Hormone replacement therapy and the endometrium

Abstract

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. (J Clin Pathol 2001;54:435-440)

Novel Hydroxysteroid (17β) Dehydrogenase 1 Inhibitors Reverse Estrogen-Induced Endometrial Hyperplasia in Transgenic Mice

“…44,46 Progestins antagonize estrogen-mediated cell proliferation in the endometrium 47,48 and are, therefore, widely included in hormone replacement therapy to decrease the risk of endometrial hyperplasia and cancer. 49,50 The endocrinology of the mouse endometrium closely resembles that of humans. As in humans, endometrial hyperplasia and carcinoma can be induced by continuous estrogen exposure in rodents.…”

Effects of 8-prenylnaringenin on the hypothalamo-pituitary-uterine axis in rats after 3-month treatment

“…On the other hand, the high dose of 8PN increased uterine weight after long-term exposure, although much less than E2B. Uterotrophic effects are undesirable since they stimulate endometrial hyperplasia and the risk of development of endometrial cancer (Feeley & Wells 2001). Therefore, any treatment of postmenopausal women with estrogen at doses that stimulate endometrial proliferation must be accompanied by interval or continuous treatment with progestin, which reduces the cancer risk (Lethaby et al 2004).…”

The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers

“…These risks outweigh any benefits of HRT [3]. An estrogen replacement therapy also increases the risk of endometrial cancer [4], which is reduced by additional progestin administration [5]. The strong belief that HRT will reduce the risk for cardiovascular diseases [6,7] has been challenged by the finding of increased fatal heart attacks in women with pre-existing arteriosclerosis [8,9].…”

“…Progestin application opposes this effect [5], but often leads to uterine bleedings. Thus, the compliance of patients for HRT decreases.…”