HRT and dementia risk
The primary indication for HRT should be for the treatment of vasomotor symptoms and bone health and not brain ageing or the prevention of dementia.
Another case-control study on menopausal hormone replacement therapy (HRT) and the risk of dementia. The main finding was that the risk of dementia differed depending on the use of progestogens. Oestrogen alone was associated with a 15% decreased odds of dementia overall among women younger than 80 years who received treatment for at least 10 years, with a 1.1% decrease in risk for each year of treatment. Conversely, oestrogen and progestogen combined were associated with an 11% increased risk of Alzheimer’s disease dementia among women who had used hormone therapy for 5-9 years and a 19% increased risk among women treated for 10 years or more.
These findings are at odds with the risk of dementia with HRT that was previously reported from the Women’s Health Initiative Memory Study (WHIMS), which showed that incidence of all-cause dementia doubled in women aged 65 years and older on HRT (conjugated equine oestrogens and medroxyprogesterone acetate) (Shumaker et al. JAMA 2003;289:2651-62.). However, a later analysis from the WHIMS study found no increased risk of all-cause dementia with conjugated equine oestrogens alone (Shumaker et al JAMA 2004;291:2947-58.), which is in keeping with this study.
Observational studies of HRT have limitations with potential confounding by indication; it has previously been thought that HRT might protect against dementia could have led to bias in prescribing HRT to women with cognitive concerns or frank dementia.
Based on these and other findings HRT should not be used to prevent dementia. However, it looks as of HRT does not increase your risk of dementia with oestrogen alone HRT. The risk with oestrogen plus progestogen HRT increases dementia risk by 5-7 extra cases per 10,000 woman-years.
The primary indication for HRT should be for the treatment of vasomotor symptoms and bone health and not brain ageing or the prevention of dementia.
Vinogradova et al. Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases. BMJ. 2021 Sep 29;374:n2182. doi: 10.1136/bmj.n2182.
Objective: To assess the risks of developing dementia associated with different types and durations of menopausal hormone therapy.
Design: Two nested case-control studies.
Setting: UK general practices contributing to QResearch or the Clinical Practice Research Datalink (CPRD), using all links to hospital, mortality, and social deprivation data.
Participants: 118 501 women aged 55 and older with a primary diagnosis of dementia between 1998 and 2020, matched by age, general practice, and index date to 497 416 female controls.
Main outcome measures: Dementia diagnoses from general practice, mortality, and hospital records; odds ratios for menopausal hormone treatments adjusted for demographics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs.
Results: Overall, 16 291 (14%) women with a diagnosis of dementia and 68 726 (14%) controls had used menopausal hormone therapy more than three years before the index date. Overall, no increased risks of developing dementia associated with menopausal hormone therapy were observed. A decreased global risk of dementia was found among cases and controls younger than 80 years who had been taking oestrogen-only therapy for 10 years or more (adjusted odds ratio 0.85, 95% confidence interval 0.76 to 0.94). Increased risks of developing specifically Alzheimer's disease were found among women who had used oestrogen-progestogen therapy for between five and nine years (1.11, 1.04 to 1.20) and for 10 years or more (1.19, 1.06 to 1.33). This was equivalent to, respectively, five and seven extra cases per 10 000 woman-years. Detailed risk associations for the specific progestogens studied are also provided.
Conclusion: This study gives estimates for risks of developing dementia and Alzheimer's disease in women exposed to different types of menopausal hormone therapy for different durations and has shown no increased risks of developing dementia overall. It has shown a slightly increased risk of developing Alzheimer's disease among long term users of oestrogen-progestogen therapies.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.
Interesting! What does this mean for birth control hormones Prof G, of which pwMS will be likely consuming for many more years than HRT and at a younger age. I had to start a progesterone only pill to cope with peri-menopause and it’s helped me massively to normalise what suddenly became severe cyclical mood problem and it’s also helped fatigue associated with periods - so amazing for me but I thought progesterone was neuro-protective so is it only when combined with Oestrogen that it becomes dubious or is it also unhelpful on its own? Thank you!