Adjuvant tamoxifen’s proliferative impact on the endometrium has the potential to cause endometrial abnormalities, including cancer, in postmenopausal women. 

A randomized, controlled experiment was done to evaluate endometrial pathological diagnosis in postmenopausal women with early-stage, ER-positive breast cancer and no endometrial pathology at baseline. For 5 years, they were randomly allocated to either tamoxifen alone or tamoxifen + cyclical medroxyprogesterone acetate (MPA 10 mg for 14 days every 3 months). Endovaginal sonograms (EVS) plus/or endometrial biopsies (EMB) were necessary at the beginning, two, and five years. 296 of the 313 individuals enrolled were eligible, and 169 (57%; 89, tamoxifen; 80, tamoxifen+MPA) were evaluable (completed year-2 EVS, with an EMB if stripe width was ⩾5 mm). 


Sixty (67%) of those in the tamoxifen arm developed a ⩾5 mm endometrial stripe (and had later EMB), compared to 48 (60%) in the tamoxifen+MPA group (P=0.40). There were four incidences of proliferative endometrium and one simple hyperplasia in the tamoxifen arm (6% (95% CI: 2–13%) among evaluable patients and one occurrence of proliferative endometrium in the tamoxifen+MPA arm (P=0.11). In year 2, the total percentage of women with benign endometrial abnormalities was 3.6% (6/169; 95% CI: 1.3–7.6%), with only 1 (of 102) new benign proliferative events. Because the incident rate in both arms was significantly lower than expected, treatment arm comparisons were less meaningful. A normal endometrium before starting tamoxifen may provide peace of mind about future endometrial occurrences. Before modifying practice in asymptomatic postmenopausal women, however, bigger trial validation is required.