutic trial was conducted in 148 couples with unexplained infertility. Treatment consisted of 4 consecutive months of placebo or clomiphene citrate (CC) (100 mg) by mouth on cycle days 5 to 9, and placebo or human chorionic gonadotropin (hCG) (5,000 IU) intramuscularly on cycle days 19, 22, 25, and 28. There were 14 pregnancies during the trial and 39 pregnancies during observation before and after the trial. Placebo treatment resulted in no pregnancies over 4 months. Clomiphene citrate was significantly better than placebo (P less than 0.04), with a pregnancy rate of 19% over the course of 4 months. The pregnancy rate with hCG either alone (11%) or in combination with CC (7.6%), was not significantly better than placebo. Treatment-independent pregnancies, defined as those before treatment (but after enrollment), or more than 1 month after therapy, occurred in 16% of the couples, with a mean time to conception of 8.8 months. As part of their follow-up, 39 of the study couples subsequently underwent in vitro fertilization (IVF), and 43% were found to have a previously unrecognized male factor or fertilization defect. A pregnancy rate of 16% was achieved after a mean of 1.1 cycles in these 39 couples. The authors conclude that CC is useful in treating unexplained infertility and is a reasonable initial therapy. For couples who fail to conceive, IVF may be diagnostic as well as therapeutic. 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. A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe. 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.
Available data demonstrate no evidence of the benefit of danazol for unexplained subfertility. Although there is insufficient evidence to be certain of this, the need for contraception during treatment and the adverse effects and costs of danazol, make its use for this problem unwarranted. The increased pregnancy rate in the long term follow-up data may be attributable to additional therapies and did not influence the live birth/ongoing pregnancy data.