Hysterectomy, bilateral oophorectomy, and risk of type 2 diabetes: Evidence from the E3N-generations cohort

OBJECTIVES: Evidence on hysterectomy and the risk of type 2 diabetes is limited, particularly regarding age at surgery. We assessed whether hysterectomy, with or without bilateral oophorectomy, is associated with incident type 2 diabetes, and whether this association is modified by age at surgery. STUDY DESIGN: We followed 82,472 women from the E3N-Generations cohort, free of diabetes at baseline in 1992, until 2008 (median follow-up 16 years). Hysterectomy and oophorectomy were modelled as time-dependent exposures. Hazard ratios were estimated using Cox models with age as the time scale, adjusted for lifestyle, metabolic, and reproductive factors. MAIN OUTCOME MEASURE: Incidence of type 2 diabetes. RESULTS: During follow-up, 2318 women developed type 2 diabetes. In fully adjusted models, hysterectomy combined with bilateral oophorectomy was associated with a higher risk of type 2 diabetes (hazard ratio 1.23, 95% confidence interval 1.07-1.43) compared with women who underwent neither procedure, whereas hysterectomy alone was not (1.06, 0.91-1.24). Bilateral oophorectomy alone was not associated with the risk of incident type 2 diabetes. The association with hysterectomy and bilateral oophorectomy was strongest among women operated on before age 45 (1.70, 1.35-2.15); it was similarly elevated when the age threshold was changed to 40 (1.54, 1.08-2.20). There was significant heterogeneity by age at surgery for hysterectomy with bilateral oophorectomy (p = 0.001) and for hysterectomy alone (p = 0.010). CONCLUSIONS: Hysterectomy with bilateral oophorectomy was associated with an increased risk of incident type 2 diabetes, independently of conventional metabolic risk factors. This excess risk was particularly pronounced among women who underwent surgery before age 45.