Hormone replacement therapy (HRT) has been linked to a reduced risk of dementia according to a prospective study involving nearly 185,000 postmenopausal women in the U.K. Biobank.
After 13 years of follow-up, results indicated that HRT use was associated with a lower risk of all-cause dementia with a hazard ratio (HR) of 0.90 (95% CI 0.84-0.96), as reported by Anne-Marie Minihane, PhD, from the University of East Anglia.
The most significant benefits were observed in women who began HRT between the ages of 46 and 56. For those starting HRT at ages 46 to 50, the HR was 0.87 (95% CI 0.80-0.95, P=0.002); for women starting HRT at ages 51 to 56, the HR was even lower at 0.77 (95% CI 0.70-0.86, P<0.001).
These associations were also evident among women who experienced surgical menopause (HR 0.74, 95% CI 0.65-0.84), those carrying the APOE4 gene (HR 0.87, 95% CI 0.80-0.95), and among women with lower endogenous estrogen exposure (HR 0.84, 95% CI 0.77-0.93).
The study stands out as the largest of its kind, reinforcing findings from previous research that indicated estrogen-only menopause hormone therapy may lower Alzheimer’s disease risk.
Notably, women represent approximately two-thirds of Alzheimer’s disease cases. Minihane pointed out that the higher prevalence is likely linked to the effects of menopause on brain metabolism and the influence of the predominant genetic risk factor, APOE4, in women.
While earlier studies had suggested that HRT could guard against both Alzheimer’s and cardiovascular disease, a 2003 Women’s Health Initiative Memory Study (WHIMS) indicated that estrogen-plus-progestin formulations could increase dementia risk in women aged 65 and older.
The same Women’s Health Initiative study also identified links between combined estrogen and progestin with increased risks of breast cancer and heart disease, which resulted in significant warnings that were partly lifted by the FDA in 2026.
In the United States, HRT usage among postmenopausal women declined significantly, from 26.9% in 1999 to just 4.7% in 2020, making the topic a matter of ongoing debate.
Aimee Spector, PhD, from University College London, noted that the novelty of the U.K. Biobank research lies in the timing of HRT initiation, supporting the ‘window of opportunity’ hypothesis which emphasizes the importance of HRT during the menopause transition phase.
Moreover, UCL’s Sarah James, PhD, underscored the necessity for extensive studies with long-term follow-up to connect menopausal experiences with future brain health.
Interestingly, findings regarding surgical menopause and early HRT initiation provide compelling evidence that both timing and individual circumstances play essential roles in the observed relationship with dementia risk.
The U.K. Biobank study tracked 183,450 postmenopausal women for an average of 13.3 years, analyzing the effects of HRT on long-term dementia outcomes among those who used HRT for at least one year.
Overall, 3,948 dementia cases were identified, with 1,993 classified as Alzheimer’s disease. The reported associations were adjusted for various covariates influencing both dementia risk and HRT use.
While HRT was associated with a reduced risk of Alzheimer’s (HR 0.84, 95% CI 0.77-0.92, P<0.001), it showed no significant association with non-Alzheimer’s dementia (HR 0.95, 95% CI 0.87-1.04, P=0.28).
The researchers acknowledged that the U.K. Biobank contains generic information about HRT, suggesting the need for further studies to explore how different hormone therapy compositions, doses, and administration routes may affect dementia risk.
These findings highlight the varying responses of different subgroups of women, accentuating the requirement for randomized controlled trials to guide HRT prescriptions in the context of reducing dementia risk.
Disclaimer: Always consult with a healthcare provider before starting or changing any medication or treatment regimen.
Fuente: https://www.medpagetoday.com/neurology/dementia/122798
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