Hormone Replacement Therapy with Testosterone and the Vascular System

Abstract

The diagnosis and treatment of androgen deficiency in boys and adult men with classical syndromes of hypogonadism are well established. Older men show a progressive decline of total and free testosterone levels, which have been related to sexual, somatic, and psychological symptoms. Some comorbid diseases, such as obesity, metabolic syndrome, diabetes, and atherosclerosis, further accentuate age-related testosterone deficiency, also named late-onset hypogonadism. Epidemiological data indicate that late-onset hypogonadism can be considered a new marker of cardiovascular health and mortality. The diagnosis of this emergent condition is challenged by the limitations of laboratory methods, the lack of standardized age-dependent thresholds of testosterone concentrations, and the uncertainties about the clinical significance of the symptoms attributable to hypogonadism. Whether low testosterone is just a consequence of metabolic imbalance and/or cardiovascular disease or a contributory factor to the progression of atherosclerosis is currently unclear, but it is likely that a bidirectional effect between decreased testosterone concentrations and disease pathology exists. Current indications for testosterone replacement therapy are limited to men with consistent symptoms and signs, and clearly low levels of testosterone. Nevertheless, testosterone treatment, beyond their known physiological actions on sexual function, bone mineralization, and body composition, has demonstrated modest positive effects on insulin resistance, glycemic control, and lipid profile in some trials performed in hypogonadal men with metabolic syndrome and/or diabetes. Furthermore, acute and chronic effects of testosterone suggest a vasodilator action on coronary vessels. Periodic monitoring of patients will be necessary to assess the treatment outcome, to decide the need for continuing treatment, and to avoid adverse effects, especially erythrocytosis and prostate cancer. While the old paradigm of testosterone being a dangerous hormone for the heart is no longer valid, the available evidence on the benefits and long-term risks of testosterone replacement therapy is still limited, especially in older men, and more basic and clinical research is needed to expand our knowledge on the role and the possibilities of testosterone.