Female reproductive factors and the risk of dementia: a nationwide cohort study

Abstract

Background and purpose: The aim was to investigate whether female reproductive factors are associated with dementia.

Methods: In all, 4 696 633 post-menopausal women without dementia were identified using the Korean National Health Insurance System database. Data on reproductive factors were collected using a self-administered questionnaire. Dementia was determined using dementia diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression was conducted to assess the hazard ratio (HR) for dementia according to reproductive factors.

Results: During a median follow-up of 5.74 years, there were 212 227 new cases of all-cause dementia (4.5%), 162 901 cases of Alzheimer's disease (3.5%) and 24 029 cases of vascular dementia (0.5%). The HR of dementia was 1.15 [95% confidence interval (CI) 1.03-1.16] for menarcheal age ≥17 years compared with menarcheal age 13-14 years, 0.79 (0.77-0.81) for menopausal age ≥55 years compared with menopausal age <40 years, and 0.81 (0.79-0.82) for fertility duration ≥40 years compared with fertility duration <30 years. Whilst being of parity one (HR 0.89, 95% CI 0.85-0.94) and breastfeeding <6 months (HR 0.92, 95% CI 0.88-0.95) was associated with lower risk of dementia, being of parity two or more (HR 1.04, 95% CI 0.99-1.05) and breastfeeding ≥12 months (HR 1.14, 95% CI 1.01-1.07) was associated with a higher risk of dementia than women without parity or breastfeeding history. Use of hormone replacement therapy and oral contraceptives independently reduced the dementia risk by 15% and 10%, respectively.

Conclusions: Female reproductive factors are independent risk factors for dementia incidence, with higher risk associated with shorter lifetime endogenous estrogen exposure.

Keywords: dementia; duration of fertility; hormone replacement therapy; menarche; menopause.