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

ObjectiveTo compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects.DesignProspective, randomized, double-blind.SettingAcademic institution.ParticipantsOut of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study.InterventionsA 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo.Main outcome measuresWithdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E2) concentrations at baseline and P concentrations during treatment were correlated with bleeding response.ResultsWithdrawal 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.ConclusionsProgesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E2 and P concentrations.