Male hypogonadism and pre-diabetes interplay: association or causal interaction? A systematic review

Aim: The association between type 2 diabetes mellitus (T2DM) and male hypogonadism has been largely demonstrated. Testosterone (T) serum levels are often lower in men with T2DM compared to the general population, and, conversely, men with higher T serum levels have shown lower risk of T2DM. On the contrary, the association between pre-diabetes and male hypogonadism has been less investigated thus far. Pre-diabetes is a common clinical condition preceding T2DM and has been recognized as a potential risk factor for other metabolic disorders and cardiovascular diseases. Therefore, the aims of this review are to investigate the association between pre-diabetes and male hypogonadism and to evaluate the potential effect of T treatment on glucose metabolism and anti-diabetic therapy on T serum levels. Methods: We conducted this systematic review developing different literature searches, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol. Page 2 of Greco et al. Metab Target Organ Damage 2022;2:11 https://dx.doi.org/10.20517/mtod.2021.14 18 Results: In our analysis, male hypogonadism has a prevalence of around 24%-35% in pre-diabetic men. Moreover, we observed improvement of metabolic parameters in pre-diabetes with T treatment. On the contrary, antidiabetic therapy seems to have no particular effects on T serum levels. Conclusion: Overall, we demonstrated that, although T administration could be considered in pre-diabetic men, pre-diabetes-related treatments should be confined to the control glucose metabolism, since no evidence for a positive effect on total T serum levels is available. Future research should be oriented to study the role of new antidiabetic drugs in the sex hormonal status in hypogonadal men.