Objective: Evidence regarding relationships of serum 25-hydroxyvitamin D (25(OH)D) with sex hormones and gonadotropin concentrations remains inconsistent. Polymorphisms in vitamin D-related genes may underly these relationships. Our aim was to examine the relationship of vitamin D status and polymorphisms in vitamin D-related genes with sex hormone and gonadotropin levels. Design and measurements: We analysed data from the Longitudinal Aging Study Amsterdam, an ongoing population-based cohort study of older Dutch individuals (65-89 years). We included data of men with measurements of serum 25-hydroxyvitamin D (25(OH)D) (n =. 643) and determination of vitamin D-related gene polymorphisms (n =. 459). 25(OH)D concentrations were classified into four categories: <25, 25-50, 50-75 and >75. nmol/L. Outcome measures were total testosterone, calculated bioavailable and free fraction testosterone, SHBG, estradiol, LH and FSH concentrations. Hypogonadism was defined as a total testosterone level <8.0. nmol/L. Results: Serum 25(OH)D was positively associated with total and bioavailable testosterone levels. After adjustments for confounders, men with serum 25(OH)D less than 25 (n =. 56), 25-50 (n =. 199) and 50-75. nmol/L (n =. 240) had lower total testosterone levels compared to men with serum 25(OH)D higher than 75. nmol/L (n =. 148) (β (95% confidence interval): -2.1 (-3.7 to -0.4. nmol/L), -0.8 (-1.9 to 0.4. nmol/L) and -1.4 (-2.4 to -0.3. nmol/L), respectively). For bioavailable testosterone the association was significant only for men with serum 25(OH)D less than 25. nmol/L (-0.8 (-1.4 to -0.1. nmol/L)) compared to men with serum 25(OH)D >75. nmol/L. Serum 25(OH)D was not related to SHBG, estradiol or gonadotropin levels. Hypogonadism (n =. 29) was not associated with lower serum 25(OH)D. No significant differences were found in hormone levels between the different genotypes of the vitamin D-related gene polymorphisms. Also, the polymorphisms did not modify the relationships of serum 25(OH)D with sex hormones or gonadotropins. Conclusion: Vitamin D status is positively associated with testosterone levels. No association was found between vitamin D-related gene polymorphisms and hormone levels.

Gonadotropins, Polymorphisms, Sex hormones, Vitamin D, Vitamin D receptor
dx.doi.org/10.1016/j.jsbmb.2015.11.013, hdl.handle.net/1765/85949
The Journal of Steroid Biochemistry and Molecular Biology
Department of Internal Medicine

Rafiq, R, van Schoor, N.M, Sohl, E, Zillikens, M.C, Oosterwerff, M.M, Schaap, L.A, … de Jongh, R.T. (2016). Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men. The Journal of Steroid Biochemistry and Molecular Biology (Vol. 164, pp. 11–17). doi:10.1016/j.jsbmb.2015.11.013