HORMONE REPLACEMENT THERAPY AND ENDOMETRIAL CANCER RISK - A METAANALYSIS

Objective: To assess the association of unopposed estrogen or estrogen plus progestin and the risk of developing endometrial cancer or dying of that disease. Data Sources: A literature search of English-languag e studies was performed using MEDLINE, a review of bibliographies, and consultations with experts. Methods of Study Selection: We identified 30 studies with adequate controls and risk estimates. Data Extraction and Synthesis: Risk estimates were extracted by two authors and summa rized using meta-analytic methods. The summary relative risk (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval [ CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use (RR 9.5 for 10 or more years). The summary RR of endometrial c ancer remained elevated 5 or more years after discontinuation of unopp osed estrogen therapy (RR 2.3). Interrupting estrogen for 5-7 days per month was not associated with lower risk than daily use. Users of uno pposed conjugated estrogen had a greater increase in RR of developing endometrial cancer than users of synthetic estrogens. The risk for end ometrial cancer death was elevated among unopposed estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users, cohort stud ies showed a decreased risk of endometrial canter (RR 0.4), whereas ca se-control studies showed a small increase (RR 1.8). Conclusions: Endo metrial cancer risk increases substantially with long duration of unop posed estrogen use, and this increased risk persists for several years after discontinuation of estrogen. Although not statistically signifi cant, the risk of death from endometrial cancer among unopposed estrog en users is increased, similar to the increased risk of developing the disease. Data regarding risk for endometrial cancer among estrogen pl us progestin users are limited and conflicting.