title: Endometrial expression of steroid receptors in postmenopausal hormone replacement therapy users: relationship to bleeding patterns.
abstract: BACKGROUND
  Mechanisms of menopausal hormone replacement therapy (HRT)-related bleeding, undoubtedly mediated through endometrial steroid receptors, are poorly understood. We aimed to determine the steroid receptor expression in HRT-exposed endometrium in relation to disturbances of bleeding patterns.
  
  
  METHODS
  Prospective observational study in a tertiary referral menopause clinic in Western Australia. Thirty-eight outpatient endometrial biopsies (seven from women not on HRT, 31 from HRT users) were collected from 21 postmenopausal women during and outside bleeding episodes. Eleven women provided multiple biopsies. We performed an immunohistochemical analysis of endometrial glandular, stromal, epithelial, perivascular and endothelial expression of progesterone receptor (PR), glucocorticoid receptor (GR), androgen receptor (AR), estrogen receptors alpha and beta (ERalpha and ERbeta) and studied their relationship to bleeding patterns.
  
  
  RESULTS
  In HRT users, during a bleeding episode, there was a trend (non-significant) towards a decrease in PR and an increase in GR in endometrial glandular cells. No differences were observed in AR and ER expression.
  
  
  CONCLUSIONS
  We have been unable to demonstrate significant differences in steroid receptor expression in endometrium of women using HRT who report unscheduled bleeding episodes. These observations differ from the endometrial steroid receptor expression observed with normal menstruation and long-term progestogen-only administration, suggesting that different local mechanisms are involved in HRT-related unscheduled bleeding.
authors.affiliation: University of Edinburgh Centre for Reproductive Biology, The Queen's Medical Research Institute, Little France Crescent, Edinburgh, UK.
authors.forename: Susheel
authors.initials: S
authors.lastname: Vani
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Ian S
authors.initials: IS
authors.lastname: Fraser
authors.forename: Martha
authors.initials: M
authors.lastname: Hickey
mesh_terms: D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011987:Receptors, Steroid / Q000378:metabolism*; D014592:Uterine Hemorrhage / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014904:Western Australia
chemical_list: D011987:Receptors, Steroid