Hormone therapy tied to lower dementia risk in postmenopausal women

Clinical takeaway: These findings suggest menopause type and age at initiation may help clinicians better individualize hormone therapy counseling, including discussions of potential long-term effects on dementia risk.

Evidence on menopausal hormone therapy and cognition has been conflicting, with age at initiation and treatment type potentially influencing outcomes. A large UK Biobank observational study suggests the association with dementia also differs across groups of postmenopausal women.

Researchers followed 183,450 women without dementia for an average of 13.3 years. Hormone therapy use was defined as current use or at least one year of prior use. The data did not distinguish estrogen-only from combined therapy or capture dose or route. During follow-up, 3,948 women developed dementia.

The strongest signal appeared among women categorized as having surgical menopause, which the study defined as hysterectomy and/or bilateral oophorectomy. Hormone therapy use was associated with a 26% lower risk of all-cause dementia in this group, compared with no clear reduction after natural menopause.

Timing also mattered. Starting therapy at ages 46 to 50 and 51 to 56 was associated with 13% and 23% lower dementia risks, respectively. Starting before age 46 or after 56 was not associated with a clear overall reduction. Women with fewer than 37 years between menarche and menopause also showed a stronger association.

“Rather than asking simply whether HRT affects dementia risk, we've been able to identify which women are most likely to benefit, and when,” said study coauthor David Llewellyn, PhD.

Source: Squires S, et al. (2026 Aug 26) Alzheimers Dement. Hormone replacement therapy and dementia risk among postmenopausal women: Identifying responsive subgroups in the UK Biobank