Prebiotic supplementation improves metabolic dysfunction and hyperandrogenism in polyendocrine metabolic ovarian syndrome: A systematic review with meta-analysis and trial sequential analysis

Background and aim: Previous studies have pointed out that intestinal flora imbalance is the key cause of polyendocrine metabolic ovarian syndrome (PMOS, previously named polycystic ovary syndrome (PCOS). However, the clinical studies of results on the effects of prebiotics, probiotics, and synbiotics in improving the metabolism and hyperandrogenism of PMOS patients are highly controversial. This study analyzed the appropriate randomized controlled trials (RCTs) to compare the effects of three interventions - prebiotics, probiotics, and synbiotics - on hyperandrogenemia and metabolic disorders in PMOS women. Methods: We conducted the searches up to 30 March 2025 in the five included databases. The inclusion criteria for studies considered the impact of the three interventions on PMOS women's metabolic and hormonal parameters. The relevant data was rigorously extracted. Results: The study included totally 14 RCTs, and intervention durations ranged from 8 weeks to 6 months. Prebiotics, probiotics or synbiotics significantly reduced total testosterone (TT), fasting insulin, total cholesterol (TC), and triglyceride (TG), improved high-density lipoprotein cholesterol (HDL-C). There were no significant differences showed in the results on body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose, HOMA-IR, sex hormone-binding globulin (SHBG), modified Ferriman-Gallwey (FG) score and free androgen index (FAI) between the intervention and control groups. Sensitivity analyses confirmed the results although moderate to high heterogeneity was observed. The interventions differentially modulated TG ( P = 0.03), TT, SHBG, FG scores and BMI ( P < 0.001). Prebiotics achieved the most significant improvement of TT, SHBG, FG scores, TG and BMI compared with synbiotics and probiotics. The trial sequential analysis shows that the results of all indicators, except SHBG, are conclusive. Conclusions: Overall efficacy of probiotics and synbiotics may be less pronounced than previously reported, isolated prebiotic supplementation demonstrates a distinct and robust potential in ameliorating hyperandrogenism and dyslipidemia in PMOS. Rigorously designed RCTs are warranted to validate these observations. Registration: https://www.crd.york.ac.uk/PROSPERO/ , indentifier CRD420251039514.