Objective: To determine compliance, the incidence of untoward effects, and endometrial safety in postmenopausal women treated with 3-month sequential hormone therapy for up to 5 years.
Design: A prospective, uncontrolled multicenter study of 129 women treated with 0.625 mg conjugated estrogens daily plus 10 mg medroxyprogesterone acetate for 14 days every third month. Endometrial biopsy samples were taken before the initiation of the study and then yearly during the next 5 years. Bleeding patterns were recorded.
Results: Upon completion of the first 12 months of treatment, 76 of 126 biopsied women (60%) had secretory endometrium. After 5 years, this finding was reversed in biopsy specimens completed by 59 women, among whom 32 (56%) had insufficient or atrophic endometrium. We did not find any hyperplasia when the biopsy specimen was taken according to the protocol. One endometrial cancer was found by biopsy after 12 months, but the subsequent hysterectomy showed no sign of cancer. Ultrasound determinations of mean endometrial thickness during therapy showed a thin endometrium (mean = 4 mm, range = 1-13 mm). Amenorrhea was reported by 6.2% of 129 women after 12 months of treatment. Among the 59 women who completed the study, 71.2% had regular bleeding patterns every third month, 25.4% reported amenorrhea, and 3.4% had irregular bleeding patterns.
Conclusions: The addition of 10 mg of medroxyprogesterone acetate for 14 days every third month to treatment with 0.625 mg of conjugated estrogens daily was well tolerated, and was associated with high endometrial safety.