Use of Hormone Replacement Therapy and Risk of Dementia: A Nationwide Cohort Study

Abstract

Background and objectives: Estrogen has the potential to influence brain physiology implicated in dementia pathogenesis. Hormone replacement therapy (HRT) might be expected to influence the risk of dementia. Observational data indicated that HRT was associated with reductions in dementia risk, but experimental evidence demonstrates that HRT increases the incidence of dementia. To determine the effect of HRT on the risk of dementia, a retrospective cohort study was performed using a nationwide claims dataset in Taiwan.

Methods: A population-based longitudinal study was performed using data from the Longitudinal Health Insurance Database in Taiwan. A total of 35,024 women with HRT were enrolled as the exposed cohort and 70,048 women without HRT were selected on the basis of propensity matching as the comparison cohort. All participants were followed up until the diagnosis of dementia, death, or at the end of December 31, 2013, whichever occurred first. Overall, the average duration of follow-up (±SD) in the HRT and comparison cohorts was 12.3 (±2.3) and 12.2 (±2.4), respectively. The Cox proportional hazards regression models were conducted to produce hazard ratios (HRs) with 95% CIs to evaluate the association of HRT with the risk of dementia.

Results: In the follow-up period, the cumulative incidence of dementia for the HRT cohort (20.04 per 1,000) was significantly higher than the corresponding cumulative incidence for the comparison cohort (15.79 per 1,000), resulting in an adjusted HR of 1.35 (95% CI 1.13-2.62). There was an increased risk of dementia with a higher cumulative dose of HRT prescription (p for trend <0.0001).

Discussion: This cohort study documented that HRT was associated with an increased risk of dementia. The clinical implications of this study merit further investigations.