Initiation of menopausal hormone therapy (HT) after the age of 65 is linked to significantly increased risks for cancer and vascular events, new data have suggested after a study of more than 80 000 women.
Medscape Medical News reports that the research focused on women aged 50 or older in an Israeli health system during 2000-2022, which showed that HT use overall was associated with several types of hormone-sensitive and non-hormone-sensitive cancers.
While the therapy offered some cardiovascular benefit when started between the ages of 50 and 65, it also raised stroke and cancer risks. And when initiated in women who were 65 or older, it significantly raised the risk for both cancer and cerebrovascular events.
The study was published in the journal Menopause.
“Our findings largely reinforce current guidelines, which discourage initiating systemic HT after 60 or more than 10 years’ post-menopause. The significantly elevated risks of stroke and cancer we observed in late initiators who were 65 and older provide strong empirical support for these cautious recommendations,” said study author Alon Carney, MD.
Clinicians should move toward a model of individualised risk-benefit assessment, said Carney of Clalit Health Services and the Department of Family Medicine and Siaal Research Centre for Family Practice and Primary Care at Ben-Gurion University of the Negev, Israel.
“While hormone therapy is the most effective treatment for vasomotor symptoms, the risk profile shifts significantly with age,” he added. “For women who are 65 and older, discussions should emphasise the substantially increased risks of stroke and malignancy.”
Risks increase with age
The study included 83 147 women aged 50 or older of whom 6.6% initiated hormone therapy at 50-65, and 1% at 65 or older. Study participants were divided by age of the therapy’s initiation: those started it at 50-65 (n = 5500), those who initiated it after 50 and continued use beyond 65 (n = 854), those who initiated it at 65 or older (n = 847), and those who never used hormone therapy at all (n = 75,946).
“It is important to remember that real-world practice often diverges from guidelines. We found that nearly 40% of women in the 50-65 group continued therapy for more than 10 years,” Carney noted.
In multivariable-adjusted analysis, women who initiated HT at 50-65 had significantly increased risks for cerebrovascular accident compared with those who never used it (hazard ratio [HR], 16.69, P < .001), cancer (HR, 8.49, P < .001), and ischaemic heart disease or myocardial infarction (HR, 9.17, P < .001).
Among those initiating hormone therapy at 65 or older, risks were significantly increased for both cancer (HR, 2.22, P < .001) and stroke (HR, 2.70, P < .001).
Those who initiated at 50-65 and continued use beyond 65 had significantly increased risks for cerebrovascular accidents (HR, 4.15, P < .001), cancer (HR, 1.36, P = .048), and ischaemic heart disease or myocardial infarction (HR, 2.34, P < .001).
Although the crude analysis suggested that women who initiated HT at 50-65 had lower risks for both ischaemic heart disease or myocardial infarction (3.6% vs 9.2% in never-users, P < .001) and cancer (19.2% vs 31.9%, P < .001), those lost significance after adjustment, “indicating residual confounding in unadjusted comparisons”, the authors wrote.
Moreover, longer duration of therapy was associated with even greater morbidity risks.
“This ‘long-term use’ carries a cumulative burden of risk. Clinicians should be proactive in discussing discontinuation or transitioning to non-hormonal alternatives as women age into their mid-60s,” said Carney.
Bias inherent in who gets hormones
Nanette Santoro, MD, Professor and E Stewart Taylor chair of Obstetrics & Gynaecology at the University of Colorado School of Medicine, said the new findings “support current guidelines in that risks of hormone therapy increase for women as they age because the background risk of the diseases they are slightly more likely to get, like heart disease and cancers, just goes up”.
“It’s important to revisit the indications and need for hormone therapy over time and assure that it still makes sense to continue it,” she told Medscape Medical News.
Both the authors and Santoro pointed out one of the limitations of the study findings was that the initial lower heart disease risk in those aged 50-65 may be due to the fact that only those at low risk for heart disease were prescribed HT to begin with.
Santoro noted: “This is not a randomised trial, so there is bias inherent in who gets hormones and who does not, and most of the prescribing was past-(Women’s Health Initiative) when physicians were reluctant to give hormones for fear of increasing risks of heart disease and cancer.”
Study details
Health outcomes of hormone therapy initiated or continued after age 65
Carney, Alon; Gluzman, Milana; Kolushev-Ivshin, Ilona; Amar, Shimon.
Published in Menopause on 3 February 2026
Abstract
Objective
Menopausal hormone therapy (HT) is effective for alleviating vasomotor symptoms but remains controversial regarding long-term safety, particularly in women over 65. Despite guidelines recommending initiation before age 60, a notable proportion of older women continue or begin HT later in life. The health outcomes of HT in women aged 65 and older, especially those initiating therapy after 65, compared with younger users and nonusers were evaluated.
Methods
This retrospective cohort study included 83,147 women aged 50 years or older enrolled in Clalit Health Services (2000-2022). Women were categorised by age at HT initiation: never-users, initiators at 50-65, initiators 65 or older, or initiators after 50 continuing beyond 65. Outcomes included malignancies, cardiovascular events, osteoporosis, and dementia. Group differences were evaluated using χ2 tests, and time-to-event associations were examined using Cox proportional hazards models with age as the underlying time scale. To evaluate the health outcomes of HT in women aged 65 and older, especially those initiating therapy after 65, compared with younger users and non-users.
Results
HT use was associated with increased risks of several malignancies, including both hormone-sensitive and non-hormone-sensitive cancers. In crude analyses, women initiating HT at 50-65 years had lower ischemic heart disease/myocardial infarction prevalence (3.6% vs. 9.2%) but higher hypertension (11.0% vs. 6.2%). In adjusted Cox models, initiation at 65 years or older was associated with increased hazards of any cancer (hazard ratio [HR]: 2.216, 95% confidence interval [CI]: 1.833-2.677) and cerebrovascular accident (HR: 2.695, 95% CI: 2.358-3.079). Among women initiating HT at 50-65 years, hazards were markedly elevated for cerebrovascular accident (HR: 16.692, 95% CI: 15.571-17.893), cancer (HR: 8.490, 95% CI: 7.281-9.900), and ischemic heart disease/myocardial infarction (HR: 9.169, 95% CI: 8.321–10.102); the crude cardiovascular advantage was not observed after adjustment.
Conclusions
Initiation of HT after 65 is linked to significantly increased risks of cancer and vascular events, supporting current guidelines discouraging late initiation. While HT may offer some cardiovascular benefits when started earlier, use in older women should involve individualised risk-benefit assessment and close monitoring. These findings underscore the need to align clinical practice with evolving evidence and guideline recommendations. Given the retrospective design, incomplete pre-2000 medical history, and potential residual confounding, findings should be interpreted with caution.
Medscape article – Hormone Therapy Past Age 65 Tied to Cancer, Vascular Events (Open access)
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