2. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3. Department of Community and Environmental Health, Old Dominion University, Norfolk, VA, USA.
4. Laboratory of Epidemiology and Population Sciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
Background: In men, hypovitaminosis D as well as high and low testosterone levels have been linked to adverse events, including death. A biological interaction has been previously suggested between vitamin D and androgens. In a cohort study using Third National Health and Nutrition Examination Survey data, we simultaneously investigated circulating vitamin D and biomarkers of sex steroid hormones as predictors of all-cause mortality.
Methods: Age-adjusted and fully-adjusted Cox regression models were constructed to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Whereas the vitamin D sufficient group (25(OH)D3≥30 ng/ml) was selected as a referent, biomarkers of sex steroid hormones (testosterone, estradiol, SHBG) were defined as Loge-transformed continuous variables.
Results: Of 1,472 men with a mean age of 42.1 years at baseline, 382 died over a median of 192 months of follow-up. Estradiol levels were significantly higher among vitamin D deficient compared to vitamin D sufficient men and sex hormone binding globulin level was significantly higher in vitamin D sufficient compared to vitamin D insufficient or deficient groups. An inverse non-linear relationship was observed between all-cause mortality rate and levels of testosterone, estradiol and vitamin D, in fully-adjusted models. There were no significant interaction effects between vitamin D and sex steroid hormones in relation to all-cause mortality rate.
Conclusions: Vitamin D and sex steroid hormones, but not sex hormone binding globulin, may be inversely and non-linearly related to all-cause mortality among adult men, after adjustment for baseline demographic, socioeconomic, lifestyle and clinical characteristics.
Keywords: All-cause mortality, androgens, cohort study, estradiol, sex hormone binding globulin, testosterone, vitamin D