The effect of submucous fibroids on the dose-dependent modulation of uterine bleeding by trimegestone in postmenopausal women treated with hormone replacement therapy

Objective To assess the value of identifying endometrial structural abnorma lities at baseline hysteroscopy in predicting the pattern of bleeding in po stmenopausal women treated with hormone replacement therapy. Design A randomised, double-blind, dose-ranging study. Setting A teaching hospital in the UK. Population One hundred and seventy-six healthy postmenopausal women. Methods Women were randomised to receive one of four doses of oral trimeges tone (0.05, 0.1, 0.25 and 0.5 mg per day), from day 15-28, land a daily dos e of 2 mg oral micronised oestradiol for six treatment cycles. Women comple ted diaries in which the bleeding episodes were recorded. Hysteroscopy unde r local anaesthesia and endometrial biopsy were performed at baseline and o n day 24 of the last treatment cycle. Results Women with submucous fibroids had more prolonged (P = 0.026) and he avier (P = 0.002) progestogen-associated bleeding (odds ratio 4.54). The in cidence of intermenstrual bleeding, but not its duration or severity, was h igher in women with submucous fibroids (P = 0.017). There was a clear dose- dependent effect of trimegestone, with a consistently later onset of proges togen-associated bleeding occurring with increasing doses of trimegestone ( P < 0.001), and such episodes became progressively lighter and of shorter d uration over time (P < 0.001). Conclusion Hysteroscopic evaluation of the endometrial cavity in women trea ted with hormone replacement therapy, predicts the occurrence of heavy and unscheduled bleeding.