Heliyon · 5 authors, 5 centres
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This meta-analysis of 13 RCTs with 840 PCOS patients found that vitamin D supplementation significantly increased serum vitamin D levels and endometrial thickness, while reducing hs-CRP, parathyroid hormone, total cholesterol, and total testosterone. No significant effects were observed on SHBG levels or hirsutism scores (mF-G). These findings suggest vitamin D may improve endocrine and metabolic parameters in PCOS, though higher-quality studies with larger samples are needed.
**Background:** Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, characterized by hyperandrogenemia, inflammation, and metabolic disturbances. Vitamin D deficiency is highly prevalent in PCOS patients (up to 85.16% have serum 25-hydroxyvitamin D <50 ng/mL). Previous studies have suggested links between low vitamin D and infertility, ovulation disorders, and insulin resistance, but results on supplementation benefits have been inconsistent. This meta-analysis aimed to systematically evaluate the effects of vitamin D supplementation on PCOS-related outcomes.
**Methods:** The authors searched eight databases (PubMed, Medline, EMbase, Cochrane Library, Web of Science, WanFang, CNKI, Weipu) from inception to August 31, 2022. Two reviewers independently screened literature, extracted data, and assessed risk of bias using the Cochrane Risk of Bias Tool. Only RCTs comparing vitamin D supplementation to placebo in clinically diagnosed PCOS patients were included. Meta-analysis was performed using RevMan 5.3 with mean difference (MD) and 95% confidence intervals (CI). Heterogeneity was assessed using I² and Chi-square tests; random-effects models were used when significant heterogeneity was present.
**Key Results:** Thirteen RCTs involving 840 PCOS patients (433 vitamin D, 407 placebo) were included. Studies were from Iran, United States, China, and Egypt, with intervention durations of 8–24 weeks. Meta-analysis showed: - Serum vitamin D level: significantly increased in the vitamin D group [MD = 17.81, 95%CI (10.65, 24.97), P < 0.001; I² = 96%, random-effects] - hs-CRP: significantly reduced [MD = −0.54, 95%CI (−1.00, −0.08), P = 0.02; I² = 54%, random-effects] - Parathyroid hormone: significantly reduced [MD = −14.76, 95%CI (−28.32, −1.19), P = 0.03; I² = 78%, random-effects] - Total cholesterol: significantly reduced [MD = −12.00, 95%CI (−18.36, −5.56), P < 0.001; I² = 0%, fixed-effects] - Total testosterone: significantly reduced [MD = −0.17, 95%CI (−0.29, −0.05), P = 0.004; I² = 71%, random-effects] - Endometrial thickness: significantly increased [MD = 1.78, 95%CI (0.49, 3.06), P = 0.007; I² = 84%, random-effects] - SHBG: no significant difference [MD = 1.33, 95%CI (−2.70, 5.36), P = 0.52; I² = 71%, random-effects] - mF-G score: no significant difference [MD = 0.04, 95%CI (−0.79, 0.86), P = 0.93; I² = 0%, fixed-effects] Sensitivity analysis by excluding individual studies did not significantly change results. Egger's tests showed no publication bias for any outcome (all P > 0.05).
**Clinical Implications:** Vitamin D supplementation appears beneficial for improving several endocrine and metabolic parameters in PCOS, including reducing inflammation (hs-CRP), hyperandrogenism (total testosterone), and cardiovascular risk markers (total cholesterol, PTH), while increasing endometrial thickness which may support fertility. However, the lack of effect on SHBG and hirsutism scores suggests limited impact on clinical hyperandrogenism manifestations. The high heterogeneity in several analyses, small sample sizes for some outcomes (e.g., endometrial thickness from only 2 RCTs), and variability in vitamin D dosing regimens limit the strength of recommendations. The authors appropriately call for larger, higher-quality RCTs with standardized protocols to confirm these findings and establish optimal dosing strategies.