Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study

Background: This study aimed to determine whether there is an association between hysterectomy and dementia. Methods: All female Danish residents born before 1966, alive on their 40th birthday and without a dementia diagnosis prior to 1977 (n = 2,313,388) were followed from January 1, 1977, or the age of 40, whichever came later, until dementia diagnosis, death, emigration or December 31, 2006, whichever came first. The relative risks (RR) for developing dementia in women with hysterectomy/oophorectomy compared to referent women were calculated. Results: Overall, hysterectomy did not increase the risk of dementia. When stratified by age at dementia diagnosis, hysterectomy was associated with an increased risk for early-onset dementia before the age of 50: hysterectomy alone (RR = 1.38, 95% confidence interval (CI) = 1.07–1.78), with unilateral oophorectomy (RR = 2.10, 95% CI = 1.28–3.45), with bilateral oophorectomy (RR = 2.33, 95% CI = 1.44–3.77). The younger the age at hysterectomy/oophorectomy, the greater was the risk. Conclusions: Although statistically significant, the association between premenopausal hysterectomy and early-onset dementia is uncertain due to study limitations. Premenopausal bilateral oophorectomy is associated with a higher risk, suggesting a dose effect of premature estrogen deficiency on dementia. The age-dependent effect suggests that the younger brain is probably more vulnerable to estrogen deficiency.