Case-Control Study of Postmenopausal Hormone Replacement Therapy and Endometrial Cancer

This study evaluated recent inconsistent findings that adding progestins to postmenopausal estrogen replacement therapy protects against endometrial cancer. Using a population-based case-control study, the authors compared 511 endometrial cancer cases aged 50–79 years in the Philadelphia, Pennsylvania, region during 1999–2002 with 1,412 random-digit-dialing controls regarding postmenopausal hormone replacement therapy (HRT) use. Telephone interviews were performed with memory aids mailed in advance. An increased risk of endometrial cancer was observed among postmenopausal women using only unopposed estrogen for 3 or more years, compared with women who never used HRT (adjusted odds ratio = 3.4, 95% confidence interval (CI): 1.4, 8.3). Using combination HRT (of any duration) was associated with a substantial reduction in risk (odds ratio = 0.8, 95% CI: 0.6, 1.1). Comparing women using only combined estrogen and progestin for 3 or more years with women using only unopposed estrogen for 3 or more years, the authors found that the adjusted odds ratio was 0.2 (95% CI: 0.1, 0.6). Long-term use of unopposed estrogen is associated with increased risk for endometrial cancer, whereas combined estrogen plus progestin hormone therapy is not. Thus, if HRT is to be used in women with an intact uterus, this study confirms the benefit of adding progestins to the regimen.