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—Dr Abrams states that endometrial cancer was a known complication of unopposed estrogen at the time PEPI began, and that despite annual endometrial biopsies, the risk was unacceptable and led to seven hysterectomies.The rationale for the unopposed estrogen arm was to determine whether risk factor changes were different with this regimen compared with estrogen and progestin, because nearly all previous observational studies suggesting cardioprotection were based on women who took estrogen without progestin. In addition, progestin-associated symptoms are common reasons why women fail to continue estrogen when it is prescribed with a progestin. Therefore, we thought it was extremely important to contrast unopposed estrogen with opposed estrogen regimens.The published literature showed that estrogen-associated endometrial cancer was rare and preceded by adenomatous or atypical hyperplasia. Adenomatous hyperplasia was reported to be reversible after estrogen withdrawal and 3 months of treatment with medroxyprogesterone acetate (10 mg/d). No invasive
Barrett-Connor E. The Postmenopausal Estrogen/Progestin Interventions Trial-Reply. JAMA. 1995;274(21):1676. doi:10.1001/jama.1995.03530210029023