Hormone replacement therapy and the endometrium

Modern hormone replacement therapy (HRT) regimens contain oestrogen and progestogen, given either in a cyclical or continuous combined manner. Most endometrial biopsies from women on sequential HRT show weak secretory features. Approximately 15% show proliferative activity, although this figure may be less if more than nine days of progestogen is given in each cycle. A small proportion will show an inactive or atrophic endometrium. Up to 50% of biopsies from women on continuous combined HRT contain minimal endometrial tissue for histopathological analysis: this correlates well with an atrophic endometrium with no appreciable pathology. Of the 50% with more substantial material, approximately one half will show endometrial atrophy, and one half will show weak secretory features. Proliferative, menstrual, and pseudodecidual changes are rare. Approximately 20% of women given unopposed oestrogen for one year develop endometrial hyperplasia. The relative risk of endometrial carcinoma is two to three. This is dramatically reduced by the addition of progestogen to the regimen, but cyclical progestogen as part of a sequential HRT regimen does not completely eliminate the risk of carcinoma. The prevalence of endometrial hyperplasia associated with sequential HRT is 5.4%, and that of atypical hyperplasia (endometrial intraepithelial neoplasia) is 0.7%. Continuous combined HRT is not associated with the development of hyperplasia or carcinoma, and may normalise the endometrium of women who have developed complex hyperplasia on sequential HRT. The probability of a histopathologist finding clinically relevant pathology in an endometrial biopsy specimen of a patient on HRT is low and is more likely to be a manifestation of pre-existing disease.