HRT and Heart Health: Rethinking the ‘Window of Opportunity’ Theory
The old theory: a limited window of safety
For years, menopause education and medical guidelines suggested that hormone replacement therapy (HRT) should only be started within ten years of menopause — the so-called “window of opportunity” — to protect heart health. Beyond that point, it was thought to carry higher cardiovascular risk.
That idea stemmed from early interpretations of the Women’s Health Initiative (WHI) trials in the early 2000s, which reported an increase in heart and stroke events in older women taking HRT. But most WHI participants were in their mid-60s and many already had established vascular disease. The findings were never intended to apply to healthy women newly entering menopause.
What new research reveals
A 2025 systematic review published in Post Reproductive Health (Contreras-Garza et al.) has now pooled data from nine randomised controlled trials including over 36,000 women aged 60–79 or more than ten years post-menopause.
The authors found:
No statistically significant increase in heart attack, stroke or cardiovascular mortality with either oestrogen-only or combined HRT.
No age-related gradient in cardiovascular risk, meaning older age alone did not predict harm.
Slight, non-significant increases in stroke and DVT risk with higher-dose oral regimens (especially conjugated equine oestrogens and medroxyprogesterone acetate).
Tibolone (an older synthetic hormone) was associated with increased stroke risk and is not recommended for women with cardiovascular risk factors.
Data on transdermal oestrogen were limited in trials, but observational studies continue to suggest a lower clotting risk compared with oral routes.
In summary: even when HRT is started later, the supposed “increased risk” is not supported by statistical evidence.
Why the myth persists
The “timing hypothesis” once seemed biologically plausible — that oestrogen might protect arteries only if started before atherosclerosis develops. However, modern imaging studies like ELITE and KEEPS found no accelerated vascular damage when HRT was begun later.
Instead, the key determinants of cardiovascular safety are:
Route of administration (transdermal oestrogen bypasses the liver and does not increase clotting factors).
Type of progestogen (micronised progesterone and dydrogesterone are metabolically neutral).
Overall cardiovascular health — lifestyle factors such as smoking, obesity and inactivity matter far more than age itself.
What this means for women in midlife and beyond
The updated evidence base — including both the Contreras-Garza et al. review and long-term WHI follow-ups — shows that there is no defined age limit for initiating HRT in otherwise healthy women.
For women in their 50s, and even into their 60s or beyond, HRT remains safe and effective when:
Started for symptom relief under medical supervision,
Prescribed in physiological (body-identical) doses, and
Delivered via the lowest-risk routes, usually transdermal oestrogen combined with natural progesterone.
The decision should always be individualised, balancing symptom relief, quality of life, and personal risk factors — not dictated by arbitrary cut-offs.
The take-home message
The so-called “window of opportunity” theory has not stood the test of time. The newest data confirm that even women well beyond menopause can use HRT safely, provided the treatment is appropriately chosen and monitored.
Rather than thinking of a closing window, it’s time to think of an open continuum of care — one where timing is flexible, treatment is personalised, and heart health is supported by modern, evidence-based hormone therapy.
References:
Contreras-Garza NY et al. Cardiovascular outcomes of menopause hormone therapy initiated in women aged ≥60 years or ≥10 years post-menopause: A systematic review. Post Reproductive Health 2025;31(3):173–183.
Manson JAE et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative trials. JAMA 2017;318(10):927–938.
Ghosh M et al. The timing hypothesis revisited. The Obstetrician & Gynaecologist 2023.
FAQ
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No fixed age limit. New evidence (including a 2025 systematic review of women ≥60 or ≥10 years post-menopause) found no statistically significant increase in cardiovascular events when HRT is appropriately prescribed and monitored.
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Not inherently. Risk relates more to route, dose, progestogen type, and individual cardiometabolic profile than age alone.
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Transdermal oestrogen (patch/gel/spray) avoids first-pass liver effects and is associated with a lower VTE risk than oral oestrogen in observational data.
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Micronised progesterone or dydrogesterone are generally considered more cardiometabolically neutral than older progestins like medroxyprogesterone acetate (MPA).
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Yes. Many women gain meaningful relief, particularly with vasomotor and genitourinary symptoms, using physiological-dose, transdermal oestrogen plus micronised progesterone when indicated.
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In women <60 or near menopause, HRT is cardiovascularly neutral to favourable in some outcomes, but it’s prescribed primarily for symptom relief and bone—not as a CVD drug.
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As long as benefits outweigh risks and you wish to continue, with annual review and shared decision-making.