Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial

Abstract

Objective: To explore whether significant differences exist between bleeding patterns with common regimens of hormone replacement therapy using two different progestogens.

Methods: A total of 875 women in the Postmenopausal Estrogen and Progestin Interventions Trial took either placebo, conjugated equine estrogen 0.625 mg, conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg in a continuous fashion, or conjugated equine estrogen 0.625 mg daily plus either cyclical medroxyprogesterone acetate 10 mg or cyclical micronized progesterone 200 mg/day for 12 days per month. Bleeding days, amounts, and episodes were recorded in diaries and aggregated by 6-month intervals for 3 years for the 596 participants with a uterus. Any bleeding for women on continuous regimens, or more than 6 episodes of bleeding per 6-month period for cyclical regimens, was considered excess.

Results: Conjugated equine estrogen plus micronized progesterone cyclical was associated with fewer excess episodes of bleeding than conjugated equine estrogen plus medroxyprogesterone acetate continuous in the first 6 months. Quantities of bleeding for conjugated equine estrogen plus micronized progesterone cyclical were less than for conjugated equine estrogen plus medroxyprogesterone acetate cyclical through 30 months and for the number of bleeding days through study end. The 3-year cumulative quantities, days, and episodes of bleeding were significantly lower for conjugated equine estrogen plus micronized progesterone cyclical than for conjugated equine estrogen plus medroxyprogesterone acetate cyclical. Placebo treated women had scant bleeding and conjugated equine estrogen had modest amounts relative to the combination therapies.

Conclusion: The bleeding measures for conjugated equine estrogen plus micronized progesterone cyclical showed consistent advantages over those for cyclical conjugated equine estrogen plus medroxyprogesterone acetate in terms of quantity, length, and episodes of bleeding. In the first 6 months, conjugated equine estrogen plus micronized progesterone cyclical had fewer excess bleeding episodes than continuous conjugated equine estrogen plus medroxyprogesterone acetate.