Age, menstruation history, and the brain

Objectives: To investigate the cross-sectional association between measures of menstruation history (including menopausal status, age of menopause, age of menarche, and duration of reproductive stage) and brain volume. 
Methods: Women (aged 45 to 79 years) from the UK Biobank were included (n = 5,072) after excluding those who had (1) hysterectomy or bilateral oophorectomy, (2) ever used menopausal hormone therapy, (3) ever had a stroke, or (4) were perimenopausal. Multiple linear hierarchical regression models were computed to quantify the cross-sectional association between measures of menstruation history and brain volume. Sensitivity analysis based on propensity matching for age (and other demographic/health covariates) were applied to estimate differences in brain volumes between matched premenopausal and postmenopausal women. 
Results: Postmenopausal women had 1.06% (95% confidence interval [CI]; 1.05-1.06) and 2.17% (95% CI, 2.12-2.22) larger total brain volume (TBV) and hippocampal volumes (HV), respectively, than premenopausal women. Sensitivity analysis with age matched samples produced consistent results (TBV: 0.82%, 95% CI, 0.25-1.38; HV: 1.33%, 95% CI, 0.01-2.63). For every year increase in age above 45 years, postmenopausal women experienced 0.23% greater reduction in TBV than premenopausal women (95% CI, −0.60 to −0.14), which was not observed for HV. Moreover, every 1 year delayed onset of menopause after 45 was associated with 0.32% (95% CI, −0.35 to −0.28) and 0.31% (95% CI, −0.40 to −0.22) smaller TBV and HV, respectively. Every additional year in age of menarche was associated with 0.10% (95% CI, 0.04-0.16) larger TBV, which was not detected for HV. Similarly, every 1 year increase in duration of reproductive stage was associated with 0.09% smaller TBV (95% CI, −0.15 to −0.03), which was not detected for HV. 
Conclusions: Menopause may contribute to brain volume beyond typical aging effects. Furthermore, early age of menarche, delayed age of menopause and increasing duration of reproductive stage were negatively associated with brain volume. Further research is required to determine whether the negative association between age of menopause and HV is potentially an indicator of future vulnerability for dementia.