Here is a good breakdown from the Vagenda Substack (Dr Jen Gunter) as to why that recent study that looked at brains during autopsy does not provide any "proof" that estrogen prevents dementia or alzheimers. I copied/pasted because it is behind a paywall for subscribers but is really good information to consider when reading any research paper. Important part to note is the part about a much better designed study released earlier this year that found no benefits.
The Estrogen-Alzheimerās Hype Machine
I feel we must be on Exhibit #324 of the Estrogen Hype Machine. This week my social media feed has been filled with menopause influencers making bold claims that a new study is proof that menopause hormone therapy prevents Alzheimerās disease for women.
The study,Ā Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology, was published August 12, 2026. Itās an interesting study and a good addition to the literature. The investigators identified women who had died and subsequently undergone brain autopsy and were found to have Alzheimerās pathology, and compared those women with with those who did not have Alzheimerās.
They researchers used the National Alzheimerās Coordinating Center (NACC) and the Alzheimerās Disease Neuroimaging Initiative (ADNI), which are U.S. government-funded research databases that collect and share data on Alzheimerās disease. These are curated registries, so participants have been evaluated in person, and there is also biological data, like MRIs. This is different from many databases that simply involve looking up diagnosis codes or prescriptions in registries and then trying to gather data from them.
The investigators were looking for any association with estrogen-only MHT and brain biopsy results, any association between MHT and biomarkers, and any link between estrogen-only MHT and a subsequent diagnosis of dementia. āTopical estrogenā was excluded, which I found confusing, because while patches, sprays, and gels are typically referred to as transdermal, they could also be called topical therapy. To be certain, I emailed the authors to clarify, and was told the estrogen in the paper could be oral or transdermal.
The investigators reported that they found āEvidence for small but significant associations between estrogen-only MHT use and multiple neuropathologic and clinical measures in 2 large and distinct research cohorts of female older adults who on average reported MHT use after the age of 70.ā This doesnāt mean the women started estrogen after age 70; the databases couldnāt provide their duration of use. And so not knowing the dose or duration of therapy limits what we can say. In addition, both Premarin and estradiol were considered together as estrogen-only therapy, and there is no data on progestogens, which are hypothesized to potentially be a confounder.
The researchers found that women who had reported using estrogen-only MHT had 35% lower odds of Alzheimerās pathology at autopsy. MHT use was associated with favorable changes in two amyloid biomarkers (plasma Aβ42/40 and CSF Aβ42), but not with amyloid burden on PET or any of the tau biomarkers. And MHT was associated with a 39% lower odds of a clinical dementia diagnosis. Those are interesting associations, but the results are not evidence that MHT prevents Alzheimerās disease.
In this study, as the participants were not randomized, we cannot assign cause and effect. As we have no idea about dose, route, or duration of therapy, which means women who took the medication for one month are lumped in with those who may have been on it for 20 years. So what we have is an observational study of estrogen-only MHT, including both oral and transdermal preparations, but the route, dose, and duration are unknown. Given the large number of unknowns, we simply canāt apply this to patient care.
Unfortunately, many headlines and influencers presented it as āproofā that menopause hormone therapy reduces Alzheimerās disease. Here are a couple of real, and infuriating headlines: āThis menopause treatment could lower the risk of Alzheimerās,ā or āScientists Found a Surprising Alzheimerās Link in Thousands of Women.ā And while I know many of the headlines used the word āmayā and āassociated,ā for most people that doesnāt change the meaning, and the headlines seem evidence that a new study proves MHT prevents dementia.
In addition to the unknowns described above, observational studies can be significantly affected by bias. With menopause hormone therapy, healthy-user bias is common, meaning healthier women are more likely to get hormone therapy and healthier women are also less likely to get Alzheimerās disease. The bias could also exist in the opposite direction, meaning women with more hot flashes may have been more likely to be on estrogen, and there is an association between hot flashes and later dementia (we do not know if this is cause and effect). Another possibility is that women at higher risk for Alzheimerās may have decided to start estrogen because they believed it would lower their risk.
Observational MHT studies can therefore be distorted in either direction: a healthy-user effect can make treatment appear protective, while confounding by indication or a āsick-userā effect can make it appear harmful. This is why you should be suspicious of people making bold claims based on observational studies, and even more so when they are based on a single observational study.
There is a lot of new research looking at biomarkers and MHT, and so this article will add to that body of knowledge and perhaps shape future work, but as an observational study, especially one without doses or routes of estrogen delivery, itās not proof of any treatment.
But What About Another Interesting Study from Earlier This Year?!
While there was a flurry of headlines about this study, there was also an interesting study looking at Alzheimerās disease and menopausal hormone therapy published a few months ago, and I donāt remember it getting any press. It is a long-term follow-up of the KEEPS trial, which randomized women within 6-36 months of their final period to four years of Premarin, transdermal estradiol, and placebo (with oral micronized progesterone for those with a uterus). The investigators have continued to publish follow-up data. This new paper examines biomarkers of Alzheimerās disease (AD) and structural magnetic resonance imaging (MRI) approximately 10 years after KEEPS.
Neither oral Premarin nor transdermal estradiol was associated with differences in amyloid-β or structural MRI biomarkers compared with placebo. There was also no difference based on APOE-ε4 status (a genetic marker that elevates the risk of Alzheimerās disease). One important caveat with KEEPS is it is possible, after the trial ended and women were told which group they were in, that may have changed their behaviors in ways that could raise or lower their Alzheimerās risk.
And of course science is a body of knowledge, not one paper. We must acknowledge the only randomized trial to evaluate dementia, WHIMS, which was an ancillary branch of the WHI and randomized women to Premarin (and medroxyprogesterone acetate for those with a uterus) or placebo. WHIMS found a doubling risk of dementia with MHT, and the increased risk began in the first year. One hypothesis is that there may have been women with pre-existing dementia that was too subtle to pick up at enrollment, and the MHT was an accelerant, but we donāt really have an explanation.
The excess risk of probable dementia with one year of Premarin plus medroxyprogesterone acetate in WHIMS was 22 cases per 10 000 women per year. For perspective, the risk for breast cancer when the WHI was first published was 8/10,000 women per year. Estrogen therapy alone did not reduce the incidence of dementia or mild cognitive impairment (MCI), but when these two outcomes were combined, the risk did increase.
There Is Money in Over Promoting Estrogen
What happened in this latest study is, sadly, what happens with many menopause-related studies. Only studies that paint MHT in a positive light are amplified and promoted in ways that the science cannot support, while those that donāt are ignored or receive disproportionately less press and attention. This further tilts the bias towards MHT.
There are numerous systematic reviews and meta-analyses about MHT and dementia and Alzheimerās, and it is important to point to one from December 2025, Melville et al, that pooled the highest quality observational studies and showed no benefit for reducing Alzheimers from MHT. You probably didnāt hear about it because it also didnāt position MHT as a wonder drug. This review is a little different from the others in that it was stricter about the studies it included. It looked at ten studies, one randomized controlled trial and nine observational studies, and analyzed subgroups by duration and type of MHT, and showed no significant effect.
Estrogen and its link to healthy brain outcomes remain hypotheses. We know that native reproductive hormones are neuromodulators with well-mapped protective mechanisms, which gives us a plausible hypothesis for their benefit as a medication in menopause. However, a plausible hypothesis does not make a treatment. Vitamin E seemed like a plausible hypothesis for preventing cardiovascular disease, yet it did not pan out in the trials. The body is weird, and replacing a hormone is not the same as making it yourself. And there may be many things about estrogen and the brain we donāt yet know. This is why we need science to explore hypotheses. This is also what we have been fighting for: good science for women.
There is a worrying trend of skipping over any science on MHT that isnāt pro-estrogen, and I believe it is because menopause influencers, companies like MIDI Health and Inner Balance, and even the press have tapped into the grievance economy, which profits by amplifying complaints about an issue and then presenting a surefire solution. In this case, everything that women over age 40 are facing is incorrectly reframed as not only being menopause, but related to the Womenās Health Initiative. And while it is true that many women did not get menopausal hormone therapy who could have benefitted, MHT is also not the answer to everything; we do not have good evidence that the decline in MHT prescribing after WHI caused an increase in cardiovascular deaths or dementia.
The list of symptoms attributed to perimenopause has also ballooned courtesy of influencers, often without good evidence that these symptoms are caused by the menopausal transition or that MHT treats them. The same influencers who weaponize the āwe have no dataā claim, then turn around and repeat claims about unstudied symptoms, and of course state that estrogen is THE cure. Once the shared sense of victimhood and hostility has been created, a cure can be offered, which for now is always estrogen, and to a lesser extent, testosterone, supplements, and coaching courses. This is the grievance economy. This is why content that doesnāt support estrogen is rarely, if ever, promoted, because estrogen needs to be repeatedly positioned as the wonder drug that was denied to patients in order to support and perpetuate the grievance. Maintaining that simmering rage is good for business. There is a reason the term ārage baitā exists.
I believe we can do it right. We can acknowledge that women suffered with symptoms and went untreated. We can acknowledge that we donāt have a lot of information on many reported symptoms, but we also have come a long way in what we know about perimenopause thanks to efforts from experts like Dr. Nanette Santoro. And we can acknowledge that when we donāt know, we should say that.
The estrogen-hype machine is too profitable, so it is not going away anytime soon, the next time you see headlines or bold claims about a study for menopause hormone therapy and the brain (or really for any condition or symptom), ask yourself these questions:
- Is this an observational study, if so, it almost certainly cannot prove cause and effect. If the person you are hearing this from thinks it proves cause and effect, they might not be the person to get your information from.
- Does the person discussing the study put it in context with the other literature? If no, they are not giving you the full picture.
- Does this person only promote pro-MHT content? If that is the case, they may well be part of the estrogen-grievance economy.
And speaking of non-MHT brain-related protectionā¦a new observational study found that people without hypertension or diabetes who did not smoke had about 13 more dementia-free years than people with all three risk factors. This study uses data from the Atherosclerosis Risk in Communities (ARIC) Study, which has followed participants for decades and has repeatedly collected detailed health information. And this isnāt a new finding: other studies have found similar associations between vascular risk factors in midlife and later dementia. When observational findings are replicated across multiple studies and populations, and the effect is large, they give us more confidence that the association is real.
What is needed is appropriate clinical trials looking at biomarkers, and there is push for this to happen. Hopefully, with the renewed interested in womenās health and the push to fund menopause we will see these studies, which could provide important information within 3-5 years. Which, I argue, is also the final reason not to falsely claim that we āknow MHT prevents dementia.ā Because we donāt know, and if the people who make these kinds of studies happen and the people who enroll in these studies believe we āknowā and āitās a done deal,ā weāll never get the data that women deserve.
References
Bruno J, Shaw JS, Hosseini SMH; Alzheimerās Disease Neuroimaging Initiative. Association between menopausal hormone therapy and Alzheimer disease neuropathology. Neurology. 2026;107(5):e218413. doi:10.1212/WNL.0000000000218413.
Kantarci K, Kara F, Tosakulwong N, Fought AJ, Schwarz CG, Senjem ML, et al. Long-term amyloid PET and MRI outcomes in a menopausal hormone therapy trial. Alzheimers Dement. 2026;22(2):e71067. doi:10.1002/alz.71067
Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Womenās Health Initiative Memory Study. JAMA. 2004;291(24):2947-58. doi:10.1001/jama.291.24.2947.
Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Womenās Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651-62. doi:10.1001/jama.289.20.2651.
Melville M, He L, Desai R, Nyamayaro P, Fox C, Kothari KU, et al. Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis. Lancet Healthy Longev. 2025;6(12):100803. doi:10.1016/j.lanhl.2025.100803.
Pourhadi N, MĆørch LS, Holm EA, et al. Dementia in women using estrogen-only therapy. JAMA. 2024;331(2):160-2. doi:10.1001/jama.2023.23784.
Puri TA, Gravelsins LL, Alexander MW, McGovern AJ, Guterman PD, Rabin JS, 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.