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Does Hormone Replacement Therapy Increase Alzheimer’s Risk?

Does Hormone Replacement Therapy Increase Alzheimer’s Risk?

Hormone replacement therapy (HRT) contains female hormones (estrogen and/or progestogen) and is often used for the treatment of symptoms such as hot flashes and night sweats in women undergoing menopause. In a previous blog, I discussed the history and research on HRT and their conflicting findings when it comes to how HRT relates to brain health. The debate continues with a recent study reporting that the use of HRT for over 10 years is associated with a small increased risk of Alzheimer's disease in postmenopausal women [1][2].

Findings come from a large observational study that included 84,739 women from Finland [2]. Data on their HRT use were obtained from a nationwide register that included all HRT users from 1994. Alzheimer's disease diagnosis was performed according to internationally approved criteria while ruling out other forms of dementia or cognitive decline. As for types of HRT, women with a uterus had to take estrogen along with a progestogen to reduce the risk of endometrial cancer, whereas women who had undergone hysterectomy could take an estrogen-alone therapy.

For women who initiated HRT before the age of 60, the use of HRT that included both estrogen and progestogen was associated with a 17% increase in risk for Alzheimer's disease compared to women who did not use HRT. For women who had undergone hysterectomy and started estrogen-alone HRT before the age of 60, there was a 9% increased risk for Alzheimer's. The increase in risk was only observed in women who took HRT in oral or patch forms for durations longer than 10 years. The exclusive use of vaginal estrogen was not associated with an increased risk for Alzheimer's.

For women who initiated HRT after the age of 60, the use of HRT (estrogen and progestogen or estrogen alone) was associated with a 15-38% increase in risk for Alzheimer's disease compared to women who did not use HRT. In this age group, the increased risk was evident after 3-5 years of HRT use.

Although these findings may be alarming, it is worth noting that the evidence is conflicting. Several previous observational studies have suggested a relationship between HRT use and decreased risk for Alzheimer's [3]. Also, it is important to remember that an observational study like this one is not designed to prove that HRT is responsible for Alzheimer's disease—it is designed to show an association, not causation. In fact, two randomized controlled clinical trials (which were designed to evaluate causation) have shown that short-term HRT (2-5 years) started within a few years of the onset of menopause was neither beneficial nor harmful for cognitive health [4][5].

Together, findings from the latest study combined with previous reports are consistent with the current recommendations from the North American Menopause Society. If you are interested in using HRT, talk to your healthcare provider so you can understand the benefits and risks while choosing the type, dose, formulation, route, and duration that is most appropriate for you [6]. Once you start using HRT, continued discussions with your healthcare provider are recommended so you can periodically reevaluate the benefits and risks of continuing or discontinuing HRT.


  1. Maki PM, Girard LM, Manson JE (2019) Menopausal hormone therapy and cognition. BMJ 364, l877.
  2. Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F et al. (2019) Use of postmenopausal hormone therapy and risk of Alzheimer's disease in Finland: nationwide case-control study. BMJ 364, l665.
  3. Imtiaz B, Tuppurainen M, Rikkonen T et al. (2017) Postmenopausal hormone therapy and Alzheimer disease: A prospective cohort study. Neurology.
  4. Gleason CE, Dowling NM, Wharton W et al. (2015) Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med 12, e1001833; discussion e1001833.
  5. Henderson VW, St John JA, Hodis HN et al. (2016) Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology 87, 699-708.
  6. The NHTPSAP (2017) The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 24, 728-753.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.

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