The cofactor effect: varicocele and infertility.

The varicocele may be a cofactor that, when potentiated by other cofactors (i.e., gonadotoxins), causes male infertility. This hypothesis could explain the unpredictable effects of the varicocele on fertility. Male rats with experimental varicoceles, sham surgery, or no surgery were treated for 30 days with the known gonadotoxins cyclophosphamide or nicotine. Spermatogenesis was assessed by flow cytometry. Cyclophosphamide alone caused gonadotoxicity, and its effect was accentuated by sham or varicocele surgery. Nicotine and the presence of a varicocele were more gonadotoxic than either the varicocele or nicotine by itself. This data would lend support to the cofactor hypothesis of the pathophysiology of the varicocele.