Excess morbidity and mortality associated with underuse of estrogen replacement therapy in premenopausal women who undergo surgical menopause.

Background: Contrary to clinical guidelines, there has been a decrease over time in estrogen therapy use in premenopausal women undergoing bilateral oophorectomy for benign indications.

Objective: This study aimed to estimate the excess morbidity and mortality associated with current patterns of estrogen therapy use in women who undergo bilateral oophorectomy with hysterectomy for benign indications.

Study Design: We developed 2 Bayesian sampling Markov state-transition models to estimate the excess disease incidence (incidence model) and mortality (mortality model). The starting cohort for both models were women who had undergone bilateral oophorectomy with hysterectomy for benign indications at the age of 45 to 49 years. The models tracked outcomes in 5-year intervals for 25 years. The incidence model estimated excess incidence of breast cancer, lung cancer, colorectal cancer, coronary heart disease, and stroke, whereas the mortality model estimated excess mortality due to breast cancer, lung cancer, coronary heart disease, and all-other-cause mortality. The models compared current rates of estrogen therapy use with optimal (100%) use and calculated the mean difference in each simulated outcome to determine excess disease incidence and death.

Results: By 25 years after bilateral oophorectomy with hysterectomy, there were an estimated 94 (95% confidence interval, -158 to -23) fewer colorectal cancer cases, 658 (95% confidence interval, 339-1025) more coronary heart disease cases, and 881 (95% confidence interval, 402-1483) more stroke cases. By 25 years after bilateral oophorectomy with hysterectomy, there were an estimated 189 (95% confidence interval, 59-387) more breast cancer deaths, 380 (95% confidence interval, 114-792) more coronary heart disease deaths, and 759 (95% confidence interval, 307-1527) more all-other-cause deaths. In sensitivity analyses where we defined estrogen therapy use as a duration of >2 years of use, these differences increased >2-fold.

Conclusion: Underuse of estrogen therapy in premenopausal women who undergo oophorectomy is associated with substantial excess morbidity and mortality.