Hormone replacement therapy is associated with increased dementia risk
A large Danish registry study reported a 24% increased risk of dementia after oestrogen-progestin therapy.
Study investigates link between hormone therapy and dementia
- Menopausal hormone therapy was associated with a higher risk of Alzheimer's disease and dementia of all causes in a nationwide evaluation.
- This was evident even with short-term use around the age of onset of menopause.
- Continuous and cyclical oestrogen-progestogen therapies were associated with a comparable increase in dementia rates.
Danish nationwide registry study fills knowledge gaps
An analysis published in June 2023 used registry data from all Danish women who were between 50 and 60 years old at baseline (New Year 2000) and had no history of dementia.1,2 The age restriction was set to ensure a nearly complete exposure history in all women. Women with contraindications to HRT or with various possible confounding variables (e.g. hysterectomy) were excluded. By the end of the year 2018, 5,589 new dementia cases and 55,890 age-matched controls were identified.
Compared to women who did not receive hormone therapy, the rate of dementia increased by 24% after oestrogen-progestin therapy. The longer the hormone use, the greater the increase in risk: this ranged from a 21% increase for a HRT duration of one year or less, to 39% after 8 to 12 years of hormone therapy, to 74% at 12 years or more.
Further research into the correlations is needed
The correlation of long-term use of hormone therapy with the risk of later cognitive decline has already been documented by large observational studies and one of the largest randomised, double-blind, placebo-controlled studies on this topic: The Women's Health Initiative Memory Study reported an increased incidence of dementia in women over 65 years of age who had been treated with oestrogen and progestin for one year as early as 2003.3
The effects of short-term hormone therapy at an earlier stage, i.e. menopause, had not yet been extensively studied. The current study reports that the risk remained elevated even after HRT at a younger age (under 55 years). Previous studies often did not differentiate between continuous versus cyclical regimens. According to the new data, both forms were associated with a relevant increase in new cases: 31% after continuous versus 24% after cyclical HRT. The associations were also evident when restricted to late-onset dementia (21%) and Alzheimer's disease (22%).
However, due to the nature of the registry study, the new data do not provide information on whether there might be a common underlying factor that predisposes to both the need for HRT and the development of dementia, as the study authors acknowledge. However, they see the risk increase with duration of use described above, as a strong indication of a direct link that should be further explored.
- Pourhadi, N., Mørch, L. S., Holm, E. A., Torp-Pedersen, C. & Meaidi, A. Menopausal hormone therapy and dementia: nationwide, nested case-control study. BMJ 381, e072770 (2023).
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New study shows hormone replacement therapy may raise women’s risk for dementia - UPI.com. UPI.
- Shumaker, S. A. et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289, 2651–2662 (2003).
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