Male hypogonadism is “a clinical syndrome that results from failure of the testis to
produce physiological concentrations of testosterone and/or a normal number of spermatozoa due
to pathology at one or more levels of the hypothalamic– pituitary–testicular axis”. The diagnostic
protocol of male hypogonadism includes accurate medical history, physical exam, as well as
hormone assays and instrumental evaluation. Basal hormonal evaluation of serum testosterone, LH,
and FSH is important in the evaluation of diseases of the hypothalamus-pituitary-testis axis. Total
testosterone levels < 8 nmol/l profoundly suggest the diagnosis of hypogonadism. An inadequate
androgen status is moreover possible if the total testosterone levels are 8-12 nmol/L. In this “grey
zone” the diagnosis of hypogonadism is debated and the appropriateness for treating these patients
with testosterone should be fostered by symptoms, although often non-specific. Up to now, no
markers of androgen tissue action can be used in clinical practice. The identification of markers of
androgens action might be useful in supporting diagnosis, Testosterone Replacement Treatment
(TRT) and clinical follow-up. The aim of this review is to analyze the main findings of recent
studies in the field of discovering putative diagnostic markers of male hypogonadism in seminal
plasma by proteomic techniques. The identified proteins might represent a “molecular androtest”
useful as a seminal fingerprint of male hypogonadism, for the diagnosis of patients with moderate
grades of testosterone reduction and in the follow-up of testosterone replacement treatment.
