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

Authors

  • May Wahab,

    Clinical Research Fellow/Specialist Registrar
    1. Gynaecology Research Group, Department of Obstetrics and Gynaecology, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary
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  • John Thompson,

    Senior Lecturer
    1. Gynaecology Research Group, Department of Obstetrics and Gynaecology, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary
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  • Farook Al-Azzawi

    Senior Lecturer/Consultant (Gynaecology), Corresponding author
    1. Gynaecology Research Group, Department of Obstetrics and Gynaecology, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary
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Correspondence: Dr F. Al-Azzawi, Department of Obstetrics and Gynaecology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK.

Abstract

Objective 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.

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 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.

Results 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).

Conclusion Hysteroscopic evaluation of the endometrial cavity in women treated with hormone replacement therapy, predicts the occurrence of heavy and unscheduled bleeding.

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