title: The effect of submucous fibroids on the dose-dependent modulation of uterine bleeding by trimegestone in postmenopausal women treated with hormone replacement therapy.
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.
  
  
  METHODS
  A randomised, double-blind, dose-ranging study.
  
  
  METHODS
  A teaching hospital in the UK.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Hysteroscopic evaluation of the endometrial cavity in women treated with hormone replacement therapy, predicts the occurrence of heavy and unscheduled bleeding.
authors.affiliation: Department of Obstetrics and Gynaecology, Leicester Royal Infirmary, UK.
authors.forename: M
authors.initials: M
authors.lastname: Wahab
authors.forename: J
authors.initials: J
authors.lastname: Thompson
authors.forename: F
authors.initials: F
authors.lastname: Al-Azzawi
mesh_terms: D004305:Dose-Response Relationship, Drug; D004717:Endometrium; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D007889:Leiomyoma / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D017698:Postmenopause; D045167:Progesterone Congeners / Q000627:therapeutic use*; D011397:Promegestone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014592:Uterine Hemorrhage / Q000188:drug therapy*; D014594:Uterine Neoplasms / Q000150:complications / Q000188:drug therapy*
chemical_list: D045167:Progesterone Congeners; C050319:trimegestone; D011397:Promegestone