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

Abstract

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.

Investigation of gene expression and genetic simultaneous control associated with erectile dysfunction and diabetes

“…TT, FT and IIEF were measured and compared at the beginning of the study and after treatment. The results showed that the levels of these two hormones, as well as IIEF, increased after treatment and NFG was significantly effective in improving ED and testosterone decline due to type 2 diabetes (9).…”

“…The pathogenesis of DMED is complex. Diabetic vascular disease includes macrovascular disease, vascular disease and endothelial dysfunction, all of which are related to the pathophysiological process of ED (7)(8)(9).…”

“…ED in diabetic men is usually caused by neuropathic factors or vascular insufficiency. However, non-diabetic factors sometimes cause sexual dysfunction in these patients (7,9,13).…”

“…ED in diabetic patients is usually caused by underlying neuropathic factors, and these people also show several other neuropathic manifestations (9,16).…”

Comparison of the therapeutic effects of adipose‑derived and bone marrow mesenchymal stem cells on erectile dysfunction in diabetic rats

“…The incidence of diabetes mellitus-induced ED (DMED) is 19.0-86.3%, which is three times the rate of ED in non-diabetic patients (1,2). The mechanism of DMED is not entirely clear, but it is associated with problems in blood vessels, nerves, neurotransmitters, and the endocrine system, among others (3-5). Vascular lesions caused by diabetes may induce atheromatous plaque formation in the cavernous arteries of the penis, resulting in reduced blood flow and structural or functional destruction of arterioles and sinusoidal endothelial cells in the cavernous body, further affecting erectile function.…”