The Effect of Vitamin D Supplementation on the Androgenic Profile in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

It is suggested that vitamin D status is associated with androgenic profile in women with polycystic ovarian syndrome (PCOS). Although several clinical trials are known in this regard, the results were inconsistent. Therefore, this study was aimed to conduct a systematic review and meta-analysis of published clinical trials to elucidate the possible effect of vitamin D supplementation on the androgen levels in adult females with PCOS. PubMed, SCOPUS, and Google Scholar were searched to identify related articles published up to January 2017. Mean ± standard deviation (SD) of changes in serum total testosterone, sex hormone binding globulin (SHBG), and free testosterone were extracted to calculate Hedges' g to be used as effect size for meta-analysis. DerSimonian and Liard random effects model was incorporated to summarize the effects. Six clinical trials with 183 participants aged 18-41 years with follow-up period between 3-24 weeks were included. Our analysis revealed that vitamin D supplementation significantly reduces total testosterone (Hedges' g=-0.32, 95% CI: -0.55 to -0.10; p=0.005); this effect remained significant in single group trials after subgroup analysis. Vitamin D supplementation did not affect serum free testosterone (Hedges' g=-0.21, 95% CI: -0.44 to 0.079; p=0.08) or SHBG levels (Hedges' g=0, 95% CI, 0.22-0.22; p=0.98). The present systematic review and meta-analysis revealed that vitamin D supplementation might significantly affect serum total testosterone while it is not effective in improving other markers of androgenic profile. Future double-blind, placebo-controlled clinical trials are highly recommended.

Vitamin D is associated with bioavailability of androgens in eumenorrheic women with prior pregnancy loss

“…With regard to SHBG, the positive relationship with vitamin D concentration that we observed is consistent with results observed previously among both women with PCOS 22,23 and postmenopausal women. 14,24 However, our positive finding conflicts with results from the aforementioned meta-analysis; 21 our study’s larger cohort (and therefore greater power) may also explain why we found a relationship between vitamin D and SHBG while the meta-analysis did not.…”

“…13 A systematic review and meta-analysis of vitamin D supplementation among a total of 183 women with PCOS found that supplementation with vitamin D significantly reduces TT. 21 Our null results may differ from these studies because our population was, respectively, eumenorrheic, premenopausal, and not being supplemented with vitamin D.…”

Pharmacological and surgical treatment of nonreproductive outcomes in polycystic ovary syndrome: An overview of systematic reviews

“…Seven reviews evaluated vitamin D (Appendix S3, found in the Supporting Information) either as monotherapy vs placebo or metformin, as combination therapy with metformin vs metformin or comparing the effects of before and after vitamin D. Only one review had a high rating while the majority of the reviews (n = 5) were of moderate quality, and one review was of low quality. A total of 75 trials and 5701 participants women with PCOS were involved.…”

Nutritional support and dietary interventions for women with polycystic ovary syndrome

“…137 Some studies have demonstrated lower serum vitamin D concentrations in women with PCOS compared to women without PCOS, whereas a case-control study, with 85 women with PCOS and 115 healthy controls, found higher serum vitamin D concentrations in women with PCOS compared to controls. [138][139][140] Low serum vitamin D levels or insufficiency has been positively associated with PCOS-related symptoms, such as central obesity, IR, infertility and hirsutism, whereas serum 25-hydroxy vitamin D (25OHD) seems to be an independent predictor of measures of reproductive success following ovulation induction.…”

“…[141][142][143][144] A recent systematic review and meta-analysis showed that vitamin D supplementation significantly decreased total testosterone, without any effects on serum SHBG and free testosterone. 137 Another systematic review discussed the association between vitamin D status and metabolic disturbances and suggested an inverse association between vitamin D status and IR in women with PCOS. 145 One study showed that 1000 mg/day calcium plus 50,000 IU/week vitamin D supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on serum insulin levels, IR, TG and very-LDL (VLDL) levels, without affecting fasting glucose and other lipid profiles.…”