Background: Earlier studies have suggested that total testosterone concentrations influence the lipid metabolism. Whether these concentrations are prospectively associated with an adverse lipid profile and an increased risk of incident dyslipidemia has not yet been investigated.

Methods and results: Our study population consisted of 1468 men, aged 20–79 years, who were repeatedly examined as part of the population-based Study of Health in Pomerania. Serum total testosterone concentrations measured by the chemiluminescent enzyme immunoassays were categorized into age-specific quartiles. We used generalized estimating equations models to assess the prospective association between total testosterone concentrations and lipid profile components including total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride (TG) concentrations, as well as incident dyslipidemia after 5 years of follow-up. Multivariate models revealed that total testosterone concentrations in the lowest quartile were associated with higher TC and TG concentrations in both cross-sectional [TC: 0.23 mmol/l (95% confidence interval, CI, 0.02–0.42); TG: 0.73 mmol/l (95% CI, 0.53–0.94)] and longitudinal analyses [TC: 0.20 mmol/l (95% CI, 0.03–0.27); TG: 0.62 mmol/l (95% CI, 0.43–0.80)], but not with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol concentrations. Baseline prevalence of dyslipidemia was 57.1% with a crude incidence rate of 46.6 per 1000 person-years. Total testosterone concentrations in the lowest quartile predicted dyslipidemia; age-adjusted relative risks (RR) for men in quartiles 1, 2, and 3 as compared to quartile 4 (highest, reference) were 1.28 (95% CI, 1.06–1.54), 1.10 (95% CI, 0.91–1.33), and 1.05 (95% CI, 0.86–1.29), respectively. This effect was particularly strong among men aged 20–39 years (relative risk, 1.51; 95% CI, 1.08–2.10).

Conclusion: Low total testosterone concentrations are prospectively associated with an adverse lipid profile and increased risk of incident dyslipidemia. These findings are particularly interesting and may contribute to an explanation for the higher cardiovascular disease risk in men with lower total testosterone concentrations.