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

Abstract

To assess the value of identifying endometrial structural abnormalities at baseline hysteroscopy in predicting the pattern of bleeding in postmenopausal women treated with hormone replacement therapy. A randomised, double-blind, dose-ranging study. A teaching hospital in the UK. One hundred and seventy-six healthy postmenopausal women. Women were randomised to receive one of four doses of oral trimegestone (0.05, 0.1, 0.25 and 0.5 mg per day), from day 15-28, and a daily dose of 2 mg oral micronised oestradiol for six treatment cycles. Women completed diaries in which the bleeding episodes were recorded. Hysteroscopy under local anaesthesia and endometrial biopsy were performed at baseline and on day 24 of the last treatment cycle. Women with submucous fibroids had more prolonged (P = 0.026) and heavier (P = 0.002) progestogen-associated bleeding (odds ratio 4.54). The incidence of intermenstrual bleeding, but not its duration or severity, was higher in women with submucous fibroids (P = 0.017). There was a clear dose-dependent effect of trimegestone, with a consistently later onset of progestogen-associated bleeding occurring with increasing doses of trimegestone (P < 0.001), and such episodes became progressively lighter and of shorter duration over time (P < 0.001). Hysteroscopic evaluation of the endometrial cavity in women treated with hormone replacement therapy, predicts the occurrence of heavy and unscheduled bleeding.