Reduction of Menstrual Blood Loss by Danazol in Unexplained Menorrhagia: Lack of Effect of Placebo

Abstract

Summary 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±25ml 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.

Efficacy of vaginal danazol treatment in women with menorrhagia during fertile age

“…A danazol-loaded IUD has been shown to be an effective and conservative treatment for dysmenorrhea, pelvic pain, and dyspareunia associated with endometriosis (14). This is probably due to the elevated uterine/ pelvic efficacy with limited systemic absorption leading to undetectable serum levels (6).…”

The combination of a depot gonadotrophin releasing hormone agonist and cyclical hormone replacement therapy for dysfunctional uterine bleeding

“…Ours was an uncontrolled study and there was potential for placebo effect. Most studies are unable to demonstrate such an effect (Chimbira et al 1980b) in the treatment of DUB, but this must be verified by further controlled studies.…”

“…It may be that the bleeding was consistent during therapy and not intermittent as in her normal period which meant that she did not flood or pass clots even though the objective menstrual loss was greater. The effect on symptoms compares favourably with danazol (Chimbira et al 1980b) and the prostaglandin synthesis inhibitors (Fraser et al 1981; Mira et al 1986). Ours was an uncontrolled study and there was potential for placebo effect.…”

Medical management of menstrual disorders

“…It has both antiestrogenic and antiprogestogenic activity. It reduces estrogen levels and thereby causes endometrial atrophy and amenorrhea in some women [31]. In the Cochrane Review by Beaumont et al [14], despite wide confidence intervals, danazol (100 -200 mg daily) was found to be more effective in reducing menstrual blood flow than placebo, progestins, NSAIDs and oral contraceptive pills, but it has more side effects than NSAIDs and progestins.…”