Menopausal Hormone Therapy and Cardiovascular Risk: Current Evidence and Treatment Recommendations

Abstract

In 2025, the US Food and Drug Administration (FDA) removed its prior class-wide boxed warnings for menopausal hormone therapy (MHT), paving the way for increased clinical use. Menopause accelerates cardiovascular risk independently of chronological aging, manifesting as a 7.5% increase in carotid-femoral pulse wave velocity within 1 year and a hypertension prevalence of 66.6% in women aged 55-64 years. Risk stratification for MHT hinges on the timing of initiation and the administered formulation. The 2025 Women's Health Initiative secondary analysis suggests that in symptomatic women aged 50-59 years, combination (estrogen-progestogen) MHT maintains atherosclerotic neutrality while reducing vasomotor symptoms by 59%. Conversely, atherosclerotic risk increases in women aged 70-79 years (hazard ratio 3.22 for combined therapy). Route of administration dictates the metabolic effect: oral estrogens undergo hepatic first-pass metabolism, elevating venous thromboembolism risk and increasing triglycerides by 5-15%, whereas transdermal formulations bypass hepatic first-pass metabolism, decrease triglycerides by 5-30%, and carry a neutral thromboembolic risk profile. When concurrent progestogen therapy is required, natural micronized progesterone is favored over synthetic medroxyprogesterone acetate to preserve estrogen-mediated vascular benefits. Oral or transdermal systemic MHT can be considered for vasomotor symptom management in women <60 years or within 10 years of menopause with a 10-year atherosclerotic cardiovascular disease risk of <5% and a coronary artery calcium score of zero.