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Kong F, Chen Y, Liu D, Gao H, Yi Q, Zhang M, Li D. Marvelon suppresses MC38 tumor growth and promotes anti-tumor immunity. Mol Immunol 2025; 182:20-29. [PMID: 40158361 DOI: 10.1016/j.molimm.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/15/2025] [Accepted: 03/16/2025] [Indexed: 04/02/2025]
Abstract
Colorectal cancer is a prevalent and deadly malignancy globally, posing an important challenge due to its heterogeneity and treatment resistance. Although oral contraceptives have been shown to reduce the incidence of colorectal cancer, their impact on the anti-tumor effect of CD8+ T cells remains unclear. Here we show that the contraceptive Marvelon plays an important role in anti-MC38 tumor immunity. The contraceptive Marvelon significantly inhibits MC38 tumor growth in vivo. Marvelon treatment promotes IFN-γ expression in CD8+ tumor infiltrating lymphocytes, but shows dispensable impact on their exhausted profile. By further investigating the effects of Marvelon's primary components, Ethinylestradiol and Desogestrel, we reveal that Ethinylestradiol enhances IFN-γ production in Type 1 Cytotoxic T (Tc1) cells and significantly inhibits the viability of MC38 tumor cells, whereas Desogestrel exhibits minimal effects. This study not only redefines the role of oral contraceptives but also provides valuable insights for the development of novel immunotherapeutic strategies.
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Affiliation(s)
- Fandi Kong
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
| | - Yongyan Chen
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
| | - Dantong Liu
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
| | - Hongying Gao
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
| | - Qiaoru Yi
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
| | - Mengjuan Zhang
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
| | - Dan Li
- Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
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Carriero VC, Forte G, Dinicola S, Oliva MM, Mudarris GA, Unfer V. Insights from the EGOI-PCOS patient survey: Diagnosis, treatment, and quality of life according to Italian PCOS patients. Eur J Obstet Gynecol Reprod Biol 2025; 310:113947. [PMID: 40179473 DOI: 10.1016/j.ejogrb.2025.113947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/03/2025] [Accepted: 03/29/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder; however, the current guidelines do not adequately address the metabolic aspect. By gathering patients' perspectives, this survey investigates potential issues with the current diagnostic process to identify key points that need addressing in the future. METHOD A survey comprising of 49 multiple-choice question was distributed to members of the Italian PCOS community NoiPCOS, including topics such as demographics, PCOS diagnosis experience, symptom management, quality of life, and access to information about PCOS. RESULTS 769 women aged 18-40 responded to the survey. 72.2% of responders were employed and perceived their socio-economic status as "good". PCOS diagnosis was primarily obtained in adolescence (35.1%) or late adolescence (33.6 %), with the most common symptoms being polycystic ovaries (85.8%), irregular menses (80.4%), and hirsutism (64.1%). Moreover, PCOS symptoms were seen to severely impact the mental health for 64.7% of responders. Treatments prescribed for PCOS were diet (49.5%), exercise (46.9%), metformin (27.6%), hormonal contraception (26.4%), and myo-inositol and D-chiro-inositol (25.2%). When accessing information about PCOS, women often relied on unofficial sources (i.e. internet sources) rather guidance from their physician. CONCLUSION Findings of this survey highlight that a thorough update of PCOS diagnostic criteria is required, which should consider the endocrine and metabolic aspects of the syndrome. Such revision should enable a more accurate, precise diagnosis that translates to effective therapy. Finally, any reconsideration of the PCOS guidelines should increase the perceived reliability by patients of medical care, reducing the communication gap between specialists and patients.
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Affiliation(s)
| | | | - Simona Dinicola
- The Experts Group On Inositol in Basic and Clinical Research and On PCOS (EGOI-PCOS), Rome, Italy; Systems Biology Group Lab, Sapienza University of Rome, Rome, Italy
| | - Mario Montanino Oliva
- The Experts Group On Inositol in Basic and Clinical Research and On PCOS (EGOI-PCOS), Rome, Italy; Department of Obstetrics and Gynecology, Santo Spirito Hospital, Rome, Italy
| | | | - Vittorio Unfer
- The Experts Group On Inositol in Basic and Clinical Research and On PCOS (EGOI-PCOS), Rome, Italy; UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.
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Gomes MDO, Gomes JDO, Ananias LF, Lombardi LA, da Silva FS, Espindula AP. Anti-Müllerian hormone as a diagnostic marker of polycystic ovary syndrome: a systematic review with meta-analysis. Am J Obstet Gynecol 2025; 232:506-523.e7. [PMID: 39922442 DOI: 10.1016/j.ajog.2025.01.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 01/14/2025] [Accepted: 01/29/2025] [Indexed: 02/10/2025]
Abstract
OBJECTIVE To determine whether serum anti-Müllerian hormone measurement can be used as a diagnostic marker for polycystic ovary syndrome compared to serum androgen measurement and transvaginal/transabdominal ultrasound. DATA SOURCES A systematic literature review and meta-analysis were conducted. Electronic and manual searches were carried out in the Cochrane Library, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), PubMed, Scopus, Web of Science, and Google Scholar databases. STUDY ELIGIBILITY CRITERIA Studies conducted in humans, published in any language up to August 2023, and addressing the following research question were included: "Can serum anti-Müllerian hormone levels be used as a diagnostic marker of polycystic ovary syndrome in comparison to serum androgen levels and transvaginal/transabdominal ultrasound?" Furthermore, only articles that used the Rotterdam (2003) criteria, the National Institutes of Health (1990) criteria, the Androgen Excess and Polycystic Ovary Syndrome Society criteria, or the Evidence-based Guidelines on polycystic ovary syndrome from 2013, 2018, and 2023 for diagnosing women with polycystic ovary syndrome were included. STUDY APPRAISAL AND SYNTHESIS METHODS Two independent reviewers selected the studies and extracted and analyzed the data. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grades of Recommendation, Assessment, Development, and Evaluation Working Group tools were used to analyze the risk of bias and certainty of evidence. RESULTS This systematic review included 45 studies. The studies exhibited a low risk of bias in the "Reference standard" and "Flow and time" domains but showed a moderate risk of bias in the "Patient selection" domain and a high risk of bias in the "Index test" domain. The meta-analysis of the case-control studies demonstrated a sensitivity of 81% and specificity of 82%, whereas the meta-analysis of the cross-sectional studies showed a sensitivity of 80% and specificity of 85%, both with 95% confidence intervals. The certainty of the evidence was rated as "low." CONCLUSION This systematic review showed that serum anti-Müllerian hormone levels can serve as a diagnostic marker for polycystic ovary syndrome when factors such as age, test standardization, polycystic ovary syndrome phenotypes, and body mass index are considered. Otherwise, anti-Müllerian hormone should be used as an adjuvant to the polycystic ovary syndrome diagnostic criteria established through consensus and/or guidelines. Additionally, serum concentrations reflected the severity of this syndrome.
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Affiliation(s)
- Mariane de Oliveira Gomes
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro - UFTM, Abadia, Uberaba-MG, Brazil.
| | - Juliane de Oliveira Gomes
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro - UFTM, Abadia, Uberaba-MG, Brazil
| | - Lucas Fernandes Ananias
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro - UFTM, Abadia, Uberaba-MG, Brazil
| | - Leonardo Augusto Lombardi
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro - UFTM, Abadia, Uberaba-MG, Brazil
| | - Fernando Seiji da Silva
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro - UFTM, Abadia, Uberaba-MG, Brazil
| | - Ana Paula Espindula
- Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro - UFTM, Abadia, Uberaba-MG, Brazil
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Hadi S, Khoshraftar SH, Kiani Darabi AH, Soleimani A, Nejabati HR. Extracellular fluid miRNAs in PCOS. Clin Chim Acta 2025; 576:120404. [PMID: 40446894 DOI: 10.1016/j.cca.2025.120404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2025] [Revised: 05/27/2025] [Accepted: 05/27/2025] [Indexed: 06/02/2025]
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition that impacts both reproductive and metabolic functioning. Despite thorough research, the exact causes of PCOS remain unclear. Recent studies indicate that microRNAs (miRNAs), which are small non-coding RNAs that regulate gene expression, could be crucial for comprehending PCOS. This review article investigates the variations in extracellular fluids miRNAs expression in individuals diagnosed with PCOS and assesses their viability as diagnostic biomarkers, and determines their involvement in the mechanisms underlying the disease. The related reports show that miRNA expression profiles demonstrate notable differences between PCOS patients and healthy subjects. Several miRNAs exhibit dysregulation in essential biological processes such as follicular development, steroidogenesis, insulin signaling, and metabolic pathways. These results imply that miRNAs could lead to hormonal imbalances and metabolic problems linked to PCOS. The variations in miRNA expression noted in patients with PCOS underscore their possible role as biomarkers for the early detection and characterization of the condition. Continued investigation into miRNA-based diagnostic and therapeutic strategies may enhance our comprehension of PCOS. and facilitate the advancement of more precise therapeutic alternatives.
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Affiliation(s)
- Saba Hadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Hossein Khoshraftar
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Hossein Kiani Darabi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Anahita Soleimani
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Reza Nejabati
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Zeng Z, Shan H, Lin M, Bao S, Mo D, Deng F, Yu Y, Yang Y, Zhou P, Li R. SIRT3 protects endometrial receptivity in patients with polycystic ovary syndrome. Chin Med J (Engl) 2025; 138:1225-1235. [PMID: 38721809 PMCID: PMC12091677 DOI: 10.1097/cm9.0000000000003127] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Indexed: 05/21/2025] Open
Abstract
BACKGROUND The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
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Affiliation(s)
- Zhonghong Zeng
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
- Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China
| | - Hongying Shan
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
- Reproductive Medical Center, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang 832000, China
| | - Mingmei Lin
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
| | - Siyu Bao
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
| | - Dan Mo
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
- Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China
| | - Feng Deng
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
| | - Yang Yu
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
| | - Yihua Yang
- Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China
| | - Ping Zhou
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
| | - Rong Li
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
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Maan P, Gautam R, Vasudevan S, Menon GR, Arora A, Nair A, Jabbar PK, Arora T. Pharmacological and Non-Pharmacological Interventions for Polycystic Ovary Syndrome (PCOS) in Indian Women: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel) 2025; 18:680. [PMID: 40430499 PMCID: PMC12114445 DOI: 10.3390/ph18050680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 04/09/2025] [Accepted: 04/14/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient's age, symptoms, requirements, and geographical location. Objective: This systematic review aims to conduct a comprehensive and evidence-based analysis of the various available treatment options and identify knowledge gaps in PCOS management in India. Methods: A comprehensive search was conducted in PubMed, Scopus, and Embase databases from January 2010 till February 2024. We included randomized control trials (RCTs) using any pharmacological drugs (e.g., insulin sensitizers, anti-androgens, anti-obesity drugs, oral contraceptive pills, ovulation induction drugs, etc.) or non-pharmacological intervention (e.g., yoga, diet, herbal supplements, etc.) with Indian PCOS patients for improving common manifestations of PCOS and written in the English language. Studies were screened by two authors independently in a two-level process. Data extraction was also performed by two authors. Risk of bias was performed using the RoB 2 Tool. Subgroup analysis and meta-analysis were performed using the RevMan tool. Results: Thirty RCTs on pharmacological and eight on non-pharmacological interventions were included in the study. However, all the RCTs were so heterogeneous in terms of intervention used, subject recruited, and outcomes measured that meta-analysis was possible for only three subgroups (metformin vs. inositol, metformin vs. metformin+ inositol, and letrozole vs. clomiphene citrate), with only two or three studies per analysis. Most studies were single-centric and small-sized and had a high risk of bias, limiting their generalizability. Conclusions: This systematic review synthesized existing research and evaluated the effectiveness and safety of existing treatments. Limitations and gaps in the current research were identified, which may inform future research for better understanding and management of PCOS in the Indian context.
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Affiliation(s)
- Pratibha Maan
- Indian Council of Medical Research (ICMR) Headquarters, New Delhi 110029, India; (P.M.); (R.G.); (S.V.)
| | - Rohit Gautam
- Indian Council of Medical Research (ICMR) Headquarters, New Delhi 110029, India; (P.M.); (R.G.); (S.V.)
| | - Sudharsan Vasudevan
- Indian Council of Medical Research (ICMR) Headquarters, New Delhi 110029, India; (P.M.); (R.G.); (S.V.)
| | - Geetha R. Menon
- Department of Health Research, Ministry of Health and Family Welfare, Government of India, New Delhi 110001, India;
| | - Amit Arora
- Sir Ganga Ram Hospital, New Delhi 110060, India;
| | - Abilash Nair
- Department of Endocrinology, Government Medical College, Thiruvananthapuram 695011, India
| | | | - Taruna Arora
- Indian Council of Medical Research (ICMR) Headquarters, New Delhi 110029, India; (P.M.); (R.G.); (S.V.)
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Mandvia A, George R, Kumari K, Kumari K, Sabbagh LI, Bhullar A, Mohamed Ismail D, Kolanu ND, Ali A. Comparative Efficacy of Metformin and Combined Oral Contraceptives in the Management of Adolescent Polycystic Ovary Syndrome: A Systematic Review of Randomized Controlled Trials. Cureus 2025; 17:e83850. [PMID: 40491634 PMCID: PMC12148199 DOI: 10.7759/cureus.83850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2025] [Indexed: 06/11/2025] Open
Abstract
This systematic review explores the comparative efficacy of metformin, combined oral contraceptives (COCs), and their combination in the management of polycystic ovary syndrome (PCOS) among adolescent females. A comprehensive literature search was conducted across PubMed, Scopus, and Cochrane CENTRAL in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, yielding 645 records, of which seven randomized controlled trials (RCTs) met the inclusion criteria. The included studies varied in design, population size, and outcome focus but consistently evaluated metabolic, hormonal, and reproductive endpoints. Results indicated that, while COCs were effective in reducing hyperandrogenic symptoms and regulating menstrual cycles, they were often associated with adverse metabolic effects, such as increased hepatic enzymes and insulin resistance. In contrast, insulin-sensitizing agents, particularly in combination regimens such as SPIOMET (spironolactone, pioglitazone, and metformin combination), showed superior outcomes in improving ovulation rates, insulin sensitivity, and body composition, with fewer metabolic side effects. Combination therapy with metformin and COCs also demonstrated a balanced improvement in both reproductive and metabolic profiles. The overall quality of included studies was rated as having some concerns due to variability in study design and reporting. Despite these limitations, the evidence supports a more individualized and metabolically focused approach to managing adolescent PCOS, emphasizing the benefits of early intervention with insulin-sensitizing therapies.
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Affiliation(s)
- Aqsa Mandvia
- Obstetrics and Gynaecology, Gloucester Royal Hospital, Gloucester, GBR
| | - Rebecca George
- Obstetrics and Gynaecology, Malankara Orthodox Syrian Church Medical College, Kochi, IND
| | - Komal Kumari
- Internal Medicine, Akbar Niazi Teaching Hospital, Islamabad, PAK
| | - Katee Kumari
- Internal Medicine, Akbar Niazi Teaching Hospital, Islamabad, PAK
| | - Leen I Sabbagh
- Gynecology and Obstetrics, Dubai Medical College for Girls, Dubai, ARE
| | - Amritveer Bhullar
- Internal Medicine, Dr. D. Y. Patil Medical College, Pimpri-Chinchwad, IND
| | - Danyah Mohamed Ismail
- Internal Medicine, Indira Gandhi Medical College and Research Institute, Puducherry, IND
| | | | - Amir Ali
- Internal Medicine, Services Hospital Lahore, Lahore, PAK
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Gheshlagh RA, Topsakal S. A Complex Clinical Situation in Polycystic Ovary Syndrome: HAIR-AN Syndrome ''Case Report". Case Rep Med 2025; 2025:5825601. [PMID: 40330136 PMCID: PMC12055325 DOI: 10.1155/carm/5825601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 04/08/2025] [Indexed: 05/08/2025] Open
Abstract
Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome is a distinct and uncommon form of polycystic ovarian syndrome. It manifests through hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN), along with symptoms like acne, hirsutism, irregular menstruation, and other androgen-related issues. A 17-year-old female with a history of childhood obesity and irregular menstrual cycles presented with weight gain and amenorrhea. Previously assessed for hirsutism with a Ferriman-Gallwey score of 14, she was found to have hepatic steatosis, ovarian cysts, and IR. She was advised to lose weight and prescribed metformin but did not adhere to the treatment. Four years later, she returned with further weight gain and hirsutism and was diagnosed with androgenetic alopecia. The presence of AN, HA, and severe IR led to a diagnosis of HAIR-AN syndrome, and she was placed under observation. We used next-generation sequencing (NGS) to screen 70 genes for mutation and identify relevant genetic variations. The investigation targeted all exons and exon-intron junctions in genes, including ACOX1, GM2A, ACSF3, and others. Bioinformatics tools and in silico algorithms were used to assess the impact of the variants. No significant mutations associated with the patient's symptoms were identified. HAIR-AN syndrome can present in various forms and should be considered in cases of unexplained AN and menstrual irregularities. Early detection, diagnosis, and treatment of HAIR-AN syndrome can alleviate symptoms and improve patients' quality of life. This case presentation aims to evaluate the findings of a HAIR-AN syndrome that became very severe due to treatment noncompliance.
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Affiliation(s)
| | - Senay Topsakal
- Faculty of Medicine, Department of Endocrinology and Metabolism, Pamukkale University, Denizli, Türkiye
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Akpang N, Kwiatkowski J, Zaborowska L, Ludwin A. Autoantibodies Targeting the Hypothalamic-Pituitary-Ovarian Axis in Polycystic Ovary Syndrome: Emerging Key Players in Pathogenesis? Int J Mol Sci 2025; 26:4121. [PMID: 40362363 PMCID: PMC12072038 DOI: 10.3390/ijms26094121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 04/23/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common female endocrinopathy associated with reproductive and metabolic abnormalities. PCOS is characterized by complex pathogenesis and pathophysiology. Its multifactorial etiology and heterogeneous presentation make effective treatment difficult. Endocrine abnormalities in PCOS create a vicious cycle of overriding dysfunction involving the hypothalamic-pituitary-ovarian (HPO) axis. Most research has primarily focused on identifying genetic, epigenetic, or immunological factors underlying PCOS. In recent years, new reports have emerged on the possible involvement of antibodies directed against HPO axis components in the development of PCOS. Some of these have been shown to be able to interfere with hormone receptors or receptor binding by targeting the key domains for their function. However, the evidence is heterogeneous and challenging to interpret, given the overall predisposition to high levels of various autoantibodies found in women with PCOS. This review focuses on autoantibodies affecting the HPO axis in PCOS and their potential role in the pathogenesis of PCOS. The authors discuss PCOS as a potential antibody-mediated autoimmune disease in light of recent reports on its possible pathogenesis.
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Affiliation(s)
- Nicole Akpang
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland
| | - Jakub Kwiatkowski
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland
| | - Lucja Zaborowska
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland
- Doctoral School of Medical and Health Sciences, Jagiellonian University Collegium Medicum, 31-530 Cracow, Poland
| | - Artur Ludwin
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland
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Chen L, Yan X, Lian Y, Wang D, Cai J, Yin C, Cao J. Dingkun Pill-Mediated TGF-β1/Smad2 Pathway Effects on Granulosa Cell Proliferation and Apoptosis. Mol Biotechnol 2025:10.1007/s12033-025-01439-z. [PMID: 40278965 DOI: 10.1007/s12033-025-01439-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 04/04/2025] [Indexed: 04/26/2025]
Abstract
To investigate influences of Dingkun Pill on granulosa cell proliferation and apoptosis (P&A) in polycystic ovary syndrome (PCOS) mice and its association with the TGF-β1/Smad2 signaling pathway (SPW) activity. Forty-eight female SD mice were rolled into experimental group (EG, Dingkun Pill), control group (CG, metformin), model group (MG, distilled water), and normal group (NG, distilled water), with 12 mice per group. The Beloosesky method was employed to establish the PCOS mouse model. Serum hormone (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T)), expression of vascular endothelial growth factor (VEGF) in rat ovarian tissue and expression of HOXA10 in endometrial tissue, cell P&A, and expression level (EL) of TGF-β1 and Smad2 were compared among groups. Compared to the MG, the EG and CG exhibited significantly reduced levels of FSH, LH, and testosterone, while estradiol levels were significantly elevated. Furthermore, granulosa cell proliferation was notably enhanced, and the apoptosis rate was significantly decreased (P < 0.05). In addition, the expression of VEGF in ovarian tissue, as well as the expression of TGF-β1 and Smad2, was significantly lower in EG and CG compared to MG, while the expression of the HOXA10 gene in the endometrium was significantly increased (P < 0.05). Compared to CG, EG showed higher ovarian VEGF expression and lower HOXA10 gene expression (P < 0.05).Dingkun Pill notably improves serum hormone in a PCOS mouse model, inhibits granulosa cell apoptosis, and enhances granulosa cell proliferation activity. This effect is likely mediated through the inhibition of the TGF-β1/Smad2 SPW, suggesting a protective role of Dingkun Pill in PCOS.
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Affiliation(s)
- Lan Chen
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China
| | - Xiaojing Yan
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China.
| | - Yuanpei Lian
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China
| | - Dijun Wang
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China
| | - Jiali Cai
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China
| | - Chunyan Yin
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China
| | - Ji Cao
- Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China
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11
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Henney AE, Gillespiec CS, Lai JYM, Schofield P, Riley DR, Caleyachetty R, Barber TM, Miras AD, Dobbie LJ, Hughes DM, Alam U, Hydes TJ, Cuthbertson DJ. Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2025; 110:1235-1246. [PMID: 38986027 PMCID: PMC12012816 DOI: 10.1210/clinem/dgae481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 07/02/2024] [Accepted: 07/10/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype. METHODS Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes. RESULTS We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01). CONCLUSION Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.
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Affiliation(s)
- Alex E Henney
- Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool L69 7ZX, UK
- Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
- Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L69 7ZX, UK
| | - Conor S Gillespiec
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 3PT, UK
| | - Jonathan Y M Lai
- Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
| | - Pieta Schofield
- Department of Public Health, Policy & Systems, University of Liverpool, Liverpool, Merseyside L69 7ZX, UK
| | - David R Riley
- Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool L69 7ZX, UK
- Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
| | | | - Thomas M Barber
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Alexander D Miras
- Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Hospital, London SW7 2AZ, UK
| | - Laurence J Dobbie
- Department of Diabetes and Endocrinology, Guy's and St Thomas’ NHS Foundation Trust, London SE1 7EH, UK
| | - David M Hughes
- Institute of Population Health, University of Liverpool, Liverpool L69 7ZX, UK
| | - Uazman Alam
- Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool L69 7ZX, UK
- Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
- Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L69 7ZX, UK
| | - Theresa J Hydes
- Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool L69 7ZX, UK
- Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
- Department of Gastroenterology and Hepatology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
| | - Daniel J Cuthbertson
- Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool L69 7ZX, UK
- Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L9 7AL, UK
- Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside L69 7ZX, UK
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Najdgholami Z, Sedgi FM, Ghalishourani SS, Feyzpour M, Rahimlou M. Flaxseed intervention and reproductive endocrine profiles in patients with polycystic ovary syndrome: an open-labeled randomized controlled clinical trial. Front Endocrinol (Lausanne) 2025; 16:1531762. [PMID: 40260281 PMCID: PMC12010250 DOI: 10.3389/fendo.2025.1531762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 03/13/2025] [Indexed: 04/23/2025] Open
Abstract
Introduction Polycystic Ovary Syndrome (PCOS), affecting 6-15% of women of reproductive age, is characterized by hormonal imbalances and metabolic disturbances. Flaxseed, rich in omega-3 fatty acids and phytoestrogens, may offer a natural approach to improve reproductive hormone profiles in PCOS patients. This study is aimed at evaluating the effects of flaxseed supplementation on reproductive endocrine profiles in women with PCOS. Methods In this open-labeled, randomized controlled trial, 70 women with PCOS were randomly assigned to either the intervention group (n=35), receiving 30 grams of milled flaxseed daily along with lifestyle modifications, or the control group (n=35), receiving only lifestyle modifications, for 12 weeks. The primary outcome was the change in follicle-stimulating hormone (FSH) levels. Secondary outcomes included changes in serum concentrations of luteinizing hormone (LH), the LH/FSH ratio, anti-Müllerian hormone (AMH), estradiol, dehydroepiandrosterone sulfate (DHEAS), and androstenedione. Results After 12 weeks, the flaxseed group showed a significant increase in FSH levels compared to the control group. FSH levels increased from 9.72 ± 11.95 µU/mL at baseline to 10.59 ± 12.14 µU/mL after the intervention (p = 0.027). The mean treatment effect was 0.87 (95% CI: 0.086 to 1.75). The LH/FSH ratio also significantly decreased in the flaxseed group (mean treatment effect: -0.341, 95% CI: -0.63 to -0.08, p = 0.031). No significant changes were observed in AMH, LH, estradiol, DHEAS, or androstenedione levels. Conclusion Flaxseed supplementation may benefit women with PCOS by increasing FSH levels and decreasing the LH/FSH ratio, suggesting its potential as a complementary intervention for managing hormonal disturbances in PCOS. Further studies are needed to confirm these findings and elucidate the underlying mechanisms.
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Affiliation(s)
- Zahra Najdgholami
- Department of Midwifery, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Fatemeh Maleki Sedgi
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Marzieh Feyzpour
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehran Rahimlou
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
- Metabolic Diseases Research Center, Health and Metabolic Research Institute, Zanjan University of Medical Science, Zanjan, Iran
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13
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Wang F, Wei W, Liu PJ. Evaluation of Effects of a High-Protein Hypocaloric Diet on Body Composition and Cardio-Metabolic Factors in Women with Polycystic Ovary Syndrome and Overweight or Obesity. Diabetes Metab Syndr Obes 2025; 18:931-939. [PMID: 40171413 PMCID: PMC11960474 DOI: 10.2147/dmso.s501972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 03/24/2025] [Indexed: 04/03/2025] Open
Abstract
Background The optimal composition of a hypocaloric diet for women with polycystic ovary syndrome (PCOS) remains uncertain. The aim of this study was to evaluate and compare the impacts of a hypocaloric high-protein diet (HPD) versus an isocaloric conventional calorie-restricted diet (CRD) with normal protein intake on the body composition and biochemical profiles of women diagnosed with PCOS combined with overweight or obesity. Methods This was a dietary intervention study evaluating the effects of two types of diets on women with PCOS who initiated weight loss independently at the Clinical Nutrition Clinic of Peking Union Medical College Hospital from March 2023 to March 2024 was carried out. Specifically, the records of 72 women with PCOS who were overweight or obese and underwent a 3-month weight management program were examined in a retrospective manner. The hypocaloric dietary intervention was adopted to achieve weight reduction, with either HPD or CRD. Body composition, serum lipids, glucose, insulin, and total testosterone (TT) were evaluated at baseline and post-intervention, and the differences were compared between and within groups. Results Both groups achieved significant weight loss, with the HPD group losing an average of -8.9 ± 4.6 kg and the CRD group losing -10.0 ± 9.4 kg, without a significant difference between them (P > 0.05). However, the HPD was superior in preserving fat-free mass (FFM) and fat-free mass index (FFMI), with losses of -1.5 ± 1.6 kg and -0.7 ± 1.1 kg/m², respectively, compared to the CRD group's losses of -4.4 ± 4.2 kg and -2.1 ± 1.9 kg/m² (P < 0.01). Additionally, the HPD group showed a more significant reduction in body fat percentage (-5.3 ± 3.3% vs -3.2 ± 4.5%, P < 0.05). Biochemical indicators were comparable in both groups. Conclusion Compared to an isocaloric standard-protein CRD, the dietary intervention with a HPD appears to be more helpful in preserving FFM in women with PCOS during a short-term weight loss program. Further well-designed trials are needed to verify our findings.
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Affiliation(s)
- Fang Wang
- Department of Clinical Nutrition, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China
| | - Wei Wei
- Department of Clinical Nutrition, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China
| | - Peng Ju Liu
- Department of Clinical Nutrition, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China
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14
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Khamineh Y, Ghiasvand M, Panahi-Alanagh S, Rastegarmand P, Zolghadri S, Stanek A. A Narrative Review of Quercetin's Role as a Bioactive Compound in Female Reproductive Disorders. Nutrients 2025; 17:1118. [PMID: 40218878 PMCID: PMC11990684 DOI: 10.3390/nu17071118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/14/2025] Open
Abstract
Lifestyle, nutrition, and metabolic status are central to maintaining women's reproductive health. With the rising prevalence of infertility, the need for effective strategies to preserve and enhance women's reproductive well-being has become increasingly urgent. Quercetin, a plant-derived polyphenol, has attracted growing interest for its potential to support reproductive health, regulate the hormonal balance, and improve fertility. This narrative review examines Quercetin's role in women's reproductive health and delineates its possible mechanisms of action in female reproductive system disorders, including polycystic ovary syndrome, recurrent miscarriage, and cervical, ovarian, and endometrial cancer (EC). By highlighting the biological pathways through which quercetin may exert its effects, this article underscores the need for further research and clinical trials to validate its therapeutic potential and its applications as a bioactive compound in foods aimed at enhancing women's reproductive health.
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Affiliation(s)
- Yasaman Khamineh
- Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran 1983969411, Iran; (Y.K.); (M.G.)
| | - Mahsa Ghiasvand
- Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran 1983969411, Iran; (Y.K.); (M.G.)
- Department of Stem Cells and Developmental Biology, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran 3365166571, Iran
| | - Sanaz Panahi-Alanagh
- Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 817467344, Iran;
| | - Parisa Rastegarmand
- Department of Microbiology, College of Science, Shiraz Branch, Islamic Azad University, Shiraz 1477893780, Iran;
| | - Samaneh Zolghadri
- Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom 7414785318, Iran
| | - Agata Stanek
- Department of Internal Medicine, Metabolic Diseases and Angiology, Faculty of Health Sciences in Katowice, Medical University of Silesia, Ziolowa 45/47 St., 40-635 Katowice, Poland
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15
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Shekarian A, Mazaheri-Tehrani S, Shekarian S, Pourbazargan M, Setudeh M, Abhari AP, Fakhrolmobasheri M, Heidarpour M. Prevalence of subclinical hypothyroidism in polycystic ovary syndrome and its impact on insulin resistance: a systematic review and meta-analysis. BMC Endocr Disord 2025; 25:75. [PMID: 40102852 PMCID: PMC11921581 DOI: 10.1186/s12902-025-01896-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 03/06/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Although recent studies indicate a high prevalence of subclinical hypothyroidism (SCH) in women with polycystic ovary syndrome (PCOS), the reported prevalence rates vary widely. Therefore, we conducted this study to estimate the pooled prevalence of SCH among women with PCOS. Additionally, emerging evidence suggests that SCH may negatively impact insulin resistance in PCOS. Thus, we examined its effect on insulin resistance indices as our secondary objective. METHODS We searched PubMed, Web of Science, Scopus, and Embase from their inception to February 25, 2024. Observational studies reporting the prevalence of SCH among women with PCOS were included. Joanna Briggs Institute's (JBI) critical appraisal checklist for prevalence studies was adopted for the risk of bias assessment. The random-effects model was employed to estimate the pooled prevalence with its 95% confidence intervals (CI). The weighted mean difference (WMD) was used to compare the insulin resistance indices between PCOS patients with and without SCH. RESULTS Twenty-nine studies comprising 5765 women with PCOS were included. The meta-analysis demonstrated that 19.7% (95% CI: 16.1%; 23.5%) of women with PCOS have SCH. PCOS patients with SCH had significantly higher HOMA-IR (WMD = 0.78, 95% CI: 0.34; 1.22) and fasting insulin (WMD = 2.38, 95% CI: 0.34; 4.42) levels than those without SCH. Differences in fasting plasma glucose and 2-hour postprandial glucose did not reach statistical significance. CONCLUSION This systematic review and meta-analysis found that approximately 20% of women with PCOS have SCH. This underscores the need for regular thyroid function testing in these patients. The prevalence of SCH is influenced by the TSH cut-off used for diagnosis, highlighting the need for establishing a standardized TSH cut-off value. Furthermore, SCH significantly elevates the HOMA-IR index and fasting insulin levels, highlighting its potential impact on insulin resistance. Whether these metabolic changes are clinically important and put these individuals at higher risk of developing type 2 diabetes mellitus and cardiovascular disease requires further investigation. SYSTEMATIC REVIEW REGISTRATION NUMBER IN PROSPERO CRD42024510798. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Arman Shekarian
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sadegh Mazaheri-Tehrani
- Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
- Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
- Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saba Shekarian
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Melika Pourbazargan
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahsa Setudeh
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Parsa Abhari
- Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Fakhrolmobasheri
- Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Heidarpour
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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Ayesh H, Nasser SA, Ferdinand KC, Carranza Leon BG. Sex-Specific Factors Influencing Obesity in Women: Bridging the Gap Between Science and Clinical Practice. Circ Res 2025; 136:594-605. [PMID: 40080532 DOI: 10.1161/circresaha.124.325535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 01/21/2025] [Accepted: 01/21/2025] [Indexed: 03/15/2025]
Abstract
Obesity in women is a significant public health issue with serious implications for cardiovascular-kidney-metabolic syndrome and cardiovascular disease. This complex challenge is influenced by physiological, hormonal, socioeconomic, and cultural factors. Women face unique weight management challenges due to hormonal changes during pregnancy, perimenopause, and menopause, which affect fat distribution and increase cardiovascular-kidney-metabolic syndrome risk. Current clinical guidelines often overlook these sex-specific factors, potentially limiting the effectiveness of obesity management strategies in women. This review explores the sex-specific aspects of obesity's pathophysiology, epidemiological trends, and associated comorbidities, focusing on cardiovascular and metabolic complications. This review synthesizes literature on obesity in women, emphasizing sex-specific factors influencing its development and progression. It examines the limitations of body mass index as an obesity measure and explores alternative classification methods. Additionally it investigates the relationship between obesity and comorbidities such as diabetes, hypertension, and dyslipidemia, with a focus on postmenopausal women. Obesity in women is linked to increased risks of cardiovascular-kidney-metabolic syndrome and cardiovascular disease. Hormonal fluctuations throughout life contribute to weight gain and fat distribution patterns specific to women, increasing cardiovascular disease risk. Effective obesity management strategies in women must account for these sex-specific variations. Postmenopausal women are particularly affected by obesity-related complications. Lifestyle interventions, pharmacotherapy, and bariatric surgery have shown efficacy in weight management, though success rates vary. Addressing obesity in women requires a comprehensive approach that considers sex-specific physiological factors, life-stage challenges, and sociocultural barriers. Integrating precision medicine and emerging therapies offers potential for more personalized and effective interventions. Personalized strategies that consider women's biological and life-stage challenges can enhance obesity management and improve cardiovascular outcomes. Future research and clinical practice should focus on developing tailored strategies that address women's unique vulnerabilities to obesity and its associated health risks and on validating sex-specific interventions to improve obesity management in women.
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Affiliation(s)
- Hazem Ayesh
- Deaconess Clinic Endocrinology, Deaconess Health System, Evansville, IN (H.A.)
| | - Samar A Nasser
- Department of Clinical Research and Leadership, School of Medicine and Health Sciences, The George Washington University, Washington, DC (S.A.N.)
| | - Keith C Ferdinand
- Section of Cardiology, Tulane University School of Medicine, New Orleans, LA (K.C.F.)
| | - Barbara Gisella Carranza Leon
- Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN (B.G.C.L.)
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Palomba S, Seminara G, Tomei F, Marino A, Morgante G, Baldini D, Papaleo E, Ragusa G, Aversa A, Allegra A, Guglielmino A, Somigliana E. Diagnosis and management of infertility in patients with polycystic ovary syndrome (PCOS): guidelines from the Italian Society of Human Reproduction (SIRU) and the Italian Centers for the Study and Conservation of Eggs and Sperm (CECOS Italy). Reprod Biol Endocrinol 2025; 23:37. [PMID: 40055752 PMCID: PMC11889853 DOI: 10.1186/s12958-025-01372-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 02/21/2025] [Indexed: 05/13/2025] Open
Abstract
The polycystic ovary syndrome (PCOS) is a multifaced disease of the reproductive age associated with several comorbidities including infertility. Very few documents regarding the management of the infertility in women with PCOS, including guidelines, position papers and consensus conferences, are available in the literature. The Italian Law indicates that health professionals must comply with the recommendations set out in the guidelines developed by public and private bodies and institutions, as well as scientific societies and technical-scientific associations of the health professions, except for specific cases. Unfortunately, no guideline for the diagnosis and the management of infertility in women with PCOS is currently available in Italy. In 2024, the Italian Society of Human Reproduction (SIRU) and the Italian Centers for the Study and Conservation of Eggs and Sperm (CECOS Italy) pointed out the need to produce Italian guidelines on this topic and established a specific working group to develop those guidelines. The working group chose to adapt the guideline with highest quality to the Italian context rather than developing a de novo document. The International Evidence-Based Guideline for the Assessment and Management of PCOS guidelines were selected. All recommendations regarding the diagnosis and the management of women with PCOS and infertility extracted, adapted to the Italian context and improved incorporating new recommendations or practical comments and suggestions where needed.
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Affiliation(s)
- Stefano Palomba
- Department of Medical-Surgical Science and Translational Medicine, Obstetrics & Gynecology, Sapienza University of Rome, Via Di Grottarossa 1039, Rome, Italy.
| | - Giuseppe Seminara
- Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | | | | | - Giuseppe Morgante
- Unit of Medically Assisted Reproduction and Department of Molecular and Developmental Medicine, Siena University Hospital and University of Siena, Siena, Italy
| | | | - Enrico Papaleo
- Obstetrics and Gynecology Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Guglielmo Ragusa
- Unit of Reproductive Medicine, Hospital "Borgo Trento", Verona, Italy
| | - Antonio Aversa
- Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | | | - Antonino Guglielmino
- Unit of Reproductive Medicine (U.M.R.), HERA Center, Sant'Agata li Battiati, CT, Italy
| | - Edgardo Somigliana
- Infertility Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy
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18
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Gokkaya N, Gecmez G, Ozcelik S, Biyikli M, Aydin K. Increased ferritin with contraceptives containing ethinyl estradiol drospirenone in polycystic ovary syndrome: a paradox of iron storage and iron deficiency. Endocrine 2025; 87:1314-1322. [PMID: 39738891 DOI: 10.1007/s12020-024-04150-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 12/23/2024] [Indexed: 01/02/2025]
Abstract
OBJECTIVES The relationship between elevated ferritin levels and metabolic abnormalities in PCOS patients, and whether ferritin is a cause or a consequence, is still debated. This study aimed to evaluate the impacts of the fourth generation combined oral contraceptive containing ethinyl estradiol/drospirenone (EE 30 mcg/DRSP 3 mg), known for its favorable metabolic profile and lower side effect risk, on iron metabolism in PCOS patients, while also exploring the potential relationship between metabolic parameters and iron status. METHODS The retrospective analysis was conducted on 81 women aged 18-45, diagnosed with PCOS according to the Rotterdam criteria and treated with EE/DRSP for six months. Exclusion criteria were lack of data, secondary hyperandrogenemia, major medical conditions, or recent use of medications affecting hormone levels or iron metabolism. Pre- and post-treatment anthropometric measurements, hormonal and metabolic markers, and iron parameters were obtained from records. RESULTS Post-treatment ferritin levels significantly increased (p = 0.001), while hemoglobin, hematocrit, and transferrin saturation decreased especially in overweight/obese patients (p = 0.012, p = 0.002, p = 0.017 respectively), suggesting a response to inflammation rather than iron storage disorders. Although overall CRP levels did not change significantly, post-treatment CRP levels were higher in overweight/obese patients compared to lean PCOS patients (p = 0.003). Ferritin levels were positively correlated with body mass index (p = 0.008, r = 0.310), insulin resistance indices (p = 0.027, r = 0.248), and the free androgen index (p = 0.001, r = 0.367) after treatment. Pre-treatment menstrual cycle length had no effect on ferritin. CONCLUSIONS The study revealed a paradoxical increase in ferritin levels with EE/DRSP treatment, highlighting the complex role of ferritin as a metabolic marker in PCOS patients, particularly in relation to obesity, which is typically associated with low-grade chronic inflammation.
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Affiliation(s)
- Naile Gokkaya
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, Kartal, Istanbul, Turkey.
| | - Gizem Gecmez
- Department of Internal Medicine, University of Health Sciences, Bakirkoy Sadi Konuk Training and Research Hospital, Bakirkoy, Istanbul, Turkey
| | - Serhat Ozcelik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, Kartal, Istanbul, Turkey
| | - Mithat Biyikli
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, Kartal, Istanbul, Turkey
| | - Kadriye Aydin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, Kartal, Istanbul, Turkey
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Zhang Y, Yang K, Fan T, Zheng D, Liu H. Diagnosis and Treatment of Adolescent Polycystic Ovary syndrome:A Review. Int J Womens Health 2025; 17:459-474. [PMID: 39995885 PMCID: PMC11847718 DOI: 10.2147/ijwh.s506498] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. Diagnosing adolescent PCOS is challenging due to the overlap between adult PCOS diagnostic criteria and normal physiological changes in adolescence. This review examines the diagnosis and treatment strategies for adolescent PCOS. The diagnosis of adolescent PCOS should meet two primary criteria-ovulatory dysfunction and biochemical or clinical hyperandrogenism-after excluding other causes. Defining these criteria accurately aids in early diagnosis and management of adolescent PCOS. However, due to limited research, age-specific diagnostic standards remain lacking. Once diagnosed, timely interventions-such as lifestyle, exercise, and dietary changes, along with targeted treatments like metformin and antiandrogens-should be initiated. In addition, the management of adolescent PCOS presents several challenges, including the absence of standardized medication guidelines, adolescent psychological factors that may impede adherence to dietary and exercise recommendations, and parental concerns about the long-term effects of medication on bone health and metabolism. Therefore, additional research is required to establish optimal management protocols to enhance patients' quality of life and prevent complications.
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Affiliation(s)
- Yaoyang Zhang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China
| | - Kaiyu Yang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China
- Department of Obstetrics and Gynecology, Changchun Obstetrics and Gynecology Hospital, Changchun, Jilin, 130000, People’s Republic of China
| | - Ting Fan
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China
| | - Dongying Zheng
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China
| | - Hongxiu Liu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China
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20
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Bo Y, Zhao J, Liu C, Yu T. Comparative efficacy of pharmacological interventions on metabolic and hormonal outcomes in polycystic ovary syndrome: a Network Meta-Analysis of Randomized controlled trials. BMC Womens Health 2025; 25:64. [PMID: 39955537 PMCID: PMC11829492 DOI: 10.1186/s12905-025-03594-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 02/05/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic and hormonal abnormalities. This study aimed to evaluate the comparative efficacy of pharmacological interventions on these outcomes. METHODS We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing pharmacological treatments for PCOS. Searches in PubMed, MEDLINE, Embase, and Web of Science were conducted up to October 20, 2023. Eligible studies were RCTs with at least 12 weeks of follow-up and outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), testosterone, sex hormone-binding globulin (SHBG), lipid profiles, HOMA-IR, fasting blood glucose (FBG), and fasting insulin (FINS). RESULTS Twenty-nine RCTs with 1476 participants were included. The combination of standard therapy with GLP-1 receptor agonists significantly reduced BW (MD= -3.44; 95% CI= -6.20 to -0.67), BMI (MD= -2.05; 95% CI= -3.55 to -0.55), and WC (MD= -4.39; 95% CI= -6.75 to -2.02) compared to standard therapy alone. Orlistat significantly lowered testosterone (SMD= -2.16; 95% CI= -3.84 to -0.48) and increased HDL-C levels (SMD = 0.90; 95% CI = 0.02 to 1.79) compared to placebo. The combination therapy also reduced HOMA-IR (MD= -1.29; 95% CI= -2.38 to -0.21) and FBG (SMD= -1.80; 95% CI= -3.04 to -0.55) compared to placebo. CONCLUSION Combining standard therapy with GLP-1 receptor agonists offers superior efficacy in improving metabolic and hormonal outcomes in women with PCOS. Orlistat effectively reduces androgen levels. These findings support the use of combination pharmacotherapy for comprehensive management of PCOS.
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Affiliation(s)
- Yali Bo
- Department of Gynecology of Chinese Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510000, China
| | - Jie Zhao
- Department of Pharmacy, Affiliated Mengchao Cancer Hospital of Shanghai University, Shanghai, China
| | - Chengjiang Liu
- Department of General Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, Anhui, China.
| | - Ting Yu
- Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
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21
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Yuan J, Li Z, Yu Y, Wang X, Zhao Y. Natural compounds in the management of polycystic ovary syndrome: a comprehensive review of hormonal regulation and therapeutic potential. Front Nutr 2025; 12:1520695. [PMID: 40008316 PMCID: PMC11850276 DOI: 10.3389/fnut.2025.1520695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/28/2025] [Indexed: 02/27/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) is a multifaceted endocrine disorder characterized by irregularities in gonadotropin secretion, hyperandrogenism, chronic anovulation, and polycystic ovarian morphology. In addition, it is often associated with metabolic dysfunctions, most notably insulin resistance (IR). This disorder affects approximately 6-20% of individuals, primarily emerging during early adolescence, and considerably increases the risk of conditions such as impaired glucose tolerance, type 2 diabetes, endometrial cancer, cardiovascular diseases, dyslipidemia, and postpartum complications. To date, there is no standardized protocol for treating PCOS. Existing therapies primarily rely on personalized pharmacotherapy and lifestyle modifications. However, these treatments may often lead to adverse effects, and most medications prescribed for PCOS are used off-label and have not secured approval from the U.S. Food and Drug Administration specifically for this condition. Recently, natural compounds have garnered considerable attention due to their efficacy in hormone modulation and minimal toxicity. Substances such as myo-inositol, resveratrol, berberine, and quercetin have shown promise in mitigating PCOS symptoms. Their multi-target properties offer the potential to achieve outcomes unattainable by single-target pharmaceuticals, particularly in managing heterogeneous conditions. This review aims to comprehensively analyze in vivo and in vitro research alongside clinical interventions to evaluate the influence of natural compounds on the prevalence of PCOS and their therapeutic potential. These investigations lay the groundwork for developing innovative therapeutic strategies for PCOS.
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Affiliation(s)
- Jingyi Yuan
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Zhenmin Li
- College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Yongjiang Yu
- Department of Endocrine and Metabolic Disease, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Xiuge Wang
- Department of Endocrine and Metabolic Disease, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Yunyun Zhao
- Department of Endocrine and Metabolic Disease, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China
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22
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Ranjbar S, Akinsiku O, Hefner M, Jafari F, Kudchadkar G, Zaroudi M, Nathan AN, Booe H, Dhurandhar NV. Management of obesities with a cause specific approach. Int J Obes (Lond) 2025; 49:192-195. [PMID: 38769423 DOI: 10.1038/s41366-024-01539-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 05/03/2024] [Accepted: 05/09/2024] [Indexed: 05/22/2024]
Affiliation(s)
- S Ranjbar
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA
| | - O Akinsiku
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA
| | - M Hefner
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA
| | - F Jafari
- Department of Nutritional Sciences, Penn State University, University Park, PA, USA
| | - G Kudchadkar
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA
| | - M Zaroudi
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA
| | - A N Nathan
- Center for Community Health Impact, University of Texas Health Sciences Center at Houston, El Paso, TX, USA
| | - H Booe
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
| | - N V Dhurandhar
- Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA.
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23
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Xavier-Santos D, Bedani R, de Almeida Vieira I, Padilha M, Lima CMG, Silva JDR, Ferreira BM, Giraldo PC, Pagnossa JP, Sivieri K, Antunes AEC, Sant'Ana AS. Exploring the Potential Use of Probiotics, Prebiotics, Synbiotics, and Postbiotics as Adjuvants for Modulating the Vaginal Microbiome: a Bibliometric Review. Probiotics Antimicrob Proteins 2025:10.1007/s12602-024-10444-8. [PMID: 39821884 DOI: 10.1007/s12602-024-10444-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2024] [Indexed: 01/19/2025]
Abstract
Women's health is related to several factors that include physical, mental, and reproductive health. Additionally, the vaginal microbiota modulation performs a fundamental role in the regulation of physiological homeostasis and dysbiosis, which provides us a potential overview of the use of different biotic agents and their implications for female health. The objective of this work was propitiated insights and conception about the influence of probiotics, prebiotics, synbiotics, and postbiotics as adjuvants for prevention/treatment on the main infections that can affect women's health. Therefore, seventy-one studies published in the Web of Science Core Collection database from 1999 to 2024 were evaluated and performed to a bibliometric analysis employing the VOSviewer software for scientific mapping and network analysis. Our results suggest that administration of biotic agents as adjuvants are relevant for the prevention and/or treatment of the main diseases that affect female health, since they contribute to a healthy vaginal microbiota through anti-inflammatory and antimicrobial activities. Most clinical studies have demonstrated the effectiveness of intervention using probiotics to the detriment of other biotic agents in women's health, being bacterial vaginosis, polycystic ovary syndrome, and vulvovaginal candidiasis, the main diseases evaluated. However, preclinical studies have emphasized that the inhibition of pathogens responsible for the process of vaginal dysbiosis may be due to the formation of biofilm and the synthesis of compounds that could prevent the adhesion of these microorganisms. Future perspectives point to the beneficial modulation of the vaginal microbiota by biotic agents as a promising adjuvant approach to improve women's health.
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Affiliation(s)
- Douglas Xavier-Santos
- Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil
- Fraunhofer Institute for Process Engineering and Packaging (IVV), Freising, Germany
| | - Raquel Bedani
- Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil
| | | | - Marina Padilha
- Department of Social and Applied Nutrition, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Clara Mariana Gonçalves Lima
- Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil
| | - Juliana Dara Rabêlo Silva
- Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil
| | - Beatriz Manfrinato Ferreira
- Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil
| | - Paulo César Giraldo
- Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil
| | - Jorge Pamplona Pagnossa
- Department of Biological Sciences, Pontifical Catholic University, Poços de Caldas, MG, Brazil
| | - Katia Sivieri
- Department of Food and Nutrition, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, SP, Brazil
| | | | - Anderson S Sant'Ana
- Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, Brazil.
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24
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Wang A, Corley J, Jaswa EG, Lin J, Smith DL, McCulloch CE, Huddleston H, Cedars MI. Association of polycystic ovary syndrome with endothelial health, cardiovascular risk, and cellular aging. Fertil Steril 2025:S0015-0282(25)00030-5. [PMID: 39818356 DOI: 10.1016/j.fertnstert.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 01/08/2025] [Accepted: 01/09/2025] [Indexed: 01/18/2025]
Abstract
OBJECTIVE To study measures of endothelial health, cardiovascular risk, and cellular aging between patients with polycystic ovary syndrome (PCOS) and a reproductive age normative cohort. DESIGN Cross-sectional study. SUBJECTS Community-based patients with PCOS and a normative ovarian aging cohort as controls, aged ≤45 years at the time of evaluation. EXPOSURE Noninvasive measure of endothelial health measured by the EndoPAT reactive hyperemia index. MAIN OUTCOME MEASURES Reactive hyperemia index as measure of endothelial health. The secondary outcomes included Framingham score, telomere length, and mitochondrial deoxyribonucleic acid copy number from leukocyte cells. RESULTS Our cohort included 63 participants with PCOS and 130 non-PCOS participants. The mean age was significantly lower in the PCOS cohort (33.1; standard deviation, 4.7 years) than in the non-PCOS cohort (40.8; standard deviation, 2.9 years). In multivariable-adjusted models, we found that PCOS was significantly associated with endothelial dysfunction as both categorical (odds ratio for PCOS, 0.31; 95% confidence interval [CI], 0.10-0.97) and continuous (PCOS coefficient, -0.37; 95% CI, -0.69 to -0.05) outcomes. For secondary outcomes, PCOS status was not significantly associated with mitochondrial deoxyribonucleic acid (PCOS coefficient, -48.1; 95% CI, -175.0 to 78.9), telomere length (PCOS coefficient, 0.05; 95% CI, -0.05 to 0.15), Framingham score (PCOS coefficient, 0.002; 95% CI, -0.01 to 0.02), or metabolic syndrome (odds ratio for PCOS, 1.29; 95% CI, 0.31-5.44). CONCLUSION Our findings suggest that patients with PCOS have impaired endothelial function compared with non-PCOS patients, although measures of cellular aging and cardiovascular risk as measured by the Framingham score did not differ between the cohorts.
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Affiliation(s)
- Ange Wang
- Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, San Francisco, California.
| | - Jamie Corley
- Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, San Francisco, California
| | - Eleni G Jaswa
- Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, San Francisco, California
| | - Jue Lin
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California
| | - Dana L Smith
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California
| | - Charles E McCulloch
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Heather Huddleston
- Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, San Francisco, California
| | - Marcelle I Cedars
- Division of Reproductive Endocrinology and Infertility, University of California, San Francisco, San Francisco, California
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25
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Sun J, Wang C, Zhao J, Nie X, Lu C, Ye X, He D. The effect of anterior disc displacement with polycystic ovarian syndrome on adolescent condylar bone remodeling. BMC Oral Health 2025; 25:37. [PMID: 39773212 PMCID: PMC11706174 DOI: 10.1186/s12903-024-05324-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Adolescent females have a high prevalence of temporomandibular joint (TMJ) anterior disc displacement (ADD), which can lead to condylar resorption and dentofacial deformity. Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that disrupts bone metabolism. However, the effects of PCOS on bone remodeling especially after disc repositioning (DR) surgery are not well understood. MATERIALS AND METHODS This was a retrospective study. Patients aged 12 to 20 years diagnosed with ADD were reviewed and matched into 3 groups: A (ADD without PCOS), B (ADD with untreated PCOS), and C (ADD with treated PCOS). Each group was divided into 2 subgroups according to ADD observation (A1, B1, C1) and DR (A2, B2, C2). Condylar height (CH) was measured by MRI at the start (T0) and after more than 6 months follow-up (T1). ∆CH (T1-T0) were compared within and between groups. RESULTS 93 patients (157 joints) with an average age of 15.17 ± 2.35 years and follow-up period of 14.04 ± 9.11 months were selected in the study. ∆CH in Group B1 was significantly larger than that in Groups A1 and C1 (p = 0.048, p = 0.018). While in Group B2, it was significant smaller than Groups A2 and C2 (p < 0.001, p = 0.023). There was no significant difference of ∆CH between Groups C2 and A2. DR acquired larger ∆CH than observation within each A, B, C Groups (p < 0.05). Multiple linear regression analysis showed that ∆CH was related to the presence of PCOS (p = 0.003), PCOS treatment (p < 0.001), and DR (p < 0.001). CONCLUSIONS Adolescent ADD with untreated PCOS can aggravate condylar degeneration and affect bone remodeling after DR. PCOS treatment can improve bone remodeling.
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Affiliation(s)
- Jiali Sun
- Department of Oral Surgery, Shanghai Ninth People's Hospital, School of Medicine, College of Stomatology, National Center for Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Chuyao Wang
- Department of Oral Surgery, Shanghai Ninth People's Hospital, School of Medicine, College of Stomatology, National Center for Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Jieyun Zhao
- Department of Oral Surgery, Shanghai Ninth People's Hospital, School of Medicine, College of Stomatology, National Center for Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Xin Nie
- Biostatistics Office of Clinical Research Unit, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Chuan Lu
- Department of Oral Surgery, Shanghai Ninth People's Hospital, School of Medicine, College of Stomatology, National Center for Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, China.
| | - Xiang Ye
- Department of Gynecology and Obstetrics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
| | - Dongmei He
- Department of Oral Surgery, Shanghai Ninth People's Hospital, School of Medicine, College of Stomatology, National Center for Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, China.
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Mody AP, Lodish MB, Auchus RJ, Turcu AF, Jiang F, Huddleston HG. Exploring the Predictive Role of 11-Oxyandrogens in Diagnosing Polycystic Ovary Syndrome. Endocrinol Diabetes Metab 2025; 8:e70022. [PMID: 39815717 PMCID: PMC11735743 DOI: 10.1002/edm2.70022] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/14/2024] [Accepted: 12/15/2024] [Indexed: 01/18/2025] Open
Abstract
CONTEXT Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS), yet the androgen(s) responsible remain ambiguous. Recent studies have suggested that 11-oxygenated C19 steroids (11-oxyandrogens), specifically 11-ketotestosterone, may be a good marker for hyperandrogenism in PCOS. OBJECTIVE To investigate the utility of 11-oxyandrogens to differentiate women with and without PCOS relative to classical androgens. DESIGN SETTING Case-control study performed at a PCOS clinic and research center in an academic setting. PATIENTS 114 women with PCOS and 78 healthy controls. INTERVENTIONS Using the PCOS Tissue Bank, serum samples and data from 114 women registered from 2013 to 2017 between the ages of 18-40 years, were obtained and classified using Rotterdam PCOS criteria. Data were compared to 78 healthy women of similar age, with serum samples obtained between 2017 and 2020. 11-oxyandrogens and sex steroids were measured using mass spectrometry, and their associations to Rotterdam PCOS, age, and BMI were assessed. MAIN OUTCOME MEASURES 11-oxyandrogens and sex steroids. RESULTS Total testosterone, androstenedione, and four 11-oxyandrogens were significantly elevated in women with PCOS compared to age matched controls, controlling for age and BMI (p < 0.01 for all). When considered together, the four 11-oxyandrogens were more predictive of PCOS compared to testosterone and androstenedione. When all androgens were considered individually, 11-ketoandrostenedione was the most predictive of PCOS. Of the six androgens studied, 11-ketotestosterone was the only androgen that demonstrated a weak association with hirsutism score (r = 0.17; p = 0.07) within the PCOS group. CONCLUSION 11-oxyandrogens were statistically higher in women with PCOS and may serve as better predictors of PCOS than testosterone and androstenedione.
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Affiliation(s)
- Armaiti Parvez Mody
- Division of Pediatric EndocrinologyUniversity of CaliforniaDavisCaliforniaUSA
| | - Maya Beth Lodish
- Division of Pediatric EndocrinologyUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Richard Joseph Auchus
- Division of Metabolism, Endocrinology and DiabetesUniversity of MichiganAnn ArborMichiganUSA
| | - Adina F. Turcu
- Division of Metabolism, Endocrinology and DiabetesUniversity of MichiganAnn ArborMichiganUSA
| | - Fei Jiang
- Division of Epidemiology & BiostatisticsUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Heather Gibson Huddleston
- Division of Reproductive Endocrinology and InfertilityUniversity of CaliforniaSan FranciscoCaliforniaUSA
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27
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Revanasiddappa S, Dhananjaya MS, Kansal N, Lila A, Sarathi V. Baseline and Corticotropin-Stimulated Blood Steroid Profiles in Women of Reproductive Age in India: A Cross-Sectional Study and Global Literature Review. Cureus 2025; 17:e77748. [PMID: 39981462 PMCID: PMC11840271 DOI: 10.7759/cureus.77748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
INTRODUCTION Corticotropin (adrenocorticotropic hormone (ACTH))-stimulated blood steroid profile is useful in the diagnosis of rare adrenal disorders but their utility is limited due to lack of assay- and population-specific reference ranges. Hence, we conducted this study to establish the reference ranges for basal and ACTH-stimulated blood steroid profiles in Indian women of reproductive age. METHODS This cross-sectional study included 30 apparently healthy female volunteers aged 18-40 years. Blood samples were collected during the early follicular phase of the menstrual cycle at baseline and 60 minutes after intramuscular administration of 250 µg of ACTH 1-24. Serum steroid levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS After ACTH stimulation, 11-deoxycorticosterone (24.8±19.4 ng/dl from 2.44±0.8 ng/dl, 10.16-fold), corticosterone (from 226.0±184.0 to 2159.0±779.0 ng/dl, 9.55-fold) and 11-deoxycortisol (from 47.4±52.4 to 344.7±246.0 ng/dl, 7.28-fold) demonstrated greater than seven-fold elevation whereas 17α-hydroxyprogesterone (from 38.0±39.0 ng/dl to 129.0±75.0 ng/dl, 3.39-fold), dehydroepiandrosterone (from 340.0±221.8 to 998.0±580 ng/dl, 2.94-fold), cortisol (from 10.90±3.80 to 24.72±4.46 µg/dl, 2.27-fold) and aldosterone (from 6.65±5.19 to 13.88±8.11 ng/dl, 2.09-fold) showed 2-3.5-fold elevation. CONCLUSIONS This study presents reference ranges for baseline and ACTH-stimulated steroid panels in Asian Indian women of reproductive age and summarises the available blood steroid profiles for reproductive-age women from the literature.
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Affiliation(s)
| | - Melkunte S Dhananjaya
- Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
| | - Nimmi Kansal
- Clinical Chemistry and Biochemical Genetics, Dr Lal PathLabs Ltd, New Delhi, IND
| | - Anurag Lila
- Endocrinology, Seth Gordhandas Sunderdas Medical College, Mumbai, IND
| | - Vijaya Sarathi
- Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, IND
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Huang X, Geng H, Liang C, Xiong X, Du X, Zhuan Q, Liu Z, Meng L, Zhou D, Zhang L, Fu X, Qi X, Hou Y. Leonurine restrains granulosa cell ferroptosis through SLC7A11/GPX4 axis to promote the treatment of polycystic ovary syndrome. Free Radic Biol Med 2025; 226:330-347. [PMID: 39547522 DOI: 10.1016/j.freeradbiomed.2024.11.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 11/02/2024] [Accepted: 11/12/2024] [Indexed: 11/17/2024]
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder marked by ovarian dysfunction and metabolic abnormality. This study explores the therapeutic potential of leonurine (SCM-198) in PCOS. Our results show that SCM-198 treatment significantly improved ovarian function, hormone disorders and insulin resistance while reducing granulosa cell ferroptosis. This study provides the first evidence that SCM-198 modulates the gut microbiota composition, increases the abundance of Christensenella minuta, and boosts butyrate levels. Transcriptomic and metabolomic analyses revealed that PCOS patients exhibit granulosa cell ferroptosis and decreased butyrate levels in follicular fluid. Butyrate was shown to alleviate ferroptosis in granulosa cells via the SLC7A11/TXNRD1/GPX4 pathway, as confirmed in vitro with KGN cells. The therapeutic mechanism of SCM-198 in the management of PCOS via the gut microbiota-ovary axis involves the enhancement of gut microbiota and its metabolites. This intervention improves ovarian function and alleviates PCOS symptoms by targeting ferroptosis in granulosa cells.
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Affiliation(s)
- Xiaohan Huang
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Hucheng Geng
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Chunxiao Liang
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Xianglei Xiong
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
| | - Xingzhu Du
- State Key Laboratory of Animal Biotech Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Qingrui Zhuan
- State Key Laboratory of Animal Biotech Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhiqiang Liu
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Lin Meng
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Dan Zhou
- State Key Laboratory of Animal Biotech Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Luyao Zhang
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Xiangwei Fu
- State Key Laboratory of Animal Biotech Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Xinyu Qi
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
| | - Yunpeng Hou
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
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Motta AB. Polycystic Ovary Syndrome and Oxidative Stress. Natural Treatments. Curr Med Chem 2025; 32:1457-1468. [PMID: 38549535 DOI: 10.2174/0109298673270372231130071320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 10/17/2023] [Accepted: 10/24/2023] [Indexed: 05/01/2025]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathology affecting women in their reproductive ages. However, PCOS is also related to metabolic abnormalities such as metabolic syndrome (MS), insulin resistance (IR), and type 2 diabetes, among others. Consequently, an inflammatory and pro-oxidative status is also present in these patients, aggravating the syndrome's symptoms. This work aims to discuss some late treatments that focus on oxidative stress (OS) as a central feature related to primary PCOS abnormalities. Therefore, this review focuses on the evidence of anti-oxidant diets, natural compounds, mineralocorticoids, and combined therapies for PCOS management. Oxidative stress (OS) is important in PCOS pathogenesis. In this regard, increased levels of oxidative oxygen species and decreased levels of anti-oxidant agents’ impact PCOS's reproductive and metabolic features. In the last years, non-pharmacological therapies have been considered a first line of treatment. For these reasons, several natural compounds such as Kelult honey (KH), Foeniculum Vulgare, Calendula officinalis Linn, Eugenia caryophyllus and Myristicafragrans, vitamin C, vitamin E, selenium, zinc, beta-carotene, magnesium, curcumin, mineralocorticoids and melatonin alone or in combination are powerful anti-oxidant agents being used for PCOS management. Data presented here suggest that natural therapies are essential in managing both reproductive and metabolic features in PCOS patients. Due to the results obtained, these incipient therapies deserve further investigation.
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Affiliation(s)
- Alicia Beatriz Motta
- Laboratorio de Fisio-patología ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Paraguay 2155, CP1121, Ciudad Autónoma de Buenos Aires, Argentina
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Parveen S, Khan S, Moin S, Nigar A, Khan MM, Alam R. Association of FTO protein with hyperandrogenism metabolic disturbances in women with polycystic ovary syndrome. Endocr Regul 2025; 59:33-41. [PMID: 40258223 DOI: 10.2478/enr-2025-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/23/2025] Open
Abstract
Objective. Polycystic ovary syndrome (PCOS) is one of the commonest endocrinopathies in women characterized by hyperandrogenism, ovulatory dysfunction, and insulin resistance affecting 5-20% of reproductive-aged women worldwide. Recent studies have emphasized the role of the fat mass and obesity-associated (FTO) gene in the development of PCOS, specifically the rs9939609 A/T polymorphism, which is linked to an increased risk of PCOS. The study aimed to investigate the levels of FTO protein and its association with luteinizing hormone (LH), follicle-stimulating hormone (FSH) and anthropometric parameters in patients with PCOS compared to healthy controls. Materials. A total of 298 women, comprising 149 patients and 149 healthy controls, enrolled in the study. Anthropometric parameters (body mass index, BMI; waist circumference, WC; hip circumference, HC; waist-to-hip ratio, WHR), and hormonal assays (LH, FSH, LH/FSH ratio) were performed. FTO protein levels were measured by ELISA kit and their association with these parameters was analyzed. A receiver operator characteristic (ROC) curve analysis was performed to evaluate the discriminatory power of FTO protein levels in distinguishing PCOS cases and controls. A value p<0.05 was considered statistically significant. Results. FTO protein levels were significantly elevated in PCOS women with increased BMI, WC, HC, and WHR (p=<0.05). The mean of BMI showed a positive correlation with both WC (r=0.367, p<0.001) and HC (r=0.395, p<0.001). WC strongly correlated with HC (r=0.780, p<0.001) and WHR (r=0.465, p<0.001). LH significantly correlated with FSH (r=0.543, p<.001), and LH/FSH (r=0.553, p<.001). FTO protein showed a positive correlation with LH (r=0.364, p<0.001), and FSH (r=0.166, p<0.001). Additionally, a negative correlation of FTO protein with BMI (r=-0.190, p<0.05), WC (r=-0.277, p<0.05), and WHR (r=-0.408 p<0.001) was observed. The levels of FTO protein were significantly higher in PCOS patients compared to controls. Significant correlations were also found between FTO protein levels and the anthropometric or hormonal parameters. The AUC for FTO protein levels was 0.624 (p=0.550), indicating moderate discriminatory power, but lacking statistical significance. Conclusion. The study found that FTO protein levels are significantly higher in PCOS women correlating with anthropometric and hormonal parameters (increased LH, decreased FSH). This highlights potential involvement of FTO protein in the hormonal and metabolic disturbances characteristics of the syndrome indicating its biomarker character for the condition.
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Affiliation(s)
- Sadaf Parveen
- 1Department of Biochemistry, Integral Institute of Medical Sciences & Research (IIMSR), Integral University, Lucknow, Uttar Pradesh, India
| | - Saba Khan
- 1Department of Biochemistry, Integral Institute of Medical Sciences & Research (IIMSR), Integral University, Lucknow, Uttar Pradesh, India
| | - Shagufta Moin
- 2Department of Biochemistry, Jawaharlal Nehru Medical College Aligarh Muslim University Aligarh, India
| | - Asma Nigar
- 3Department of Obstetrics and Gynaecology, Integral Institute of Medical Sciences & Research (IIMSR), Integral University, Lucknow, Uttar Pradesh, India
| | - Mohammad Mustufa Khan
- 4Department of Basic Medical Sciences, Integral Institute of Allied Health Sciences & Research (IIAHSR), Integral University, Lucknow, Uttar Pradesh, India
| | - Roshan Alam
- 1Department of Biochemistry, Integral Institute of Medical Sciences & Research (IIMSR), Integral University, Lucknow, Uttar Pradesh, India
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Góral A, Żywot K, Zalewski W, Jagodziński A, Murawski M. Polycystic Ovary Syndrome and Eating Disorders-A Literature Review. J Clin Med 2024; 14:27. [PMID: 39797110 PMCID: PMC11720544 DOI: 10.3390/jcm14010027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/21/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age and is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS is often associated with hormonal imbalances, metabolic dysfunction and comorbid psychiatric disorders, including eating disorders (EDs). The review identifies key hormonal factors-serotonin, leptin, insulin, ghrelin, kisspeptin and cortisol-and their roles in the pathophysiology of PCOS and associated psychiatric symptoms. Serotonin deficiency, commonly seen in PCOS patients, is associated with mood and eating disorders. Fluctuations in leptin, the satiety hormone, affect hypothalamic-pituitary-ovarian axis function and ovarian follicle maturation, increasing the risk of infertility. Elevated levels of kisspeptin in PCOS patients contribute not only to hormonal dysregulation but also to increased susceptibility to eating disorders such as bulimia and binge eating, likely due to its influence on the limbic system and glucose metabolism. Hyperinsulinemia and insulin resistance further impair reproductive and metabolic health, while promoting eating disorders such as binge eating and bulimia. Ghrelin and cortisol also emerge as significant factors. The review emphasizes the bidirectional relationship between PCOS and eating disorders, in which hormonal imbalances perpetuate psychiatric conditions, creating a vicious cycle. A multidisciplinary approach including gynecologists, endocrinologists, psychiatrists and nutritionists is recommended to ensure complex treatment. Early identification of those at risk through targeted screening and personalized interventions is key. Future research should focus on discovering the underlying hormonal mechanisms to improve treatment strategies and quality of life for women with PCOS.
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Affiliation(s)
- Agata Góral
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (K.Ż.); (W.Z.)
| | - Klaudia Żywot
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (K.Ż.); (W.Z.)
| | - Wojciech Zalewski
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (K.Ż.); (W.Z.)
| | - Adam Jagodziński
- Clinical Department of Gynecologic Surgery and Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (A.J.); (M.M.)
| | - Marek Murawski
- Clinical Department of Gynecologic Surgery and Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (A.J.); (M.M.)
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Nandakumar M, Das P, Sathyapalan T, Butler AE, Atkin SL. Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome. Biomolecules 2024; 15:4. [PMID: 39858399 PMCID: PMC11763313 DOI: 10.3390/biom15010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
OBJECTIVE Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder with an increased risk for cardiovascular disease (CVD) that is enhanced by obesity. This study sought to determine whether a panel of cardiovascular risk proteins (CVRPs) would be dysregulated in overweight/obese PCOS patients, highlighting potential biomarkers for CVD in PCOS. METHODS In this exploratory cross-sectional study, plasma levels of 54 CVRPs were analyzed in women with PCOS (n = 147) and controls (n = 97). CVRPs were measured using the SOMAscan proteomic platform (version 3.1), with significant proteins identified through linear models, regression analysis, and receiver operating characteristic (ROC) analysis. Analysis on BMI-matched subsets of the cohort were undertaken. Functional enrichment and protein-protein interaction analyses elucidated the pathways involved. RESULTS Eleven CVRPs were dysregulated in PCOS (whole set, without matching for body mass index (BMI) or insulin resistance (IR)): leptin, Interleukin-1 receptor antagonist protein (IL-1Ra), polymeric immunoglobulin receptor (PIGR), interleukin-18 receptor (IL-18Ra), C-C motif chemokine 3 (MIP-1a), and angiopoietin-1 (ANGPT1) were upregulated whilst advanced glycosylation end product-specific receptor, soluble (sRAGE), bone morphogenetic protein 6 (BMP6); growth/differentiation factor 2 (GDF2), superoxide dismutase [Mn] mitochondrial (MnSOD), and SLAM family member 5 (SLAF5) were downregulated versus the controls. In BMI-matched (overweight/obese, BMI ≥ 26 kg/m2) subset analysis, six CVRPs were common to the whole set: ANGPT1 and IL-1Ra were upregulated; and sRAGE, BMP6, GDF2, and Mn-SOD were downregulated. In addition, lymphotactin (XCL1) was upregulated and placenta growth factor (PIGF), alpha-L-iduronidase (IDUA), angiopoietin-1 receptor, and soluble (sTie-2) and macrophage metalloelastase (MMP12) were downregulated. A subset analysis of BMI-matched plus insulin resistance (IR)-matched women revealed only upregulation of tissue factor (TF) and renin in PCOS, potentially serving as biomarkers for cardiovascular risk in overweight/obese women with PCOS. CONCLUSIONS A combination of upregulated obesity-related CVRPs (ANGPT1/IL/1Ra/XCL1) and downregulated cardioprotective proteins (sRAGE/BMP6/Mn-SOD/GDF2) in overweight/obese PCOS women may contribute to the increased risk for CVD. TF and renin upregulation observed in the BMI- and IR-matched limited sample PCOS subgroup indicates their potential risk of CVD.
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Affiliation(s)
- Manjula Nandakumar
- Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
| | - Priya Das
- Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RU, UK;
| | - Alexandra E. Butler
- Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
| | - Stephen L. Atkin
- Research Department, Royal College of Surgeons of Ireland, Adliya, Busaiteen 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
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Palomba S, Seminara G, Costanzi F, Caserta D, Aversa A. Chemerin and Polycystic Ovary Syndrome: A Comprehensive Review of Its Role as a Biomarker and Therapeutic Target. Biomedicines 2024; 12:2859. [PMID: 39767764 PMCID: PMC11672894 DOI: 10.3390/biomedicines12122859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/12/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Chemerin, an adipokine implicated in inflammatory, metabolic, and adipogenic processes, has been detected in high serum concentration in women with polycystic ovary syndrome (PCOS) and seems to play a role in PCOS pathogenesis. Moreover, at present, no comprehensive and critical document is available in the literature on this topic. The aim of the current study was to comprehensively review the latest available data to confirm the evidence about the association between chemerin and PCOS, highlighting its potential role as an upcoming biomarker and therapeutic target. Methods: A search in the literature of studies published between 2019 and 2024 was conducted using PubMed, Cochrane Library, and Web of Science, focusing on research related to chemerin, PCOS, and PCOS-related features, comorbidities, and complications. A qualitative structured synthesis of key findings was performed according to the specific thematic areas selected, including and discussing clinical data on women with PCOS and experimental studies in humans and animal models of PCOS. Results: Available data confirm increased serum levels of chemerin in women with PCOS compared with controls, independent of obesity and body mass index. Chemerin is associated with insulin resistance, hyperandrogenism, and ovarian dysfunction in PCOS individuals, inhibiting folliculogenesis and steroidogenesis. Experimental animal models underscore chemerin's regulatory roles through its receptors within the hypothalamic-pituitary-ovarian axis and peripheral tissues. High systemic levels of chemerin in PCOS may also be related to the increased risk of pregnancy complications, especially gestational diabetes mellitus and preeclampsia. Conclusions: The current review study highlights the role of chemerin in PCOS pathophysiology, severity, and associated comorbidities and complications, assessing its value as a future biomarker and foreshadowing its potential as a therapeutic target.
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Affiliation(s)
- Stefano Palomba
- Unit of Obstetrics and Gynecology, Grande Ospedale Metropolitano of Reggio Calabria, University Sapienza of Rome, 89124 Reggio, Italy
| | - Giuseppe Seminara
- Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (G.S.); (A.A.)
| | - Flavia Costanzi
- Unit of Gynecology, Sant’Andrea Hospital of Rome, University Sapienza of Rome, 00185 Roma, Italy; (F.C.); (D.C.)
| | - Donatella Caserta
- Unit of Gynecology, Sant’Andrea Hospital of Rome, University Sapienza of Rome, 00185 Roma, Italy; (F.C.); (D.C.)
| | - Antonio Aversa
- Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (G.S.); (A.A.)
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Marginean CM, Pirscoveanu D, Cazacu SM, Popescu MS, Marginean IC, Iacob GA, Popescu M. Non-Alcoholic Fatty Liver Disease, Awareness of a Diagnostic Challenge—A Clinician’s Perspective. GASTROENTEROLOGY INSIGHTS 2024; 15:1028-1053. [DOI: 10.3390/gastroent15040071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease globally. NAFLD is a complex pathology, considered to be the hepatic expression of metabolic syndrome (MetS). It is supposed to become the main indication for liver transplantation in the coming years and is estimated to affect 57.5–74.0% of obese people, 22.5% of children and 52.8% of obese children, with 50% of individuals with type 2 diabetes being diagnosed with NAFLD. Recent research has proved that an increase in adipose tissue insulin resistance index is an important marker of liver injury in patients with NAFLD. Despite being the main underlying cause of incidental liver damage and a growing worldwide health problem, NAFLD is mostly under-appreciated. Currently, NAFLD is considered a multifactorial disease, with various factors contributing to its pathogenesis, associated with insulin resistance and diabetes mellitus, but also with cardiovascular, kidney and endocrine disorders (polycystic ovary syndrome, hypothyroidism, growth hormone deficiency). Hepatitis B and hepatitis C, sleep apnea, inflammatory bowel diseases, cystic fibrosis, viral infections, autoimmune liver diseases and malnutrition are some other conditions in which NAFLD can be found. The aim of this review is to emphasize that, from the clinician’s perspective, NAFLD is an actual and valuable key diagnosis factor for multiple conditions; thus, efforts need to be made in order to increase recognition of the disease and its consequences. Although there is no global consensus, physicians should consider screening people who are at risk of NAFLD. A large dissemination of current concepts on NAFLD and an extensive collaboration between physicians, such as gastroenterologists, internists, cardiologists, diabetologists, nutritionists and endocrinologists, is equally needed to ensure we have the knowledge and resources to address this public health challenge.
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Affiliation(s)
- Cristina Maria Marginean
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Denisa Pirscoveanu
- Neurology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Sergiu Marian Cazacu
- Research Center of Gastroenterology and Hepatology, Gastroenterology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Marian Sorin Popescu
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Endocrinology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Bazarganipour F, Taghavi SA, Montazeri A, Ahmadi F, Derakhshideh Z, Asadikalameh Z. Psychometric properties of the Iranian version of the polycystic ovary syndrome quality of life questionnaire for married and unmarried women with PCOS: PCOSQoL-47 and PCOSQoL-42. BMC Psychol 2024; 12:722. [PMID: 39633465 PMCID: PMC11619310 DOI: 10.1186/s40359-024-02158-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 11/05/2024] [Indexed: 12/07/2024] Open
Abstract
INTRODUCTION The incidence of PCOS is notably elevated in Iran, making it crucial to examine the quality of life among these individuals. This study aimed to thoroughly evaluate the psychometric properties of the Iranian adaptations of the PCOSQoL-47 and PCOSQoL-42 questionnaires. The application of these tools is significant as they could enhance further research in in communities with similar social norms concerning marriage and sexuality. METHODS This study employed a cross-sectional design. Following the linguistic validation of the Iranian adaptation of the PCOSQoL-47 and PCOSQoL-42, a panel of experts reviewed the items through an evaluation of the content validity index (CVI) and content validity ratio (CVR). Subsequently, a semi-structured interview was carried out to evaluate face validity. Consequently, discriminant validity was assessed using the known groups comparison. Convergent validity was evaluated by assessing the correlation between similar content on the PCOSQoL-47 and PCOSQoL-42, SF-12 and body image questionnaire. Responsiveness was assessed by comparing two scales scoring in baseline and eight-week follow-up data of prescription contraceptive Daine-35. In addition, reliability analyses including internal consistency and test-retest analysis were carried out. RESULTS The CVR in this study for the total scale was 0.98 for two scales, indicating a satisfactory result. The CVI for the scale was found to be 0.98 and 0.99 for PCOSQoL-42 and PCOSQoL-47, respectively suggesting that it had a good content validity. Known groups comparison revealed that the two scales effectively distinguished between sub-groups of women with varying symptoms specific to PCOS, thereby supporting their discriminant validity. Additionally, convergent validity was evaluated and, as anticipated, a strong positive correlation was observed between corresponding subscales of the two instruments. The paired t-test showed significant changes in PCOSQoL-47 and PCOSQoL-42 scores (p < 0.001) indicating as a responsive outcome measure to detect significant changes over time before and after treatment. Additional analyses indicated satisfactory results of PCOSQoL-42 for internal consistency (Cronbach's alpha ranging from 0.72 to 0.78) and intraclass correlation coefficients (ranging 0.67 to 0.92; P < 0.05). regarding PCOSQoL-47, Cronbach's alpha ranging from 0.80 to 0.82 and intraclass correlation coefficients (ranging 0.61 to 0.73; P < 0.05). CONCLUSION The PCOSQoL-47 and PCOSQoL-42 have undergone thorough testing in Iran and may be utilized as outcome measures in forthcoming studies within this demographic.
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Affiliation(s)
- Fatemeh Bazarganipour
- Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
- Department of Midwifery, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Seyed Abdolvahab Taghavi
- Department of Gynecology and Obstetrics, Yasuj University of Medical Sciences, Yasuj, Iran
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Ali Montazeri
- Mental Health Research Group, Health Metrics Research Center, Iranian Institute for Health Sciences Research, ACECR, Tehran, Iran
| | | | - Zahra Derakhshideh
- Department of Midwifery, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Zahra Asadikalameh
- Department of Gynecology and Obstetrics, Yasuj University of Medical Sciences, Yasuj, Iran.
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Han SJ, Kim H, Ku SY, Suh CS. Comparison of resumption of ovulation after cessation of oral contraceptives and medroxyprogesterone acetate in women with polycystic ovary syndrome. Gynecol Endocrinol 2024; 40:2309349. [PMID: 38306179 DOI: 10.1080/09513590.2024.2309349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 12/04/2023] [Accepted: 01/17/2024] [Indexed: 02/04/2024] Open
Abstract
OBJECTIVE Both oral contraceptive pills (OCPs) and cyclic medroxyprogesterone acetate (MPA) are widely used to control menstrual abnormalities in women with polycystic ovary syndrome (PCOS). We aimed to evaluate the chance of ovulation resumption after cessation of OCPs and MPA in women with PCOS. METHODS A retrospective study was conducted of women with PCOS who were treated with OCPs or cyclic MPA from September 2015 to March 2019. After cessation of medication, ovulation was assessed using basal body temperature and/or measurement of serum progesterone. The odds ratio for ovulation resumption was assessed with multivariable logistic regression. Additionally, doubly robust analysis was performed with inverse-probability-weighted analysis and regression adjustment based on the covariate balancing propensity score to adjust for the effect of covariates on the treatment assignment. RESULTS Among 272 women with PCOS, 136 were prescribed OCPs and 136 were prescribed cyclic MPA. Ovulation resumed in 18.4% of women (n = 25) after cessation of MPA and in 24.3% of women (n = 33) after cessation of OCPs. The odds of ovulation resumption in MPA users were comparable with those in OCP users (adjusted odds ratio (aOR) 1.00, 95% confidence interval (CI) 0.89-1.12). After multiple imputation due to missing values, the results did not change substantially (aOR 0.99, 95% CI 0.89-1.10). CONCLUSIONS Among women with PCOS, MPA users have a similar chance of ovulation resumption as OCP users after cessation of medication. Cyclic MPA can be a good alternative to OCPs in women for whom OCPs are contraindicated or who decline to take OCPs.
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Affiliation(s)
- Soo Jin Han
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
| | - Hoon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
| | - Seung-Yup Ku
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
| | - Chang Suk Suh
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
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Theodorou A, Karagiannakis DS, Stefanaki K, Kassi E, Peppa M, Vryonidou A, Paschou SA. Female-specific risk factors for cardiovascular disease: an update. Hormones (Athens) 2024; 23:637-653. [PMID: 38922384 DOI: 10.1007/s42000-024-00576-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 06/11/2024] [Indexed: 06/27/2024]
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. While it was previously believed that men have greater susceptibility to CVD, recent research suggests that women face an increased risk of CVD after the onset of menopause, primarily due to the loss of the protective effects of estrogens. Premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), and gestational factors, such as gestational diabetes mellitus (GDM), recurrent pregnancy loss, preterm delivery, and preeclampsia, are specific reproductive disorders that may contribute to an elevated risk of CVD at earlier ages, i.e., before the onset of menopause. This suggests that women with these conditions should be closely monitored for CVD risk factors even before reaching menopause. Such early intervention may help reduce the incidence of CVD and improve overall cardiovascular health in this population. The precise pathophysiological mechanism underlying the development of CVD in women with menopause, premature POI, PCOS, and gestational factors remains elusive. This review article seeks to elucidate the latest research on the relationship between these conditions and CVD in women, aiming to explore the underlying pathogenic mechanisms contributing to this association.
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Affiliation(s)
- Angeliki Theodorou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vasilisis Sophias Avenue, Athens, PC, 11528, Greece
| | - Dimitrios S Karagiannakis
- Academic Department of Gastroenterology, Laiko General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Katerina Stefanaki
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vasilisis Sophias Avenue, Athens, PC, 11528, Greece
| | - Evanthia Kassi
- Endocrine Unit, First Department of Propaedeutic and Internal Medicine, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Melpomeni Peppa
- Endocrine Unit and Diabetes Center, Second Department of Internal Medicine, School of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Andromachi Vryonidou
- Department of Endocrinology and Diabetes Center, Hellenic Red Cross Hospital, Athens, Greece
| | - Stavroula A Paschou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vasilisis Sophias Avenue, Athens, PC, 11528, Greece.
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Zuchelo LTS, Alves MS, Baracat EC, Sorpreso ICE, Soares JM. Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis. Gynecol Endocrinol 2024; 40:2360077. [PMID: 38818646 DOI: 10.1080/09513590.2024.2360077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 05/21/2024] [Indexed: 06/01/2024] Open
Abstract
OBJECTIVE To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.
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Affiliation(s)
- Lea T S Zuchelo
- Laboratório em Ginecologia Molecular e Estrutural da Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Mayara S Alves
- Laboratório em Ginecologia Molecular e Estrutural da Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Edmund C Baracat
- Laboratório em Ginecologia Molecular e Estrutural da Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Isabel C E Sorpreso
- Laboratório em Ginecologia Molecular e Estrutural da Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - José M Soares
- Laboratório em Ginecologia Molecular e Estrutural da Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Palomba S, Costanzi F, Caserta D, Vitagliano A. Pharmacological and non-pharmacological interventions for improving endometrial receptivity in infertile patients with polycystic ovary syndrome: a comprehensive review of the available evidence. Reprod Biomed Online 2024; 49:104381. [PMID: 39454320 DOI: 10.1016/j.rbmo.2024.104381] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 07/08/2024] [Accepted: 07/15/2024] [Indexed: 10/28/2024]
Abstract
Direct and indirect evidence suggests that endometrial receptivity may play a crucial role in the reduced fertility rate of women with polycystic ovary syndrome (PCOS). Various pharmacological and non-pharmacological strategies with potential effects on endometrial receptivity in patients with PCOS have been proposed. The aim of this study was to summarize the rationale and the clinical and experimental evidence of interventions tested for improving endometrial receptivity in infertile patients with PCOS. A systematic review was conducted by consulting electronic databases. All interventions with a potential influence on endometrial receptivity in infertile patients with PCOS were evaluated, and their main biological mechanisms were analysed. In total, 24 interventions related to endometrial receptivity were identified. Notwithstanding a strong biological rationale, no intervention aimed at improving endometrial receptivity in women with PCOS is supported by an adequate body of evidence, limiting their use in clinical practice. Further high-quality research is needed in this field to limit potentially ineffective and unsafe add-on treatments in infertile patients with PCOS.
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Affiliation(s)
- Stefano Palomba
- Unit of Gynaecology, Department of Medical-Surgical Sciences and Translational Medicine, University 'Sapienza' of Rome, Sant'Andrea Hospital, Rome, Italy.
| | - Flavia Costanzi
- Unit of Gynaecology, Department of Medical-Surgical Sciences and Translational Medicine, University 'Sapienza' of Rome, Sant'Andrea Hospital, Rome, Italy; University 'Sapienza' of Rome, Sant'Andrea Hospital, Rome, Italy
| | - Donatella Caserta
- Unit of Gynaecology, Department of Medical-Surgical Sciences and Translational Medicine, University 'Sapienza' of Rome, Sant'Andrea Hospital, Rome, Italy
| | - Amerigo Vitagliano
- Unit of Obstetrics and Gynaecology, Department of Interdisciplinary Medicine, University of Bari, Bari, Italy
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Ting Z, Xinghua T, Xiao X, Lingchuan L, Xiaomei W, Tao Y. The impact of androgen levels on serum metabolic profiles in patients with polycystic ovary syndrome. Gynecol Endocrinol 2024; 40:2352136. [PMID: 38733359 DOI: 10.1080/09513590.2024.2352136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/24/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVE This study aimed to investigate the impact of serum androgen levels on metabolic profiles in patients with polycystic ovary syndrome (PCOS). METHODS We included 216 patients with PCOS and 216 healthy individuals selected as the control group. According to the measured serum androgen levels, patients with PCOS were divided into the hyperandrogenism group and non-hyperandrogenism group. Clinical metabolic indicators were assessed and compared between the two groups. Additionally, we assessed the correlation between androgen levels and clinical metabolic indicators. RESULTS The body mass index, waist-to-hip ratio, mF-G score, and acne score, as well as T, LH, LSH/FSH, FPG, Cr, UA, TG, TC, and LDL-C levels were significantly higher in the PCOS group than in the control group. The incidence of hyperandrogenism and clinical hyperandrogenism in the PCOS group was significantly higher than that in the control group. Regarding clinical hyperandrogenism, hirsutism, acne, and acanthosis nigricans were significantly more common in the PCOS group than in the control group. Serum androgen levels were significantly correlated with the mF-G score, acne score, FSH, glucose concentration at 30 min, glucose concentration at 60 min, glucose concentration at 120 min, FINS, N120, HOMA-IR, HbA1c, AUCG, UA, TG, and hHDL-Clevels. CONCLUSION Elevated serum androgen levels are commonly observed in patients with PCOS and are associated with multiple metabolic abnormalities. Therefore, it is recommended to regularly monitor glucose and lipid metabolism-related indicators in patients with PCOS who have elevated androgen levels.
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Affiliation(s)
- Zhao Ting
- Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Tao Xinghua
- Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- Department of Gynecology, The People's Hospital of Hezhou, Hezhou, China
| | - Xiao Xiao
- Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Li Lingchuan
- Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Wu Xiaomei
- Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Yuan Tao
- Department of Gynecology, The First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
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Underland LJ, Kenigsberg Fechter L, Agarwal C, Sin S, Punjabi N, Heptulla R, Arens R. Insulin sensitivity and obstructive sleep apnea in adolescents with polycystic ovary syndrome. Minerva Endocrinol (Torino) 2024; 49:372-380. [PMID: 35388662 DOI: 10.23736/s2724-6507.22.03619-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) in adults is linked with insulin resistance (IR) and obstructive sleep apnea (OSA). However, less is known about these associations in adolescents. METHODS We studied three groups of adolescents: 27 obese PCOS (OPCOS) (ages 13-21), 11 normal-weight PCOS (NPCOS) (ages 13-21 years), and eight healthy controls (ages 18-21 years). A hyperinsulinemic euglycemic clamp study was performed in all groups to determine IR by insulin sensitivity (M/I). Polysomnography was performed to assess for OSA in OPCOS and NPCOS groups. We compared indices of IR among all groups and OSA among OPCOS, and NPCOS. RESULTS We noted that OPCOS and NPCOS and controls differed significantly in their IR. M/I was significantly lower in OPCOS vs. controls (P=0.0061), and also lower for NPCOS vs control but this approached but did not reach statistical significance (P=0.084). In addition, none of the NPCOS subjects had OSA compared to 42% of OPCOS (P=0.03). CONCLUSIONS Our study suggests OPCOS adolescents have increased IR compared to controls and NPCOS subjects. Higher IR for NPCOS vs controls approached but did not reach statistical significance. Larger studies are needed. In addition, adolescents with OPCOS are at a high risk for OSA.
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Affiliation(s)
- Lisa J Underland
- Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA -
| | | | - Chhavi Agarwal
- Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Sanghun Sin
- Division of Respiratory and Sleep Medicine, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Netra Punjabi
- Division of Pediatric Endocrinology, Lucile Packard Children's Hospital, Palo Alto, CA, USA
| | - Rubina Heptulla
- Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Raanan Arens
- Division of Respiratory and Sleep Medicine, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
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Xie J, Cao Y, Wen Q, Song X, Shi Y, Gao X. Research trend and hotspots of polycystic ovary syndrome with depression from 1993 to 2024: a bibliometric analysis. Front Glob Womens Health 2024; 5:1468471. [PMID: 39669109 PMCID: PMC11634872 DOI: 10.3389/fgwh.2024.1468471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 11/05/2024] [Indexed: 12/14/2024] Open
Abstract
Background Polycystic ovary syndrome (PCOS), a common endocrine disorder, affects women of reproductive age, and its adverse consequences affect women throughout their lifespan, from adolescence to postmenopause. The prevalence of depression is much higher in women with PCOS than in healthy controls. Thus, it is recommended that depressive syndrome be screened routinely in all patients with PCOS at diagnosis. To date, no comprehensive bibliometric analysis has been conducted in this field. Therefore, we conducted a bibliometric analysis to describe the current status, trends, and hotspots of PCOS research related to depression. Materials and methods Using data retrieved from the Web of Science (WoS) Core Collection database from 1993 to 2024, bibliometric analyses were performed using WoS and CiteSpace software. Results Since the first paper was published in 1993, studies related to PCOS and depression have remained rare in the following decade. Since the establishment of the Rotterdam criteria in 2003, research on the etiology, pathogenesis, and treatment of PCOS with depressive syndrome has entered a booming period. The United States and Australia indisputably took leading positions in this area, with the most outstanding institutions in the world being the University of Pennsylvania and Monash University. Although achievements have flourished since 2003, the exact pathogenesis of PCOS remains uncertain owing to its heterogeneity. New research is rapidly increasing to fill these gaps and to push forward the goal of improving the quality of life in women with PCOS and depression. Along with progress in research, the world's leading societies organize conferences every 5 years to update guidelines for the assessment and management of PCOS. "Oxidative stress," "inflammation," "obstructive sleep apnea," "gut microbiota," and "single nucleotide polymorphism" appeared as new hotspots in the recent 5 years. Conclusion A bibliometric analysis was performed to describe the trends and hotspots of research in women with PCOS and depression to attract the attention of more researchers to this topic. Systematic Review Registration https://www.webofscience.com/wos/woscc/basic-search.
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Affiliation(s)
- Jing Xie
- Biomedical Center, Qingdao University, Qingdao, Shandong, China
| | - Yi Cao
- Biomedical Center, Qingdao University, Qingdao, Shandong, China
| | - Qian Wen
- Biomedical Center, Qingdao University, Qingdao, Shandong, China
| | - Xuxia Song
- Biomedical Center, Qingdao University, Qingdao, Shandong, China
| | - Yuanyuan Shi
- Biomedical Center, Qingdao University, Qingdao, Shandong, China
| | - Xia Gao
- Department of Acupuncture, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, Shandong, China
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Bai T, Deng X, Bi J, Ni L, Li Z, Zhuo X. The effects of acupuncture on patients with premature ovarian insufficiency and polycystic ovary syndrome: an umbrella review of systematic reviews and meta-analyses. Front Med (Lausanne) 2024; 11:1471243. [PMID: 39655237 PMCID: PMC11627218 DOI: 10.3389/fmed.2024.1471243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 10/31/2024] [Indexed: 12/12/2024] Open
Abstract
Background Previous studies have suggested that acupuncture could improve the clinical outcomes of women with premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). However recent meta-analyses have provided inconclusive findings. This umbrella meta-analysis aimed to explore the effect of acupuncture therapies on PCOS and POI outcomes. Methods A systematic literature search was carried out in in PubMed, Scopus, Web of Science, and Chinese databases, including Wan Fang Data Knowledge Service Platform, CBM, CNKI, and VIP up until April 2024 to gather relevant studies. Inclusion criteria were meta-analyses on the effect of acupuncture or combined therapies with standard medications or traditional Chinese medicine (TCM) on PCOS and POI. The outcomes were pregnancy rates, ovulation rates, hormone levels, glycemic indices, resumption of menstruation, endometrial thickness, live birth rates, abortion rates, and body mass index (BMI). Studies with irrelevant interventions, animal studies, reviews without quantitative analysis, and studies with insufficient data were excluded. Standardized mean difference (SMD) with a 95% confidence interval (CI) and relative risk (RR) with a 95% CI were used as effect sizes to pool the data using a random effects model. Results A total of 38 meta-analyses, 20 studies (sample size: 27,106 patients) for PCOS and 18 studies (sample size: 19,098 patients) for POI, were included. Overall, in women with PCOS, acupuncture therapies were significantly associated with a higher pregnancy rate, ovulation rate, and reduced serum levels of luteinizing hormone (LH), testosterone, LH/follicle-stimulating hormone (FSH), insulin resistance, and BMI. Moreover, FSH, fasting glucose, and fasting insulin levels were improved in subgroup analyses. For POI, acupuncture significantly improved serum levels of LH, FSH, LH/FSH ratio, and estradiol. Conclusion Acupuncture-related therapies improve pregnancy rate, and metabolic and hormonal imbalances in patients with POI and PCOS. Systematic review registration The protocol of the study was registered in PROSPERO (CRD42024572893). Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024572893.
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Affiliation(s)
- Tianyu Bai
- Department of Acupuncture-Moxibustion and Tuina, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Xinyun Deng
- Center for Reproductive Medicine, Zibo Maternal and Child Health Hospital, Zibo, Shandong, China
| | - Jieyu Bi
- Department of Acupuncture-Moxibustion and Tuina, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Linlin Ni
- Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Zhaohui Li
- Integrated Chinese and Western Medicine Assisted Pregnancy Clinic, Hohhot First Hospital, Hohhot, Inner Mongolia, China
| | - Xiumei Zhuo
- Department of Acupuncture-Moxibustion and Tuina, Gaomi Maternity and Child Health Hospital, Gaomi, Shandong, China
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Greenwell S, Jones A, Smith YR, Marriott D, Aikens JE, Padmanabhan V, Saslow LR. Protocol for a randomized comparative effectiveness trial comparing a very low-carbohydrate diet to DASH diet for polycystic ovary syndrome: the SUPER (Supporting Understanding of PCOS Education and Research) trial. Trials 2024; 25:750. [PMID: 39516828 PMCID: PMC11549875 DOI: 10.1186/s13063-024-08583-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS), the most common endocrine disorder for women of reproductive age, is associated with increased risk for insulin resistance and type 2 diabetes. Current PCOS treatments insufficiently address the spectrum and severity of the disorder, and there is little evidence-based guidance available for lifestyle management of PCOS, especially through nutritional approaches. Some evidence shows that a very low-carbohydrate diet can improve glucose control compared to low-fat or moderate-carbohydrate diets, leading to improved glucose control and insulin levels that may help to treat symptoms of PCOS. This research investigates whether a very low-carbohydrate diet is more effective in improving glucose control and decreasing symptoms of PCOS in comparison to a DASH diet. METHODS The SUPER study aims to address the gap in knowledge about nutritional advice for people with PCOS through a randomized, comparative effectiveness trial comparing two approaches to glucose control: the dietary approaches to stopping hypertension (DASH) diet, and a very low-carbohydrate (VLC) diet. We will randomize 184 women with PCOS with body mass indexes (BMIs) between 25 and 50 kg/m2 to a VLC or DASH diet. All participants will follow a 24-session, 12-month, online diet, and lifestyle intervention that teaches their assigned diet. Participants will receive nutritional education, support from diet coaches, and education about behavioral strategies to improve dietary adherence. The primary outcome measure is HbA1c, and secondary outcomes include glucose variance, lipid and hormone levels (including total and free testosterone), PCOS symptoms, inflammation (measured by high-sensitivity C-reactive protein), body composition and weight, psychological well-being, and intervention feasibility and acceptability. DISCUSSION The SUPER study is a randomized comparative effectiveness trial that compares two promising approaches to glucose control in people with PCOS. The study also aims to assess the effects of each diet on PCOS symptoms. The research addresses an important gap in knowledge regarding nutritional advice for people with PCOS. TRIAL REGISTRATION ClinicalTrials.gov NCT05452642. Registered 6 July 2022.
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Affiliation(s)
- Sarah Greenwell
- University of Michigan, Ann Arbor, MI, USA
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, USA
| | - Aubree Jones
- University of Michigan, Ann Arbor, MI, USA
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, USA
| | - Yolanda R Smith
- University of Michigan, Ann Arbor, MI, USA
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
| | - Deanna Marriott
- University of Michigan, Ann Arbor, MI, USA
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, USA
| | - James E Aikens
- University of Michigan, Ann Arbor, MI, USA
- Department of Family Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Vasantha Padmanabhan
- University of Michigan, Ann Arbor, MI, USA
- Department of Pediatrics, University of Michigan, Medical Professional Building, Ann Arbor, MI, USA
| | - Laura R Saslow
- University of Michigan, Ann Arbor, MI, USA.
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, USA.
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Zhu J, Wang JX, Jin ZY, Li D, Qi S, Han SZ, Chang SY, Yan J, Kang JD, Quan LH. Eicosatrienoic acid inhibits estradiol synthesis through the CD36/FOXO1/CYP19A1 signaling pathway to improve PCOS in mice. Biochem Pharmacol 2024; 229:116517. [PMID: 39236935 DOI: 10.1016/j.bcp.2024.116517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 08/11/2024] [Accepted: 09/02/2024] [Indexed: 09/07/2024]
Abstract
Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder characterized by abnormal elevation in hormone levels, with currently lacking effective treatment options. N-3 polyunsaturated fatty acids (PUFA) have broad pharmacological activity and play a beneficial role in the development of PCOS. In this study, we observed that n-3 PUFA-eicosatrienoic acid (ETA) improves the estrous cycle and ovarian morphology in dehydroepiandrosterone (DHEA)-induced PCOS mice, particularly serum hormone levels. Additionally, it suppresses the expression of CYP19A1 and E2 synthesis in human granulosa-like tumor cell line (KGN) cells. Further investigation revealed that ETA significantly upregulates the expression of CD36, cAMP, P-PKA, and FOXO1 in KGN cells and mouse ovaries to lower E2 levels. This conclusion was supported by inhibiting CD36 and FOXO1 at both the mouse and cellular levels. Additionally, ETA treatment decreased the expression of ESR1, Kiss1, Gnrh in the hypothalamus, and GnRHR, Lhβ, Egr1, Pitx1, Sf1 in the pituitary of PCOS mice. No differences were observed after ETA treatment in the CD36 and FOXO1 inhibitor groups, indicating that ETA improves PCOS mice by regulating the hypothalamic-pituitary axis through E2 synthesis inhibition. In summary, we have elucidated for the first time the mechanism by which CD36 regulates E2 synthesis in ovarian granulosa cells and demonstrated that ETA activates the CD36 receptor to inhibit E2 synthesis through the cAMP/PKA/FOXO1/CYP19A1 signaling pathway, thereby improving hormonal imbalance and treating PCOS. This provides a new strategy for the effective prevention and treatment of PCOS.
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Affiliation(s)
- Jun Zhu
- College of Integration Science, Yanbian University, Yanji 133002, China
| | - Jun-Xia Wang
- Department of Animal Science, College of Agricultural, Yanbian University, Yanji 133002, China
| | - Zheng-Yun Jin
- Department of Animal Science, College of Agricultural, Yanbian University, Yanji 133002, China
| | - Dongxu Li
- College of Integration Science, Yanbian University, Yanji 133002, China
| | - Shaobo Qi
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China
| | - Sheng-Zhong Han
- Department of Animal Science, College of Agricultural, Yanbian University, Yanji 133002, China
| | - Shuang-Yan Chang
- Department of Animal Science, College of Agricultural, Yanbian University, Yanji 133002, China
| | - Jin Yan
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China
| | - Jin-Dan Kang
- Department of Animal Science, College of Agricultural, Yanbian University, Yanji 133002, China.
| | - Lin-Hu Quan
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China.
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Palomba S, Molinaro M, Ingargiola A, Aversa A. Recent developments in drug treatment strategies for infertility in patients with polycystic ovary syndrome. Expert Opin Pharmacother 2024; 25:2191-2202. [PMID: 39428640 DOI: 10.1080/14656566.2024.2418985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 10/16/2024] [Indexed: 10/22/2024]
Abstract
INTRODUCTION Infertility related to polycystic ovary syndrome (PCOS) represents a significant challenge for women of reproductive age. Over the last few years, evidence-based medicine has driven new approaches for treating infertility in patients with PCOS, changing rapidly and deeply the clinical practice. AREAS COVERED The authors provide an in-depth examination of recent developments in drug treatment strategies that have impacted the clinical practice and changed the previous approach to infertility in patients with PCOS. EXPERT OPINION The authors identify four primary areas of interest that have impacted clinical practice in the last few years. Specifically, they discuss the current role of metformin administration in women with PCOS and infertility, the choice for using clomiphene citrate or letrozole as first-line treatment for ovulation induction, the use of new gonadotropin formulations for in vitro fertilization (IVF) program, and the elective embryo transfer in IVF cycles as golden standard treatment for patients with PCOS at high-risk for ovarian hyperstimulation syndrome.
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Affiliation(s)
- Stefano Palomba
- Department of Medical-Surgical Science and Translational Medicine, University Sapienza of Rome, Rome, Italy
- Unit of Obstetrics and Gynecology, Grande Ospedale Metropolitano of Reggio Calabria, Reggio Calabria, Italy
| | - Marianna Molinaro
- Department of Endocrinology, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Alice Ingargiola
- Department of Endocrinology, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Antonio Aversa
- Department of Endocrinology, University Magna Graecia of Catanzaro, Catanzaro, Italy
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Liu D, Wei C, Guan L, Ju W, Xiang S, Lian F. Combining single-cell RNA sequencing and network pharmacology to explore the target of cangfu daotan decoction in the treatment of obese polycystic ovary syndrome from an immune perspective. Front Pharmacol 2024; 15:1451300. [PMID: 39539629 PMCID: PMC11557475 DOI: 10.3389/fphar.2024.1451300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 09/26/2024] [Indexed: 11/16/2024] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is a heterogeneous gynecological endocrine disorder linked to immunity. Cangfu Daotan Decoction (CFDT), a classic Chinese medicine prescription, is particularly effective in treating PCOS, specifically in patients with obesity; however, its specific mechanism remains unclear. Methods Part 1: Peripheral blood mononuclear cells were collected on egg retrieval day from obese and normal-weight patients with PCOS and healthy women undergoing in vitro fertilization (IVF)-embryo transfer. Next, scRNA-seq was performed to screen the key genes of bese patients with PCOS. Part 2: Active ingredients of CFDT and obesity-related PCOS targets were identified based on public databases, and the binding ability between the active ingredients and targets was analyzed. Part 3: This part was a monocentric, randomized controlled trial. The obese women with PCOS were randomized to CFDT (6 packets/day) or placebo, and the healthy women were included in the blank control group (43 cases per group). The clinical manifestations and laboratory outcomes among the three groups were compared. Results Based on the scRNA-seq data from Part 1, CYLD, ARPC3, CXCR4, RORA, JUN, FGL2, ZEB2, GNLY, FTL, SMAD3, IL7R, KIR2DL1, CTSD, BTG2, CCL5, HLA, RETN, CTSZ, and NCF2 were potential key genes associated with obese PCOS were identified. The proportions of T, B, and natural killer cells were higher in patients with PCOS compared to healthy women, with even higher proportions observed in obese patients with PCOS. Gene ontology and the Kyoto encyclopedia of genes and genomes analysis depicted that the differentially expressed genes were related to immune regulation pathways. Network pharmacology analysis identified that the key active components in CFDT were quercetin, carvacrol, β-sitosterol, cholesterol, and nobiletin, and TP53, AKT1, STAT3, JUN, SRC, etc. were the core targets. The core targets and their enrichment pathways overlapped with those in Part 1. Clinical trials in Part 3 found that CFDT reduced the dosage of gonadotropins use in patients with PCOS, increased the number of high-quality embryos, and improved the ongoing pregnancy rate. Conclusion CFDT can improve the immune microenvironment of patients to some extent, reduce their economic burden, and enhance IVF outcomes. The improvement in the immune microenvironment in obese patients with PCOS may be linked to targets such as JUN and AKT.
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Affiliation(s)
- Danqi Liu
- The First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada
| | - Chaofeng Wei
- The First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Lu Guan
- The First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Wenhan Ju
- The First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Shan Xiang
- The First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- Integrative Medicine Research Centre of Reproduction and Heredity, Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Fang Lian
- The First Clinical Medicine School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- Integrative Medicine Research Centre of Reproduction and Heredity, Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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Krishnan N, B S, AJ H. Evaluation of Sleep Disturbances in Women with Polycystic Ovary Syndrome. INTERNATIONAL JOURNAL OF INFERTILITY & FETAL MEDICINE 2024; 15:83-92. [DOI: 10.5005/jp-journals-10016-1341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Gao X, Zhao H, Shi Q, Zou T, Zhu Y. Exploring the causal pathway from gut microbiota to polycystic ovary syndrome: A network Mendelian randomization study. Medicine (Baltimore) 2024; 103:e40115. [PMID: 39432652 PMCID: PMC11495796 DOI: 10.1097/md.0000000000040115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 09/27/2024] [Indexed: 10/23/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complicated endocrine and metabolic syndrome with unclear pathogenesis. The gut microbiota sheds light on the etiology and pathophysiology of PCOS. We used Mendelian randomization (MR) studies to systematically evaluate the pathological mechanism gut microbiota causally associated with PCOS risk. A network MR analysis was performed to estimate the causal effects of gut microbiota and risk factors on PCOS, as well as the mediation effect of risk factors linking gut microbiota to PCOS. The investigation of side effects for the important gut microbiota was subsequently broadened to include phenotypes by performing Phenowide-MR analysis for a range of diseases. Genus Sellimonas id.14369 were causally associated with reduced PCOS risk (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.58-0.84, P = 1.22 × 10-4) after multiple testing correction. And Sellimonas retained consistent causal effect estimates after a series of sensitivity analyses. In addition, we observed an indirect effect of Sellimonas on PCOS through body mass index (BMI) using network MR (b = -0.05, 95% CI: -0.09 to -0.01), with a mediated proportion of 12.82% of the total effect. Further, Phenowide-MR analyses showed that the protective effects of Sellimonas on type 2 diabetes and depression (for type 2 diabetes: OR = 0.95, 95% CI: 0.90-0.99, P = .0366; for depression: OR = 0.99, 95% CI: 0.98-1.00, P = .0210). We summarized that the causal path between gut microbiota and type 2 diabetes are also jointly mediated by BMI. Sellimonas may be a protective factor of PCOS, which can affect the occurrence of PCOS through BMI, supporting future studies on the importance of addressing obesity and metabolic issues in preventing and managing PCOS.
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Affiliation(s)
- Xueyan Gao
- Department of General Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Huijuan Zhao
- Department of General Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Qingling Shi
- Department of General Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Zou
- Department of General Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Yidan Zhu
- Department of General Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China
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50
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Tanılır Çağıran F, Mavral N, Kalı Z, Ecin SM. Serum pentraxin-3 expression varies according to polycystic ovary syndrome phenotypes. Medicine (Baltimore) 2024; 103:e40155. [PMID: 39432595 PMCID: PMC11495740 DOI: 10.1097/md.0000000000040155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 10/01/2024] [Indexed: 10/23/2024] Open
Abstract
Pentraxin-3 (PTX-3) is a multibiological protein involved in cumulus cell expansion, fertilization, and implantation. This study was designed to analyze how circulating PTX-3 levels change in women with polycystic ovary syndrome (PCOS). A total of 50 Turkish participants, 35 of whom had PCOS and 15 of whom were fertile, were included in the study. Patients in the PCOS group were divided into 4 different phenotypes according to the NIH criteria (phenotypes A-D). The number of patients in phenotype A was the highest 13 (37.1%). In the calculations made without phenotyping, the serum ptx3 levels of the PCOS group were found to be significantly lower compared to the fertile control group (3.32 ± 0.73 ng/mL vs 4.97 ± 1.29 ng/mL; P < .001). The ptx3 value of phenotypes A and B was significantly lower than phenotype D (P = .008 and P = .009, respectively). When the phenotypes were compared with the fertile control group, the PTX-3 levels of phenotypes A and B were significantly lower than the fertile group. Although the ptx3 levels of phenotypes C and D were lower than the fertile group, the difference did not reach statistical significance. This is the first study to investigate serum ptx3 levels by phenotype in PCOS. While serum PTX-3 levels decreased in phenotypes A and B, ptx3 levels in phenotypes C and D were similar in fertile patients.
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Affiliation(s)
- Fatma Tanılır Çağıran
- Department of Obstetrics and Gynecology, Private Gynecology and Diseases Clinic, Diyarbakir, Turkey
| | - Nihal Mavral
- Department of Obstetrics and Gynecology, Private Lotus Hospital, Şanliurfa, Turkey
| | - Zercan Kalı
- Department of Obstetrics and Gynecology, Private Gözde Hospital, Malatya, Turkey
| | - Seval Müzeyyen Ecin
- Department of Occupational Medicine and Internal Medicine, Mersin City Training and Research Hospital, Mersin, Turkey
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