Does HRT Cause Dementia?

You may have heard on social media that Hormone Replacement Therapy (HRT) increases the risk of dementia. This comes from a recent observational study that showed increased “tau” plaques in women who used HRT. Tau plaques accumulation may drive Alzheimer’s disease risk. 

An observational study watches real-world choices and outcomes without interference, showing associations rather than proving cause and effect. Observational studies cannot prove causation. 

For example, if you looked at car crashes and more of the drivers wore something red, you can observe and conclude that wearing red is associated with more car crashes but not that it caused more car crashes. 

There are lot of problems with the study.

• It is observational and observational studies cannot prove causation
• They don’t know when people started on HRT 
• They don’t know what type of HRT was used.
• The great majority of people they studied were mainly women over 70. 
• They did not do cognitive testing. 

Because hormone therapy has been prescribed differently over the decades, women who start treatment at different ages may experience different effects on tau accumulation independent of age alone. Even the type of hormone therapy has changed. 

HRT and Dementia – Type and Timing Are Important

A crossover study in Nature showed that giving bioidentical estradiol and progesterone in early menopause has beneficial effects on cognitive control and task switching. These effects were measured by neuroimaging fMRI and showed increase brain activity in the prefrontal cortex. 

A review if the literature also showed that when estrogen was given close to menopause age <65, verbal memory improved. There was no improvement if HRT was given to women over the age of 65. Yet studies showed if synthetic estrogen and progesterone were given to women over 65, there was a decrease in cognitive performance.  

When it comes to hormone therapy and dementia – the route of administration matters as well. Bioidentical estradiol given transdermal (through the skin) improved memory of past experiences whereas bioidentical estradiol given orally improved memory for doing something in the future as compared to women who were never on HRT. 

The KEEPS trial showed no long term harm or benefit of HRT, however the trials had a mix of bioidentical and synthetics. 

The big problem is that most studies used synthetics and the numbers using the more modern versions of HRT were small. There are no randomized controlled trials that use the combination of hormones given today that have been found to be safer such as transdermal estradiol and oral micronized progesterone. 

A large meta analysis that eliminated the results from the Women’s Health Initiative where oral synthetic hormones were given to women whose average age was 63, showed a 30% reduction in Alzheimer’s disease risk.

Therefore, more studies using the newer formulas can provide better answers. There are a lot of risks not taking hormone replacement therapy and the North American Menopause Society and about 20 other organizations say the benefits outweigh the risks. 

Brain Changes When Estrogen Drops

Dr. Lisa Mosconi, a neuroscientist at Weill Cornell, and the Director of the Women’s Brain Initiative and Alzheimer’s Prevention Program, has used brain scans to show that hormone changes in menopause change the brain. During perimenopause and the first few months after menopause, women’s brains use up to 30% less energy in the temporal cortex, which is near the memory centers of the brain. It’s like turning down the lights in a room. You can still see, but everything feels tougher, slower, and less acute. 

This is why so many women have trouble remembering things, focusing, and having brain fog. This is also why up to 62% of women in their 40s and 50s say their brains are changing. This is not dementia, which is important. These changes in the brain are only transitory, not permanent. In fact, a lot of women’s brains bounce back within two to six years after menopause. Estrogen is fuel for the brain and when it drops the brain goes into low power mode.

Dr. Mosconi reviewed many studies and concluded that: Timing matters. Studies now show that starting hormone therapy within 10 years of menopause can lower the risk of Alzheimer’s disease by about 32% with estrogen alone, and around 23% with estrogen plus progesterone. If started too late, the brain’s estrogen receptors may already have diminished, reducing effectiveness.

Estrogen Effects on the Brain  

• Estrogen exerts anti-oxidant and anti-inflammatory effects, promotes DNA repair, and induces Brain Derived Neurotrophic Factors (BDNF), supporting neuronal survival under stress.

• It promotes growth of neurons and modulates genes that are involved in lipid metabolism and dilates blood vessels improving blood flow.

• It modulate neurotransmitters that can improve mood, reduce anxiety and influence stress. 

• It enhances neuroplasticity, the brains ability to change and make new pathways and facilitates leaning and long term memory. 

Mixed Data

While the study data on risk is mixed due to different formulations, ages women started therapy and the route of administration, there are clear benefits to HRT and most studies did not show harm or increased dementia. The best time to start is under the age of 65.

HRT preserves bone and cardiovascular health and improve quality of life and the decision to start it is a personal one. If you need support and live in NY, NJ, PA, AZ or FL, apply for a clarity call to see if we are a good fit. 

You can enjoy the benefits and minimize the risks. 

FAQ

Does HRT Cause Dementia?

The short answer is no. There have been several studies done, and so far there hasn’t been any strong evidence that HRT causes dementia. In fact, studies do show that HRT can actually be very protective and even help lower the risk of Alzheimer’s disease if started before age 65 or within 10 years of menopause. 

References 1–9

1. Puri TA, Gravelsins LL, Alexander MW, et al. Association Between Menopause Age and Estradiol-Based Hormone Therapy With Cognitive Performance in Cognitively Normal Women in the CLSA. Neurology. 2025;105(6):e213995. doi:10.1212/WNL.0000000000213995
2. Coughlan GT, Rubinstein Z, Klinger H, et al. Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease. Sci Adv. 11(10):eadt1288. doi:10.1126/sciadv.adt1288
3. Kantarci K, Tosakulwong N, Lesnick TG, et al. Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial. Neurology. 2018;90(16):e1404-e1412. doi:10.1212/WNL.0000000000005325
4. Bagger YZ, Tankó LB, Alexandersen P, Qin G, Christiansen C, PERF Study Group. Early postmenopausal hormone therapy may prevent cognitive impairment later in life. Menopause. 2005;12(1):12-17. doi:10.1097/00042192-200512010-00005
5. Girard R, Météreau E, Thomas J, Pugeat M, Qu C, Dreher JC. Hormone therapy at early post-menopause increases cognitive control-related prefrontal activity. Sci Rep. 2017;7(1):44917. doi:10.1038/srep44917
6. Andy C, Nerattini M, Jett S, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition. Front Endocrinol (Lausanne). 2024;15:1350318. doi:10.3389/fendo.2024.1350318
7. Daniel JM, Bohacek J. The critical period hypothesis of estrogen effects on cognition: Insights from basic research. Biochim Biophys Acta. 2010;1800(10):1068-1076. doi:10.1016/j.bbagen.2010.01.007
8. Song YJ, Li SR, Li XW, et al. The Effect of Estrogen Replacement Therapy on Alzheimer’s Disease and Parkinson’s Disease in Postmenopausal Women: A Meta-Analysis. Front Neurosci. 2020;14:157. doi:10.3389/fnins.2020.00157
9. O’Brien J, Jackson JW, Grodstein F, Blacker D, Weuve J. Postmenopausal Hormone Therapy Is Not Associated With Risk of All-Cause Dementia and Alzheimer’s Disease. Epidemiol Rev. 2014;36(1):83-103. doi:10.1093/epirev/mxt008

QUICK LINKS

Hormone Health Course  | Food Sensitivity Testing | Stress Management | Is HRT Right For You?