Jul 2026· Reviews in Endocrine & Metabolic Disorders· Vol 27, pp. 893 - 932· 0 citations· 227 references
Medicine
TL;DR
FF metabolomics reveals a PCOS signature characterized by lipid, amino acid, and energy metabolism dysregulation, potentially contributing to follicular dysfunction, and should consider PCOS phenotypic heterogeneity.
Abstract
Polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder, affects women of reproductive age. Follicular fluid (FF) reflects the biochemical microenvironment surrounding the oocyte, providing valuable insight into molecular mechanisms associated with PCOS. Metabolomics enables comprehensive profiling of small-molecule metabolites allowing the identification of disease-specific metabolic signatures, dysregulated pathways, and potential diagnostic/therapeutic targets. This systematic review summarizes available evidence on the FF metabolomic profile of women with PCOS compared to normo-ovulatory controls, aiming to identify PCOS-specific metabolic signatures and dysregulated metabolic pathways. PubMed, Web of Science, and Scopus were searched up to September 2025. Eligible studies were conducted in humans, included at least one group of women with PCOS and a control group with normal ovarian function and normal-weight. Thirty-one studies were included. FF from women with PCOS exhibited consistent metabolomic signatures across analytical platforms and cohorts. The most robust differences involved extensive lipidome alterations, along with amino acid and energy metabolism disturbances. Steroidogenic profiles showed higher testosterone and androsterone sulfate levels, while progesterone, 17-hydroxyprogesterone, and pregnenolone were decreased, suggesting impaired steroidogenesis. Fatty acid alterations included increased saturated, monounsaturated, and polyunsaturated fatty acids. Phosphatidylethanolamine species, triglycerides, and prostaglandin E2 were elevated, whereas phosphatidylcholine and lysophosphatidic acid species were reduced. Among water-soluble metabolites, isoleucine, succinate, malate, glycerol, hypoxanthine, and uracil were increased, while threonine, glutamine, arginine, citrulline, and 4PY were decreased. FF metabolomics reveals a PCOS signature characterized by lipid, amino acid, and energy metabolism dysregulation, potentially contributing to follicular dysfunction. Future studies should consider PCOS phenotypic heterogeneity.
It is suggested that OEM is associated with concurrent immune-related and metabolic alterations detectable in the circulation and provides limited independent support for a platelet-associated circulating signal, with PPBP showing the most consistent validation.
Na Chen, Yubing Hu, Tianxia Xiao et al.· Frontiers in Medicine· 0 citations
Pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications need validation in larger cohorts for diagnostic or therapeutic applications.
Polycystic Ovary Syndrome (PCOS) is a complex reproductive disorder characterized by irregular menstrual cycles, polycystic ovaries, and hyperandrogenism.
Diagnosis is often complicated by phenotype variability and inconsistent biomarker use. This metaanalysis, conducted according to PRISMA 2020 guidelines and based on studies published between
2010 and May 2023, investigates the heterogeneity in key PCOS biomarkers, testosterone and
LH/FSH ratio, using a random-effects model.
Thirteen studies were included in the meta-analysis. Biomarker-specific
analyses were conducted using R to evaluate variations in testosterone and LH/FSH ratios. Sample
sizes consisted of 500 PCOS cases and 592 controls for testosterone, and 1184 PCOS cases and
1410 controls for the LH/FSH ratio. Heterogeneity and subgroup variability were assessed independently for each biomarker.
Marked heterogeneity was observed across studies, with I² values of 95% for testosterone
and 99% for the LH/FSH ratio. Contributing factors included variability in population demographics, diagnostic criteria, and assay methodologies. Traditional assays often fail to sensitively
detect testosterone in women, while visual scoring methods are vulnerable to observer bias
The observed heterogeneity underscores the limitations of conventional biomarkers in
diagnosing PCOS. A move toward standardised, sensitive, and phenotype-specific diagnostic tools
is crucial. Multi-steroid panels and integrative omics-based approaches can address variability and
enhance diagnostic accuracy.
Integrating novel biomarkers such as DAPK2, S100A9, Bacteroides vulgatus, and microRNA-6767-5p holds promise for improved diagnosis of PCOS subtypes. AGP may help identify
normoandrogenic presentations. Embracing immune-metabolic insights supports the development
of diverse, accessible, and validated diagnostics aligned with the goals of precision medicine and
improved women's reproductive health.
Ashitha Washington, Heera T Shenoy, Ravindra Kumar· Current Women s Health Revie...· 0 citations
Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), is a common endocrine and metabolic disorder in reproductive-age women, characterized by marked clinical and biological heterogeneity. Accumulating evidence suggests that gut microbiota dysbiosis is associated with metabolic disturbances, hormonal imbalance, and ovarian dysfunction in PMOS. However, the pathways linking gut microbiota alterations to PMOS pathogenesis remain incompletely understood, and most evidence remains associative. This review aims to summarize current evidence regarding interactions between gut microbiota and PMOS, clarify the roles of key microbiota-derived metabolites, and evaluate the potential and limitations of gut microbiota–targeted interventions. A major novelty is the proposal of an integrated gut–metabolism–endocrine–ovary axis incorporating phenotypic heterogeneity, methodological variability, and evidence grading across clinical and preclinical studies. A narrative review with a systematic literature search was conducted. PubMed, Web of Science, Embase, and CNKI were searched from inception to March 2026 using terms related to PMOS, gut microbiota, microbial metabolites, and microbiota-targeted interventions. Eligible studies included human observational or interventional studies, animal experiments exploring microbiota–PMOS mechanisms, and peer-reviewed full-text articles in English or Chinese. Case reports, letters, conference abstracts, non-English publications, and irrelevant studies were excluded. Duplicate records were removed. Two authors independently screened records and resolved disagreements by consensus. No meta-analysis was performed, and clinical registration was not applicable. Gut microbiota dysbiosis may contribute to PMOS through chronic low-grade inflammation, insulin resistance, and hyperandrogenism. Microbiota-derived metabolites link intestinal dysbiosis with metabolic and endocrine dysfunction. Bile acids and short-chain fatty acids exert regulatory effects, whereas amino acid disorders and LPS-mediated endotoxemia amplify metabolic and inflammatory abnormalities. Considerable heterogeneity exists across studies regarding obesity, insulin resistance, hyperandrogenism, diet, ethnicity, region, and methodology. Microbiota-targeted interventions show potential, although evidence quality varies and most findings remain associative. Gut microbiota dysbiosis is a critical regulatory node within the integrated gut–metabolism–endocrine–ovary axis in PMOS. This review highlights phenotypic stratification, evidence hierarchy, and clinical translation potential. Although microbiota-targeted strategies may serve as adjunctive therapies, their causal roles and long-term efficacy require confirmation in well-designed longitudinal and randomized controlled trials.
Shengyu Jin, Mengle Zhu, Yiyang Lu et al.· Experimental biology and med...· 0 citations