Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion

This proof-of-concept study investigated whether kisspeptin-10 could restore reproductive axis function in men with type 2 diabetes who had mild biochemical hypogonadism, a comorbidity affecting up to 40% of diabetic men. The researchers administered intravenous kisspeptin-10 as a bolus and evaluated the hormonal response through serial blood sampling.

The results demonstrated that kisspeptin-10 was able to significantly increase LH pulse frequency and raise serum testosterone levels in diabetic participants. This indicates that the reproductive axis defect in these patients is located above the GnRH neurons, likely in the hypothalamic kisspeptinergic system, and that exogenous stimulation can overcome this barrier.

An important aspect of the study was the demonstration that pituitary and gonadal mechanisms remained functional in men with type 2 diabetes and hypogonadism — that is, the pituitary responded to GnRH released by kisspeptin and the testes responded to LH. The problem lay in hypothalamic signaling.

These findings opened a new therapeutic perspective for diabetes-associated hypogonadism, suggesting that interventions targeting the kisspeptin system could represent a more physiological alternative to direct testosterone replacement, which has various side effects and suppresses spermatogenesis.