The modifying effect of progestogen on the response of the post-menopausal endometrium to exogenous oestrogens.

Cyclical regimes of unopposed oestrogens are associated with the development of both cystic glandular and atypical hyperplasia, and the incidence of hyperplasia is related to the dose of oestrogen prescribed. Atypical hyperplasia develops later than, and perhaps from, cystic glandular hyperplasia. With sequential oestrogen/progestogen therapy the incidence of this condition was greatly reduced, and therefore, progestogens appear to protect against the development of this condition. In all cases but one, sequential regimes also reversed both spontaneously-arising and oestrogen-induced hyperplasia to a normal endometrium. Cyclical high-dose unopposed oestrogen therapy may not be capable of reversing spontaneously-arising hyperplasia, and this condition may progress to endometrial adenocarcinoma. Spontaneously-arising hyperplasia can be present before therapy commences, but may be unsuspected, as it can occur in the absence of abnormal vaginal bleeding. Therefore, cyclical oestrogen therapy should not be prescribed unless pre-treatment curettage has been performed and spontaneously-arising hyperplasia has been excluded; and unless subsequent monitoring of the endometrial response is being performed by serial biopsy.