Menopause & Longevity
Menopause and Longevity
Menopause before 45 is linked to modestly higher mortality. In the Women's Health Initiative, hormone therapy didn't change survival over 18 years.
Menopause arrives with its own reading list: symptom apps, supplement ads and, for more than two decades, a boxed warning on hormone-therapy labels. Humanic Blue is interested in the quieter question beneath that noise: does menopause, its timing or its treatment change how long, and how well, you’ll live?
On menopause and longevity, the clearest signal in the research is timing. In a review of 32 studies covering about 310,000 women, those who reached menopause before 45 were about 12% more likely to die during follow-up. That’s an association, not evidence of cause. Hormone therapy is a separate question: in the Women’s Health Initiative trials, it didn’t change death rates over 18 years. The Menopause Society supports it for hot flashes and bone protection in the right candidates, not as a way to live longer.
In This Article
- Reaching menopause before 45 is linked to higher death rates
- Removing both ovaries early, without estrogen, was linked to higher death rates in one study
- Before 40, a guideline recommends hormones until the usual age of menopause
- Hormone therapy didn’t change survival over 18 years
- What the FDA’s label change did and didn’t change
- Where heart and bone health come in
- The studies and numbers behind all of this
Key Takeaways
- Women who reach menopause before 45 have modestly higher death rates and more heart disease in long-term studies. These studies show an association, not a cause.
- One Mayo Clinic study linked removing both healthy ovaries before 45 to higher death rates, mainly in women who didn’t take estrogen afterward. This comes from one observational study.
- For menopause before 40, an international guideline recommends hormone therapy until the usual age of menopause, while rating its own evidence low or very low. The recommendation rests on low-certainty evidence.
- In the Women’s Health Initiative, hormone therapy didn’t change death rates over 18 years.
- The Menopause Society supports hormone therapy for bothersome hot flashes and bone protection in women under 60 or within 10 years of menopause who have no medical reason to avoid it.
- Whether starting hormone therapy early helps women live longer is still debated.
Is menopause before 45 linked to longevity?
Some women reach menopause much earlier than their peers. As many as 10% reach natural menopause by 45, according to epidemiologists led by Taulant Muka at Erasmus University Medical Center in Rotterdam.
Their 2016 review in JAMA Cardiology pooled 32 observational studies of about 310,000 women. Compared with women whose menopause came at 45 or later, those who reached it earlier had about 50% more coronary heart disease, about 19% higher risk of dying from cardiovascular disease and about 12% higher risk of dying from any cause. Stroke risk wasn’t clearly different. Women whose menopause came at 50 to 54 were somewhat less likely to die of coronary heart disease than women who reached it before 50.
The review was sponsored and funded by Metagenics, a nutritional supplement company; the paper says the funder had no role in the analysis. See the numbers
These were observational studies. They can’t separate the timing of menopause from whatever else differs between women who reach it early and those who don’t. The authors wrote that early menopause “could be an important factor affecting risk of disease and mortality among middle-aged and older women.” The existing article Does Menopause Increase Heart Disease Risk? covers how clinicians use it in heart-risk assessment.
Surgical menopause
Removing both ovaries before natural menopause brings menopause on abruptly. For women with harmful BRCA gene changes, the National Cancer Institute says removing the ovaries and fallopian tubes “can help reduce the risk of ovarian cancer and, possibly, breast cancer.”
The less settled question is what happens when healthy ovaries come out. Mayo Clinic researcher Walter Rocca and colleagues followed about 2,400 women in Olmsted County, Minnesota, who had one or both ovaries removed for reasons other than cancer between 1950 and 1987, alongside a similar number of women who hadn’t.
Overall, women who had both ovaries removed didn’t die at higher rates. But among those who had both removed before 45, death rates were about two-thirds higher, mainly in women who hadn’t taken estrogen up to age 45. Removing one ovary wasn’t linked to higher death rates. The team, publishing in The Lancet Oncology in 2006, was careful about cause: it said it’s uncertain whether the surgery causes the higher death rate or simply marks women who were already at higher risk. How the study worked
The study looked only at ovaries removed for non-cancer reasons. For women with a strong inherited cancer risk, the calculation is different and belongs with a specialist.
How does the reason for ovary removal change the comparison of risks and benefits?
Menopause before 40
Premature ovarian insufficiency, or POI, means ovarian function becomes disrupted before 40, with absent or irregular periods and hormone-test findings that confirm the diagnosis. It does not always mean the ovaries have permanently stopped all activity: the 2024 guideline notes that ovarian activity can still occur in nonsurgical POI. The guideline cites recent estimates of about 3.5% of women.
That guideline, from four organizations including the European Society of Human Reproduction and Embryology and the International Menopause Society, is direct about the stakes: it says women with POI should be told that POI without hormone therapy is associated with reduced life expectancy, largely because of cardiovascular disease.
The guideline recommends hormone therapy for women with POI until the usual age of menopause, whether or not they have symptoms. It rates the evidence behind that advice as low to very low, mostly observational, and calls for more research. Several authors reported fees from drugmakers, including Bayer, Besins and Theramex. The guideline’s details
Does hormone therapy change survival?
For hormone therapy itself, much of the evidence comes from one enormous experiment. The Women’s Health Initiative (WHI), funded by the US National Heart, Lung, and Blood Institute, randomly assigned about 27,000 women aged 50 to 79 to hormone therapy or placebo in the 1990s.
Women with a uterus took estrogen plus a progestin, a hormone that protects the uterine lining, for about five and a half years. Women who’d had a hysterectomy (surgery to remove the uterus) took estrogen alone for about seven years. The drugmaker Wyeth Ayerst donated the pills. Researchers then tracked deaths for 18 years.
In a 2017 JAMA analysis led by JoAnn Manson of Brigham and Women’s Hospital and Harvard Medical School, 27.1% of women on hormones and 27.6% on placebo had died. That gap wasn’t statistically meaningful. Deaths from heart disease and cancer didn’t differ either. The authors concluded that hormone therapy “was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.”
Age at the start seemed to matter. Compared with placebo, women who started in their 50s fared better than women who started in their 70s, most clearly during the years they took the pills. That pattern underpins what’s called the timing hypothesis. The age comparison was planned in advance, but it’s a comparison of subgroups, which is weaker evidence than the main result, and over the full 18 years the difference was borderline. The trial in detail
What separates symptom relief from a demonstrated survival effect in hormone-therapy evidence?
The label change
On November 10, 2025, Robert F. Kennedy Jr., who heads the Department of Health and Human Services, and FDA Commissioner Marty Makary announced that the FDA was starting to remove the boxed warnings about cardiovascular disease, breast cancer and probable dementia from menopausal hormone therapy. Those warnings trace back to class-wide label changes the FDA began in 2003, after the early WHI results. The FDA noted that WHI participants averaged 63, “over a decade past the average age of a woman experiencing menopause.”
The FDA kept the boxed warning for endometrial cancer (cancer of the uterine lining) on systemic estrogen-alone products, which deliver estrogen throughout the body. On February 12, 2026, it approved the first six relabeled products; as of September 25, 2026, the FDA’s list of updated labels still shows those six. The FDA said its labeled recommendation would be to start systemic therapy within 10 years of menopause or before 60.
The FDA’s February announcement goes further than the WHI paper does, stating that “randomized studies show that women who initiate HRT within 10 years of the onset of menopause (generally before age 60) have a reduction in all-cause mortality and fractures.” The 2017 WHI analysis found no overall mortality difference and reported the age pattern as a subgroup result.
Some clinicians welcomed the change. Kathryn Corelli, an internist and menopause specialist at Brigham and Women’s Hospital, told Harvard Health Publishing that the old warnings “frightened many women who were very appropriate for hormone therapy and told them it was dangerous, when in reality the risks were quite low and just need to be discussed on an individualized basis.”
The Menopause Society agreed with the decision and added a caution: “Systemic estrogen still comes with potential risks in certain individuals that should be reviewed in detail with women initiating therapy.” Its 2022 position statement, still its most recent on hormone therapy as of September 25, 2026, and written when it was called the North American Menopause Society, says the benefit-risk balance is favorable for bothersome hot flashes and bone-loss prevention in women under 60 or within 10 years of menopause who have no contraindications (medical reasons to avoid treatment), and less favorable when therapy starts later. The societies’ full wording
Those are symptom and bone uses. Neither the Menopause Society statement nor the WHI mortality results establish hormone therapy as a way to live longer.
Where do heart and bone health come in?
Hormone therapy has not been established as a way to extend life. Heart and bone health raise separate questions about disease, fractures and daily function as women age.
Heart. Cholesterol, body composition and blood vessels change measurably during the transition. That’s covered in Does Menopause Increase Heart Disease Risk?
Bone. Bone density and fracture risk are a central post-menopause question. Screening timing is covered in When Should Women Get a Bone Density Test?
Muscle, sleep and brain. Each has its own evidence base, beyond the scope of this article.
What’s Interesting
The pills in the Women’s Health Initiative never changed. The story told about them has changed twice. Early results led to class-wide warnings starting in 2003, and US hormone therapy use fell from about 27% of postmenopausal women in 1999 to about 5% by 2020, according to a national survey analysis in JAMA Health Forum. The 18-year follow-up then found no difference in overall survival, and in 2025 the FDA began taking the warnings off.
The studies gathered here link the age at menopause with later disease and death rates, without establishing that the timing itself causes those outcomes. That’s why the research on living longer and better separates menopause timing from the effects of treatment.
What This Means in Practice
Every woman’s history is different, and these findings are averages across large groups. The distinctions to discuss with a clinician include:
- Tell your clinicians your age at menopause. Menopause before 45, natural or surgical, is relevant to heart and bone risk assessment.
- If menopause came before 40, ask about the POI guideline. Its authors recommend hormone therapy until the usual age of menopause, whether or not there are symptoms.
- Separate the two hormone questions. The Menopause Society supports treatment for symptoms and bone protection in eligible women. A survival benefit has not been established.
- Ask about timing and type. The Menopause Society says the risks depend on age, years since menopause, type, dose, route and whether a progestogen is needed.
- If ovary removal is being discussed, ask whether it’s necessary and whether estrogen would be recommended afterward, especially before 45.
A gynecologist or a clinician certified in menopause care can weigh hormone therapy against your history. Primary care or cardiology handles heart-risk assessment. A genetic counselor can help with inherited cancer risk and questions about preventive surgery.
Sleep has its own set of menopause-specific patterns and treatment questions in Sleep Problems During Menopause.
Bottom Line
Menopause and longevity connect most clearly through timing. Menopause before 45 is linked to modestly higher death rates and more heart disease, and early removal of healthy ovaries without estrogen was linked to higher death rates in one study. For menopause before 40, a 2024 guideline recommends hormone therapy until the usual age of menopause, on low-certainty evidence. Hormone therapy didn’t change 18-year survival in the Women’s Health Initiative, and the FDA’s label change didn’t alter that result. Whether starting therapy early helps women live longer is still debated. A clinician experienced in menopause care can help weigh your timing, symptoms, and heart and bone risks together.
A NOTE FROM LONGEVITY365
We read research, consult expert perspectives and work to make complicated health information easier to understand. What you’re reading here reflects how we’ve interpreted and organized that information. It is educational content—not personal medical advice, diagnosis or treatment guidance.
We’re not perfect, and neither is the available research. Evidence changes, new studies emerge and what’s appropriate for one person may not be appropriate for another.
Use this article as a starting point for your own research and conversations with qualified professionals. Always talk with your doctor or another trusted healthcare professional before making decisions that could affect your health, particularly if you take medications, are receiving treatment, have existing health conditions, are pregnant or have other circumstances that could affect what’s appropriate for you.
Reader Questions
A few questions to carry into the comments or your next conversation. Please leave out identifying or personal medical details.
- 01Which part of the menopause conversation still feels most under-explained: muscle, bone, heart health, sleep, body composition, or symptoms?
- 02Where did this article help separate a normal transition from something worth bringing into care?
- 03What question would make a midlife health visit more specific without overgeneralizing from population evidence?
Extra Insights & Sources
For readers who want the details behind each claim above.
What We Know
- Menopause before 45 is associated with a 12% higher relative risk of death from any cause and a 50% higher relative risk of coronary heart disease. Supported (observational).
- Bilateral oophorectomy before 45 without estrogen was associated with higher mortality in one long-term cohort. Preliminary (single cohort; causality uncertain).
- For premature ovarian insufficiency (before 40), the international guideline described below recommends hormone therapy until the usual age of menopause. Supported (guideline; low to very low certainty).
- Hormone therapy didn’t change all-cause mortality over 18 years in the WHI trials.
- According to the Menopause Society, hormone therapy is the most effective treatment for hot flashes and prevents bone loss and fracture. Established.
What We Don’t Know
- Whether early menopause causes shorter life or marks other risks. Unknown.
- Whether starting hormone therapy in the early 50s lowers mortality. Subgroup results point that way but aren’t conclusive, and the FDA’s 2026 reading is stronger than the WHI authors’ own conclusion.
- How much of the WHI experience, which used oral conjugated equine estrogens and medroxyprogesterone acetate, applies to other doses, types and routes, such as patches and gels. Uncertain.
- Whether the POI guideline’s advice applies to menopause at 40 to 44. The guideline says its recommendations may be relevant to early menopause but places it outside its scope. Unknown.
Early menopause: the meta-analysis
Muka and colleagues at Erasmus University Medical Center, with co-authors at the University of Cambridge and University Medical Center Utrecht, searched Medline, EMBASE and Web of Science through March 2015. They included 32 observational studies (cohort, case-control or cross-sectional) covering 310,329 nonoverlapping women and pooled results with random-effects models, which allow the underlying effects to vary across studies. Compared with women whose menopause came at 45 or later, those who reached it before 45 had:
Relative risk compares the groups: 1 means no difference, and 1.50 means a 50% higher relative risk, not 50 extra cases per 100 women. The 95% confidence interval (CI) describes statistical uncertainty; an interval that includes 1 does not clearly distinguish an increase from no difference.
| Outcome | Relative risk (95% CI) |
|---|---|
| Coronary heart disease | 1.50 (1.28–1.76) |
| Fatal coronary heart disease | 1.11 (1.03–1.20) |
| Cardiovascular death | 1.19 (1.08–1.31) |
| All-cause death | 1.12 (1.03–1.21) |
| Stroke | 1.23 (0.98–1.53), not statistically significant |
| Stroke death | 0.99 (0.92–1.07), not statistically significant |
Women whose menopause came at 50 to 54 had lower risk of fatal coronary heart disease than those who reached it before 50 (relative risk 0.87; 95% CI 0.80–0.96), with no effect on stroke. Four studies on time since menopause gave inconsistent results. The authors concluded that the findings “indicate a higher risk of CHD, CVD mortality, and overall mortality in women who experience premature or early-onset menopause.”
Disclosures, per the paper: “This study was sponsored and funded by Metagenics.” Drs Muka and Franco received research support from Metagenics, and Dr Kavousi was supported by the AXA Research Fund. The paper states that “The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.”
Surgical menopause: the Mayo Clinic cohort
Rocca and colleagues in the Mayo Clinic’s Division of Epidemiology drew on all women who had a unilateral or bilateral oophorectomy for a non-cancer indication before menopause while living in Olmsted County, Minnesota, in 1950–87. The study included 1,097 women with bilateral oophorectomy, 1,293 with unilateral oophorectomy and 2,390 age-matched referent women, followed until death or the end of the study (staggered over 2001–06).
Unilateral oophorectomy means removal of one ovary; bilateral means both. Referent women are the comparison group. A hazard ratio (HR) compares death rates over time; 1 means no difference. The p-value describes how compatible the result is with no difference under the statistical model; it does not establish causation.
Overall mortality was not increased after bilateral oophorectomy. Among women who had prophylactic bilateral oophorectomy before 45, mortality was higher than in referent women (hazard ratio 1.67; 95% CI 1.16–2.40; p=0.006). The increase was seen mainly in women who had not received estrogen up to age 45. Unilateral oophorectomy was not associated with higher mortality in overall or stratified analyses. The study was funded by the US National Institutes of Health (NIAMS and NINDS). The authors wrote that although preventive removal of both ovaries before 45 is associated with increased mortality, it is uncertain whether the link is causal or merely a marker of underlying risk.
Menopause before 40: the POI guideline
The 2024 evidence-based guideline on premature ovarian insufficiency was developed by the European Society of Human Reproduction and Embryology (ESHRE), the American Society for Reproductive Medicine, the Centre for Research Excellence in Women’s Health in Reproductive Life (CRE-WHiRL) and the International Menopause Society. It describes POI as disrupted ovarian function before 40, with absent or irregular menstrual cycles and confirmatory hormone-test results. The guideline explicitly says ovarian activity may still occur in nonsurgical POI. It notes that reported prevalence of non-iatrogenic POI (not caused by medical treatment) ranges from about 1% in older studies to 3.5% in recent publications. Walter Rocca, author of the Mayo cohort above, is one of its authors.
On life expectancy, it recommends informing women with POI that POI without hormone therapy (HT) is associated with reduced life expectancy, largely due to cardiovascular disease (strong recommendation, low-certainty evidence). It also recommends HT for women with POI until the usual age of menopause, to reduce future illness and death before they occur (primary prevention), whether or not they have estrogen-deficiency symptoms (strong recommendation, very low certainty). The authors acknowledge that for most of the management options it describes, supporting evidence in POI is limited. Menopause at 40–44 is termed early menopause and falls outside the guideline’s scope, though the authors say its evidence and recommendations may be relevant to women with early menopause.
Disclosures: the guideline was funded by the four organizations, and group members were not paid. Several authors reported industry ties, including the lead author, then IMS president Nick Panay (grants from Bayer; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex and Viatris), and Rossella E. Nappi, then IMS president-elect (consulting fees from Astellas, Bayer, Besins Healthcare, Fidia and Theramex, among others).
Hormone therapy: the WHI mortality analysis
In this analysis, all-cause mortality means deaths from any cause. A ratio of hazard ratios compares treatment effects between age groups; it is not the treatment effect for either group alone.
The WHI recruited 27,347 postmenopausal women aged 50 to 79 at 40 US clinical centers from 1993 to 1998 (mean age 63.4; 80.6% white). In one trial, 16,608 women with a uterus took daily oral conjugated equine estrogens (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg; Prempro) or placebo; that trial was stopped early, after a median 5.6 years, because of increased breast cancer risk and overall risks exceeding benefits. In the other, 10,739 women with hysterectomy took CEE alone (Premarin) or placebo; it stopped after a median 7.2 years because of increased stroke risk.
Over 18 years of cumulative follow-up, 7,489 women died. All-cause mortality was 27.1% with hormone therapy vs 27.6% with placebo (HR 0.99; 95% CI 0.94–1.03). By trial: CEE plus MPA HR 1.02 (0.96–1.08); CEE alone HR 0.94 (0.88–1.01). Cardiovascular mortality: 8.9% vs 9.0% (HR 1.00). Cancer mortality: 8.2% vs 8.0% (HR 1.03). Comparing women aged 50–59 with those aged 70–79 at enrollment, in prespecified age-group analyses, the ratio of hazard ratios for all-cause mortality was 0.61 (0.43–0.87) during the intervention phase and 0.87 (0.76–1.00) over 18 years.
Disclosures, per the paper: the WHI is funded by the NHLBI, NIH and US Department of Health and Human Services, and “Wyeth Ayerst donated the study drugs.” Among the authors, Dr LaCroix reported personal fees from Sermonix (scientific advisory board) and Pfizer (consultancy); Dr Chlebowski reported consulting fees or honoraria from several drug companies, including Novartis, Genentech, Amgen, AstraZeneca, Novo Nordisk and Genomic Health, and fees for review activities from Pfizer.
The label change and the societies’ wording
In its November 10, 2025 release, the FDA said it “is initiating removal of the boxed warnings following a comprehensive review of the scientific literature, an expert panel in July, and a public comment period.” The panel met July 17, 2025. The FDA said it “is not seeking to remove the boxed warning for endometrial cancer for systemic estrogen-alone products” and that “the FDA’s labeled recommendation will be to start HRT within 10 years of menopause onset or before 60 years of age for systemic HRT.” The FDA’s own labeling page says that “In 2003, FDA began approving class-wide labeling changes” for these products.
On February 12, 2026, the FDA approved labeling changes for a first batch of six products across all four categories of menopausal hormone therapy, and said that “At the FDA’s request, 29 drug companies have submitted proposed labeling changes.” As of September 25, 2026, the FDA’s page listing menopausal hormone therapies with updated prescribing information still names those six: Prometrium, Divigel, Cenestin, Enjuvia, Estring and Bijuva.
The Menopause Society’s November 10, 2025 response also said that “the risks are low for younger, healthy women initiating hormone therapy closer to the menopause transition. Risks are greater when initiated in older women and in those who are further from menopause onset.”
Its 2022 position statement says hormone therapy “remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture.” For women younger than 60 or within 10 years of menopause onset without contraindications, “the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss.” For women who start more than 10 years after menopause onset or after 60, “the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.” It adds that “The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.”
In that quotation, vasomotor symptoms (VMS) means hot flashes and night sweats. Genitourinary syndrome of menopause covers vaginal, vulvar and urinary symptoms, such as vaginal dryness. Venous thromboembolism means blood clots in veins, including clots that travel to the lungs.
The usage figures come from Yang and Toriola’s 2024 analysis in JAMA Health Forum of 13,048 US postmenopausal women in the National Health and Nutrition Examination Survey: use fell from 26.9% in 1999 to 4.7% in 2020 (the 2017–March 2020 cycle), across all age and racial and ethnic groups.
Sources
- Muka T, et al. Age at onset of menopause and cardiovascular outcomes and all-cause mortality, JAMA Cardiology, 2016: PubMed 27627190
- Rocca WA, et al. Survival patterns after oophorectomy in premenopausal women, The Lancet Oncology, 2006: PubMed 17012044
- ESHRE, ASRM, CRE-WHiRL and IMS Guideline Group on POI (Panay N, et al.). Evidence-based guideline: premature ovarian insufficiency, Human Reproduction Open, 2024: PubMed 39660328
- Manson JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality, JAMA, 2017: PubMed 28898378
- The North American Menopause Society. The 2022 hormone therapy position statement, Menopause, 2022: PubMed 35797481
- Yang L, Toriola AT. Menopausal hormone therapy use among postmenopausal women, JAMA Health Forum, 2024: PubMed 39331372
- US Food and Drug Administration: HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy (November 10, 2025)
- US Food and Drug Administration: FDA Approves Labeling Changes to Menopausal Hormone Therapy Products (February 12, 2026)
- US Food and Drug Administration: FDA Requests Labeling Changes Related to Safety Information to Clarify the Benefit/Risk Considerations for Menopausal Hormone Therapies
- The Menopause Society: The Menopause Society Comments on the FDA Announcement on Hormone Therapy (November 10, 2025)
- Harvard Health Publishing (Maureen Salamon): FDA removes menopause hormone therapy black box warnings (November 13, 2025)
- National Cancer Institute: BRCA Gene Changes: Cancer Risk and Genetic Testing
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