The short answer is: it depends — on when you start, what kind of hormones you take, how long you continue, and possibly your genetic makeup. Hormone replacement therapy (HRT), also called menopause hormone therapy (MHT), does not appear to uniformly increase or decrease dementia risk across all women. The most comprehensive recent evidence, a systematic review and meta-analysis published in The Lancet Healthy Longevity in December 2025, found no overall evidence that MHT either raises or lowers dementia risk in postmenopausal women as a group. But that headline finding obscures a more nuanced story — one where timing, hormone type, and individual biology make a substantial difference.
Consider two women, both starting HRT at different points in their lives. One begins estrogen therapy at 51, shortly after her final menstrual period, and continues for several years. Another starts a combined estrogen-progestogen regimen at 68, well over a decade after menopause. The current body of research suggests these two women may face meaningfully different outcomes when it comes to dementia risk. This article breaks down what the science actually says, where the evidence conflicts, what the “critical window” theory means for timing decisions, and what women and caregivers need to know before drawing conclusions.
Table of Contents
- Does Hormone Replacement Therapy Increase or Decrease Dementia Risk in Women?
- What Is the Critical Window Hypothesis, and Why Does Timing Matter So Much?
- Does the Type of Hormone Matter — Estrogen-Only Versus Combined Therapy?
- What Does Genetics Have to Do With It — The APOE-ε4 Factor?
- Does HRT Affect How Alzheimer’s Pathology Develops in the Brain?
- Why Are Women Disproportionately Affected by Dementia in the First Place?
- What Is Coming Next — Updated Guidelines and Where the Research Is Heading
- Conclusion
- Frequently Asked Questions
Does Hormone Replacement Therapy Increase or Decrease Dementia Risk in Women?
The honest answer is that researchers still do not have a clean consensus — and the conflicting data is not a sign of sloppy science but of genuine biological complexity. The December 2025 Lancet Healthy Longevity meta-analysis, which synthesized data across multiple studies, concluded that menopause hormone therapy does not appear to impact dementia risk overall. Researchers at University College London summarized it plainly: the therapy neither protects against nor causes dementia in postmenopausal women when you look at the full population. However, that same analysis found a more specific signal worth noting: MHT was associated with an 11.3% reduced risk of Alzheimer’s disease specifically, particularly when estrogen-only therapy was initiated during midlife and sustained for longer periods.
That’s a modest but meaningful reduction — not a cure, not a guarantee, but a statistically detectable association. The distinction between Alzheimer’s disease and all-cause dementia matters here, since Alzheimer’s is only one form of dementia, and the mechanisms by which estrogen interacts with the brain may be disease-specific. On the other side of the ledger, a Danish nationwide nested case-control study published in the BMJ found that MHT was positively associated with all-cause dementia and Alzheimer’s disease — and notably, this association held even among women who began treatment at age 55 or younger. That finding complicates the picture considerably. It does not mean HRT causes dementia, but it does mean women and clinicians cannot dismiss the question on the assumption that earlier use is always safer.
What Is the Critical Window Hypothesis, and Why Does Timing Matter So Much?
The “critical window” theory holds that estrogen’s effects on brain health are highly dependent on when a woman is first exposed to declining estrogen levels and when she begins replacement therapy. Proponents of this model argue that the brain’s estrogen receptors are most responsive — and most protective — when activated during perimenopause or in the years immediately following the final menstrual period. Once the brain has adapted to a low-estrogen environment for a decade or more, reintroducing hormones may have neutral or even harmful effects. The data supporting this timing hypothesis is substantial. A 2023 meta-analysis cited by CNN found that HRT initiated in midlife or within 10 years of the final menstrual period was associated with a 23 to 32 percent reduced risk of dementia and Alzheimer’s disease.
That is a notable reduction. By contrast, research published in Frontiers in Aging Neuroscience found that estrogen-progestogen therapy begun after age 65, or more than 10 years post-menopause, was associated with an increased dementia risk. The same intervention, different timing — opposite directions of effect. The limitation here is practical and important: most women who receive an HRT prescription are doing so to manage menopausal symptoms, not to prevent dementia. The decision is typically made well within the critical window by default. But for women who are considering starting HRT in their 60s or beyond — whether for ongoing symptom relief or other health reasons — the dementia risk question deserves a direct conversation with a physician rather than a dismissal.
Does the Type of Hormone Matter — Estrogen-Only Versus Combined Therapy?
Not all HRT is the same, and the research increasingly suggests that the formulation matters when it comes to brain outcomes. Estrogen-only therapy appears to carry the more favorable signal in several studies. The Lancet Healthy Longevity analysis specifically noted that the reduced Alzheimer’s risk association was most pronounced with estrogen-only regimens, particularly those initiated during midlife and maintained for longer durations. Combined therapy — estrogen paired with a synthetic progestogen — is typically prescribed for women who still have a uterus, since unopposed estrogen can increase the risk of endometrial cancer.
The addition of progestogen may blunt some of estrogen’s potentially neuroprotective effects, though the exact mechanism is not fully understood. This matters clinically: a woman who had a hysterectomy and can safely take estrogen alone may be in a different position than a woman who requires combined therapy, at least as far as the dementia evidence goes. That said, this is not a reason for women to refuse combined therapy if they need it. The trade-off between endometrial safety and any potential brain health difference is one that requires individualized assessment. The point is that the HRT-dementia relationship is not a single question with a single answer — the answer shifts depending on which hormones, in which doses, in what formulation, and in which patient.
What Does Genetics Have to Do With It — The APOE-ε4 Factor?
Genetic background appears to be one of the most important modifiers of HRT’s effect on dementia risk, and the APOE-ε4 allele is the gene variant at the center of this picture. APOE-ε4 is the strongest known genetic risk factor for late-onset Alzheimer’s disease, and carriers of this variant appear to respond differently to HRT than non-carriers. Research published in Frontiers in Dementia found that the protective effects of early HRT initiation — specifically, starting within five years of menopause — were most pronounced in women who do not carry the APOE-ε4 allele. For APOE-ε4 carriers, the evidence showed little to no benefit, and potentially some harm with later or prolonged use.
This is a meaningful distinction. It suggests that genetic testing could eventually play a role in personalizing HRT decisions for women who are concerned about dementia risk, though that level of precision medicine is not yet standard practice in most clinical settings. The takeaway is not that APOE-ε4 carriers should automatically avoid HRT — they may still benefit from it for symptom relief, bone health, or cardiovascular reasons. But it does mean that a woman who knows she carries the variant should have a more detailed conversation about the dementia risk question with her doctor, rather than assuming the general population findings apply equally to her.
Does HRT Affect How Alzheimer’s Pathology Develops in the Brain?
Beyond the question of dementia diagnosis, some researchers are examining whether HRT influences the biological processes underlying Alzheimer’s disease at the cellular level. One particularly notable finding comes from a study published in Science Advances, which found that HRT use in older women — the study commonly included women around age 70 and above — may accelerate tau accumulation in brain regions that are particularly vulnerable to Alzheimer’s disease. Tau is a protein that, when it misfolds and accumulates in brain tissue, forms the tangles that are one of the hallmarks of Alzheimer’s pathology. The Science Advances finding does not prove that HRT causes Alzheimer’s, but it raises a specific mechanistic concern: that in older women, long after the critical window has closed, the biological impact of hormone exposure on the brain may shift from potentially protective to potentially harmful at the cellular level.
This is a warning worth heeding — not as a reason to panic, but as a reason to avoid treating HRT as a straightforward anti-aging or brain-protective intervention in later life. The limitation here is that this line of research is relatively new and the long-term clinical implications are still being worked out. Tau accumulation is a marker of risk, not a guaranteed diagnosis. But it adds to the overall picture suggesting that older women initiating or continuing HRT face a different risk-benefit profile than younger women who began therapy near menopause.
Why Are Women Disproportionately Affected by Dementia in the First Place?
Women account for approximately two-thirds of all dementia cases globally, a disparity that goes well beyond the fact that women live longer on average. Researchers increasingly point to the hormonal transition of menopause as a contributing biological factor. Estrogen appears to play a neuroprotective role — influencing brain metabolism, inflammation, and the clearance of amyloid and tau proteins — and the sharp decline in estrogen during and after menopause may leave the female brain more vulnerable to the processes that drive Alzheimer’s disease.
This biological context is part of why the HRT-dementia question has attracted so much scientific attention. If falling estrogen contributes to dementia risk in women, the logic goes, could replacing that estrogen reduce the risk? The evidence reviewed here suggests the relationship is real but conditional. Simply restoring estrogen levels does not automatically translate to brain protection, particularly if the timing is wrong or the genetic profile is unfavorable.
What Is Coming Next — Updated Guidelines and Where the Research Is Heading
The regulatory and clinical guidance around HRT and dementia is still catching up to the science. Updated WHO guidelines on dementia prevention are expected to be released in 2026, and those guidelines may directly address menopause hormone therapy for the first time in a substantive way.
The field is moving toward more nuanced, personalized recommendations that account for timing, hormone type, duration, and genetic risk factors rather than issuing blanket statements. What women and families can reasonably expect in the coming years is a clearer framework — not a simple yes or no, but a set of decision criteria that physicians can use to have better-informed conversations with individual patients. In the meantime, the current consensus is consistent: HRT is not recommended as a standalone strategy for preventing dementia, but it does not need to be avoided solely out of dementia concern when it is started appropriately in midlife for symptom management.
Conclusion
The relationship between hormone replacement therapy and dementia risk in women is genuinely complicated, and the honest answer to the question in this article’s title is: it can, but whether it increases or decreases that risk depends on several interacting factors. The timing of initiation relative to menopause is the most consistently important variable — early use near menopause carries a more favorable signal, while late initiation appears associated with increased risk. The type of hormone formulation, the duration of use, and a woman’s APOE-ε4 genetic status all further shape that equation. The December 2025 Lancet Healthy Longevity meta-analysis provides the most current and comprehensive view: no net impact across the full population, but meaningful differences within subgroups.
For women navigating these decisions — or for family members and caregivers trying to understand the research on behalf of someone they love — the practical guidance is to treat this as an individualized question rather than a population-level one. Women who started HRT during perimenopause for symptom relief can note with some reassurance that they are likely within the window where the evidence is most favorable. Women considering starting or continuing HRT in their late 60s or beyond should raise the dementia research explicitly with their physicians. And as the science continues to develop, including the updated WHO guidelines expected in 2026, the guidance around this issue will only become more specific and useful.
Frequently Asked Questions
Is HRT recommended for preventing dementia in women?
No. Current medical consensus does not support starting HRT solely to prevent dementia. While some studies show a reduced Alzheimer’s risk with early initiation, the evidence is not strong enough to justify using HRT as a dementia prevention strategy. It may be prescribed for other reasons — menopause symptoms, bone health — and the dementia risk picture should be part of that broader conversation.
What is the “critical window” for HRT and brain health?
The critical window refers to the period during or shortly after menopause — generally within 10 years of the final menstrual period — when estrogen therapy may be most beneficial for the brain. Initiating HRT within this window has been associated with reduced dementia risk in some studies. Starting therapy well outside this window, particularly after age 65, appears to carry different and potentially increased risks.
Does it matter whether HRT is estrogen-only or combined estrogen-progestogen?
Yes, the evidence suggests it does. Estrogen-only therapy shows the stronger association with reduced Alzheimer’s risk in several studies. Combined therapy, which includes a synthetic progestogen to protect the uterus, may not carry the same brain-health benefit. Women who have had a hysterectomy can take estrogen alone and may face a different risk profile than those who require combined therapy.
Does the APOE-ε4 gene affect whether HRT helps or hurts dementia risk?
Research suggests yes. Women who do not carry the APOE-ε4 allele appear to gain the most benefit from early HRT initiation. APOE-ε4 carriers showed little to no benefit in some analyses and possible harm with longer or later use. Genetic testing is not currently a standard part of HRT prescribing, but carriers who are concerned about dementia risk should discuss this specifically with their doctor.
Does HRT affect Alzheimer’s pathology in the brain directly?
A study published in Science Advances found that HRT use in older women may be associated with accelerated tau accumulation in brain regions vulnerable to Alzheimer’s disease. Tau tangles are one of the defining features of Alzheimer’s pathology. This finding does not prove causation, but it is a specific biological signal suggesting that older women who use HRT may face different brain-level effects than younger women who initiate therapy near menopause.
Why do women get dementia more than men?
Women account for roughly two-thirds of dementia cases globally. While part of this reflects women’s longer average lifespan, researchers increasingly believe that the hormonal changes of menopause — particularly the sharp decline in estrogen — contribute independently to dementia risk. Estrogen appears to play roles in brain metabolism, inflammation, and clearance of Alzheimer’s-related proteins, and losing it during menopause may leave the brain more vulnerable over time.
