Menopause, Perimenopause and Cardiovascular Risk

The Question

I am seeing a lot of discussion about hormone replacement therapy and heart health at the moment, which I think is long overdue.

Menopause affects every woman who lives long enough to experience it. The symptoms are very often significant. I went back to my medical school text book and they were useless because they were frankly wrong. I won’t quote the book but it was published in 2001 - “menopause does not have an effect on mental health” should tell you what we are trying to undo now. Clearly women were excluded from any important scientific enquiry, which is why the trials below were so disappointing.

The answer also wasn’t quite as simple as "good" or "bad."

It depends on timing.

What Changed Our Understanding

For about two decades, many women were told that HRT increased their risk of heart attacks and strokes. This advice came from two major studies published in the early 2000s: the Heart and Estrogen/progestin Replacement Study (HERS) and the Women's Health Initiative (WHI).

These studies showed increased rates of heart attacks, strokes, and blood clots in women taking HRT.

The results were concerning enough that HRT use dropped significantly. Many women stopped taking it. Many doctors stopped prescribing it.

But there was something important about those studies that wasn't immediately obvious.

The average age of women enrolled was 63 in HERS and 67 in WHI. Most were already well past menopause, often 10 to 20 years beyond it. Many already had established cardiovascular disease or significant risk factors.

That timing matters more than we initially realised.

The Timing Hypothesis

What we've learned since is that timing of HRT makes a substantial difference to cardiovascular outcomes.

When HRT is initiated in women under 60, or within 10 years of menopause, the data looks very different. Multiple studies now suggest that early initiation is associated with reduced all-cause mortality and lower rates of coronary artery disease.

In women who start HRT closer to menopause, estrogen appears to have protective effects on the arteries: improving vascular function, reducing plaque formation, and supporting healthier blood lipid profiles.

But when started much later, particularly in women with established atherosclerosis, those same hormones may interact with already-diseased arteries in ways that might increase risk.

The treatment was the same, but the people studied were different.

Or more accurately, the state of the cardiovascular system at the time treatment begins has changed.

What This Means in Practice

For women experiencing menopausal symptoms in their early 50s or earlier, with no history of cardiovascular disease, blood clots, or stroke, current evidence suggests HRT can be both effective for symptom relief and potentially cardioprotective.

For women who are already past 60, or more than 10 years beyond menopause, particularly those with existing cardiovascular disease, the risk-benefit calculation shifts.

This doesn't mean HRT is universally good or universally bad. It means the question is more nuanced than that.

It requires individual assessment, looking at a woman's age, time since menopause, cardiovascular risk factors, family history, and personal priorities around symptom management and long-term health.

The Numbers

It helps to look at what the absolute risks actually mean.

The UK's Medicines and Healthcare Regulatory Agency (MHRA) publishes risk tables that put the numbers in context. For combined HRT (estrogen plus progestogen) used for 5 years starting at menopause:

• Breast cancer: 8 extra cases per 1000 women
• Venous thromboembolism: 7 extra cases per 1000 women
• Stroke: 1 extra case per 1000 women
• Hip fracture: 5 fewer cases per 1000 women

For 10 years of use, the breast cancer risk increases to 20 extra cases per 1000 women with combined HRT.

Estrogen-only HRT (for women who have had a hysterectomy) shows lower breast cancer risk at 3 extra cases per 1000 women over 5 years, 7 over 10 years, but a significantly increased risk of endometrial cancer if the uterus is still present, which is why it's only used after hysterectomy.

These are small absolute increases in risk for most outcomes. But they're not zero. And for individual women, the calculation will differ based on their baseline risk profile.

What's also become clearer since the original WHI study is that not all HRT formulations carry the same risk. A 2023 review in Maturitas examined the evidence on bioidentical hormone preparations, particularly micronised progesterone, compared to the synthetic progestogen (medroxyprogesterone acetate) used in WHI. [1]

The data suggests micronised progesterone may have a more favourable risk profile, particularly for breast cancer and venous thromboembolism, though the evidence base is still evolving. Route of administration matters too. Transdermal estrogen (patches or gels) appears to carry lower VTE risk than oral preparations.

The WHI studied one specific formulation but women now have options that weren't widely available 20 years ago.

The Friction

The challenge is that our healthcare system isn't always set up to deliver this kind of nuanced, personalised care at scale. Women are more disadvantaged and dismissed in the healthcare setting. [2] Women of ethnic minorities even more so. [3]

Menopause typically happens around age 51, defined as complete cessation of menstrual bleeding for 1 year. [4] Perimenopause, the hormonal transition leading up to it, typically starts in the mid-to-late 40s and lasts 4 to 8 years [5], so many women are already deep into that transition well before the average age-51 marker is reached. Many women see their GP. The appointment is often brief. There may not be time to discuss personal risk factors in detail, or to explore the difference between starting HRT at 52 versus 62.

Guidelines help. But they can't capture every individual situation.

And so some women who might benefit don't get treatment. Others who face higher risks may not have those risks properly explored.

That gap matters.

Looking at Your Own Risk

If you're considering HRT, the questions to discuss with your doctor include:

• How long has it been since your menopause started?
• What is your current cardiovascular risk profile: blood pressure, cholesterol, diabetes, smoking status, family history?
• Do you have a history of blood clots or stroke?
• What are your most troublesome symptoms, and how are they affecting your quality of life?
• Are there specific types or formulations of HRT that might be more suitable for you, such as transdermal estrogen, which carries lower clot risk than oral preparations?

For women with established heart disease, HRT may still be an option in some cases, but it requires specialist cardiovascular input and careful monitoring.

For healthy women in early menopause, the evidence increasingly supports it as a safe and effective option, not just for symptom relief, but potentially for longer-term cardiovascular health as well.

Where We Are Now

The pendulum has swung. From widespread use in the 1990s, to near-abandonment after 2002, to a more measured, evidence-based approach now.

HRT isn't right for everyone. But it isn't wrong for everyone either.

The question is whether the right woman is getting the right information at the right time.

And whether the system is set up to support that conversation.

Because the treatment works. The evidence is there. The benefits for many women are real.

What often gets in the way is implementation: time, access, clarity of communication, and the ability to personalise the decision.

Until that changes, many women will continue to navigate menopause without the treatment that could help them most, and one that could reduce their heart risks.

---

References

1. Stute P, et al. Reappraising 21 years of the WHI study, with a focus on micronised progesterone. Maturitas 2023. maturitas.org
2. Wilkinson C, Bebb O, Dondo TB, et al, Gale CP. Sex differences in quality indicator attainment for myocardial infarction: a nationwide cohort study. Heart 2019;105:516–523. Leeds summary
3. Hildreth E, et al. Inequalities in hormone replacement therapy prescribing in UK primary care: population based cohort study. BMJ Medicine 2025;4:e001349. bmjmedicine.bmj.com
4. NICE Clinical Knowledge Summaries, Menopause: definition (revised July 2025). cks.nice.org.uk
5. Definition and Stages, Canadian Menopause Society, on STRAW+10. canadianmenopausesociety.org
6. British Menopause Society, Menopause Practice Standards (March 2026). thebms.org.uk
7. NHS inform, Menopause. nhsinform.scot
8. NHS, Early or premature menopause. nhs.uk
9. NICE NG23, Menopause: identification and management (published 2015, updated November 2024). nice.org.uk
10. Pokoradi AJ, Iversen L, Hannaford PC. Factors associated with age of onset and type of menopause in a cohort of UK women. Am J Obstet Gynecol 2011;205:34.e1-13. doi.org
11. Zhu D, et al. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data (InterLACE). Lancet Public Health 2019. doi.org
12. Schoenaker DAJM, Jackson CA, Rowlands JV, Mishra GD. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents. Int J Epidemiol 2014;43:1542–62. doi.org
13. Hillman S, Shantikumar S, Ridha A, Todkill D, Dale J. Socioeconomic status and HRT prescribing: a study of practice-level data in England. Br J Gen Pract 2020;70(700):e772–e777. bjgp.org
14. Department of Health and Social Care, Women's Health Strategy for England (2022). gov.uk
15. Fawcett Society, Menopause and the Workplace (2022). fawcettsociety.org.uk
16. Balakumar H, Ayoade A, Oliver D, Garuba Y, Brown A-A, Harper J. Black women's knowledge and attitudes to menopause: an online survey. Post Reproductive Health 2026;32(1):15–33. tandfonline.com, see also the UCL summary
17. Menopause care is neglected and inequitable. BMJ 2025;390:r2038. bmj.com
18. MBRRACE-UK, Saving Lives Improving Mothers' Care (2022–24 data). npeu.ox.ac.uk
19. British Heart Foundation, Bias and Biology: how the gender gap in heart disease is costing women's lives (2019). bhf.org.uk
20. Wu J, Gale CP, Hall M, Dondo TB, Metcalfe E, Oliver G, West RM. Impact of initial hospital diagnosis on mortality for acute myocardial infarction: a national cohort study. Eur Heart J Acute Cardiovasc Care 2018;7(2):139–148. journals.sagepub.com
21. Wellbeing of Women / Eclipse, Health of the Nation Report in Relation to HRT (2024). wellbeingofwomen.org.uk
22. History of women's participation in clinical research, NIH Office of Research on Women's Health, covering the 1977 FDA guideline and the 1993 Revitalization Act. orwh.od.nih.gov
23. Jin X, Chandramouli C, Allocco B, et al. Women's participation in cardiovascular clinical trials from 2010 to 2017. Circulation 2020;141:540–548. ahajournals.org
24. Q&A: how can medical science better serve women? Imperial College London 2023, on the UK Clinical Research Collaboration's 2% female reproductive health research funding figure. imperial.ac.uk
25. Dismissed, ignored and belittled: the long road to endometriosis diagnosis in the UK. Endometriosis UK 2024. endometriosis-uk.org
26. Chen EH, Shofer FS, Dean AJ, et al. Gender disparity in analgesic treatment of emergency department patients with acute abdominal pain. Acad Emerg Med 2008;15:414–418. pubmed.ncbi.nlm.nih.gov
27. Survey: menopause training in medical schools. Menopause Support 2021. menopausesupport.co.uk
28. UK has the largest gender health gap in the G20, 2020 analysis. news-medical.net
29. Perimenopause: Age, Stages, Signs, Symptoms & Treatment. Cleveland Clinic. my.clevelandclinic.org
30. Menopause and Perimenopause A to Z. Harvard Health. health.harvard.edu
31. Gold EB. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am 2011;38(3):425–440. pmc.ncbi.nlm.nih.gov
32. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175(4):531–539. pmc.ncbi.nlm.nih.gov
33. Symptoms of menopause and perimenopause. NHS. nhs.uk
34. Insights into Perimenopause: A Survey of Perceptions, Opinions on Treatment, and Potential Approaches (2025 perception survey). pmc.ncbi.nlm.nih.gov