Background: Lower levels of anabolic hormones in older age are well documented. Several studies have suggested that low serum levels of like insulin-like growth factor I (IGF-I) or total testosterone in men were related to higher morbidity and mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low total testosterone levels on mortality in adult men. Methods: From two German prospective cohort studies, the DETECT study and SHIP, 4,092 men aged 18–91 years were available for the analyses. Low levels of serum IGF-I and total testosterone levels were defined as values below the age-specific 10th percentile separately in both studies. Cox proportional hazard models were conducted to assess the association between hormones and mortality. Results: During the 22,900 person-years of follow-up 8.5% (n=346) of men died. Analyses adjusted for body mass index, smoking, and physical activity revealed that men with low levels of at least one hormone [hazard ratio (HR) 1.52 (95% confidence interval (CI) 1.19; 1.95), p<0.01] and two hormones [HR 3.59 (95%-CI 1.73; 7.47), p<0.01] showed a higher risk of all-cause mortality compared to men with moderate levels of both hormones. The inclusion of low IGF-I and low total testosterone to the prediction model of all-cause mortality resulted in integrated discrimination improvement of 0.8% (95% CI 0.5%-1.0%; p=0.19). Conclusions: Our results confirm former studies showing that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency in men. Therefore our results suggest that assessment of more than one anabolic hormone as a biomarker is not superior for the prediction of all-cause mortality.