Table 4.

Summary of clinical intervention studies investigating the effects of vitamin D treatment on androgen levels in men.

Author/Study	Study design	Subjects	Age	25(OH)D levels (baseline)	TT levels (baseline)	Primary outcome	Study duration	Study medication	TT levels (study end)	25(OH)D levels (study end) vitamin D group
Pilz et al. (20)	RCT	54 obese men (vitamin D n = 31, placebo n = 23)	48.1 ± 11.1 years	<50 nmol/L; 31.1 ± 21.9 nmol/L	11.4 nmol/L	Weight loss	1 year	3332 IU/day vs placebo	Significant increase in TT, bioactive testosterone, and FT levels	86.4 ± 68.8 nmol/L
Jorde et al. the Tromsø study (84)	RCT (pooled data from 3 independent RCTs)	Study 1 (vitamin D and obesity): 129 men with BMI 28–47 kg/m², study 2 (insulin sensitivity): 53 men, study 3 (depression study): 100 men	Study 1: 48.9 ± 10.6 years; study 2: 51.2 ± 10.0 years; study 3: 53.0 ± 11.1 years	Study 1: 52.6 ± 17.8 nmol/L, study 2: 39.9 ± 14.0 nmol/L (25(OH)D <50 nmol/L), study 3: 45.8 ± 15.0 nmol/L (25(OH)D ≤ 55 nmol/L)	Study 1: 13.5 ± 4.2 nmol/L, study 2: 16.9 ± 6.4 nmol/L, study 3: 14.2 ± 4.9 nmol/L	Study 1: weight loss, study 2: change in insulin sensitivity as evaluated with a hyperglycemic glucose clamp, study 3: change in depression scores	Study 1: 1 year, study 2: 6 months, study 3: 6 months	Study 1: 40 000 IU/week vitamin D (~5714 IU/day), 20 000 IU/week vitamin D (~2857 IU/day), or placebo for 1 year (all subjects: 500 mg calcium/day); study 2 & 3: 40 000 IU vitamin D/week (~5714 IU/day) vs placebo for 6 months	No significant effect	118.8 ± 52.2 nmol/L
Heijboer et al. (86)	RCT (pooled data from 3 independent RCTs)	92 male patients with heart failure (study 1), 49 male nursing home residents (study 2) and 42 male non-Western immigrants in the Netherlands (study 3)	Study 1: 63 (range 42–86) years, study 2: 82 (range 71–97) years, study 3: 53 (range 20–70) years	Study 1: 46.5 (38.5–62.5) nmol/L, study 2: 27.0 (23.0–31.5) nmol/L, study 3: (25OHD <50 nmol/L), 27.5 (18–33) nmol/L	Study 1: 15 (11–19) nmol/L, study 2: 11 (8–15.8) nmol/L, study 3: 13 (11–17) nmol/L	Vitamin D effects on the renin-angiotensin-aldosterone system (study 1), effects of different vitamin D doses (study 2), and vitamin D effects on insulin sensitivity (study 3)	Study 1: 6 weeks, study 2: 16 weeks, study 3: 16 weeks	Study 1: 2000 IU/day, study 2: 600 IU per day, 4200 IU per week or 18 000 IU/month, study 3: 1200/d vs placebo (+500 mg calcium carbonat: all subjects)	No significant effect	Study 1: 73.5 nmol/L, study 2: 57 nmol/L, study 3: 49 nmol/L
Ferlin et al. (99)	Uncontrolled intervention study	20 men with Klinefelter syndrome (substudy of a cross-sectional study of 127 Klinefelter men and 60 healthy controls); 12 men treated with testosterone + calcifediol (group 1), 8 men treated with calcifediol (group 2)	31.5 ± 8.5 years (all 127 men with Klinefelter syndrome)	Baseline 25(OH)D <50 nmol/L; 31.3 ± 8.9 nmol/L (group 1: testosterone+calcifediol); 23.2 ± 18.9 nmol/L (group 2: calficediol)	10.5 ± 4.9 nmol/L (all 127 men with Klinefelter syndrome)	Maintain 25(OH)D levels above 50 nmol/L	2 years	Calcifediol treatment with Didrogyl, Calcifediol starting dose of 4000 IU/week, adjusting the dosage to maintain 25(OH)D levels >50 nmol/L, by determining the levels every 6 months	No significant effect	Group 1: 94.3 ± 12.9 nmol/L, group 2: 102.5 ± 28.7 nmol/L
Foresta et al. (100)	Uncontrolled intervention study	66 patients with hypogonadism (classic hypogonadism (TT<12 nmol/L, LH ≥ 8 IU/L) (n = 26) and subclinical hypogonadism (TT ≥ 12 nmol/L, LH ≥ 8 IU/L) (n = 40))	34.5 ± 6.8 years	Baseline 25(OH)D <50 nmol/L; cholecalciferol group : 33.8 ± 10.5 nmol/L ; calcidiol group: 33.4 ± 9.5 nmol/L	Not given	Effects of cholecalciferol vs calcidiol on 25(OH)D levels	3 months	5000 IU cholecalciferol per week (~714 IU/d; n = 20) or 4000 IU calcidiol per week (~571 IU/d; n = 36)	No significant effect	Cholecalficerol: 42.6 ± 11.6 nmol/L; calcidiol: 81.4 ± 25.0 nmol/L
Canguven et al. (101)	Uncontrolled intervention study	102 middle-aged men	53.2 ± 10.4 years	Baseline 25(OH)D <75 nmol/L; 37.9 ± 11.6 nmol/L	12.46 ±  3.30 nmol/L	Not specifically stated (vitamin D effects on biochemical and hormonal parameters as well as on erectile dysfunction)	1 year	Men received an initial vitamin D dose (Ergocalciferol; oral solution 600 000 IU/1.5 ml), and followed a vitamin D treatment regime thereafte	Significant increase in TT levels (12.46  ±  3.30 to 15.99 ±  1.84 nmol/L	121.4 ± 29.1 nmol/L
Lerchbaum et al. Graz Vitamin D&TT-RCT (102)	RCT	100 healthy men with TT levels ≥10.4 nmol/L (vitamin D n = 50, placebo n = 50)	37 (27–50) years	<75 nmol/L; 52 (42–66) nmol/L	18.0 (15.8–21.5) nmol/L	TT measured using mass spectrometry	12 weeks	20,000 IU/week (~2,857 IU/day) vs placebo	No significant effect	107 (89–119) nmol/L

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

25(OH)D, 25 hydroxyvitamin D; BMI, body mass index; IU, international unit; LH, luteinizing hormone; RCT, randomized controlled trial; TT, total testosterone.