Reduced number of circulating endothelial progenitor cells in hypogonadal men

CONTEXT: Endothelial dysfunction seems to be the first step of the atherosclerotic process. In the past few years, it has been demonstrated that injured endothelial monolayer is restored by a premature pool of circulating progenitor cells (PCs) and a more mature one of circulating endothelial PCs (EPCs). Even though there is increasing evidence that estrogens play a beneficial role on EPCs and, even if debated, on the cardiovascular system, less is known about androgens. OBJECTIVE: Our objective was to evaluate the levels of circulating PCs and EPCs in men with hypogonadotropic hypogonadism (HH) and the effect of prolonged testosterone (T) replacement therapy on these cells. DESIGN AND SETTING: We conducted a prospective study on males with HH at a university andrological center. PATIENTS: The study included 10 young HH patients (28.6 +/- 3.1 yr) and 25 age-matched controls. INTERVENTIONS: Idiopathic HH patients were treated with T gel therapy, 50 mg/d for 6 months. MAIN OUTCOME MEASURES: We assessed circulating PC and EPC concentrations and immunocytochemistry for androgen receptor expression on cultured EPCs. RESULTS: At baseline, HH patients showed a significant reduction of both PCs and EPCs with respect to controls. T replacement therapy induced a significant increase of these cells with respect to baseline. Immunocytochemistry on cultured EPCs showed strong expression of the androgen receptor. CONCLUSIONS: Hypotestosteronemia is associated with a low number of circulating PCs and EPCs in young HH subjects. T treatment is able to induce an increase in these cells through a possible direct effect on the bone marrow.