Bilateral oophorectomy, accelerated aging: Late breaking news on a controversial issue

In this presentation, I will discuss the controversial question: Is bilateral oophorectomy a cause or a consequence of accelerated aging? In 2016, Levine and colleagues reported that the premature loss of ovarian function may lead to an increase in DNA methylation, a biological marker of accelerated aging (Levine et al., 2016). In the same year, Rocca and colleagues reported an association between bilateral oophorectomy performed before menopause and the rate of accumulation of multimorbidity using 18 defined chronic conditions (Rocca et al., 2016). However, it remains difficult in a non-experimental setting to definitively test whether accelerated aging leads to symptoms that prompt bilateral oophorectomy, or whether bilateral oophorectomy prompts accelerated aging (cause-effect uncertainty and confounding by indication). In a 2017 publication, we addressed the cause-effect uncertainty with new analyses restricted to women who did not have any of 18 chronic conditions at baseline (Rocca et al., 2017). The Rochester Epidemiology Project records-linkage system was used to identify 420 premenopausal women who underwent bilateral oophorectomy for a non-cancerous condition before age 46 years from 1988 to 2007 in Olmsted County, MN, and 592 age matched referent women (±1 year) who had not undergone bilateral oophorectomy. After adjustments for several possible confounding variables present at baseline, women who underwent oophorectomy experienced an accelerated rate of accumulation of the 18 chronic conditions considered together (HR = 1.24; 95% CI = 1.12–1.37; p < .001). The single-year incidence rate of new conditions was most different in the first 6 years after oophorectomy, but the difference attenuated thereafter. Findings did not vary by surgical indication for the oophorectomy (benign condition vs. no ovarian condition). Current biomarker data and clinical evidence suggests that bilateral oophorectomy is causally linked to accelerated aging.