Androgens and Hypertension in Men and Women: a Unifying View

This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality.

Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension. Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be a major determinant of the increased prevalence of hypertension. The relationship between androgen signalling and NF-kB might explain the pathophysiological mechanism leading to the development of endothelium dysfunction and hypertension.