Menopausal Hormone Therapy and Cardiovascular Disease Risk: Utility of Biomarkers and Clinical Factors for Risk Stratification

Abstract

Menopausal hormone therapy (HT) continues to have a clinical role in symptom management, but identifying women for whom benefits will outweigh the risks remains a challenge. Although hormone therapy (HT) is the most effective strategy for ameliorating vasomotor and other symptoms, randomized clinical trials show an unfavorable balance of benefits and risks for many women. However, closer examination of data from these trials suggests that it may be possible to classify women as better or worse candidates for HT by using individual risk stratification. Data from 2 landmark trials-the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS)-suggest an important role for clinical characteristics, serum biomarkers, genomic markers, and gene-environment interactions in developing a personalized approach to the prediction of risk for cardiovascular disease (CVD) events for women while on HT. The available data suggest several characteristics of women who are optimal candidates for HT use: younger age (<60 years), recent onset of menopause (<10 years), favorable lipid profile (LDL cholesterol <130 mg/dL or LDL/HDL cholesterol ratio <2.5), absence of metabolic syndrome, and absence of factor V Leiden genotype. The identification of other characteristics is an area of active investigation. In addition, women at high risk for venous thromboembolism should avoid systemic HT or choose a transdermal rather than oral delivery route. Personalized medicine-i.e., the use of the specific biological profile of an individual to guide the choice of treatment-is highly relevant for clinical decision-making regarding HT and offers promise for improved treatment efficacy and safety.