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.