Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17 beta-estradiol combined with sequential 5-20 mg dydrogesterone.
OBJECTIVE
To assess the endometrial safety and bleeding patterns of 17 beta-estradiol sequentially combined with dydrogesterone.


METHODS
Endometrial safety and bleeding patterns were assessed in 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17 beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17 beta-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, endometrial hyperplasia 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 an insufficient 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 in 193 women, most of whom did not remain on treatment for the full 26 cycles. The 1-mg 17 beta-estradiol dose was associated with less cyclic and intermittent bleeding than the 2-mg dose. Higher doses of dydrogesterone 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 dydrogesterone dose.


CONCLUSIONS
Sequential combinations of 1 mg 17 beta-estradiol with 5 or 10 mg dydrogesterone and 2 mg 17 beta-estradiol with 10 or 20 mg dydrogesterone are associated with very good endometrial safety. The incidence of bleeding is lower with the 1-mg dose of 17 beta-estradiol.
Ferenczy
A
A
Departments of Pathology and Obstetrics and Gynecology, McGill University, Sir Mortimer B. Davis Jewish General Hospital, 3755 Côte Ste Catherine Road, Montreal, Quebec, Canada H3T IE2.
Gelfand
M M
MM
van de Weijer
P H M
PH
Rioux
J E
JE
D000368:Aged; D001706:Biopsy; D004311:Double-Blind Method; D004394:Dydrogesterone / Q000008:administration & dosage* / Q000009:adverse effects; D004717:Endometrium / Q000033:anatomy & histology*; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D014592:Uterine Hemorrhage
D010919:Placebos; D004958:Estradiol; D004394:Dydrogesterone