Prostate-specific antigen, testosterone, sex-hormone binding globulin and androgen receptor CAG repeat polymorphisms in subfertile and normal men

The aim of this study was to understand the androgen-related factors which may regulate concentrations of the tumour marker, prostate-specific antigen (PSA). We therefore measured the serum concentrations of total and free te stosterone and of sex hormone-binding globulin (SHBG) and determined the an drogen receptor (AR) gene CAG repeat length, then compared these values to total and free PSA concentrations in 91 subjects with proven fertility, and 112 subfertile men with defective spermatogenesis. Concentrations of free testosterone and total testosterone, adjusted for SHBG, were 17-20% lower i n subfertile men compared with those in their fertile counterparts. This su btle, but highly significant (P < 0.001), difference in testosterone betwee n fertile and subfertile men was accentuated by the positive correlation be tween testosterone and AR gene CAG repeat length in fertile, but not subfer tile, subjects. In subfertile subjects, testosterone strongly correlated (r = 0.354, P < 0.001) with PSA concentrations, and independent of testostero ne, total PSA negatively correlated (r = -0.229, P = 0.011) with AR CAG len gth. Overall our data suggest that, firstly, PSA correlates with testostero ne only in an environment of relatively low androgenicity, such as in subfe rtile men. Secondly, in such a low androgenic environment, short CAG tracts (associated with high AR activity) correlate positively with PSA concentra tions. These results suggest that interpretation of PSA is best made in con junction with testosterone concentrations and AR CAG length.