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Relationship of Vitamin D status with testosterone levels: a systematic review and meta-analysis

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Abstract

Purpose

Despite a biological plausibility of a direct link between low vitamin D and androgen deficiency, the association remains inconclusive in epidemiological studies. Therefore, this systematic review and meta-analysis of case-control studies aim to assess whether and in what populations such an association can be demonstrated.

Methods

A systematic search was performed in PubMed, EMBASE, Cochrane Library, Web of science, Science Direct, and CINAHL. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) in total testosterone (TT) levels between men with 25-hydroxyvitamin D (25(OH)D) <20 and ≥20 ng/mL were combined using random-effects models. Funnel plot and trim-and-fill analysis were used to assess publication bias. Heterogeneity source was explored by a sub-group analysis according to health-related characteristics of the study populations.

Results

Eighteen included studies collectively gave information on 9892 men with vitamin D deficiency and 10,675 controls. The pooled SMD revealed a slight, albeit just significant, positive association between 25(OH)D and TT (pooled SMD: −0.23, 95% CI: −0.45 to −0.01; P = 0.04) with a large between-study heterogeneity (I2 = 98%, Pfor heterogeneity < 0.00001). At the sub-group analysis, a significant positive association, along with noticeable decrease in heterogeneity, could only be demonstrated in studies of patients with frailty states (pooled SMD: −0.19; 95% CI: −0.27, −0.10,  P < 0.0001; I2 = 51%, Pfor heterogeneity = 0.06). A sensitivity analysis revealed a high stability of the result and the trim-and-fill adjustment for publication bias did not affect pooled estimate.

Conclusions

Both hypovitaminosis D and androgen deficiency should be regarded as markers of a poor health status, sharing common underlying aetiologies and risk factors.

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Funding

This work was supported by the Ministero dell’Istruzione, Università e Ricerca (MIUR), PRIN 2017.

Author contributions

S.D.A. systematic literature search, evaluation of selected studies for eligibility, quality assessment of the studies; A.M. systematic literature search, evaluation of selected studies for eligibility, quality assessment of the studies; F.C. evaluation of selected studies for eligibility, data extraction; C.C. data extraction, data analysis; E.M. systematic literature search; M.T. data extraction; A.P. data extraction; S.F. quality assessment of the studies, revising the article for intellectual content; F.F. revising the article for intellectual content; A.B. conception and design, data analysis, drafting the article.

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  1. These authors contributed equally: S. D’Andrea, A. Martorella

Authors and Affiliations

  1. Andrology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    S. D’Andrea, A. Martorella, F. Coccia, C. Castellini, E. Minaldi, M. Totaro, A. Parisi, F. Francavilla, S. Francavilla & A. Barbonetti

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D’Andrea, S., Martorella, A., Coccia, F. et al. Relationship of Vitamin D status with testosterone levels: a systematic review and meta-analysis. Endocrine 72, 49–61 (2021). https://doi.org/10.1007/s12020-020-02482-3

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