Hormonal regulation and reproductive improvement with adjunctive Zishen Yutai Pill in polycystic ovary syndrome: a systematic review with meta-analysis

Objective: To systematically evaluate the therapeutic efficacy and safety of Zishen Yutai Pill (ZYP) as an adjunctive treatment for women with polycystic ovary syndrome (PCOS) through systematic review and meta-analysis of randomized controlled trials. Materials and methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Seven major databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, and Wan Fang Database, were searched from inception through March 1, 2025. Randomized controlled trials comparing ZYP combined with Western medicines vs. Western medicines alone were included. Results: Eighteen randomized controlled trials encompassing 1,751 participants with PCOS met the inclusion criteria. Meta-analysis demonstrated that ZYP, when combined with Western medicines, produced statistically significant improvements compared with Western medicines alone. Combination therapy significantly enhanced pregnancy rates [relative risk [RR] = 1.52, 95% confidence interval [CI] = 1.35–1.76, P < 0.00001] and ovulation rates (RR = 1.20, 95% CI = 1.12–1.30, P < 0.00001). ZYP combination therapy significantly increased endometrial thickness [mean difference (MD) = 1.34, 95% CI = 1.03–1.65, P < 0.00001]. Hormonal analysis revealed significant reductions in testosterone levels [standard mean difference (SMD) = −1.90, 95% CI = −2.94 to −0.86, P = 0.0003] and luteinizing hormone levels (SMD = −0.77, 95% CI = −1.21 to −0.33, P = 0.0006). Combination therapy significantly reduced miscarriage rates (RR = 0.54, 95% CI = 0.40–0.72, P < 0.0001). Conclusion: This systematic review and meta-analysis suggests that adjunctive ZYP combined with Western medicines may improve reproductive outcomes in women with PCOS. However, the certainty of evidence for most outcomes was low or very low, and many trials had high or unclear risk of bias. Accordingly, these findings should be interpreted as hypothesis-supporting rather than practice-changing, and well-designed, independently funded multicenter randomized controlled trials with standardized outcome definitions are required before routine clinical use or guideline integration can be considered. Systematic Review Registration: PROSPERO CRD42024522660.