In adults, does vitamin D supplementation raise or lower sex hormone‑binding globulin (SHBG)?

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Does Vitamin D Raise or Lower SHBG?

Vitamin D supplementation does not significantly affect SHBG levels in adults. The highest-quality evidence from systematic reviews and meta-analyses consistently demonstrates no meaningful change in sex hormone-binding globulin concentrations following vitamin D supplementation.

Evidence from Systematic Reviews and Meta-Analyses

Men

  • A 2019 systematic review and meta-analysis of 8 randomized controlled trials (10 effect sizes) in men found that vitamin D supplementation had no significant effect on SHBG (MD = 1.56,95% CI: -0.85,3.97, p = 0.204), with doses ranging from 600 to 4,000 IU daily (or 60,000 IU weekly) over 6 weeks to 36 months 1
  • Subgroup analyses by duration, dosing frequency (daily vs. weekly), and baseline vitamin D status all confirmed no significant effect on SHBG 1

Women with PCOS

  • A 2017 systematic review and meta-analysis of 6 clinical trials (183 participants) in women with polycystic ovary syndrome found that vitamin D supplementation did not affect SHBG levels (Hedges' g = 0,95% CI: -0.22 to 0.22; p = 0.98) over 3-24 weeks of follow-up 2

Infertile Men

  • A 2024 double-blind randomized controlled trial of 307 infertile men receiving 300,000 IU cholecalciferol bolus followed by 1,400 IU daily plus 500 mg calcium for 150 days found no differences in SHBG between vitamin D and placebo groups after intervention 3

Cross-Sectional Observational Data

While intervention trials show no effect, cross-sectional studies reveal a positive association between vitamin D status and SHBG:

  • In NHANES III (n = 1,315 men) and NHANES 2001-2004 (n = 318 men), higher serum 25(OH)D was associated with higher SHBG concentrations (Q1 = 33.8 nmol/L vs. Q5 = 38.4 nmol/L, p-trend = 0.0005) after adjusting for age, race/ethnicity, body fat percentage, and smoking 4
  • In the MrOS study of 1,468 older men (mean age 74 years), men with vitamin D deficiency (<20 ng/mL) combined with high SHBG (>59 nM) had worse skeletal outcomes than those with either abnormality alone 5

Clinical Interpretation

The discrepancy between observational associations and intervention trials indicates that vitamin D supplementation does not causally alter SHBG levels. The cross-sectional associations likely reflect confounding by factors such as:

  • Body composition: Obesity lowers both vitamin D (through sequestration in adipose tissue) and SHBG (through insulin resistance) 4
  • Physical activity: Higher activity increases both vitamin D (through sun exposure) and SHBG 5
  • Age and metabolic health: These influence both vitamin D metabolism and SHBG production 5

Important Clinical Caveats

  • The lack of effect on SHBG does not mean vitamin D supplementation is without benefit—it remains essential for bone health, particularly in deficiency states 5
  • In older men, the combination of low vitamin D (<20 ng/mL) with low bioavailable estradiol and/or high SHBG was associated with 1.6-fold higher fracture risk (95% CI: 1.1-2.5) compared to men with normal levels of both 5
  • Vitamin D should be repleted for skeletal health when deficient, but clinicians should not expect changes in SHBG or use SHBG as a marker of vitamin D repletion 1, 2, 3

References

5
Research

The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: the osteoporotic fractures in men (MrOS) study.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2012

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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