Mechanisms of menopausal HRT-related bleeding, undoubtedly mediated through endometrial steroid receptors, are poorly understood. We aimed to determine the steroid receptor expression in HRT-exposed endometrium about disturbances of bleeding patterns.

The present study is a prospective observational study in a tertiary referral menopause clinic in Western Australia. Thirty-eight outpatient endometrial biopsies 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 PR, GR, AR, estrogen receptors α and β  and studied their relationship to bleeding patterns.

During a bleeding episode in HRT users, there was a non-significant trend towards a decrease in PR and an increase in GR in endometrial glandular cells. No differences were observed in AR and ER expression.

The study has been unable to demonstrate significant differences in steroid receptor expression in the 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.

Reference: https://srh.bmj.com/content/34/1/27

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