Understanding the role of hormone replacement therapy in risk of dementia

Why this matters

• Women have a higher lifetime risk for dementia, which could be associated with hormonal changes after menopause. Estrogen plays a key role in several key neuromodulation activities and has the potential to influence brain physiology implicated in dementia.
• Hormone replacement therapy has also been linked with increased inflammatory markers and risk of stroke. To date, there has been conflicting evidence surrounding the risk or benefit of HRT and dementia.
• A comprehensive understanding of the effects of postmenopausal hormone replacement therapy (HRT) on the risk of dementia is critical in providing evidence-based clinical advice for preventing or slowing progression of dementia in individuals at risk.

Study design

• Objective: to discern the association between HRT and the risk of dementia and whether the duration of treatment is significant.
• Longitudinal population study of the National Health Insurance Research Database in Taiwan of 35,024 women aged ≥40 between 2000–2005 who received HRT for the first time in this period and 70,048 women who did not receive HRT.
• Participants were followed longitudinally from index date to the first of: diagnosis of dementia, death, or end of study; an average of 12.3 years for the HRT group and 12.2 for the control.
• Additional dementia risk factors (hypertension, diabetes, hyperlipidemia, coronary artery disease, stroke, chronic obstructive pulmonary disease, chronic kidney disease, malignant neoplasms) were accounted for when creating adjusted hazard ratios.

Key results

• The cumulative incidence of dementia was significantly higher in the HRT cohort than the comparison cohort (P<0.001), with the HRT group demonstrating a 35% higher risk of dementia (aHR 1.35).
• Risk of Alzheimer’s disease and vascular dementia, in particular, were elevated in the HRT cohort (aHR 1.20 and 1.79, respectively).
• A dosage trend was identified with a higher dose of HRT associated with an increased risk for dementia (P for trend <0.0001).
• Duration of HRT treatment did not affect risk of dementia (P for trend =0.249).
• The authors concluded that there is a dose-dependent association between HRT treatment and increased risk of dementia.

Limitations

• Data exclusively from Taiwan.
• Assumption that patients take medications as prescribed.
• Reliance on physician recorded dementia diagnosis, no imaging available.
• Lack of behavioral or lifestyle data.
• APOE-e4 genotype status not considered due to lack of available data.