Cardiovascular risk in hormone replacement therapy

Hormone replacement therapy (HRT) effectively alleviates vasomotor symptoms related to menopause, but it can also raise the risk of cardiovascular disease. Several factors influence the likelihood of developing coronary artery disease or ischemic stroke, including a woman's age, the time since menopause, the type, dose, and route of hormone therapy administration, as well as woman’s personal risk factors and existing or past health conditions. Starting HRT at an older age or more than 10 years after menopause increases the risk of ischemic stroke by 21% (RR=1.21, 95% CI 1.07-1.38), without any benefit in reducing mortality (RR=1.06, 95% CI 0.95-1.18) or cardiovascular events (RR=1.03, 95% CI 0.92-1.15). In contrast, beginning HRT at a younger age and within 10 years of menopause lowers all-cause mortality by 28% (RR=0.72, 95% CI 0.54-0.97), reduces cardiovascular events by 40% (RR=0.60, 95% CI 0.41-0.86), and does not significantly increase the risk of ischemic stroke (RR=1.37, 95% CI 0.91-2.05). Oral estrogen-progestin combinations are linked to a higher risk of ischemic heart disease (HR=1.21, 95% CI 1.00-1.46), and this effect depends on the dose. Therefore, it is advised to use the lowest effective estrogen dose. Progesterone, dydrogesterone, and levonorgestrel should be selected because they do not elevate cardiovascular risk. Transdermal estrogens or estrogen-progestins do not increase the risk of cardiovascular events and are recommended for women at moderate to high risk of stroke and coronary heart disease. A multidisciplinary approach may be beneficial for the safe and effective management of both menopausal symptoms and related conditions. Graphical Abstract