Ageing in men is accompanied by a decline in serum testosterone (T) levels and increased risk of cardiovascular disease, osteopenia, visceral obesity and impaired metabolism. These conditions have complex aetiologies that may share a common pro-inflammatory state. We investigated the impact of T therapy on cytokines and angiogenic factors involved in atherosclerosis and bone loss, in hypogonadal men who underwent androgen replacement. We carried out a 6 months, randomized, double-blind, controlled, crossover trial of T gel (50 mg/d)+Sildenafil(S) (50 mg) vs Placebo(P)+(S) in a group of 25 men (age, 52±6 years) with hypogonadism and erectile dysfunction. All patients had penile CDU, IIEF, CES-D, AMS and EDITS questionnaires, DEXA for BMD, routine biochemistry and measurement of serum cytokines (IL-1, IL-6, IL-10, IL-12, TNF) and angiogenic factors (FGF, PDGF, VEGF, HGF) evaluated at baseline and at the end of each treatment period. In the T+S arm serum T levels rose from 2.6±2.3 to 3.8±2.2 ng/dl (P<0.05) with improvement in penile Peak Systolic Velocities (from 26±7.3 to 34±8.9 cm/s, P<0.01). T+S also induced a significant reduction in serum pro-inflammatory IL-1β (−27±8%; P<0.05) and TNF-α (−23±6%; P<0.05) and an increase in anti-inflammatory IL-10 (45±9%; P<0.05). Sildenafil alone induced a reduction of FGF and VEGF, compared with the association of T+Sildenafil (respectively, −18±8% and −22±9%, P<0.05), while the reduction in PDGF was inconsistent (−13±8%, P=0.05). These data suggest that: 1) T in men plays an immune-modulatory effect shifting circulating cytokine toward a favourable anti-inflammatory state; 2) PDE5 inhibitors (PDE5i) reduces markers of vascular damage; 3) the association of T and PDE5i in hypogonadal subject could potentiate the positive endothelial and vascular effects of PDE5i and counteract the pro-angiogenic effects of T. These data disclose future indications for the combined treatment of androgen and PDE5i in the rehabilitation of patients with hypogonadism and cardio-vascular disease.
03 - 07 May 2008
European Society of Endocrinology