Ying-Cheng Chiang, Hsien-Neng Huang, Kuan-Ting Kuo, Wuh-Liang Hwu, Po-Han Lin
{"title":"Whole exome sequencing-based homologous recombination deficiency test for epithelial ovarian cancer.","authors":"Ying-Cheng Chiang, Hsien-Neng Huang, Kuan-Ting Kuo, Wuh-Liang Hwu, Po-Han Lin","doi":"10.1186/s13048-024-01565-3","DOIUrl":"10.1186/s13048-024-01565-3","url":null,"abstract":"<p><strong>Background: </strong>The homologous recombination deficiency (HRD) test is an important tool for identifying patients with epithelial ovarian cancer (EOC) benefit from the treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). Using whole exome sequencing (WES)-based platform can provide information of gene mutations and HRD score; however, the clinical value of WES-based HRD test was less validated in EOC.</p><p><strong>Methods: </strong>We enrolled 40 patients with EOC in the training cohort and 23 in the validation cohort. The WES-based HRD score was calculated using the scarHRD software. We first evaluated the concordance of the HRD status defined by the Myriad MyChoice CDx and then assessed the value of HRD on clinical prognosis in patients with EOC.</p><p><strong>Results: </strong>The HRD score defined by the WES-based test was positively correlated with that of the Myriad MyChoice<sup>®</sup> CDx test (r = 0.82, p < 0.01) in the training cohort. In compared to HRD status of Myriad test, the sensitivity, specificity, positive predictive value, and negative predictive value of the WES-based HRD test were 93.5% (29/31), 77.8% (7/9), 93.5% (29/31), and 77.8% (7/9), respectively. Patients with positive HRD status defined by WES-based scarHRD test and Myriad MyChoice<sup>®</sup> CDx test were both highly associated with platinum sensitive response (both Fisher's exact test, p = 0.002) as well as the superior progression-free survival (both log-rank p = 0.002). The multi-variate Cox regression model incorporated with optimal debulking surgery showed that the recurrence risk was decreased in the patients with positive HRD status, either defined by Myriad MyChoice<sup>®</sup> CDx test (Hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.14-0.79, p = 0.013) or WES-based test Myriad MyChoice<sup>®</sup> CDx test (HR 0.34, 95% CI 0.14-0.80, p = 0.014). Nine patients had mutations in the genes involved in HR DNA repair, and all of them were positive for HRD. In the validation group, 23 patients were defined as positive HRD by WES-based testing. Six positive HRD patients and 5 negative HRD patients received maintenance PARPi. The median responsive interval of PARPi was 17 months in positive HRD patients and 3 months in negative HRD patients.</p><p><strong>Conclusion: </strong>The WES-based test is a potential option for determining the HRD status in EOC patients, and desires for further validation in large-scale cohorts.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"19"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danni Chen, Yan Tan, Tingting Chen, Qin Wang, Yan Yan, Xiaoya Zhao, Zhongxiao Zhang, Jin Qiu, Jian Zhang
{"title":"Sempervirine inhibits proliferation, invasion and metastasis of ovarian cancer cells and induces ultrastructural changes in vivo.","authors":"Danni Chen, Yan Tan, Tingting Chen, Qin Wang, Yan Yan, Xiaoya Zhao, Zhongxiao Zhang, Jin Qiu, Jian Zhang","doi":"10.1186/s13048-024-01580-4","DOIUrl":"10.1186/s13048-024-01580-4","url":null,"abstract":"<p><p>Ovarian cancer is one of the deadliest gynecological malignancies due to its late diagnosis and easy recurrence. Therefore, it is urgent to develop novel therapeutics for ovarian cancer treatment. In this study, we evaluated the anti-ovarian cancer effects of sempervirine in vitro and in vivo. CCK8 assays showed that sempervirine dose-dependently inhibited the proliferation of SKOV3 ovarian cancer cells. Transwell assays demonstrated that sempervirine significantly suppressed the invasion and metastasis of SKOV3 cells. Furthermore, in an orthotopic ovarian cancer mouse model, sempervirine dramatically inhibited tumor growth and induced pathological changes in tumor tissues, including poor development of tumor mucosa, collagen deposition, endoplasmic reticulum damage, mitochondrial swelling and vacuolar degeneration, which were similar to the positive control 5-Fu. Mechanistic studies revealed that sempervirine decreased the expression of proteins related to apelin signaling pathway. In conclusion, our results demonstrate the potent anti-ovarian cancer effects of sempervirine both in vitro and in vivo. Sempervirine may repress ovarian cancer by down-regulating apelin signaling pathway. Our study suggests that sempervirine is a promising therapeutic agent against ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"17"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the mechanism of Schisandra rubriflora in the treatment of polycystic ovary syndrome based on network pharmacology and molecular docking.","authors":"Zhengyan Dou, Qingxian Li, Jing Zhang, Xin Zhang","doi":"10.1186/s13048-025-01600-x","DOIUrl":"10.1186/s13048-025-01600-x","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproductive and metabolic abnormalities. The aim of this study was to elucidate the effects of Schisandra rubriflora (S. rubriflora) on PCOS and its related mechanisms using network pharmacology, molecular docking and in vitro experiments.</p><p><strong>Materials and methods: </strong>HERB database and SwissTargetPrediction database were used to obtain the active components and the targets of S. rubriflora. Differentially expressed genes (DEGs) associated with PCOS were obtained by analyzing GSE54248 dataset. A protein-protein interaction network was constructed, and topological analyses were performed to identify the hub targets and main bioactive components. The binding abilities between hub targets and key components were studied by molecular docking. Finally, in vitro PCOS models were constructed with KGN cells and rat ovarian granulosa cells, respectively, and the regulatory effects of schisandrin, a key bioactive component of S. rubriflora, on the cells were investigated by in vitro assays.</p><p><strong>Results: </strong>A total of 14 bioactive ingredients of S. rubriflora and 26 potential therapeutic targets of S. rubriflora in PCOS treatment were obtained. Bioinformatics analyses suggested that the mechanisms of S. rubriflora in treating PCOS were related to IL-17 signaling pathway and TNF signaling pathway. The binding affinities between key components of S. rubriflora (schisandrin, wyerone, and rugosal) and hub targets (PTGS2, MMP9, MCL1, and JUN) were high. Schisandrin could attenuate lipopolysaccharide-induced inflammation, oxidative stress, and apoptosis of KGN cells and rat ovarian granulosa cells, as well as inhibit hub target expression and TNF pathway activation.</p><p><strong>Conclusion: </strong>PTGS2, MMP9, MCL1 and JUN are potential targets for S. rubriflora to treat PCOS. Schisandrin, a main component of S. rubriflora, may be a candidate for the treatment of PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"16"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Feng Hao, Zhang Yan, Luo Shen, Wang Hui, Qiu Ling, Yang Xiaoyu, Jiang Hua
{"title":"Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers.","authors":"Feng Hao, Zhang Yan, Luo Shen, Wang Hui, Qiu Ling, Yang Xiaoyu, Jiang Hua","doi":"10.1186/s13048-025-01592-8","DOIUrl":"10.1186/s13048-025-01592-8","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators. Seurat and Harmony were employed for batch correction and dimensionality reduction. FLT3 expression was mapped with spatial data from 10 × Genomics.</p><p><strong>Results: </strong>FLT3, identified as a regulator through the PI3K/AKT pathway, showed positive correlations with T cells, NK cells, and B cells. FLT3-high regions exhibited increased immune infiltration, particularly in CC, enhancing survival outcomes.</p><p><strong>Conclusion: </strong>This study provides the first spatially resolved evidence of FLT3's immune-modulatory role in OC and CC, positioning it as a promising immunotherapeutic target. FLT3-targeted strategies may offer new options for patients resistant to conventional therapies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"14"},"PeriodicalIF":3.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiufen Zheng, Zikai Chen, Miao Liang, Liting Zhou, Miaoru Wang, Silin Zhang, Shuyun Zhang, Lei Ma, Wei Yi, Xiawen Liu
{"title":"Targeting UGT2B15 and NR1H4 interaction: a novel therapeutic strategy for polycystic ovary syndrome using naftopidil enantiomers.","authors":"Xiufen Zheng, Zikai Chen, Miao Liang, Liting Zhou, Miaoru Wang, Silin Zhang, Shuyun Zhang, Lei Ma, Wei Yi, Xiawen Liu","doi":"10.1186/s13048-025-01598-2","DOIUrl":"10.1186/s13048-025-01598-2","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects. This study investigates the role of UGT2B15, an essential enzyme for androgen metabolism, in PCOS pathogenesis and its potential as a therapeutic target.</p><p><strong>Methods: </strong>We used RNA sequencing to examine the effects of UGT2B15 knockdown in KGN cells. To modulate UGT2B15 expression, we employed siRNA and (R)/(S)-NAF (naftopidil), a chemical inducer of UGT2B15 identified in our previous studies on a prostate hyperplasia model. The effects of siRNA and (R)/(S)-NAF on dihydrotestosterone (DHT) levels, cell apoptosis, and the expression of apoptosis-related proteins in KGN cells were evaluated. In a PCOS mouse model, we assessed the effects of (R)-NAF and (S)-NAF on serum androgen levels, menstrual cycles, ovarian morphology, and UGT2Bs expression. Additionally, luciferase reporter and ChIP assays were utilized to study UGT2B15 regulation by NR1H4.</p><p><strong>Results: </strong>Elevated androgens were found to suppress UGT2B15 expression in ovarian granulosa cells, leading to DHT accumulation and apoptosis. (R)-NAF and (S)-NAF treatments reversed these effects, alleviating PCOS symptoms in mice such as hyperandrogenism, irregular menstrual cycles, and the presence of ovarian cysts. NR1H4 negatively regulated the transcription of UGT2B15 in KGN cells. (R)-NAF and (S)-NAF disrupted NR1H4 binding to the UGT2B15 promoter without affecting its protein levels, indicating direct interference with its regulation.</p><p><strong>Conclusions: </strong>UGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"13"},"PeriodicalIF":3.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Menopause mysteries: the exosome-inflammation connection.","authors":"Aarushi Sultania, Subhashini Brahadeeswaran, Aparna Eledath Kolasseri, Sivaraman Jayanthi, Ramasamy Tamizhselvi","doi":"10.1186/s13048-025-01591-9","DOIUrl":"10.1186/s13048-025-01591-9","url":null,"abstract":"<p><p>Extracellular vesicles, or exosomes, are produced by every type of cell and contain metabolites, proteins, lipids, and nucleic acids. Their role in health and disease is to influence different aspects of cell biology and to act as intermediaries between cells. Follicular fluid exosomes or extracellular vesicles (FF-EVs) secreted by ovarian granulosa cells are critical mediators of ovary growth and maturation. The movement and proteins of these exosomes are crucial in the regulation of cellular communication and the aging of cells, a process termed inflammaging. Menopause, a natural progression in the aging of females, is often accompanied by numerous negative symptoms and health issues. It can also act as a precursor to more severe health problems, including neurological, cardiovascular, and metabolic diseases, as well as gynecological cancers. Researchers have discovered pathways that reveal the diverse effects of exosome-driven cellular communication and oocyte development in the follicular fluid. It also explores the complex functions of FF exosomal proteins in the pathologies associated with menopause.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"12"},"PeriodicalIF":3.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuelan Li, Chujun Li, Jie Yang, Min Lin, Xianli Zhou, Ziyang Su, Yuting Zhang, Xinning Li, Xin Chen
{"title":"Associations of the levels of adipokines and cytokines in individual follicles with in vitro fertilization outcomes in women with different ovarian reserves.","authors":"Xuelan Li, Chujun Li, Jie Yang, Min Lin, Xianli Zhou, Ziyang Su, Yuting Zhang, Xinning Li, Xin Chen","doi":"10.1186/s13048-025-01594-6","DOIUrl":"10.1186/s13048-025-01594-6","url":null,"abstract":"<p><strong>Background: </strong>To a large extent, the ovarian reserve determines a woman's reproductive potential. The etiological and pathological mechanisms of diminished ovarian reserve (DOR) remain unclear, and no reliable treatment is currently available for DOR. Adipokines and cytokines in follicular fluid (FF) play pivotal roles in follicular development and maturation. The concentrations of adipokines and cytokines in FF from individual follicles of women with DOR undergoing in vitro fertilization (IVF) were studied. In particular, we investigated the associations between the levels of adipokines and cytokines in individual FFs from women with different ovarian reserves and between the follicular levels of adipokines and cytokines and IVF outcomes in individual follicles.</p><p><strong>Methods: </strong>A total of 115 women who underwent IVF were recruited. Patients diagnosed with DOR, defined as a basal antral follicle count < 5 or an anti-Mullerian hormone concentration < 1.1 ng/mL, were assigned to the DOR group, while patients with a normal ovarian reserve (NOR) were assigned to the NOR group. FF was sampled from the first follicle with a diameter of approximately 18-20 mm from each patient, and the IVF outcome of the oocyte from the corresponding follicle was tracked. The levels of 5 adipokines (including visfatin-1, monocyte chemoattractant protein-1 [MCP-1], resistin, leptin, and chemerin) and 3 cytokines (including interleukin [IL]-6, IL-12p70, and tumor necrosis factor [TNF]-α) in FF were determined by Luminex technology.</p><p><strong>Results: </strong>The follicular levels of TNF-α, IL-6, visafatin, MCP-1, IL-12, and chemerin were significantly lower in women with NOR than in those with DOR. The follicular level of IL-6 was negatively correlated with the quality of embryos according to the binary logistic regression analysis, while the follicular levels of adipokines and other cytokines did not correlate with IVF outcomes regardless of the woman's ovarian reserve.</p><p><strong>Conclusions: </strong>Our study demonstrated that the levels of adipokines and cytokines in individual follicles in women with DOR were different from those in women with NOR, indicating that increased intrafollicular inflammation might be related to DOR. Moreover, a high follicular level of IL-6 might negatively impact embryo quality.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"11"},"PeriodicalIF":3.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Study on the effects of Mogroside V in inhibiting NLRP3-mediated granulosa cell pyroptosis and insulin resistance to improve PCOS.","authors":"Wenqin Yang, Yujie Ma, Yafei Wu, Xiaocan Lei, Jing Zhang, Meixiang Li","doi":"10.1186/s13048-024-01563-5","DOIUrl":"10.1186/s13048-024-01563-5","url":null,"abstract":"<p><strong>Objective: </strong>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women, contributing to 75% of infertility cases due to ovulatory dysfunction. The condition poses significant health and psychological challenges, making the study of its pathogenesis and treatment a research priority. This study investigates the effects of Mogroside V (MV) on PCOS, focusing on its anti-inflammatory and anti-insulin resistance properties.</p><p><strong>Methods: </strong>Forty-five female Sprague-Dawley rats were divided into three groups: control, PCOS model, and MV treatment. The PCOS model was induced using a high-fat diet and letrozole. The MV treatment group was subsequently administered MV after the establishment of the PCOS model. The study monitored body mass, assessed estrous cycle changes, and measured serum hormone levels. Transcriptome sequencing and bioinformatics were used to identify differentially expressed genes related to inflammation and insulin resistance. Expression of pyroptosis and insulin resistance markers was analyzed using qRT-PCR, Western blot, and IHC. Additionally, an in vitro model assessed MV's impact on inflammation and insulin resistance.</p><p><strong>Results: </strong>The PCOS group exhibited elevated serum testosterone (T), luteinizing hormone (LH), insulin, and fasting glucose levels, along with increased insulin resistance (HOMA-IR) and decreased estradiol (E2), which were reversed by MV treatment. Transcriptome analysis identified significant gene expression changes between groups, particularly in pathways related to NLRP3 inflammation and insulin metabolism. MV treatment normalized the expression of ovarian pyroptosis factors (NLRP3, Caspase-1, GSDMD) and inflammatory cytokines (IL-1β, IL-18). In cellular models, MV increased E2 levels, reduced LDH release, and decreased the expression of insulin resistance and pyroptosis markers. Correlation analysis showed pyroptosis factors were positively correlated with HOMA-IR and IGF1, and negatively with IGF1R and E2 levels.</p><p><strong>Conclusion: </strong>MV improves PCOS by reducing pyroptosis and insulin resistance, enhancing insulin sensitivity, and promoting estrogen synthesis, thereby restoring granulosa cell function and follicular development.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"10"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of non-pharmacological interventions on biochemical hyperandrogenism in women with polycystic ovary syndrome: a systematic review and network meta-analysis.","authors":"Qi Jin, Ge Xu, Yuchen Ying, Lumin Liu, Huimin Zheng, Shifen Xu, Ping Yin, Yuelai Chen","doi":"10.1186/s13048-025-01595-5","DOIUrl":"10.1186/s13048-025-01595-5","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the effectiveness of non-pharmacological interventions (NPIs), including electroacupuncture, exercise, diet, and lifestyle changes, in reducing androgen levels in women with polycystic ovary syndrome (PCOS) through a systematic review and network meta-analysis.</p><p><strong>Methods: </strong>Comprehensive searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang up to June 2024. Randomized controlled trials (RCTs) comparing NPIs with other NPIs or placebo treatments in adult women with PCOS were included. Study selection was independently performed by three authors. Quality assessment followed PRISMA guidelines using the Cochrane RoB2 tool. The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Traditional meta-analysis of continuous variables was conducted using Stata 17.0 software with a random-effects model, reporting effect sizes as standardized mean differences (SMD) and weighted mean differences (WMD). Network meta-analysis (NMA) was used to synthesize data, with network diagrams illustrating comparisons between NPIs. We assessed the consistency of the results, performed sensitivity analyses, and examined publication bias to evaluate the influence of individual studies. Furthermore, subgroup analysis and network meta-regression analysis were conducted to explore potential sources of heterogeneity.</p><p><strong>Results: </strong>The review included 21 studies with 1,196 participants, with meta-analysis focusing on 17 studies involving 1,013 participants. NPIs significantly reduced serum testosterone (SMD = -0.57; 95% CI: -0.86 to -0.29, p < 0.01), A4 (SMD = -1.37; 95% CI: -2.63 to -0.12, p = 0.03), and mFG score (WMD = -0.81; 95% CI: -1.26 to -0.37, p < 0.01). Notably, the reduction in testosterone levels achieved with NPIs met the Minimum Clinically Important Difference (MCID) of 12.47 ng/dL (WMD = -12.57; 95% CI: -18.92 to -6.23; p < 0.01), affirming the clinical relevance of these reductions. No significant effects were observed on Free Androgen Index (FAI), Sex Hormone-Binding Globulin (SHBG), Dehydroepiandrosterone (DHEA), DHEA Sulfate (DHEAS), Free Testosterone (FT), or Dihydrotestosterone (DHT) levels (all p > 0.05). The NMA (18 studies, 1,067 participants) identified electroacupuncture combined with diet and exercise as the most effective intervention for reducing serum testosterone (WMD = -21.75; 95% CI: -49.58 to 6.07; SUCRA 72.3%). Evidence certainty for many interventions was low, highlighting the need for higher-quality studies. Sensitivity analysis confirmed the robustness of the findings, and no publication bias was detected.</p><p><strong>Conclusions: </strong>NPIs, particularly electroacupuncture combined with exercise and dietary management, effectively reduce androgen levels in PCOS patients. These findings provide valuable guidance for clinicians and women with PCOS, with multi-component ap","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"8"},"PeriodicalIF":3.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}