Serum PSA as a predictor of testosterone deficiency.

Introduction: The relationship between serum prostate-specific antigen (PSA) and testosterone (T) levels is still controversial. According to the "saturation hypothesis," a significant relationship is apparent only in the low T range.

Aim: To verify whether, in a large sample of male subjects seeking medical care for sexual dysfunction (SD), PSA might represent a reliable marker of T levels.

Methods: A consecutive series of 3,156 patients attending our unit for SD was studied. Among them, only subjects without history of prostate disease and with PSA levels<4 ng/mL (N=2,967) were analyzed.

Main Outcome Measures: Several hormonal and biochemical parameters were studied, along with structured interview on erectile dysfunction (SIEDY), ANDROTEST, and PsychoANDROTEST.

Results: Receiver operating characteristic curve analysis for predicting severe hypogonadism (T<8 nmol/L) showed an accuracy of PSA=0.612±0.022 (P<0.0001), with the best sensitivity and specificity at PSA<0.65 ng/mL (65.2% and 55.5%, respectively). In the entire cohort, 254 subjects (8.6%) showed T<8 nmol/L and, among them, more than half (N=141, 4.8%) had PSA<0.65 ng/mL. After adjusting for age, low PSA was associated with hypogonadism-related features (i.e., delayed puberty, lower testis volume) and associated conditions, such as metabolic syndrome (hazard ratio [HR]=1.506 [1.241-1.827]; P<0.0001), type 2 diabetes (HR=2.044 [1.675-2.494]; P<0.0001), and cardiovascular diseases (HR=1.275 [1.006-1.617]; P=0.045). Furthermore, low PSA was associated with impaired sex- and sleep-related erections. The association between low PSA and hypogonadal symptoms and signs as well as with metabolic syndrome was retained even after adjusting for T levels. Sensitivity and positive predictive values of low PSA increased, whereas specificity and negative predictive value decreased as a function of age.

Conclusions: PSA is a marker of T concentrations and it may represent a new tool in confirming hypogonadism. The determination of PSA levels might give insights not only on the circulating levels of total T but also on its active fractions.