Reduction of menstrual blood loss by danazol in unexplained menorrhagia: lack of effect of placebo. A comparative study of danazol and norethisterone in dysfunctional uterine bleeding presenting as menorrhagia. A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia. The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia.
In women with menorrhagia of unknown cause, the efficacy of the drug danazol in reducing heavy menstrual blood loss was investigated making objective measurements of menstrual blood loss. Drug regimens tested were daily administration of 200 or 100 mg danazol for 12 weeks and daily danazol given in the luteal phase or during menstruation. The results suggest that 200 mg danazol daily is the most acceptable regimen clinically since it significantly reduced menstrual blood loss and was associated with a relatively low incidence of side effects. In 16 women on this dose menstrual blood loss was suppressed from a mean pre-treatment loss of 183 +/- 25 ml to 38 +/- 11 ml (p < 0.01) in the second, and 26 +/- 9 ml (p < 0.01) in the third treatment months. The majority of women had regular episodes of bleeding with no alteration in cycle length and a reduction in the number of days of bleeding. Although 100 mg daily suppressed menstrual blood loss, particularly by the third month of treatment, it increased the number of episodes of bleeding in some women which they found unacceptable. Both 200 mg and 100 mg relieved dysmenorrhoea in the majority of women presenting with the symptoms. Danazol taken daily in the early follicular or luteal phase of the menstrual cycle did not significantly alter menstrual blood loss. There was no effect of placebo therapy on measured menstrual blood loss in a single blind trial in eight women with menorrhagia. This randomized open study compared the efficacy and safety of norethisterone, 5 mg three times a day from day 19 to 26, and danazol, 200 mg daily, in the treatment of dysfunctional uterine bleeding presenting as menorrhagia. Clinical criteria were employed to confirm the diagnosis, and subjective assessment of the condition was performed during one pre-treatment and three treatment cycles. Fourteen patients commenced norethisterone and 10 danazol. Bleeding intensity scores were significantly lower with danazol than with norethisterone, and patients assessed their blood loss to be significantly less with danazol than with norethisterone. Associated symptoms of backache and abdominal pain were improved to a similar degree by both treatments. Adverse reactions were reported with similar frequency and were of a similar nature in both treatment groups. A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group. The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and "total" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism. A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient. Our purpose was to compare the efficacy of the recommended dose of danazol, a reduced-dose danazol regimen, and norethindrone in the treatment of objectively proven menorrhagia. Recurrence after discontinuing treatment was also assessed.
                The study was a single-blind, randomized, parallel, comparative study. After a placebo run-in period over two menstrual cycles, 57 patients with a baseline mean menstrual blood loss of at least 80 ml per cycle were randomly assigned to receive one of three therapies: danazol, 200 mg/day (n = 19) for three menstrual cycles; danazol, 200 mg/day for one cycle, 100 mg/day for one cycle, and 50 mg/day for one cycle (n = 19); and norethindrone, 5 mg three times daily on days 19 through 26 of the cycle for three consecutive cycles (n = 19). Patients in whom treatment was successful (those experiencing blood loss < 80 ml) were entered in the follow-up phase of the study, receiving placebo for a maximum of four menstrual cycles.
                The final menstrual blood loss on treatment was significantly less for those patients who received both danazol regimens compared with those who received norethindrone (p = 0.017 for reducing dose danazol vs norethindrone and p = 0.043 for 200 mg of danazol vs norethindrone). Both danazol treatment regimens were significantly more successful in reducing menstrual blood loss to within the normal range than was norethindrone. The reducing-dose danazol regimen was successful in eight of 17 patients (p = 0.027), and 200 mg of danazol was successful in nine of 19 patients (p = 0.029), compared with the two successes of 18 patients treated with norethindrone. Significantly more recipients of 200 mg of danazol than of norethindrone subjectively rated their treatment to be moderately or highly effective (p = 0.033). Both danazol treatment regimens were associated with a higher incidence of adverse events than was norethindrone therapy, although the number of withdrawals were similar and infrequent in the three groups.
                Both danazol regimens were significantly more effective than norethindrone in reducing the excessive menstrual blood loss of women with unexplained menorrhagia. A subjective assessment by patients found that only the 200 mg of danazol was judged to be significantly more effective than norethindrone in controlling the heaviness of menstrual bleeding. The reduced-dose danazol regimen did not appear to markedly diminish the incidence of adverse events compared with the 200 mg of danazol regimen.
Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified.