Hysterectomy, Oophorectomy and Risk of Dementia: A Nationwide Historical Cohort Study

Abstract

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.

Risk factors for dementia with Lewy bodies

“…Notably, this is a pattern that has also been shown in parkinsonism, dementia, and cognitive impairment. 40 Compared with AD subjects, DLB subjects were 2.4 years younger at diagnosis and 4.7 years younger at death (table 1); earlier death may be attributable to earlier disease onset, more rapid progression, or reflect an interaction with male sex.…”

“…We confined our risk factor assessment to 19 demographic, genetic, or disease characteristics associated with DLB, AD, or PD and for which data were available from the studies: age, 5 sex, 5 family history of dementia 2,7,8 or PD, 9,10 APOE e4 status (any e4 alleles vs none), 11,12 history of anxiety 13 or depression, 14,15 smoking (ever vs never in lifetime), 16,17 alcohol (ever vs never) 18,19 and caffeine consumption (ever vs never), 20,21 cancer (excluding nonmelanoma skin cancer), 22,23 diabetes mellitus, 24,25 education (9 or more years vs less than 9), 26,27 head injury, 28,29 number of children in men (more than one vs zero or one child), 30 occupation as a physician (vs all other occupations), 27 oophorectomy (uni-or bilateral, with or without hysterectomy), 31,32 oophorectomy at or before age 45, 32,33 and stroke. 34,35 Data definitions are in table e-1 on the Neurology ® Web site at www.neurology.org.…”

Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women

“…In fact, the Mayo Clinic Cohort Study of Oophorectomy and Aging reported an almost doubled risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause, as well as a trend of increasing risk of cognitive impairment and dementia with younger age at the time of oophorectomy or at the time of estrogen deficiency. 7 Similarly, in a Danish cohort, earlier age at bilateral oophorectomy was associated with an increased risk of early-onset dementia, 8 and, in a Chinese study, unilateral oophorectomy prior to menopause was associated with worse word recall. 9 Nonetheless, not all studies have yielded the same conclusions.…”

“…[2][3][4] There has been strong interest in the potential influence of menopause and the associated decrease in ovarian production of estradiol on subsequent cognitive function. An earlier age at menopause, 5,6 particularly surgical menopause, [7][8][9] has been associated with increased risk of dementia and cognitive decline in some but not all 10,11 studies. [12][13][14] In general, prior studies of surgical menopause examined the risk of developing Alzheimer disease (AD) or dementia but did not assess intermediate phenotypes, such as change in performance on detailed cognitive testing or development of the neuropathologic features associated with AD.…”

Gender difference in valproic acid-induced neuroprotective effects on APP/PS1 double transgenic mice modeling Alzheimer's disease

“…Women exhibit greater SP deposition than men in the early stages of NFT development and have more affected brain regions beginning in late middle age [6,7]. Both neuroimaging and postmortem human studies revealed that AD pathology is more strongly associated with clinical dementia in women than in men [6,8].…”