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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.

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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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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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