A Revised Markov Model Evaluating Oophorectomy at the Time of Hysterectomy for Benign Indication: Age 65 Years Revisited

Abstract

Objective: To perform an updated Markov modeling to assess the optimal age for bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign indication.

Methods: We performed a literature review that assessed hazard ratios (HRs) for mortality by disease, age, hysterectomy with or without BSO, and estrogen therapy use. Base mortality rates were derived from national vital statistics data. A Markov model from reported HRs predicted the proportion of the population staying alive to age 80 years by 1-year and 5-year age groups at time of surgery, from age 45 to 55 years. Those younger than age 50 years were modeled as either taking postoperative estrogen or not; those 50 and older were modeled as not receiving estrogen. Computations were performed with R 3.5.1, using Bayesian integration for HR uncertainty.

Results: Performing salpingo-oophorectomy before age 50 years for those not taking estrogen yields a lower survival proportion to age 80 years than hysterectomy alone before age 50 years (52.8% [Bayesian CI 40.7-59.7] vs 63.5% [Bayesian CI 62.2-64.9]). At or after age 50 years, there were similar proportions of those living to age 80 years with hysterectomy alone (66.4%, Bayesian CI 65.0-67.6) compared with concurrent salpingo-oophorectomy (66.9%, Bayesian CI 64.4-69.0). Importantly, those taking estrogen when salpingo-oophorectomy was performed before age 50 years had similar proportions of cardiovascular disease, stroke, and people living to age 80 years as those undergoing hysterectomy alone or those undergoing hysterectomy and salpingo-oophorectomy at age 50 years and older.

Conclusion: This updated Markov model argues for the consideration of concurrent salpingo-oophorectomy for patients who are undergoing hysterectomy at age 50 and older and suggests that initiating estrogen in those who need salpingo-oophorectomy before age 50 years mitigates increased mortality risk.

Fig. 1.. Schematic of revised Markov model. This schematic demonstrates the initial Markov state of healthy, with uterus, and at least one ovary, and the interventions being surgery with hysterectomy alone vs hysterectomy and bilateral salpingo-oophorectomy (BSO) from age 45 to 55 years. Whether estrogen was used after surgery is modeled for those undergoing surgery before age 50 years. We report on death from cardiovascular disease, stroke, breast cancer, ovarian cancer, lung cancer, colon cancer, and all-cause. Our final outputs are proportion of patients alive to 80 years and dead from the previously listed diseases.

Fig. 2.. Long-term effects of surgery conducted at different ages without estrogen therapy. Modeled cohorts of 10,000 patients undergoing hysterectomy and bilateral salpingo-oophorectomy or hysterectomy alone between age 45 and 55 years were simulated from surgery to 80 years. We report percent survival to 80 years and percent death from cardiovascular disease in E‒F, then report percent death from disease (subplots) in A‒D. The simulation uses age-specific baseline death rates and a posterior random sampling of 500 settings of hazard ratios for various interventions. Black dots represent the average of marginal statistics over 500 simulated cohorts, and bands show 95% Bayesian posterior intervals. Death from breast cancer (A), colon cancer (B), stroke (C), lung cancer (D), and cardiovascular disease (E) and survival (F).

Fig. 3.. Results of a supporting control computation for comparison analogous to Figure 2, but in which we have removed any factors for which prior work does not establish a non-null hazard ratio and we have assumed a step-function hazard ratio across the age-50-years threshold. Death rate by cardiovascular disease (A), survival (B).