Table 3.

Summary of clinical observational studies investigating the association of vitamin D and androgen levels in men.

Author/study	Subjects	Age	Hypogonadism	Androgens	Other endocrine parameters	Adjustment
Wehr et al./LURIC study (3)	2299 men at high cardiovascular risk	62 ± 11 years	OR 2.47 (1.55–3.93) for men with 25(OH)D <25 nmol/L compared to >75 nmol/L	↑TT, ↑FAI	↓SHBG	Age, BMI, wine consumption, smoking, beta-blocker use, statin use and diabetes
Heijboer et al. (86)	183 men (101 men with chronic heart failure; 76 male nursing home residents; 43 overweight non-Western immigrants)	20–86 years (range)	na	↑TT		Unadjusted
Jorde et al. the Tromsø study (84)	893 men	60.6 ± 9.8 years	na	↑TT, no association with FT		Age, BMI, season, presence of cardiovascular disease and diabetes, and physical activity
Chin et al. (87)	382 Chinese and Malay men	≥20 years	na	No independent association with TT	↑SHBG	Age, ethnicity, BMI
Wulaningsih et al. NHANES III (94)	1412 men	≥20 years	na	No independent association with TT or FT	No independent association with SHBG or estradiol	Age, race/ethnicity, % body fat, diabetes, cigarette smoking, alcohol intake, vigorous physical activity, and serum levels of 25(OH)D, calcium, and creatinine
Anic et al. NHANES III and NHANES 2001–2004 (90)	1315 men (NHANES III) and 318 men (NHANES 2001–2004)	≥20 years	na	↑TT	↑SHBG	Adjusting for age, race/ethnicity, body fat percentage, and smoking
Blomberg Jensen et al. the Copenhagen-Bone-Gonadal Study (91)	1427 infertile men	34.1 (31–38) years	na	Higher FT in men with 25(OH)D levels <25nmol/l nmol/L compared to men with 25(OH)D levels >75 nmol/L	Lower SHBG and T/estradiol ratios and higher estradiol in men with 25(OH)D levels <25 nmol/L compared to men with 25(OH)D levels >75 nmol/L	Age, BMI, smoking, season
Lerchbaum et al. (95)	225 men	35 (30–41) years	U-shaped association of vitamin D status and risk of hypogonadism. Significantly increased risk of hypogonadism in men within the highest 25(OH)D quintile (>102 nmol/L) compared to men in quintile 4 (reference, 82–102 nmol/L). (OR 9.21, 2.27–37.35, P = 0.002)	No independent association with TT and FT	No independent association with SHBG	Adjusted for age, BMI, ethnic background, study site
Wang et al. (85)	2854 Chinese men	53.0 ± 13.5 years	Increasing quartiles of 25(OH)D were associated with significantly decreased odds ratios of hypogonadism. OR 1.50 (95% CI, 1.14, 1.97) for men in the lowest compared to men in highest 25(OH)D quartile	↑TT	↑Estradiol	Age, residence area, economic status, smoking, BMI, homeostasis model assessment-insulin resistance, DM and systolic pressure
Tak et al. (88)	652 Korean men	56.7 ± 7.9 years	Vitamin D deficiency (<50 nmol/L) was associated with an increased risk of TT (odds ratio (OR): 2.65; 95% confidence interval (CI): 1.21–5.78, P = 0.014) and FT deficiency (OR: 1.44; 95% CI: 1.01–2.06 P = 0.048)	↑TT, ↑FT		TT: body fat, WC, BMI, FPG, DM and dyslipidemia
						FT: adjusted age, total muscle mass, smooth muscle mass, TC, DM, dyslipidemia and alcohol use
						Hypogonadism: adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use)
Rafiq et al. (89)	Older Dutch individuals (n = 643)	65–89 years (range)	No independent association of 25(OH)D levels with hypogonadism	↑TT and bioavailable testosterone		Adjusted for age, BMI, alcohol consumption, smoking status, season of blood collection, number of chronic diseases, serum creatinine and physical performance
Zhao et al. (92)	3016 older men	62.1 ± 10.2 years	no independent association of 25(OH)D levels with hypogonadism	↑FT, no independent association with TT	↓SHBG	Adjusting for age, race/ethnicity, and study site, BMI, smoking, education, intentional physical exercise, and self-reported health status, diabetes, systolic blood pressure, use of antihypertensive medications, eGFR, total cholesterol, HDL cholesterol, use of lipid lowering medication usage, and hsCRP
Lee et al. the European Male Aging Study, (83)	3369 community-dwelling men	Aged 40–79 years (range)	Independent association of 25(OH)D <50 nmol/L with compensated (relative risk ratio (RRR) = 1.52, 1.03, 2.25) P = 0.03) and secondary hypogonadism (RRR = 1.16, 1.00–1.34, P = 0.05) compared to men with sufficient vitamin D status (>75 nmol/L)	No independent association with TT or FT		Adjusted for age, centre, BMI, smoking, alcohol consumption, physical activity, physical function, heart conditions, hypertension, DM, and depression
Nimptsch et al. (82)	1362 male participants of the Health Professionals Follow-up Study	65.8 ± 7.4 years	Comparing participants in the highest vs lowest quintile of 25(OH) vitamin D had a significantly decreased relative risk of hypogonadism of 0.50 (95% CI 0.31–0.93; P-trend = 0.01)	Independent association with TT and FT		Age (at blood collection), batch, time of blood collection, season, BMI at blood collection, smoking status, geographical region, physical activity
Hammoud et al. (93)	170 healthy men	29.0 ± 8.5 years	na	No independent association with TT or FT		Age, BMI, season, alcohol intake and smoking

Data are given as mean ± s.d. or median (IQR) unless otherwise stated.

25(OH)D, 25 hydroxyvitamin D; BMI, body mass index; DM, type 2 diabetes mellitus; eGFR, estimated glomerular filtration rate; FAI, free androgen index; FPG, fasting plasma glucose; FT, free testosterone; HDL, high density lipoprotein, hsCRP, high sensitive C-reactive protein; OR, odds ratio; SHBG, sex hormone binding globulin; TT, total testosterone; TC, total cholesterol; WC, waist circumference.