Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys

OBJECTIVE Prostate specific antigen (PSA) expression in the prostate gland is regulated by androgens. Serum levels of PSA are undetectable by routine assays in normal boys. Measurable values could serve as a marker for pubert al development. In order to explore this question, we measured serum PSA le vels in normal boys throughout puberty and examined the interrelationships with various hormonal and physical developmental changes. DESIGN Sera from 77 normal boys in Tanner stages I to V (T-I to T-V) were a nalysed for PSA levels by a sensitive time-resolved fluoro-immunometric ass ay (sensitivity: 0.012 mu g/l). In addition, sex hormone binding globulin ( SHBG), insulin like growth factor I (IGF-I), IGF binding protein 3(IGFBP-3) and testosterone were measured. RESULTS PSA was detectable in 0% of Stage T-l (n = 16), 33% of T-II (n = 18 ), 65% of T-III (n = 17) and 100% of T-IV (n = 10) and T-V (n = 16) boys. P SA levels rose significantly according to stage (P < 0.05). Also, there wer e significant (P < 0.05) increments in serum testosterone, IGF-I and IGFBP- 3 levels from stages T-I to T-IV. PSA showed a positive correlation with te stosterone (r = 0.86, P < 0.001), IGF-I (r = 0 .66, P < 0.001), and IGFBP-3 (r = 0.34, P = 0.004) levels. Both PSA and these analytes, however, showed significant overlap between stages T-I and T-II with only 6/18 (33%) and 1 2/18 (66%) of T-II subjects having PSA and testosterone levels, respectivel y, above the T-I range. In contrast, serum SHBG levels decreased markedly f rom stages I to II (P < 0.001). At the calculated best cut-off point for SH BG of 50 nmol/l, 16/18 T-II subjects had values below the T-I range (sensit ivity=89%). Because of this decrement of SHBG and the increasing testostero ne secretion in early puberty, the Free Androgen Index (FAI=Testosterone/SH BG) could even better differentiate the onset of puberty with all except on e of the T-II subjects having FAI levels above the T-I range (sensitivity = 94.4%). The decrease of SHBG in T-II subjects coincided with an increase i n total body weight (P = 0.001) and body mass index (BMI, P=0.0003). Despit e the continuing pubertal rise in testosterone, SHBG levels showed a reboun d increment from T-II - T-III subjects (P = 0.02) with a concomitant decrea se in BMI (P = 0.0014). CONCLUSIONS Prostate specific antigen closely reflects serum free androgen activity during puberty. However, it was unable to differentiate the earlie st pubertal development. In comparison, SHBG levels and Free Androgen Index are more sensitive markers for the onset of puberty in boys. The inverse a ssociation between SHBG levels and BMI in pubertal stages Tanner stages, I to III suggests that body fatness, via its effect on insulin sensitivity, m ay play an important role in the regulation of SHBG production during early pubertal development.