THE EFFECTS OF CYCLICAL OESTROGEN THERAPY AND SEQUENTIAL OESTROGEN/PROGESTOGEN THERAPY ON THE ENDOMETRIUM OF POST‐MENOPAUSAL WOMEN

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Abstract
In a prospective study, 127 patients attending a Menopause Clinic had uterine curettage performed prior to oestrogen therapy and at intervals during treatment with three different natural oestrogen regimes. At pre‐treatment curettage three patients (2%) were found to have carcinoma of the endometrium and nine patients (7%) were found to have endometrial hyperplasia. Thirty seven patients with normal endometrium at pre‐treatment curettage received cyclical natural oestrogen regimes or sequential oestrogen/progestogen regimes. Eleven (44%) of the 25 patients given cyclical high dose oestrogen regimes developed endometrial hyperplasia but only one (13%) of eight patients given cyclical low dose oestrogen regimes developed this condition. All four patients given sequential oestrogen/progestogen regimes continued to have normal endometrium during therapy. Four patients (33%) developed endometrial hyperplasia within seven months of the commencement of therapy but de novo development of hyperplasia could be delayed for as long as 24 months. Pre‐treatment hyperplasia was associated with elevated urinary total oestrogen excretion. During cyclical oestrogen therapy the urinary total oestrogen levels were high, in and above the range known to be associated with pre‐treatment hyperplasia. Eleven patients with endometrial hyperplasia, either pre‐treatment or oestrogen induced, were subsequently treated with sequential oestrogen/progestogen regimes; and in all cases there was a reversal from endometrial hyperplasia to normal endometrium. In one patient a reduction in exogenous oestrogens from a cyclical high dose to a cyclical low dose regime was not followed by a reversal in endometrial hyperplasia. Two patients with pre‐treatment endometrial hyperplasia developed adenocarcinoma of the endometrium during cyclical high dose oestrogen therapy. Five of the nine patients with endometrial hyperplasia at pre‐treatment curettage had experienced no abnormal vaginal bleeding. Of the patients with normal endometrium, both pre‐treatment and during cyclical oestrogen therapy, regular withdrawal bleeding was experienced by ten patients (53%) during therapy; withdrawal or breakthrough bleeding by 17 patients (90%) and two patients (10%) had no vaginal bleeding. Of the patients with normal endometrium at pre‐treatment curettage who developed endometrial hyperplasia during cyclical oestrogen therapy regular withdrawal bleeding was experienced by three patients (25%) during therapy; withdrawal or breakthrough bleeding by eight patients (67%) and four patients (33%) had no vaginal bleeding. In total, 15 patients received sequential oestrogen/progestogen regimes; 14 patients (93%) had regular withdrawal bleeding while one patient had breakthrough bleeding during sequential therapy.

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