Association of hypogonadism with vitamin D status: the European Male Ageing Study
Lee DM, Tajar A, Pye SR, Boonen S, Vanderschueren D, Bouillon R, O'Neill TW, Bartfai G, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi I, Kula K, Lean ME, Pendleton N, Punab M, Wu F. Eur J Endocrinol. 2011 Nov 2. [Epub ahead of print]


D Lee, Arthritis UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom.


Objective: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men.Design and methods: Cross-sectional survey of 3,369 community-dwelling men aged 40-79 in eight European centres. Testosterone (T), oestradiol (E2) and dihydrotestosterone (DHT) were measured by gas chromatography-mass spectrometry; luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone (PTH) by immunoassay. Free T was calculated from T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression, and hypogonadism with vitamin D using multinomial logistic regression.Results: In univariate analyses free T levels were lower (P=0.02) and E2 and LH higher (P<0.05) in men with deficient vitamin D (25(OH)D<50nmol/L). 25(OH)D was positively associated with total and free T, and negatively with E2 and LH in age and centre adjusted linear regressions. After adjusting for health and lifestyle factors no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, deficient vitamin D was significantly associated with compensated [relative risk ratio (RRR)=1.52, P=0.03] and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001).Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.