Nerve Growth Factor Improves the Outcome of Type 2 Diabetes–Induced Hypotestosteronemia and Erectile Dysfunction

Hypotestosterone and erectile dysfunction (ED) occur frequently in males with type 2 diabetes. It is still clinically challenging to manage diabetes-induced ED. Here, we conducted a 2-arm randomized clinical study and in vitro cell line experiments to investigate the effects of nerve growth factor (NGF) on serum testosterone and ED in diabetic males with sensorimotor polyneuropathy and to identify its underlying mechanisms. The analyses of serum total testosterone (TT) and free testosterone (FT), and 5-item version of the International Index of Erectile Function (IIEF-5) score at baseline and after treatment show increases in TT (3.90 nmol/L, 95% confidence interval [CI]: 3.13-4.66 nmol/L vs 1.21 nmol/L [95% CI: 0.57-1.85 nmol/L]), FT (3.79 pg/mL [95% CI: 3.05-4.54 pg/mL] vs 1.27 pg/mL [95% CI: 0.85-1.70 pg/mL]), and IIEF-5 score (1.84 [95% CI: 1.21-2.47] vs 0.24 [95% CI: −0.24 to 0.73]) in the NGF treatment compared controls (P < .005). In mouse Leydig cells, NGF significantly ameliorated the hyperglycemia-induced downregulation of steroidogenic acute regulatory protein and cytochrome P450 11A1 (P < .05). Thus, NGF treatment effectively improves type 2 diabetes–induced hypotestosterone and ED outcome through a mechanism that includes upregulation of key enzymes in testosterone biosynthesis.