The impact of hemochromatosis mutations and transferrin genotype on gonadotropin serum levels in infertile men.

OBJECTIVE To address the possibility that HFE mutations and TF gene polymorphism cause dysfunction of spermatogenesis and/or the hypothalamic-pituitary-gonadal axis via contribution to long-term iron overload in the testes and brain. DESIGN Case-control and association study. SETTING Clinic of obstetrics and gynecology and university-based research laboratory. PATIENT(S) 127 infertile men (including 97 with idiopathic infertility) and 188 controls of proven fertility. INTERVENTION(S) Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). MAIN OUTCOME MEASURE(S) HFE mutations and transferrin allelic polymorphism, and testosterone, prolactin, and gonadotropin serum levels. RESULT(S) The frequencies of the analyzed alleles and genotypes showed no statistically significant difference between infertile men and controls. Sperm count and progressive sperm motility did not correlate with HFE or TF genotype, or their combination. After excluding patients with clinical hypogonadism or varicocele from further analysis, a statistically significant correlation between serum follicle-stimulating hormone and luteinizing hormone levels and the combined HFE H63D/TFC2 genotype was found in 97 men with idiopathic infertility. CONCLUSION(S) The combined HFE H63D/TF-C2 genotype contributed to 4.1% and 10.6% of follicle-stimulating hormone and luteinizing hormone variation, respectively, in infertile men, raising mean hormonal values above the normal physiologic range. Therefore, HFE and TF genes together may influence the hypothalamic-pituitary-gonadal axis, functioning at the pituitary or testes level.