A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Higham
J M
JM
Royal Free Hospital, London, England.
Shaw
R W
RW
D000328:Adult; D003613:Danazol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008595:Menorrhagia / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008875:Middle Aged; D009640:Norethindrone / Q000009:adverse effects / Q000627:therapeutic use*
D003613:Danazol; D009640:Norethindrone