Hormone Therapy and Your Brain: What You Need to Know

Evidence is shifting back toward replacing estrogen for women in certain age and risk categories

Joelle Klein

Updated October 17, 2025

A woman in menopause sticks a transdermal patch on the skin

MStudioImages/Getty Images

In 1992, a hormone replacement therapy called Premarin, was the most common prescription in the United States. Women flocked to this remedy to help them reduce problematic menopause symptoms, such as hot flashes and sleep problems. They also relied on the drug to potentially help prevent heart disease and dementia. Then, in the early 2000s, the Women’s Health Initiative (WHI), a large-scale randomized clinical trial designed to study hormone therapy in postmenopausal women, was halted due to early results suggesting health risks outweighed benefits. The related Women’s Health Initiative Memory Study (WHIMS) also ended. Prescription rates plummeted.

It turns out the problem with the WHI was not necessarily the hormone therapy but the study’s design. Most of the participants were more than a decade past their final menstrual period and menopause-related symptoms. Newer studies show that the benefits outweigh the risks for women under 60 or within 10 years of menopause onset without contraindications. Plus, newer delivery methods and formulations that are more personally tailored to an individual’s health risks and symptoms are now available.

But the damage of the headline-grabbing results lasted for a couple of decades and persists today. Women still wonder whether hormone replacement therapy, also called menopausal hormone therapy (MHT), is safe for their brain. Research has provided conflicting results, but helpful guidelines are emerging.

Brain fog and brain drain

During the menopausal transition, about 60 percent of women report cognitive complaints such as memory, focus and attention issues. These cognitive symptoms are collectively referred to as “brain fog.” Dr. JoAnn V. Pinkerton, professor of obstetrics and gynecology and division director of midlife health at the University of Virginia, says her patients describe it as feeling like they’ve got cotton candy in their brains.

“The most important thing I tell them is that brain fog during the menopausal transition and early menopause years is not an indication of dementia or an indication that you’ll get dementia or Alzheimer’s later in life,” she notes.

It’s not surprising, though, that women would suspect that midlife memory issues could be an early indication of later-in-life dementia since women are twice as likely to develop Alzheimer’s disease as men. One theory for the discrepancy is the drop in estrogen levels that occurs with menopause. Estrogen is thought to protect neurons in the brain.

Another theory, says Pauline M. Maki, professor of psychiatry, psychology and obstetrics & gynecology at the University of Illinois at Chicago, is that hot flashes cause cognitive changes. In a study published in Neurology in 2022, increased hot flashes were linked with a brain biomarker that has been linked to an increased risk of stroke, Alzheimer’s disease and cognitive decline.

Hormone therapy, although currently not recommended to treat cognitive issues or for dementia prevention, effectively treats hot flashes, mood swings and sleep disturbances that contribute to brain fog, helping reduce issues for many women.

So MHT is useful for key menopause symptoms, but what about its long-term impact on the brain? It depends.

Hormone therapy for early menopause

In the United States, the average age of menopause is 51. Menopause before 45 is considered early menopause, and before 40, it’s premature menopause. About 10 percent of women experience early or premature menopause due to either natural or medical reasons, such as when the ovaries are removed or as a result of cancer treatment.

While studies reveal conflicting findings regarding MHT use and brain health during natural menopause, there is general agreement that MHT is beneficial for brain health in women who experience early or premature menopause.

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A UK Biobank study published in 2023 in Human Reproduction reported that women who experienced natural menopause before age 45 had a higher risk of all-cause dementia than women who experienced menopause after 45.

During natural menopause, a woman’s hormone levels fluctuate and slowly decline. With early or premature menopause, the hormone decline is steeper, and symptoms are generally more intense. “Women who have surgical menopause have a more dramatic lowering of hormone levels because they were younger and had more ovarian function, and then it abruptly stops,” Pinkerton says.

Fortunately, MHT can help. Researchers found that women treated with estrogen therapy after their ovaries were removed before the age of natural menopause did not have the same risk of cognitive decline and late-life dementia as women not treated with estrogen.

In the case of early menopause, with or without symptoms, Pinkerton says there are clear benefits to taking MHT — estrogen only in cases where the ovaries were removed and estrogen plus progesterone in cases where the ovaries are intact. The treatment is suggested until the average age of natural menopause to protect against heart disease, bone loss and cognitive changes.

The caveat is that MHT is not usually recommended for those who have a history of breast or endometrial cancer, stroke, heart attack, blood clots or liver disease.

Hormone therapy for natural, average-age menopause

Most women reach natural menopause between the ages of 45 and 58. Most, about 85 percent, experience hot flashes and night sweats, although they vary in duration, type and intensity.

MHT is the most effective treatment for women experiencing problematic symptoms, particularly hot flashes and night sweats. It can also improve sleep and mood in some cases. Alleviating these issues can help improve cognitive problems.

“Hormone therapy not only treats hot flashes and night sweats but also improves sleep quality and duration, and that’s, overall, healthy for your brain,” Pinkerton says. “I have patients who tell me that [hormone therapy] helps them sleep and feel better, which helps them focus and concentrate better.”

Study outcomes regarding MHT and dementia later in life are mixed. Some studies report MHT decreases the risk, especially if initiated close to the start of menopause. Other studies report it increases risk. However, numerous large-scale studies have found that hormone therapy is neither harmful nor helpful when it comes to dementia risk. These studies, which include Kronos Early Estrogen Prevention Study (KEEPS) Continuation, Early Versus Late Intervention Trial with Estradiol (ELITE), Cognitive Complaints in Early Menopause Trial (COGENT) and the WHI Memory Study of Younger Women (WHIMS-Y), all found the same neutral outcomes across the specific ages, formulations and methods of delivery (oral or transdermal) that were tested.

Pinkerton says determining how hormones taken in your 50s might impact your risk of dementia and Alzheimer’s disease in your 70s and 80s is challenging.

One study published in Frontiers in Dementia in 2025, titled “Hormone replacement therapy, menopausal age and lifestyle variables are associated with better cognitive performance at follow-up but not cognition over time in older-adult women irrespective of APOE4 carrier status and co-morbidities,” looked at 629 women age 65 and older and found exactly what the title suggests. APOE4 status refers to the genetic variant that puts a person at greater risk of Alzheimer’s disease, specifically.

Bottom line: MHT can help relieve problematic menopause symptoms for most women without evidence of long-term harm to brain health.

How long should you take hormone therapy?

While the Menopause Society, a nonprofit organization for healthcare professionals, recommends that women who are symptomatic, without contraindications, under age 60 or within 10 years of menopause onset use hormone therapy for symptom relief, the guidelines for duration and for women who fall outside those parameters is murkier.

Cognitive issues associated with menopause often subside within a couple of years after the last menstrual period as a woman's body adjusts to the new lower levels of estrogen. You probably only need hormone therapy for about three to five years, Pinkerton says. However, research presented at the 2024 Annual Meeting of the Menopause Society found that 40 percent of women in their 60s and 10 to 15 percent of women in their 70s still experience hot flashes.

The American College of Obstetricians and Gynecologists, the Menopause Society and the Endocrine Society recommend taking the lowest effective dose or appropriate dose of hormones for symptoms and reassessing benefits and risks regularly. The organizations don’t recommend routine discontinuation based on age alone.

“We don’t tell people that they have to stop at 60 or 65. What we say is that your health risk goes up as you age, and if you are continuing hormone therapy, you need to have a really individualized risk-benefit assessment discussion every year,” Pinkerton says.

Hormone therapy in postmenopausal women 60+

Many women in their 60s and 70s may feel like they missed the hormone therapy bandwagon, having gone through menopause during the time when it was thought hormone therapy caused more problems than benefits. They suffered through symptoms, with some still experiencing them, and are now wondering if, in their late midlife and senior years, the benefits of the new types and doses of MHT outweigh the risks when it comes to cognitive function and other health perks.

The WHIMS study published in 2005 did find that the use of estrogen with or without medroxyprogesterone acetate, a synthetic form of progesterone, in women who initiated hormone therapy at age 65 or older experienced substantial increases in dementia risk and cognitive decline. However, the study included only one type of estrogen, conjugated equine estrogen (CEE), at a particular dosage, which is a type and dosing of estrogen not commonly used today.

Newer, safer versions of estrogen, such as transdermal and vaginal estrogens at lower doses, are currently available, as well as micronized progesterone, which is thought to be safer than the synthetic form used in WHIMS. Could these newer forms convey more of the benefits of HT and fewer adverse effects? Without the findings of large-scale, randomized clinical trials in older women, the answer is unknown.

On the bright side for women wanting to try or continue using HT in their senior years, a large-scale study published in 2024 in Menopause: The Journal of the Menopause Society looked at 10 million senior women, from 2007 to 2020, who used Medicare and found that estrogen-only therapy use beyond age 65 was associated with a significant risk reduction in all-cause mortality and a slight (2 percent) reduction of risk in dementia. However, this study did not distinguish between continued use of hormone therapy into one’s 60s or initiation of the medication in one’s 60s.

Maki says a woman’s age is not as important as the status of her brain health when she starts hormone therapy. “Estrogen seems to like healthy cells, whether they’re heart cells or brain cells, and it doesn’t like unhealthy cells.”

As a result, hormone therapy is not routinely recommended for women older than 65 because, at that age, many women have already started to have some age-related brain changes and hormone therapy can accelerate those changes. Additionally, women’s risk for heart disease and stroke increases as they age.

But if you’re over 60, or more than 10 years past your final menstrual period, and experiencing hot flashes and sleep issues that are interfering with your quality of life, and you haven’t tried MHT before, you should still talk to a menopause specialist so, together, you can assess the potential risks and benefits of MHT.