Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17β-estradiol combined with sequential 5-20 mg dydrogesterone

Abstract

Objective: To assess the endometrial safety and bleeding patterns of 17β-estradiol sequentially combined with dydrogesterone.Methods: Endometrial safety and bleeding patterns wereassessed in 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17β-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle,or 2 mg/day 17β-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. Proliferative endometrium, endometrialhyperplasia and endometrial malignancy in the end-of-study biopsy were considered as inadequate progestational responses.Results: Biopsies were not available in 137 women mainly because of aninsufficient treatment period or non-compliance. An adequate progestational response was seen in more than 98% of the 442 women who underwent biopsy after treatment. Bleeding data were not available in193 women, most of whom did not remain on treatment for the full 26 cycles. The 1-mg 17β-estradiol dose was associated with less cyclic and intermittent bleeding than the 2-mg dose. Higher doses ofdydrogesterone were associated with a higher incidence of cyclic bleeds and a later day of onset, while duration, severity and regularity were similar in all groups irrespective of estradiol or dydrogesteronedose.Conclusion: Sequential combinations of 1 mg 17β-estradiol with 5 or 10 mg dydrogesterone and 2 mg 17β-estradiol with 10 or 20 mg dydrogesterone are associated with very good endometrialsafety. The incidence of bleeding is lower with the 1-mg dose of 17β-estradiol.