THE ARISING · Longevity & Healthspan
UK Biobank Study of 170,000 Women Links HRT to Higher Cardiovascular Risk
Women who had used hormone replacement therapy (HRT) were 13% more likely to develop heart and blood vessel disease over about 15 years than women who had not, according to a large study in Acta Obstetricia et Gynecologica Scandinavica. The gap was widest in women whose reproductive history put them in certain subgroups, including those aged 45 or younger.
This is an observational study in people, not a randomised trial. It followed 170,250 women aged 40 to 69 who joined the UK Biobank between 2006 and 2010. Follow-up ran to January 2024, with a median of 14.77 years. Observational work can show an association. It cannot prove that HRT caused the difference.
The researchers counted atherosclerotic cardiovascular disease, meaning disease from fatty build-up in the arteries. Their definition was a heart attack, an ischemic stroke (a stroke caused by a blocked vessel), or a procedure to restore blood flow to the heart. Events came from hospital and death records. In all, 11,357 women (6.67%) had such an event.
After adjusting for age, ethnicity, education, deprivation, body mass index, physical activity, diet, menopausal status and reproductive history, HRT users had a hazard ratio of 1.13 (95% confidence interval 1.08 to 1.18). A hazard ratio compares how fast events occur in two groups. Here it means a 13% higher relative rate. The paper reports the pattern was not a straight line (p for nonlinearity 0.004). Relative figures do not show how large the absolute risk is for any one woman.
Among women who developed disease, 32% had used HRT, compared with 30% of those who did not. Their average reported HRT duration was also longer, 1.94 years versus 1.80 years. The authors report that blood markers such as sex hormones, inflammation and cholesterol explained little of the link, so the reason for it remains unclear.
The authors say risk varied by reproductive timing. Late first period, late menopause and starting HRT around perimenopause (the transition years) marked the highestrisk groups, particularly women aged 45 or younger. They argue that clinicians' decisions about HRT should rest on a woman's reproductive profile, not on age alone.
Several limits matter. HRT use came from one baseline question: "Have you ever used hormone replacement therapy?" That does not capture the type, dose or form of treatment, or the reasons women started it. Those factors could skew the results. The authors also note that earlier observational studies suggested HRT protected the heart, while randomised trials found more heart events and strokes, especially in older postmenopausal women. Their conclusion that HRT "increases" risk is stronger than an observational design can support. This is the weakest point of the study.
This study does not give individual advice. It does not show that HRT is unsafe for everyone, and it does not weigh the symptom relief many women gain.
On October 12, The Arising reported on a separate study of testosterone therapy after menopause. That is a different treatment and a different study, but it also points to cardiovascular safety as a question for hormone treatments.
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Whether trials or analyses that record HRT type, dose, route and timing can confirm which women face the highest risk.
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