Nancy N Baxter

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study

Abstract Objectives To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. Design Population based cohort study. Setting Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. Participants 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). Exposures Bilateral salpingo-oophorectomy versus ovarian conservation. Main outcomes measures The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant. Results Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. Conclusion In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy

Opportunistic bilateral salpingo-oophorectomy is often offered to patients undergoing benign hysterectomy to prevent ovarian cancer, but the magnitude of risk reduction obtained with bilateral salpingo-oophorectomy in this population remains unclear and must be weighed against potential risks of ovarian hormone deficiency. This study aimed to quantify the relative and absolute risk reduction in ovarian cancer incidence and death associated with bilateral salpingo-oophorectomy at the time of benign hysterectomy. We performed a population-based cohort study of all adult women (≥20 years) undergoing benign hysterectomy from 1996 to 2010 in Ontario, Canada. Patients with ovarian pathology, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Inverse probability of treatment-weighted Fine-Gray subdistribution hazard models were used to quantify the effect of bilateral salpingo-oophorectomy on ovarian cancer incidence and death while accounting for competing risks and adjusting for demographic characteristics, gynecologic conditions, and comorbidities. Analyses were performed in all women and specifically in women of postmenopausal age (≥50 years) at the time of hysterectomy. We identified 195,282 patients (bilateral salpingo-oophorectomy, 24%; ovarian conservation, 76%) with a median age of 45 years (interquartile range, 40-51 years). Over a median follow-up of 16 years (interquartile range, 12-20 years), 548 patients developed ovarian cancer (0.3%), and 16,170 patients (8.3%) died from any cause. Bilateral salpingo-oophorectomy was associated with decreased ovarian cancer incidence (hazard ratio, 0.23; 95% confidence interval, 0.14-0.38; P<.001) and decreased ovarian cancer death (hazard ratio, 0.30; 95% confidence interval, 0.16-0.57; P<.001). At 20 years follow-up, the weighted cumulative incidences of ovarian cancer were 0.08% and 0.46% with bilateral salpingo-oophorectomy and ovarian conservation, respectively, yielding an absolute risk reduction of 0.38% (95% confidence interval, 0.32-0.45; number needed to treat, 260). After restricting to women aged ≥50 years at hysterectomy, the absolute risk reduction was 0.62% (95% confidence interval, 0.47-0.77; number needed to treat, 161). Bilateral salpingo-oophorectomy resulted in a significant absolute reduction in ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of bilateral salpingo-oophorectomy to inform practice guidelines, patient decision-making, and surgical management.