Taking HRT in perimenopause may ward off cardiovascular disease

Taking hormone replacement therapy during the perimenopause or early menopause may reduce the risk of heart attacks and stroke. A study of nearly 2800 women over 20 years suggests that starting HRT around this time lowers the risk of serious cardiovascular events. However, much more research is required to understand how the treatment may have this effect and the optimal time to take it. “I want to emphasise: our study does not support using menopausal [hormonal] therapy to prevent cardiovascular disease,” says Samar El Khoudary at Virginia Commonwealth University. A recent study in Spain suggests that nearly 80 per cent of women experience vasomotor symptoms – hot flushes and night sweats – around the menopause. However, other research from this year suggests this varies substantially around the world. These symptoms can be treated via HRT, which is available in different formulations, such as tablets, patches, gels and sprays. These replace oestrogen and progesterone, hormones that fall as the menopause approaches. Advertisement The controversy around HRT started in 2002, when a large trial linked it to an increased risk of breast cancer, heart attacks and stroke. The method of this trial, and subsequent ones, has since been called into question. Newer research has also put the results into context by comparing them with other lifestyle choices, such as alcohol intake. In 2021, a study found that HRT doesn’t increase the risk of early death. What’s more, earlier studies generally looked at women around the age of 60. This is despite menopause usually occurring between the ages of 45 and 55, and some people taking HRT during the perimenopause. Now, El Khoudary and her colleagues have looked at 2737 participants in the Study of Women’s Health Across the Nation, which was made up of women in the US aged 42 to 52 at enrollment. All these women experienced hot flushes and night sweats, but only 755 took some form of HRT over the 20-year study period. During this time, 224 fatal and non-fatal cardiovascular events occurred. The researchers estimated that the women who started HRT 10 years or less after the onset of vasomotor symptoms were 27 per cent less likely to experience these events than those who didn’t take HRT. The effect was much less clear among women who initiated the treatment more than 10 years after their onset, says El Khoudary. The timing seems to be “very critical”, she says. As to why HRT may have this effect, El Khoudary says the “underlying mechanisms are complex and multifactorial”. Oestrogen is involved in regulating cholesterol and blood sugar levels, and contributes to blood vessel flexibility. Previous research suggests that HRT dose and formulation – which may vary depending on the person’s age – affect artery structure, which may impact heart health. The perimenopause is also increasingly being recognised as a period of distinct vascular changes. The researchers also found that HRT’s seemingly protective effect was most pronounced among the Black participants, who may be more likely to experience vasomotor symptoms. Further research is needed to uncover why the results vary among women of different races, says El Khoudary. For now, people shouldn’t start HRT to prevent cardiovascular events. Another recent study suggests that oral HRT is linked to a 0.09 per cent higher risk of venous thromboembolism (the formation of blood clots in the veins), a 0.06 per cent higher risk for ischaemic stroke (when a blood clot or other blockage cuts off blood supply to the brain) and a 0.03 per cent higher risk of a heart attack per year. “The most important thing to understand about observational studies is that they cannot establish causality,” says Tara Iyer at Brigham and Women’s Hospital in Boston. El Khoudary now wants to see randomised, placebo-controlled trials testing the cardiovascular effects of HRT during the perimenopause and early menopause. JAMA Internal Medicine DOI: 10.1001/jamainternmed.2026.2922