Hormone replacement therapy: the good, the bad and the ugly

Abstract

The incidence of hypertension and cardiovascular diseases is lower in women than age-matched men, before women go through menopause. It has been suggested that low estradiol levels in postmenopausal women may be the culprit for the risk of cardiovascular diseases, which prompted the use of hormone replacement therapy as a prevention of hypertension and cardiovascular diseases after menopause. However, recent results from women health initiative study showed that the risk of cardiovascular events after the hormone replacement therapy was increased for myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism in the conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily administration, and for the deep venous thrombosis, pulmonary embolism and stroke in the conjugated equine estrogens (CEE) 0.625 mg daily administration. After menopause, not only the estradiol levels decrease, but androgens remain unchanged or even elevated. It is therefore proposed that an increase in the androgen/estrogen ratio may be the pathogenic mechanism for cardiovascular diseases after menopause. Experimental studies indicate that a relative increase of androgens after menopause may lead to metabolic syndrome, endothelial dysfunction, activation of the sympathetic nervous system and the renin angiotensin system. All these mechanisms act in concert to promote hypertension and cardiovascular diseases. Therefore, targeting androgens after menopause may be beneficial for reduction of cardiovascular risk in postmenopausal women.