Sex steroid hormones, gonadotropins, and risk of testicular germ cell tumors: results from the STEED study

BACKGROUND: Testicular germ cell tumors (TGCTs) are thought to be endocrine related, but the hypothesis has not been thoroughly investigated. As a result, prediagnostic serum samples from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed to assess the relationship between hormones and gonadotropins to TGCT risk. METHODS: The study included 517 men who subsequently developed a TGCT and 790 comparison men. The hormones and gonadotropins examined included testosterone; estradiol; sex hormone-binding globulin; 5α-androstane-3α,17β-diol glucuronide (3α-diol G); follicle-stimulating hormone (FSH); and luteinizing hormone (LH). Adjusted odds ratios (ORs) and 95% CIs were estimated using logistic regression. Analyses stratified by histology (seminoma, nonseminoma) were also conducted. RESULTS: Compared with men in the middle quintile of LH concentrations, men with the lowest LH concentrations had an increased risk of TGCT (OR = 1.88, 95% CI = 1.31 to 2.70), as did men with FSH concentrations in the lowest (OR = 1.77, 95% CI = 1.21 to 2.60) and highest quintiles (OR = 2.20, 95% CI = 1.53 to 3.17). An increased risk of seminoma was found with both low and high LH and high FSH levels, whereas an increased risk of nonseminoma was found with low LH levels and both low and high FSH levels. Decreased levels of 3α-diol G were associated with increased risk of seminoma (OR = 1.65, 95% CI = 1.02 to 2.67). CONCLUSION: These results suggest that gonadotropin disruption may be a critical event in the development of TGCTs. Further examination of upstream and downstream metabolites in the hormone pathways may help elucidate the underlying mechanism that distinguishes men who develop TGCTs from men who do not.