title: Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men.
abstract: 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.
  
  
  
  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 >75nmol/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 <8.0nmol/L.
  
  
  
  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 50-75nmol/L (n=240) had lower total testosterone levels compared to men with serum 25(OH)D higher than 75nmol/L (n=148) (β (95% confidence interval): -2.1 (-3.7 to -0.4nmol/L), -0.8 (-1.9 to 0.4nmol/L) and -1.4 (-2.4 to -0.3nmol/L), respectively). For bioavailable testosterone the association was significant only for men with serum 25(OH)D less than 25nmol/L (-0.8 (-1.4 to -0.1nmol/L)) compared to men with serum 25(OH)D >75nmol/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.
  
  
  
  Vitamin D status is positively associated with testosterone levels. No association was found between vitamin D-related gene polymorphisms and hormone levels.
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: ra.rafiq@vumc.nl.
authors.forename: R
authors.initials: R
authors.lastname: Rafiq
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: van Schoor
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Sohl
authors.affiliation: Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Zillikens
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Oosterwerff
authors.affiliation: Department of Health Sciences, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Schaap
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R T
authors.initials: RT
authors.lastname: de Jongh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007006:Hypogonadism / Q000097:blood; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000097:blood* / Q000235:genetics*; D015203:Reproducibility of Results; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D018167:Receptors, Calcitriol; D012738:Sex Hormone-Binding Globulin; C579457:VDR protein, human; D014807:Vitamin D; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C104450:25-hydroxyvitamin D
keywords: Gonadotropins; Polymorphisms; Sex hormones; Vitamin D; Vitamin D receptor