Sex Hormones and Their Impact on Cardiovascular Health

Clinical Case Download : Download full-size image A 51-year-old woman postmenopausal woman with a medical history significant for polycystic ovarian syndrome (PCOS), diabetes, and borderline hypertension is concerned with her symptoms of increased frequency of hot flashes. Her last period was at age 45. Her family history is significant for early-onset atherosclerotic cardiovascular disease and breast cancer. She was referred to the gynecologist and would like to initiate menopausal hormone therapy (MHT). She is a physically active nonsmoker, with no symptoms on exertion. Her weight and blood pressure are optimal and her lipid panel reveals: total cholesterol 178 mg/dL; triglycerides 81 mg/dL; high-density lipoprotein cholesterol (HDL-c) 65 mg/dL; and low-density lipoprotein cholesterol (LDL-c) 97 mg/dL. What are her underlying risk factors for MHT use? What can you counsel her about her options and the safety measures associated with these treatment modalities? What factors should be evaluated prior to initiation of MHT? Abstract The sex steroids (hormones), the androgens, estrogens, and progestogens, are all present to variable levels in each sex. Aside from typically considered feminizing and masculinizing effects, through their interactions with the sex steroid receptors present in the heart and vasculature, and their metabolic effects, they play a vital role in cardiovascular (CV) health. These effects are complex, with both negative and positive effects being noted. Endogenous estrogen in women appears to infer protection from cardiovascular disease (CVD), but exogenous estrogen has been associated with increased CVD risk. Androgens appear to exert positive effects on the vasculature and myocardium and reduced testosterone levels are associated with higher CVD risk. However, exogenous testosterone shows mixed effects on CV outcomes. Therapies targeting hormones include menopause hormonal therapy, testosterone replacement therapy, hormonal antagonism in the treatment of cancer, contraception, and gender-affirming therapy in transgender individuals. The varying effects of hormonal manipulation on CV health mandate a methodical and integrated approach to their use, considering comorbidities and patient risks.