Screening traditional Chinese medicine monomers for premature ovarian insufficiency: from network meta-analysis to the effects of a promising candidate on oxidative stress biomarkers.

Background: Therapeutic options for premature ovarian insufficiency (POI) are limited, and the comparative efficacy of traditional Chinese medicine (TCM) monomers remains unclear. This study aimed to systematically evaluate and rank the efficacy of various TCM monomers in animal models of POI and to explored the potential role of oxidative stress modulation by a promising candidate. Methods: Eight electronic databases (PubMed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Wanfang Database, and SinoMed) were searched from inception to 3 April 2026, for randomized controlled animal trials evaluating single TCM monomers in POI models. The SYRCLE tool and CINeMA were employed to assess the risk of bias and the certainty of evidence, respectively. A frequentist network meta-analysis was conducted to compare primary and secondary ovarian function outcomes, with relative efficacy ranked by the surface under the cumulative ranking curve (SUCRA) values. Pairwise meta-analyses were then performed to evaluate the effects of a candidate monomer on oxidative stress biomarkers. Three-dimensional scatter plots were used to visualize potential trends in primary outcomes regarding the relationships among dose, treatment duration, and therapeutic efficacy. Results: Thirty-two studies involving 676 animals and six TCM monomers were included. Compared with controls, all monomers significantly reduced serum follicle-stimulating hormone and increased estradiol levels. Furthermore, quercetin and icariin promoted follicular development and suppressed atresia., although the certainty of evidence was very low. Based on global mean SUCRA values, quercetin ranked first in the main analysis and emerged as a promising candidate overall. Pairwise analyses showed that quercetin increased serum superoxide dismutase and catalase while decreasing malondialdehyde levels. Exploratory three-dimensional visualization suggested a potential enhanced therapeutic trend for quercetin within the dosage range of 25-100 mg/kg over 10-30 days. Conclusion: Several TCM monomers improved ovarian function in POI models. Quercetin was considered a promising candidate, with its potential effect likely associated with the modulation of oxidative stress biomarkers. Given the substantial heterogeneity and very low evidence certainty, these findings should be interpreted with caution. Further rigorous, standardized preclinical dose-response studies and well-designed clinical trials are warranted to facilitate the clinical translation of these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261359490, identifier CRD420261359490.