Factors associated with withdrawal bleeding after administration of oral micronized progesterone in women with secondary amenorrhea.

Abstract

OBJECTIVE: To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. DESIGN: Prospective, randomized, double-blind. SETTING: Academic institution. PARTICIPANTS: Out of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study. INTERVENTIONS: A 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo. MAIN OUTCOME MEASURES: Withdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E2) concentrations at baseline and P concentrations during treatment were correlated with bleeding response. RESULTS: Withdrawal bleeding occurred in 90% of women taking 300 mg, 58% of women taking 200 mg, and 29% of women taking placebo (P less than 0.0002 for 300 mg versus placebo). Side effects occurred similarly among the groups (P = not significant). Lipid concentrations were unchanged. Endogenous E2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. CONCLUSIONS: Progesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E2 and P concentrations.