Progestin Therapy of Complex Endometrial Hyperplasia With and Without Atypia

Abstract

Women with complex or atypical endometrial hyperplasia have an increased risk of endometrial carcinoma. Generally, complex hyperplasia is treated with progestins, and women with atypical hyperplasia undergo hysterectomy despite the lack of clear evidence for the efficacy of hormonal therapy, and a continuing debate on the merits of progestins compared with hysterectomy in complex and atypical hyperplasia. The risk for persistence/progression of endometrial hyperplasia among women treated with progestin has varied widely in previous studies, but appears to be greater for atypical hyperplasia than complex hyperplasia. This observational cohort study compared the likelihood of histologic persistence/progression of complex or atypical hyperplasia among women treated over 2 to 6 months with progestin and those not treated with progestin. The study was conducted in 185 women, average age 55.9 years, with complex (n = 115) or atypical (n = 70) hyperplasia at an integrated health plan in Washington State between 1985 and 2005. Independent pathology review of endometrial specimens was performed at the time of index diagnosis and at a follow-up of 2 to 6 months (mean: 16.1weeks). Automated databases were examined linking medical and pharmacy information. Mantel-Haenszel analysis was used to estimate relative risks (RRs) adjusted for age, body mass, and other potential confounding factors. The control group was comprised of 38 (20.5%) women who received no progestin therapy. The likelihood of persistence/progression of complex hyperplasia among women who received progestin treatment in comparison to controls who did not, was similar and relatively low (30.0% vs. 28.4%, respectively); the adjusted RR was 1.20, with a 95% confidence interval (CI) of 0.53 to 2.72. In contrast, the risk of persistence/progression among women with atypical hyperplasia treated with progestin was substantially reduced compared to the controls (26.9% vs. 66.7%); the adjusted RR was 0.39, with a 95% CI of 0.21 to 0.70. Among women with atypia, treatment with progestin for a duration of at least 3 months had less than a 15% probability of persistence/progression. These data show a high frequency of spontaneous regression of complex hyperplasia. Progestin therapy for 2 to 6 months does not improve the rate of regression for complex hyperplasia in this study population, but is associated with more than a 2-fold increase in the likelihood of regression of atypical hyperplasia. The relatively small number of women in the study is problematic.