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New Challenges and Perspectives in Polycystic Ovary Syndrome
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New Challenges and Perspectives in Polycystic Ovary Syndrome

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 15743

Special Issue Editor

Dr. Jim Parker

E-Mail Website
Guest Editor
School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia
Interests: polycystic ovary syndrome; evolutionary origins; developmental origins; pathogenesis; microbiome; pathophysiology; epigenetics; nutritional biochemistry; pregnancy complications; lifestyle management
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is clear from various strands of evidence that there are a number of new perspectives and challenges that have emerged in understanding the biological nature of polycystic ovary syndrome (PCOS). PCOS is increasingly being viewed as an evolutionary mismatch disorder that arises following exposure to nutritional and environmental factors related to contemporary lifestyle. This is reflected in comprehensive international guidelines that recommend lifestyle interventions, such as diet and exercise, for all women diagnosed with PCOS. Over the past 20 years, many areas of PCOS research have undergone paradigm shifts that have changed the way we view the nature, impact, and progression of PCOS. There is now greater emphasis on the metabolic consequences of lifestyle on symptoms and disease progression, in addition to the endocrine and reproductive consequences. There is increased awareness of the risk of pregnancy complications (miscarriage, implantation failure, gestational diabetes, preterm labour, fetal growth restriction, and pre-eclampsia), and a paradigm shift in our understanding of the importance of endometrial pathophysiology (being investigated in the developing field of endometrial organoids). There is a new appreciation that the prevention of many of the consequences of PCOS is feasible, using lifestyle interventions and pharmacotherapy.

This Special Issue is inviting submissions on new perspectives and challenges in PCOS research in order to highlight innovations that can be of benefit in both clinical practice and research settings. This includes research on genetics, epigenetics, developmental origins of PCOS, endocrine disrupting chemicals, emerging models of the pathogenesis (including the role of the microbiome), increased molecular understanding of the pathophysiology (highlighting the central role of chronic systemic inflammation and insulin resistance), nutritional biochemistry, new terminology for PCOS, and lifestyle interventions. We welcome the submission of state-of-the-art and critical reviews, as well as original works related to the above research topics, or other areas that identify new perspectives and challenges in PCOS.

You may choose our Joint Special Issue in IJMS.

Dr. Jim Parker
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • polycystic ovary syndrome
  • evolutionary origins
  • developmental origins
  • pathogenesis
  • pathophysiology
  • microbiome
  • pregnancy complications
  • lifestyle

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Published Papers (6 papers)

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Research

Jump to: Review, Other

13 pages, 2135 KB  
Article
Thymoquinone Versus Metformin in Letrozole-Induced PCOS: Comparative Insights into Metabolic, Hormonal, and Ovarian Outcomes
by Onder Ercan, Recep Dokuyucu, Ergun Yuksel and Tumay Ozgur
J. Clin. Med. 2025, 14(18), 6561; https://doi.org/10.3390/jcm14186561 - 18 Sep 2025
Viewed by 126
Abstract
Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for [...] Read more.
Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for PCOS. Methods: Thirty-two female Wistar Albino rats were randomly assigned into four groups: control (I), PCOS (II), PCOS + metformin (III), and PCOS + Thymoquinone (IV). PCOS was induced using 1 mg/kg/day letrozole for 21 days, followed by treatment with either metformin (500 mg/kg/day) or thymoquinone (50 mg/kg/day) for 30 days. Metabolic (glucose, insulin, HOMA-IR, lipid profile), hormonal (estrone, estradiol, testosterone, androstenedione), and histopathological parameters were assessed. Results: PCOS induction resulted in significant metabolic, hormonal, and ovarian dysfunctions. Final body weight was significantly higher in PCOS (309.0 ± 7.5 g) vs. control (275.3 ± 8.2 g, p < 0.001), but reduced by metformin (294.0 ± 7.4 g, p < 0.01) and thymoquinone (305.7 ± 7.5 g, p < 0.01). Glucose levels were significantly elevated in PCOS (341.8 ± 16.8 mg/dL) vs. control (260.0 ± 15.8 mg/dL, p < 0.01), while metformin (290.2 ± 19.7 mg/dL, p < 0.05) and thymoquinone (320.3 ± 13.7 mg/dL, p < 0.05) reduced glucose levels. Insulin and HOMA-IR were significantly increased in PCOS (p < 0.001), but reduced by both treatments (p < 0.01). Lipid profile improvements were observed, with significant reductions in TG and LDL-C and increases in HDL-C in both treatment groups (p < 0.05–0.01). PCOS induced hyperandrogenism, with increased testosterone and androstenedione (p < 0.05), and a decreased E2/E1 ratio (p < 0.001), which were significantly improved by metformin and thymoquinone (p < 0.01). Ovarian histopathology showed increased cystic and atretic follicles and reduced corpus luteum in PCOS (p < 0.05–0.01), which were significantly improved by both treatments. Conclusions: TMQ exerts metabolic, hormonal, and ovarian protective effects comparable to metformin, supporting its potential as a natural therapeutic alternative for PCOS management. Given that metformin is already established as a first-line pharmacological therapy, our findings suggest that TMQ may provide a promising complementary or alternative approach. Further clinical studies are warranted to evaluate its safety and efficacy in human PCOS patients. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)
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19 pages, 336 KB  
Article
A Pilot Study of the Role of Salivary Biomarkers in the Diagnosis of PCOS in Adolescents Across Different Body Weight Categories
by Justyna Opydo-Szymaczek, Natalia Wendland, Dorota Formanowicz, Anna Blacha, Grażyna Jarząbek-Bielecka, Paulina Radomyska, Dominika Kruszyńska and Małgorzata Mizgier
J. Clin. Med. 2025, 14(17), 6159; https://doi.org/10.3390/jcm14176159 - 31 Aug 2025
Viewed by 588
Abstract
Background/Objectives: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting reproductive, metabolic, and inflammatory processes in women of reproductive age. This study explored the diagnostic potential of salivary cytokines, uric acid, and testosterone in distinguishing PCOS patients from healthy controls, as [...] Read more.
Background/Objectives: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting reproductive, metabolic, and inflammatory processes in women of reproductive age. This study explored the diagnostic potential of salivary cytokines, uric acid, and testosterone in distinguishing PCOS patients from healthy controls, as well as to examine their associations with hormonal and metabolic profiles within the PCOS group. Methods: Forty-one adolescent girls with PCOS and thirty healthy controls participated in the study. The PCOS group included both normal-weight and overweight individuals, allowing evaluation of salivary biomarkers across different nutritional statuses. Salivary levels of TNF-α, IL-6, IL-1β, testosterone, and uric acid were measured and compared between the groups. A receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of each biomarker. Results: Salivary TNF-α, IL-6, and IL-1β showed high diagnostic accuracy (AUC = 0.921, 0.891, and 0.870, respectively), supporting their potential as non-invasive biomarkers. The diagnostic accuracy of salivary cytokines and testosterone remained high even in normal-weight participants, suggesting that low-grade inflammation and hormonal disturbances in PCOS are not limited to excess body weight. Salivary testosterone was strongly associated with hyperandrogenism, while uric acid correlated with the cortisol/DHEA-S ratio, indicating possible links to metabolic stress. Conclusions: In conclusion, salivary assays may offer a valuable, non-invasive tool for the early diagnosis of PCOS in adolescents, including normal-weight girls. This approach could facilitate the timely detection of inflammatory and hormonal imbalances, supporting earlier interventions and more personalized care. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)
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12 pages, 230 KB  
Article
Mental Health as Assessed by the Symptom Checklist 90 (SCL-90) Scores in Women with and Without Polycystic Ovary Syndrome
by Marie-Louise Marschalek, Rodrig Marculescu, Christian Schneeberger, Julian Marschalek, Marlene Hager, Robert Krysiak and Johannes Ott
J. Clin. Med. 2025, 14(14), 5103; https://doi.org/10.3390/jcm14145103 - 18 Jul 2025
Viewed by 1013
Abstract
Background and Objectives: Polycystic ovary syndrome (PCOS) is associated with an elevated risk of impaired mental health and psychiatric disorders, such as depression and anxiety. Physical factors like weight and hirsutism, as well as psychological factors, such as self-esteem and coping strategies, [...] Read more.
Background and Objectives: Polycystic ovary syndrome (PCOS) is associated with an elevated risk of impaired mental health and psychiatric disorders, such as depression and anxiety. Physical factors like weight and hirsutism, as well as psychological factors, such as self-esteem and coping strategies, are all known to have an influence on mental health status. Aim: To assess psychological symptoms in women with and without PCOS, by use of the well-established, validated self-report questionnaire: Symptom Checklist-90-Revised (SCL-90); to determine the reliability of the SCL-90 for assessment of PCOS patients. Design: Prospective case-control study. Methods: Psychological symptoms were assessed using the German version of the SCL-90 in 31 PCOS women and 31 healthy controls. To test the impact of various parameters on numerical outcome parameters, correlation analyses were conducted. Results: PCOS women revealed significantly increased SCL-90 scores in seven out of the nine subscales (hostility subscale, anxiety subscale, depression subscale, paranoid ideation subscale, psychoticism subscale, somatization subscale, interpersonal sensitivity subscale, obsessive compulsive subscale), as well as in all three global indices (p < 0.05). SCL-90 scores were significantly positively correlated with perceived total stress and perceived helplessness and significantly negatively correlated with perceived self-efficacy (p < 0.05). Conclusions: PCOS women experienced higher levels of psychological symptoms including depressive and anxiety symptoms. Higher perceived stress, higher perceived helplessness and lower self-efficacy were associated with more psychological symptoms. Hence, there is a need to support PCOS women with their emotional regulation and coping strategies. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)

Review

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33 pages, 1454 KB  
Review
Recognizing the Role of Insulin Resistance in Polycystic Ovary Syndrome: A Paradigm Shift from a Glucose-Centric Approach to an Insulin-Centric Model
by Jim Parker, Lara Briden and Felice L. Gersh
J. Clin. Med. 2025, 14(12), 4021; https://doi.org/10.3390/jcm14124021 - 6 Jun 2025
Cited by 1 | Viewed by 4765
Abstract
Polycystic ovary syndrome (PCOS) is a common metabolic–endocrine disorder affecting women of reproductive age, and insulin resistance (IR) is a key pathophysiological feature. Current medical education and clinical practice emphasize glucose-centric approaches in PCOS management, and IR testing is often overlooked due to [...] Read more.
Polycystic ovary syndrome (PCOS) is a common metabolic–endocrine disorder affecting women of reproductive age, and insulin resistance (IR) is a key pathophysiological feature. Current medical education and clinical practice emphasize glucose-centric approaches in PCOS management, and IR testing is often overlooked due to limited emphasis in current clinical guidelines or the lack of standardized protocols. Additionally, the glucose-focused paradigm has been the standard of care for decades. However, this approach has led to delayed diagnosis of progressive metabolic and reproductive consequences, leaving many patients underdiagnosed and undertreated. Therefore, we propose a paradigm shift towards an insulin-centric model for PCOS management. This new approach aims to diagnose IR at an earlier stage, enabling the timely implementation of effective lifestyle and treatment strategies. By focusing on IR, clinicians can potentially limit the progression of PCOS-related reproductive and metabolic diseases. The insulin-centric model is a novel approach that involves comprehensive IR screening, dynamic insulin testing, personalized lifestyle and insulin-sensitizing interventions, and regular monitoring of insulin and glycemic parameters. This model could improve patient outcomes by facilitating early diagnosis of metabolic dysfunction and reducing the incidence of subsequent chronic disease. Furthermore, this model has broader implications, potentially transforming treatment approaches for various chronic diseases beyond PCOS. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)
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14 pages, 1339 KB  
Review
Metabolic Dysfunction-Associated Steatotic Liver Disease and Polycystic Ovary Syndrome: A Complex Interplay
by Konstantinos Arvanitakis, Elena Chatzikalil, Georgios Kalopitas, Dimitrios Patoulias, Djordje S. Popovic, Symeon Metallidis, Kalliopi Kotsa, Georgios Germanidis and Theocharis Koufakis
J. Clin. Med. 2024, 13(14), 4243; https://doi.org/10.3390/jcm13144243 - 20 Jul 2024
Cited by 14 | Viewed by 3316
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are prevalent conditions that have been correlated with infertility through overlapped pathophysiological mechanisms. MASLD is associated with metabolic syndrome and is considered among the major causes of chronic liver disease, while PCOS, [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are prevalent conditions that have been correlated with infertility through overlapped pathophysiological mechanisms. MASLD is associated with metabolic syndrome and is considered among the major causes of chronic liver disease, while PCOS, which is characterized by ovulatory dysfunction and hyperandrogenism, is one of the leading causes of female infertility. The pathophysiological links between PCOS and MASLD have not yet been fully elucidated, with insulin resistance, hyperandrogenemia, obesity, and dyslipidemia being among the key pathways that contribute to liver lipid accumulation, inflammation, and fibrosis, aggravating liver dysfunction. On the other hand, MASLD exacerbates insulin resistance and metabolic dysregulation in women with PCOS, creating a vicious cycle of disease progression. Understanding the intricate relationship between MASLD and PCOS is crucial to improving clinical management, while collaborative efforts between different medical specialties are essential to optimize fertility and liver health outcomes in individuals with MASLD and PCOS. In this review, we summarize the complex interplay between MASLD and PCOS, highlighting the importance of increasing clinical attention to the prevention, diagnosis, and treatment of both entities. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)
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Other

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19 pages, 3129 KB  
Systematic Review
The Impact of Diet-Induced Weight Loss on Inflammatory Status and Hyperandrogenism in Women with Polycystic Ovarian Syndrome (PCOS)—A Systematic Review and Meta-Analysis
by Salih Atalah Alenezi, Nusaiba Elkmeshi, Abdullah Alanazi, Sulaiman T. Alanazi, Raheela Khan and Saad Amer
J. Clin. Med. 2024, 13(16), 4934; https://doi.org/10.3390/jcm13164934 - 21 Aug 2024
Cited by 4 | Viewed by 4399
Abstract
Background: Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS [...] Read more.
Background: Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS women. Methods: A comprehensive search was conducted to identify randomised controlled trials (RCTs) and cohort studies assessing the impact of diet-induced weight loss on circulating inflammatory markers (CRP, IL-6, IL-1β, TNF-α), androgens (testosterone, androstenedione), SHBG, and luteinising hormone (LH) in PCOS women. The quality and risk of bias of the included studies were assessed using the Cochrane Collaboration’s tool for RCTs and the Newcastle–Ottawa Scale for cohort studies. Data were entered into RevMan software v5.9 for the calculation of standard mean difference (SMD) and the 95% confidence interval (95%CI) of circulating inflammatory markers, androgens, and LH between baseline and post-weight loss values. Results: Eleven studies (n = 323) were eligible for the systematic review, of which nine (n = 286) were included in the meta-analysis. Pooled analysis of data revealed a statistically significant decrease in circulating CRP (SMD 0.39, 95%CI 0.22, 0.56; 9 studies, n = 286), IL-6 (SMD 0.37, 95%Cl, 0.12, 0.61; 3 Studies, n = 140), TNF-α (SMD 0.30, 95%Cl, 0.07, 0.53; 4 Studies, n = 162), androstenedione (SMD 0.36, 95%Cl, 0.13, 0.60; 4 studies, n = 147) and LH (SMD 0.30, 95% Cl, 0.09, 0.51; 5 studies, n = 197) after weight loss compared to baseline levels among PCOS women. A meta-analysis of five studies (n = 173) showed a statistically significant increase in circulating SHBG after weight loss compared to baseline levels (SMD −0.43, 95%Cl, −0.65, −0.21). Conclusions: These findings suggest that weight loss induced by dietary interventions seems to improve PCOS-related chronic inflammation and hyperandrogenism. The possible causative relationship between the improvement in inflammation and hyperandrogenism remains to be determined. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)
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