Hormone Replacement Therapy Could Help Women Avoid Dementia—If It’s Taken at the Right Time

Women are at much greater risk of dementia than men—as many as two thirds of people in the US with Alzheimer’s disease are women—and likely for a mix of reasons that experts are still parsing out. One of those unique risk factors is thought to be the hormone fluctuations of menopause, leading researchers to study whether hormone replacement therapy (HRT), which can level the hormonal playing field, might help. And according to a big new analysis presented at the 2025 American Neurological Association annual meeting, HRT can indeed lower dementia risk—but with one critical caveat: You have to take it early in menopause.

Researchers analyzed more than 50 studies involving HRT that also tracked cognitive outcomes and found that women who started HRT within five years of menopause cut their risk of Alzheimer’s by as much as 32%. But the analysis also revealed that women who began HRT after age 65 were at 38% increased risk of developing the disease. Why the switch up? It has to do with how the brain reacts to hormones at different stages. Keep reading to get the full story on HRT and Alzheimer’s, and learn what this means for you.

How hormone replacement therapy may play a role in dementia risk

It helps to know a bit about how HRT works first. HRT is a prescription that comes in a variety of forms, including pills, patches, and gels, all of which contain estrogen—the main hormone that drops off precipitously after menopause—often in combination with a synthetic form of progesterone called progestin. By restoring these hormones, HRT addresses the symptoms linked with plummeting levels, like hot flashes, night sweats, and vaginal dryness, in the years leading up to menopause (a.k.a. perimenopause) and just after.

But what doctors have recently uncovered is that dropping estrogen levels around this period might also spell trouble for women’s brain health. “We know that estrogen molecules interact with brain cells,” David M. Holtzman, MD, scientific director of the Hope Center for Neurological Disorders at Washington University School of Medicine, tells SELF. It’s possible that their activity makes those cells more resilient, or prevents the development of changes linked to Alzheimer’s or keeps them from getting worse over time, he says. That may explain why taking HRT in the years right around menopause—and in turn, avoiding the steep estrogen drop-off of this phase—was shown to lower dementia risk.

The problem with waiting to start HRT until well after that estrogen dip has occurred, like at age 65-plus, may be that your brain has already experienced the related decrease in support, Dr. Holtzman explains. So serving up estrogen at that point no longer helps. As one of the authors of the study, FNU Vaibhav, MBBS, a student at Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, says in a press release: “It’s like watering a plant: It helps when the plant is growing, but if it’s already wilting, it might be too late.”

As for why the later-stage HRT seems to make matters worse? It isn’t totally clear, but “it could be that the responsiveness of the brain cells has changed by this point,” Dr. Holtzman says. So while cells in a younger person (that were continuously exposed to estrogen prior to HRT) might benefit from a fresh influx of estrogen, ones that had a break from that estrogen bath might react negatively to it. It’s also possible that by age 65 and beyond, the brain typically develops certain abnormalities linked with Alzheimer’s, and adding estrogen to the mix then just exacerbates things. That effect could be tied to inflammation too, Dr. Holtzman notes: “It’s conceivable that in younger women, estrogen supports the protective type of inflammation in the brain, but at later stages, it triggers the bad kind.”

How to tell if (and when) you should consider hormone replacement therapy

As Dr. Vaibhav notes in the release, there isn’t enough evidence yet to suggest HRT be taken specifically to prevent Alzheimer’s (even in the early stages of menopause). So the decision comes down to your personal experience of the menopause symptoms it can help treat, and what you and your doctor decide is best.

When it comes to the other potential effects of HRT, the good news is, it’s been widely proven safe and shown to benefit cardiovascular health and overall longevity in multiple studies. Prior controversy surrounding its usage can largely be traced back to a 2002 study, the Women’s Health Initiative (WHI), the results of which have largely been refuted. (Researchers initially found that participants taking HRT had a slightly increased chance of having a heart attack, stroke, breast cancer, and dementia—but what became apparent shortly after is that most of them were over the age of 60, likely several years past menopause, when we now know HRT is less effective. And a followup analysis of the WHI found that HRT actually reduced the risk of several conditions for those who started it in their 50s.)

That said, there are risks to taking HRT, particularly for anyone who has ever had breast or endometrial cancer, a heart attack or stroke, blood clots, or liver disease. And it can cause side effects in some people—including breast soreness, spotting, bloating, and headaches—which may be worth considering as you weigh your decision.

But what we know from the research above is, if you’re cleared by your doctor to take HRT and you’re struggling with menopause symptoms, there’s no reason to avoid it, Dr. Holtzman says, presuming you’re within five years of menopause. “If anything, it’s going to be helpful to start it sooner than later, not damaging,” he says. In that scenario, it’s also worth chatting with your doctor about stopping HRT after a couple years, when menopause symptoms tend to let up, to avoid the potential negative impact on your brain down the line.

 

 

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