Sensitivity to androgens: beyond the well-known facts

Abstract

Gonadal and extragonadal effects of testosterone in males have been extensively investigated in recent years. To date, there is no doubt that testosterone deficiency in males is associated with increased risk of obesity, type 2 diabetes mellitus, hypertension, and atherosclerosis. Sensitivity to androgens determined by the length of CAG-repeats in the androgen receptor gene is one of the underlying mechanisms of testosterone action. Increase in the number of CAG-repeats reduces activity of androgen receptors, which manifests in the form of low sensitivity to testosterone. On the contrary, decrease in the number of trinucleotide repeats is accompanied by increased sensitivity of the receptors to androgens. This review discusses the effect of androgen receptor gene polymorphism on embryogenesis and sex differentiation, regulation of spermatogenesis, progression of cancer and benign prostatic hyperplasia, symptoms of hypogonadism, control of carbohydrate and lipid metabolism, bone mineral density, vascular endothelium, response to replacement therapy with testosterone, as well as on the psychosocial aspects of personality in males. Implementation of the study of androgen receptor gene polymorphism into clinical practice will enable not only predicting male fertility or the risk of developing prostate cancer, but also selecting an individual therapy for testosterone deficiency.