Hormone Replacement Therapy May Lower Dementia Risk in Postmenopausal Women

Postmenopausal women who used HRT for at least 1 year had a 10% lower risk of developing dementia and a 16% lower risk of developing Alzheimer disease (AD) than women who never used it, according to a study of 183,450 women in the UK Biobank published in Alzheimer's & Dementia.¹

The study, led by researchers at the University of Exeter Medical School and the University of East Anglia (UEA), followed participants for a mean of 13.3 years and identified 3948 incident dementia cases, including 1993 cases of AD.¹

Study Design and Overall Findings

Researchers restricted their analysis to postmenopausal women who had experienced either natural (spontaneous) or surgical menopause (hysterectomy or bilateral oophorectomy), excluding those with dementia at baseline or missing HRT and menopause data. HRT use was defined as current use or use for at least 1 year. The reference group included women who never used HRT or used it for less than 12 months.¹

Using Cox proportional hazards models adjusted for age, education, smoking status, systolic blood pressure, ethnicity, body mass index, cholesterol, socioeconomic deprivation, diabetes, and use of cholesterol-lowering or antihypertensive medications, researchers found HRT use was associated with a hazard ratio (HR) of 0.90 for all-cause dementia (95% CI, 0.84-0.96; P = .001).¹

When broken out by dementia subtype, HRT use was associated with reduced risk of AD (HR, 0.84; 95% CI, 0.77-0.92; P < .001) but not with nonAD dementia, defined as dementia diagnoses without an AD-specific code (HR, 0.95; 95% CI, 0.87-1.04; P = .28).¹

Subgroups Show Stronger Associations

The association between HRT and dementia risk varied considerably by subgroup. For women who had surgical menopause, HRT use was associated with a 26% lower risk of all-cause dementia (HR, 0.74; 95% CI, 0.65-0.84; P < .001) and a 32% lower risk of AD (HR, 0.68; 95% CI, 0.56-0.82; P < .001).¹

Among women with natural menopause, the association with all-cause dementia was not statistically significant (HR, 0.94; 95% CI, 0.87-1.01; P = .091), though the AD-specific association remained significant (HR, 0.89; 95% CI, 0.80-0.99; P = .03).¹

Women who carried at least 1 APOE ε4 allele, the most significant common genetic risk factor for dementia, also showed a stronger association than noncarriers: an HR of 0.87 (95% CI, 0.80-0.95; P = .002) for all-cause dementia and 0.84 (95% CI, 0.75-0.94; P = .003) for AD. Women with shorter lifetime exposure to natural estrogen, defined as fewer than 37 years between menarche and menopause, showed an HR of 0.84 (95% CI, 0.77-0.93; P < .001) for all-cause dementia, compared with no significant association among women with 37 or more years of exposure (HR, 0.99; 95% CI, 0.90-1.09; P = .90).¹

Timing of Initiation Matters

Age at HRT initiation also shaped the association. Across all women, starting HRT between ages 46 and 50 was associated with an HR of 0.87 for all-cause dementia (95% CI, 0.80-0.95; P = .002), and starting between ages 51 and 56 years was associated with an HR of 0.77 (95% CI, 0.70-0.86; P < .001).¹

Among women with surgical menopause specifically, HRT initiated before age 46 years, between ages 46 and 50 years, or between ages 51 and 56 years was associated with reduced dementia risk, with HRs of 0.85, 0.69, and 0.57, respectively (all P < .04). The authors wrote that these findings support the "window of opportunity" hypothesis, in which HRT initiated during the perimenopausal or early postmenopausal period may be neuroprotective, with benefit strongest between ages 46 and 56 but not established beyond age 56.¹

"We found that women who had used HRT were about 10% less likely to develop dementia and 16 percent less likely to develop the Alzheimer disease form of dementia than women who had never used it," Anne-Marie Minihane, PhD, professor at UEA and cocorresponding author of the study, said in a news release.² "Our findings contribute to growing evidence that hormone therapy's effects on brain health are complex and influenced by individual biological factors."

David Llewellyn, PhD, professor at the University of Exeter and co-corresponding author, said the study moves beyond a simple yes-or-no question about HRT and dementia risk.

"These findings represent a significant step forward," Llewellyn said in the release.² "Rather than asking simply whether HRT affects dementia risk, we've been able to identify which women are most likely to benefit and when.”

Researchers Caution Against Overreach

The study authors were careful to note that their findings show association rather than causation. HRT use is subject to selection or "healthy-user" bias, since women who use HRT can differ systematically from nonusers in ways that also relate to dementia risk, including socioeconomic status, educational attainment, and lifestyle factors, even after adjustment for those variables. The authors also pointed out that UK Biobank does not capture HRT formulation, meaning the analysis could not distinguish between estrogen-only and combined estrogen-progestogen regimens or between oral, transdermal, and vaginal routes of administration.¹

The only randomized controlled trial to date assessing incident dementia as a primary outcome, the Women's Health Initiative Memory Study, reported an increased risk of dementia with combined oral conjugated equine estrogen plus progestin in women 65 years and older, a finding echoed in other studies. The study authors wrote that this contrast underscores the importance of HRT timing and formulation, and they called for confirmation in a randomized controlled trial to inform a more personalized approach to prescribing.¹

Where Pharmacists Fit In

The findings arrive as pharmacists are being pushed to take a larger role in menopause care generally. In a separate interview with Drug Topics®, Lisa Miller, PharmD, MSCP, associate dean and clinical professor in the University of Florida College of Pharmacy's Department of Pharmacy Education & Practice, said menopause care is too often reduced to a single hormone therapy decision.³

"I feel like menopause care is so often reduced to the question of whether someone should or should not take hormone therapy, but it's a whole lot broader than that," Miller said.³ "That's where pharmacists come in. It involves medication safety, cardiometabolic risk, mental health, bone health, all of those things, and the patients often come to the pharmacy first, looking for answers."

Miller said pharmacists are well suited to help patients sort reliable information from unreliable sources, including social media.

"Where I really see pharmacists helpful is that I feel like they're the best trained to step back and say, 'Is this safe, is this necessary, is this helping, and is there something here that might be making the patient feel worse?'" she said.³

Community pharmacists in particular do not need a formal menopause clinic to make an impact, Miller said, pointing to their accessibility. "Community pharmacists are the most accessible health care professionals. Study after study has shown us that," she said, adding that the first step is "just recognizing patterns" in what patients are already picking up at the counter, such as recurring sleep, mood, or vaginal symptom medications that may signal an unaddressed perimenopausal transition.³

That counseling role includes weighing risk alongside potential benefit. Hormone therapy is not risk-free, as it may raise the risk of heart disease, stroke, blood clots, breast cancer, gallbladder disease, and endometrial cancer, with risk varying by a woman's age, the therapy type, dosage, duration, and individual health history.⁴

Guidance generally favors starting hormone therapy before age 60 years or within 10 years of menopause for women with moderate to severe hot flashes, vaginal or bladder symptoms, early menopause, or osteoporosis risk, using the lowest effective dose for the shortest necessary duration.⁴

REFERENCES

1. Squires S, Saleh RN, Pilling LC, et al. Hormone replacement therapy and dementia risk among postmenopausal women: Identifying responsive subgroups in the UK Biobank. Alzheimers Dement. 2026;22(8):e71679. doi:10.1002/alz.71679

2. University of East Anglia. HRT linked to lower dementia risk in large UK study. News release. EurekAlert. August 26, 2026. Accessed August 27, 2026. https://www.eurekalert.org/news-releases/1141248

3. Nowosielski B, Miller L. Q&A: pharmacists are underutilized but essential guides in menopause care. Drug Topics. May 27, 2026. Accessed August 27, 2026. https://www.drugtopics.com/view/pharmacists-underutilized-essential-guides-menopause-care

4. Mayo Clinic Staff. Hormone therapy: is it right for you? Mayo Clinic. Accessed August 27, 2026. https://www.mayoclinic.org/diseases-conditions/menopause/in-depth/hormone-therapy/art-20046372