Editorial

5 pages, 216 KiB

Open AccessEditorial

Molecular Research on Polycystic Ovary Syndrome (PCOS)

by Simona Daniele, Elisa Chelucci, Giorgia Scarfò and Paolo Giovanni Artini

Biomedicines 2023, 11(5), 1358; https://doi.org/10.3390/biomedicines11051358 - 04 May 2023

Cited by 1 | Viewed by 1946

Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder with a prevalence of between 5% and 20% that commonly affects childbearing-aged women [...] Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

Research

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13 pages, 1076 KiB

Open AccessArticle

Diabetes Mellitus Mediates Risk of Depression in Danish Women with Polycystic Ovary Syndrome—A National Cohort Study

by Dorte Glintborg, Tanja Gram Petersen, Katrine Hass Rubin and Marianne Skovsager Andersen

Biomedicines 2022, 10(10), 2396; https://doi.org/10.3390/biomedicines10102396 - 26 Sep 2022

Cited by 2 | Viewed by 1777

Abstract

Aim: To investigate the risk of depression in Danish women with PCOS compared to controls and possible mediators for depression in PCOS. National register-based study in Danish women with PCOS (PCOS Denmark, N = 25,203) and age-matched controls (N = 112,414). PCOS [...] Read more.

Aim: To investigate the risk of depression in Danish women with PCOS compared to controls and possible mediators for depression in PCOS. National register-based study in Danish women with PCOS (PCOS Denmark, N = 25,203) and age-matched controls (N = 112,414). PCOS Odense University Hospital (PCOS OUH, N = 998) was a sub-cohort of women with PCOS with available clinical and biochemical results. The main study outcome was depression occurring after PCOS diagnosis. Depression was defined according to hospital ICD-10 diagnosis codes and/or inferred from filled medicine prescription of antidepressants. Diabetes, medical comorbidity, infertility, hormonal anti-contraception and low family income were entered as mediators in Cox regression analyses for depression. In PCOS OUH, PCOS characteristics (age, BMI, Ferriman-Gallwey score) were entered in Cox regression analyses. The median age at cohort entry was 28 (interquartile range (IQR) 23; 35) years. The median follow-up time to incident depression or censuring was 4.8 (IQR 2.2; 8.8) years in PCOS Denmark and 5.2 (IQR 2.4; 9.2) years in controls. Women with PCOS had a 40% increased risk of depression compared to controls (Hazard Ratio 1.42 (95% CI 1.38; 1.47). In regression analyses, diabetes, medical comorbidity, infertility, hormonal anticonception, and low family income were significant mediators of depression. Mediation analyses showed that the proportion of the association explained by diabetes was 12.5% (95% CI 10.4; 14.5). In PCOS OUH, BMI, waist and Ferriman-Gallwey score predicted development of depression. Conclusion: The risk of depression was increased in PCOS. Diabetes was an important mediator of depression in PCOS. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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9 pages, 269 KiB

Open AccessArticle

Level of Potassium Is Associated with Saturated Fatty Acids in Cell Membranes and Influences the Activation of the 9 and 13 HODE and 5 HETE Synthesis Pathways in PCOS

by Małgorzata Szczuko, Kamila Pokorska-Niewiada, Lidia Kwiatkowska, Jolanta Nawrocka-Rutkowska, Iwona Szydłowska and Maciej Ziętek

Biomedicines 2022, 10(9), 2244; https://doi.org/10.3390/biomedicines10092244 - 09 Sep 2022

Cited by 2 | Viewed by 1650

Abstract

Potassium helps to maintain the water–electrolyte and acid–base balance. There is little research on the relationship between plasma fatty acids (FAs), inflammatory mediators and red blood cell potassium levels in women with polycystic ovary syndrome (PCOS). This study included 38 Caucasian women with [...] Read more.

Potassium helps to maintain the water–electrolyte and acid–base balance. There is little research on the relationship between plasma fatty acids (FAs), inflammatory mediators and red blood cell potassium levels in women with polycystic ovary syndrome (PCOS). This study included 38 Caucasian women with PCOS. Potassium in the erythrocytes was determined by inductively coupled atomic plasma emission spectrometry. The FAs were analysed with gas chromatography, and liquid chromatography was used to separate the eicosanoids. The relationships between the potassium content and the amounts of fatty acids, as well as potassium and arachidonic acid (AAs) derivatives, were analysed. Significant negative correlations were found with, among others, pentadecanoic acid, palmitic acid, stearic acid and arachidic acid, whereas a positive correlation was found with neuronic acid. Positive correlations were observed with 9, 13 HODE (derivatives synthetized from linolenic acid) and 5 oxo ETE and 5 HETE (from 5 LOX pathway). Saturated fatty acids reduce the influx of potassium into the cell by destabilizing the pH of the cytosol, and thus exacerbating the inflammatory response through the activation of the AA cascade. Therefore, improving the flow of potassium inside the cell is important in the treatment of patients. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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Graphical abstract

14 pages, 303 KiB

Open AccessArticle

The Role of Oxidative Stress in the Risk of Cardiovascular Disease and Identification of Risk Factors Using AIP and Castelli Atherogenicity Indicators in Patients with PCOS

by Jolanta Nawrocka-Rutkowska, Iwona Szydłowska, Katarzyna Jakubowska, Maria Olszewska, Dariusz Chlubek, Małgorzata Szczuko and Andrzej Starczewski

Biomedicines 2022, 10(7), 1700; https://doi.org/10.3390/biomedicines10071700 - 14 Jul 2022

Cited by 7 | Viewed by 2065

Abstract

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in females of reproductive age and may affect 5–14% of women. In women with PCO syndrome, metabolic disorders such as insulin resistance, hyperinsulinemia, obesity, diabetes mellitus, and other elements of metabolic syndrome [...] Read more.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in females of reproductive age and may affect 5–14% of women. In women with PCO syndrome, metabolic disorders such as insulin resistance, hyperinsulinemia, obesity, diabetes mellitus, and other elements of metabolic syndrome may occur. Patients with PCOS often have overweight and obesity, especially abdominal obesity, which is one of the risk factors for developing atherosclerosis. The atherogenicity indicators of AIP (atherogenic index of plasma) and Castelli’s index are used to assess the risk of developing atherosclerosis. Studies have shown an increase in the concentration and activity of oxidative stress markers in patients with PCOS compared to women without the disease. The aim of the present study was to evaluate oxidative stress parameters in patients with PCOS in relation to insulin resistance, BMI, and hyperandrogenemia and to correlate them with cardiovascular risk parameters. Conclusions: The severity of oxidative stress in women with PCOS correlates with exposure to cardiovascular diseases. The assessment of additional cardiovascular disease (CVD) parameters is useful in identifying the risk groups for cardiometabolic disease among PCOS patients. When additional risk factors such as hyperandrogenism and insulin resistance (IR) are present in patients with PCOS, it is reasonable to include preventive examinations early. It is also important to evaluate lipidograms, which will make it possible to determine indicators of atherogenicity. Patients with PCOS and IR are at particular risk for cardiovascular complications. PCOS should be considered an important risk factor for CVD, which occurs independently of the occurrence of obesity. This factor is related to the important role of insulin resistance, which occurs independently of obesity. Atherogenic factors (AIP and Castelli index) are useful additional parameters to assess the risk of cardiometabolic disease in PCOS patients, especially among groups with insulin resistance. The early detection of risk factors should be an integral part of the care of PCOS patients. In laboratory studies of women with PCOS, TG, TChol, HDL-c and LDL-c levels, and glutathione peroxidase (GPx) activity were most clearly correlated with exposure to cardiovascular disease. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

10 pages, 255 KiB

Open AccessArticle

Role of Single Nucleotide Variants in the YAP1 Gene in Adolescents with Polycystic Ovary Syndrome

by Lasma Lidaka, Laine Bekere, Gunta Lazdane, Marija Lazovska, Iveta Dzivite-Krisane and Linda Gailite

Biomedicines 2022, 10(7), 1688; https://doi.org/10.3390/biomedicines10071688 - 13 Jul 2022

Cited by 5 | Viewed by 1302

Abstract

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women. It can manifest in adolescence, affecting up to 8% of adolescents. Long-term health consequences characteristic of PCOS are impaired fertility, increased risk of type 2 diabetes, metabolic disorders and [...] Read more.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women. It can manifest in adolescence, affecting up to 8% of adolescents. Long-term health consequences characteristic of PCOS are impaired fertility, increased risk of type 2 diabetes, metabolic disorders and cardiovascular disease. All of these sequelae are exacerbated by increased body weight, a major feature of PCOS. The protein encoded by the YAP1 gene plays a key role in one of the pivotal mechanisms that govern cellular/organismal metabolism and contributes to the pathogenesis of metabolic diseases. Aim: To compare the prevalence of single nucleotide variants (SNVs) in the YAP1 gene among adolescents with PCOS, adolescents at risk of PCOS development and healthy adolescents, and assess their association with the clinical characteristics of PCOS. Results: The frequencies of the five investigated YAP1 gene SNVs (rs11225161, rs11225166, rs3858420, rs11225138 and rs79981660) were not significantly different among adolescents with PCOS, risk group patients and healthy controls. Furthermore, none of the SNVs contributed to the clinical characteristics of adolescents with PCOS and adolescents at risk of PCOS development. Conclusions: No significant associations were found between PCOS in adolescents and the five investigated SNVs in the YAP1 gene. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

14 pages, 1266 KiB

Open AccessArticle

An Ovarian Steroid Metabolomic Pathway Analysis in Basal and Polycystic Ovary Syndrome (PCOS)-like Gonadotropin Conditions Reveals a Hyperandrogenic Phenotype Measured by Mass Spectrometry

by Emma S. Gargus, Yeunook Bae, Jiexi Chen, Kristine J. Moss, Asia N. Ingram, Jiyang Zhang, Nathan T. Montgomery, Christina E. Boots, William E. Funk and Teresa K. Woodruff

Biomedicines 2022, 10(7), 1646; https://doi.org/10.3390/biomedicines10071646 - 08 Jul 2022

Cited by 6 | Viewed by 2313

Abstract

Prior work has demonstrated that murine ovarian explants and isolated ovarian follicles can recapitulate human-like 28-day cycles in vitro with normal patterns of estradiol and progesterone secretion in response to gonadotropin stimulation. The objective of this study was to manipulate the gonadotropin stimulation [...] Read more.

Prior work has demonstrated that murine ovarian explants and isolated ovarian follicles can recapitulate human-like 28-day cycles in vitro with normal patterns of estradiol and progesterone secretion in response to gonadotropin stimulation. The objective of this study was to manipulate the gonadotropin stimulation protocol to mimic polycystic ovary syndrome (PCOS) and assess the resulting changes in ovarian steroidogenesis. A secondary aim of the study was to develop a high-throughput, sensitive, and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay to measure seven steroid hormones (estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and dihydrotestosterone) in conditioned culture media. Ovaries were harvested from 12-day-old CD-1 mice and cultured for 28 days, with ovulation induction on culture day 14. Media were supplemented human chorionic gonadotropin (hCG, a luteinizing hormone analog) and follicle stimulating hormone (FSH) at ratios of 1:0 (standard media), 1:1 (physiologic ratio), and 3:1 (PCOS-like ratio). Ovaries cultured in PCOS-like media displayed hyperandrogenism and impaired ovulation, two key features of a PCOS-like phenotype. Taken together, this first-of-its-kind presentation of hormone levels from single tissues creates a map of the enzymatic steps most acutely affected by gonadotropin dysregulation and may provide opportunities for assessing other potential insults in PCOS pathogenesis. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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13 pages, 293 KiB

Open AccessArticle

Evaluation of Pro/Antioxidant Imbalance in Blood of Women with Polycystic Ovary Syndrome Based on Determination of Oxidized Low-Density Lipoproteins and Ferric Reducing Ability of Plasma Values

by Justyna Niepsuj, Grzegorz Franik, Paweł Madej, Agnieszka Piwowar and Anna Bizoń

Biomedicines 2022, 10(7), 1564; https://doi.org/10.3390/biomedicines10071564 - 30 Jun 2022

Cited by 4 | Viewed by 1524

Abstract

We investigated selected pro/antioxidant parameters in a group of women with polycystic ovary syndrome (PCOS) divided according to age, body mass index (BMI), waist-to-hip ratio (WHR), homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (Quicki). We chose oxidized [...] Read more.

We investigated selected pro/antioxidant parameters in a group of women with polycystic ovary syndrome (PCOS) divided according to age, body mass index (BMI), waist-to-hip ratio (WHR), homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (Quicki). We chose oxidized low-density lipoproteins (oxLDL-C) as a marker of oxidative stress and the ferric reducing ability of plasma (FRAP) as a marker of antioxidant status. In women with PCOS, the values of BMI, WHR, age and concentration of glucose significantly affected oxLDL-C concentration and FRAP values. FRAP correlated with oxLDL-C level in the whole group and in women who were insulin sensitive (HOMA-IR < 2.0). There was a negative relationship between the concentration of Anti-Müllerian hormone and both oxLDL-C and FRAP. Furthermore, the value of FRAP was inversely correlated with luteinizing hormone (LH), follicle-stimulating hormone (FSH) and androstenedione, whereas it was positively correlated with the LH/FSH ratio. The concentration of oxLDL and the value of FRAP are significantly associated with selected metabolic and hormonal parameters in the course of PCOS. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

21 pages, 2579 KiB

Open AccessArticle

Hepatic Mitochondrial Dysfunction and Risk of Liver Disease in an Ovine Model of “PCOS Males”

by Katarzyna J. Siemienowicz, Panagiotis Filis, Jennifer Thomas, Paul A. Fowler, W. Colin Duncan and Mick T. Rae

Biomedicines 2022, 10(6), 1291; https://doi.org/10.3390/biomedicines10061291 - 31 May 2022

Cited by 4 | Viewed by 2862

Abstract

First-degree male relatives of polycystic ovary syndrome (PCOS) sufferers can develop metabolic abnormalities evidenced by elevated circulating cholesterol and triglycerides, suggestive of a male PCOS equivalent. Similarly, male sheep overexposed to excess androgens in fetal life develop dyslipidaemia in adolescence. Dyslipidaemia, altered lipid [...] Read more.

First-degree male relatives of polycystic ovary syndrome (PCOS) sufferers can develop metabolic abnormalities evidenced by elevated circulating cholesterol and triglycerides, suggestive of a male PCOS equivalent. Similarly, male sheep overexposed to excess androgens in fetal life develop dyslipidaemia in adolescence. Dyslipidaemia, altered lipid metabolism, and dysfunctional hepatic mitochondria are associated with the development of non-alcoholic liver disease (NAFLD). We therefore dissected hepatic mitochondrial function and lipid metabolism in adolescent prenatally androgenized (PA) males from an ovine model of PCOS. Testosterone was directly administered to male ovine fetuses to create prenatal androgenic overexposure. Liver RNA sequencing and proteomics occurred at 6 months of age. Hepatic lipids, glycogen, ATP, reactive oxygen species (ROS), DNA damage, and collagen were assessed. Adolescent PA males had an increased accumulation of hepatic cholesterol and glycogen, together with perturbed glucose and fatty acid metabolism, mitochondrial dysfunction, with altered mitochondrial transport, decreased oxidative phosphorylation and ATP synthesis, and impaired mitophagy. Mitochondrial dysfunction in PA males was associated with increased hepatic ROS level and signs of early liver fibrosis, with clinical relevance to NAFLD progression. We conclude that excess in utero androgen exposure in male fetuses leads to a PCOS-like metabolic phenotype with dysregulated mitochondrial function and likely lifelong health sequelae. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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11 pages, 1339 KiB

Open AccessArticle

Impact of Thyroid Function on Pregnancy and Neonatal Outcome in Women with and without PCOS

by Sarah Feigl, Barbara Obermayer-Pietsch, Philipp Klaritsch, Gudrun Pregartner, Sereina Annik Herzog, Elisabeth Lerchbaum, Christian Trummer, Stefan Pilz and Martina Kollmann

Biomedicines 2022, 10(4), 750; https://doi.org/10.3390/biomedicines10040750 - 23 Mar 2022

Cited by 12 | Viewed by 2552

Abstract

Background: Women with polycystic ovary syndrome (PCOS) are more prone to autoimmune thyroiditis, and both disorders lead to subfertility and pregnancy-related complications. The aim of this study was to investigate whether mothers with and without PCOS and their offspring have comparable thyroid parameters [...] Read more.

Background: Women with polycystic ovary syndrome (PCOS) are more prone to autoimmune thyroiditis, and both disorders lead to subfertility and pregnancy-related complications. The aim of this study was to investigate whether mothers with and without PCOS and their offspring have comparable thyroid parameters at term and how thyroid parameters are associated with perinatal outcome in this population. Methods: This cross-sectional observational study was performed in a single academic tertiary hospital in Austria. Seventy-nine pregnant women with PCOS and 354 pregnant women without PCOS were included. Blood samples were taken from the mother and cord blood at birth. Primary outcome parameters were maternal and neonatal thyroid parameters at delivery. Secondary outcome parameters were the composite complication rate per woman and per neonate. Results: Thyroid dysfunction was more prevalent among PCOS women (p < 0.001). At time of birth, free triiodothyronine (fT3) levels were significantly lower in PCOS than in non-PCOS women (p = 0.005). PCOS women and their neonates had significantly higher thyreoperoxidase antibody (TPO-AB) levels (p = 0.001). Women with elevated TPO-AB had a significantly higher prevalence of hypothyroidism (p < 0.001). There was a significant positive correlation between maternal and neonatal free thyroxine, fT3 and TPO-AB levels. There were no significant differences in thyroid parameters between women or neonates with or without complications. Conclusions: Our results demonstrate a higher prevalence of thyroid dysfunction and autoimmunity in PCOS women, supporting a common etiology of both disorders. We were not able to show an association between complication rate and thyroid parameters. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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Review

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12 pages, 951 KiB

Open AccessReview

Anti-Müllerian Hormone and Polycystic Ovary Syndrome in Women and Its Male Equivalent

by Nathalie di Clemente, Chrystèle Racine and Rodolfo A. Rey

Biomedicines 2022, 10(10), 2506; https://doi.org/10.3390/biomedicines10102506 - 07 Oct 2022

Cited by 6 | Viewed by 3351

Abstract

This article reviews the main findings on anti-Müllerian hormone (AMH) and its involvement in the pathogenesis of polycystic ovary syndrome (PCOS) and its male equivalent. In women, AMH is produced by granulosa cells from the mid-fetal life to menopause and is a reliable [...] Read more.

This article reviews the main findings on anti-Müllerian hormone (AMH) and its involvement in the pathogenesis of polycystic ovary syndrome (PCOS) and its male equivalent. In women, AMH is produced by granulosa cells from the mid-fetal life to menopause and is a reliable indirect marker of ovarian reserve. AMH protects follicles from atresia, inhibits their differentiation in the ovary, and stimulates gonadotrophin-releasing hormone neurons pulsatility. AMH overexpression in women with PCOS likely contributes to the increase of the follicle cohort and of androgen levels, leading to follicular arrest and anovulation. In the male, AMH is synthesized at high levels by Sertoli cells from fetal life to puberty when serum AMH falls to levels similar to those observed in women. AMH is involved in the differentiation of the genital tract during fetal life and plays a role in Sertoli and Leydig cells differentiation and function. Serum AMH is used to assess Sertoli cell function in children with disorders of sex development and various conditions affecting the hypothalamic–pituitary–testicular axis. Although the reproductive function of male relative of women with PCOS has been poorly investigated, adolescents have elevated levels of AMH which could play a detrimental role on their fertility. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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16 pages, 752 KiB

Open AccessReview

Therapeutic Potential of Glucagon-like Peptide-1 Agonists in Polycystic Ovary Syndrome: From Current Clinical Evidence to Future Perspectives

by Mojca Jensterle, Rok Herman and Andrej Janež

Biomedicines 2022, 10(8), 1989; https://doi.org/10.3390/biomedicines10081989 - 16 Aug 2022

Cited by 12 | Viewed by 4620

Abstract

Despite the continuous effort to understand the pathophysiology and determine potential therapeutic targets, PCOS treatment largely depends on lifestyle intervention and symptomatic management of individual signs and symptoms. International guidelines recognize the importance of weight reduction as a cornerstone for the achievement of [...] Read more.

Despite the continuous effort to understand the pathophysiology and determine potential therapeutic targets, PCOS treatment largely depends on lifestyle intervention and symptomatic management of individual signs and symptoms. International guidelines recognize the importance of weight reduction as a cornerstone for the achievement of better metabolic, reproductive, and cardiovascular outcomes in PCOS women who are overweight or obese. With its profound weight loss potential in patients with or without diabetes, the administration of GLP-1 receptor agonists has been investigated in overweight/obese women with PCOS in several single-center randomized control trials with considerable variation in the dosing regimen, follow-up duration, and outcome measurements over recent years. Most trials reported superior weight loss effects of GLP-1 receptor agonists compared to lifestyle changes or metformin, with additional metabolic, reproductive, and cardiovascular benefits in this population. However, their use is currently not widely accepted by the clinical community that treats this population. The major concern is how to balance the reproductive and metabolic treatment strategies since the use of GLP-1 receptor agonists requires effective contraception while on therapy and a washout period before pregnancy. Both approaches are not mutually exclusive, yet the best choice requires a careful assessment of the clinical context. Knowing a patient’s individual circumstances, precise clinical sub-phenotyping, and regular monitoring are crucial components for the safe and effective use of these new tools. In the present narrative review, we explore the current clinical evidence and provide the future perspectives and challenges for their implementation in PCOS management. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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26 pages, 987 KiB

Open AccessReview

Putative Complementary Compounds to Counteract Insulin-Resistance in PCOS Patients

by Tabatha Petrillo, Elisa Semprini, Veronica Tomatis, Melania Arnesano, Fedora Ambrosetti, Christian Battipaglia, Alessandra Sponzilli, Francesco Ricciardiello, Andrea R. Genazzani and Alessandro D. Genazzani

Biomedicines 2022, 10(8), 1924; https://doi.org/10.3390/biomedicines10081924 - 09 Aug 2022

Cited by 5 | Viewed by 2557

Abstract

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of [...] Read more.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of insulin resistance and compensatory hyperinsulinemia have been taken into account as the additional key features in the etiopathology of PCOS, and they have been widely studied. Since PCOS is a complex and multifactorial syndrome with different clinical manifestations, it is difficult to find the gold standard treatment. Therefore, a great variety of integrative treatments have been reported to counteract insulin resistance. PCOS patients need a tailored therapeutic strategy, according to the patient’s BMI, the presence or absence of familiar predisposition to diabetes, and the patient’s desire to achieve pregnancy or not. The present review analyzes and discloses the main clinical insight of such complementary substances. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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21 pages, 2823 KiB

Open AccessReview

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials

by Fazilah Abdul Hamid, Muhammad Azrai Abu, Abdul Kadir Abdul Karim, Mohd Faizal Ahmad, Nor Haslinda Abd. Aziz, Datu Agasi Mohd Kamal and Mohd Helmy Mokhtar

Biomedicines 2022, 10(7), 1705; https://doi.org/10.3390/biomedicines10071705 - 14 Jul 2022

Cited by 8 | Viewed by 2912

Abstract

Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including oestrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this [...] Read more.

Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including oestrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this review, we aim to provide an update on the available knowledge of these receptors and how their interactions contribute to the pathogenesis of PCOS and endometriosis. One of the main PCOS-related medical conditions is abnormal folliculogenesis, which is associated with the downregulation of ER and AR expression in the ovaries. In addition, metabolic disorders in PCOS are caused by dysregulation of sex steroid hormone receptor expression. Furthermore, endometriosis is related to the upregulation of ER and the downregulation of PR expression. These receptors may serve as therapeutic targets for the treatment of PCOS-related disorders and endometriosis, considering their pathophysiological roles. Receptor agonists may be applied to increase the expression of a specific receptor and treat endometriosis or metabolic disorders. In contrast, receptor antagonist functions to reduce receptor expression and can be used to treat endometriosis and induce ovulation. Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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22 pages, 1752 KiB

Open AccessReview

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome

by Giorgia Scarfò, Simona Daniele, Jonathan Fusi, Marco Gesi, Claudia Martini, Ferdinando Franzoni, Vito Cela and Paolo Giovanni Artini

Biomedicines 2022, 10(6), 1305; https://doi.org/10.3390/biomedicines10061305 - 02 Jun 2022

Cited by 14 | Viewed by 6360

Abstract

Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known [...] Read more.

Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known about the molecular mechanisms and signaling pathways underlying the pathogenic mechanisms. In this sense, recent research has suggested that the influence of multiple factors, including age, environment, lifestyle and the disease state environment can change the clinical presentation of PCOS via epigenetic modifications. Variants in the genes encoding for proteins involved in steroidogenesis and glucose homeostasis play a crucial role in the development of the disease. Other genes involved in inflammation and cell proliferation seem to undergo an epigenetic control. Moreover, lifestyle factors influence the PCOS course and prognosis, including diet and physical activity, which are fundamental in reducing oxidative stress, inflammation and in improving metabolic and hormonal parameters. In the present review, literature evidence on molecular and epigenetic mechanisms related to PCOS etiology will be discussed, with a particular attention on the positive influence of diet and physical activity as nonpharmacological ways of intervention in the management of the disease. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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26 pages, 8551 KiB

Open AccessReview

Polycystic Ovarian Syndrome: A Complex Disease with a Genetics Approach

by Himani Nautiyal, Syed Sarim Imam, Sultan Alshehri, Mohammed M. Ghoneim, Muhammad Afzal, Sami I. Alzarea, Emine Güven, Fahad A. Al-Abbasi and Imran Kazmi

Biomedicines 2022, 10(3), 540; https://doi.org/10.3390/biomedicines10030540 - 24 Feb 2022

Cited by 24 | Viewed by 14616

Abstract

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which [...] Read more.

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which supports the positive diagnosis of PCOS when patients present two out of the following three symptoms: biochemical and clinical signs of hyperandrogenism, oligo, and anovulation, also polycystic ovarian morphology on sonography. Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances, which include hyperandrogenism, insulin resistance, and chronic inflammation in PCOS females. At the molecular level, different proteins and molecular and signaling pathways are involved in disease progression, which leads to the failure of a single genetic diagnostic approach. The genetic approach to elucidate the mechanism of pathogenesis of PCOS was recently developed, whereby four phenotypic variances of PCOS categorize PCOS patients into classic, ovulatory, and non-hyperandrogenic types. Genetic studies help to identify the root cause for the development of this PCOS. PCOS genetic inheritance is autosomal dominant but the latest investigations revealed it as a multigene origin disease. Different genetic loci and specific genes have been identified so far as being associated with this disease. Genome-wide association studies (GWAS) and related genetic studies have changed the scenario for the diagnosis and treatment of this reproductive and metabolic condition known as PCOS. This review article briefly discusses different genes associated directly or indirectly with disease development and progression. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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Other

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20 pages, 5632 KiB

Open AccessSystematic Review

The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside—A Systematic Literature Review

by Salvatore Giovanni Vitale, Anna Maria Fulghesu, Mislav Mikuš, Rafał Watrowski, Maurizio Nicola D’Alterio, Li-Te Lin, Mohsin Shah, Enrique Reyes-Muñoz, Thozhukat Sathyapalan and Stefano Angioni

Biomedicines 2022, 10(8), 1816; https://doi.org/10.3390/biomedicines10081816 - 28 Jul 2022

Cited by 18 | Viewed by 2729

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that are essential for the regulation of post-transcriptional gene expression during tissue development and differentiation. They are involved in the regulation of manifold metabolic and hormonal processes and, within the female reproductive tract, in oocyte maturation and [...] Read more.

MicroRNAs (miRNAs) are small, non-coding RNAs that are essential for the regulation of post-transcriptional gene expression during tissue development and differentiation. They are involved in the regulation of manifold metabolic and hormonal processes and, within the female reproductive tract, in oocyte maturation and folliculogenesis. Altered miRNA levels have been observed in oncological and inflammatory diseases, diabetes or polycystic ovary syndrome (PCOS). Therefore, miRNAs are proving to be promising potential biomarkers. In women with PCOS, circulating miRNAs can be obtained from whole blood, serum, plasma, urine, and follicular fluid. Our systematic review summarizes data from 2010–2021 on miRNA expression in granulosa and theca cells; the relationship between miRNAs, hormonal changes, glucose and lipid metabolism in women with PCOS; and the potential role of altered miRNAs in fertility (oocyte quality) in PCOS. Furthermore, we discuss miRNAs as a potential therapeutic target in PCOS and as a diagnostic marker for PCOS. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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13 pages, 574 KiB

Open AccessConcept Paper

Reconsidering the Polycystic Ovary Syndrome (PCOS)

by Norbert Gleicher, Sarah Darmon, Pasquale Patrizio and David H. Barad

Biomedicines 2022, 10(7), 1505; https://doi.org/10.3390/biomedicines10071505 - 25 Jun 2022

Cited by 15 | Viewed by 4993

Abstract

Though likely the most common clinical diagnosis in reproductive medicine, the Polycystic Ovary Syndrome (PCOS) is still only poorly understood. Based on previously published research, and here newly presented supportive evidence, we propose to replace the four current phenotypes of PCOS with only [...] Read more.

Though likely the most common clinical diagnosis in reproductive medicine, the Polycystic Ovary Syndrome (PCOS) is still only poorly understood. Based on previously published research, and here newly presented supportive evidence, we propose to replace the four current phenotypes of PCOS with only two entities—a hyperandrogenic phenotype (H-PCOS) including current phenotypes A, B, and C, and a hyper-/hypoandrogenic phenotype (HH-PCOS), representing the current phenotype D under the Rotterdam criteria. Reclassifying PCOS in this way likely establishes two distinct genomic entities, H-PCOS, primarily characterized by metabolic abnormalities (i.e., metabolic syndrome) and a hyperandrogenic with advancing age becoming a hypoandrogenic phenotype (HH-PCOS), in approximately 85% characterized by a hyperactive immune system mostly due to autoimmunity and inflammation. We furthermore suggest that because of hypoandrogenism usually developing after age 35, HH-PCOS at that age becomes relatively treatment resistant to in vitro fertilization (IVF) and offer in a case-controlled study evidence that androgen supplementation overcomes this resistance. In view of highly distinct clinical presentations of H-PCOS and HH-PCOS, polygenic risk scores should be able to differentiate between these 2 PCOS phenotypes. At least one clustering analysis in the literature is supportive of this concept. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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17 pages, 728 KiB

Open AccessSystematic Review

Prospective Risk of Type 2 Diabetes in Normal Weight Women with Polycystic Ovary Syndrome

by Dorte Glintborg, Naja Due Kolster, Pernille Ravn and Marianne Skovsager Andersen

Biomedicines 2022, 10(6), 1455; https://doi.org/10.3390/biomedicines10061455 - 20 Jun 2022

Cited by 4 | Viewed by 2403

Abstract

Background: Polycystic ovary syndrome (PCOS) is associated with obesity and increased risk for type 2 diabetes (T2D). However, the prospective risk of T2D in normal weight women with PCOS is debated, together with the relevant prospective screening programs for T2D in normal weight [...] Read more.

Background: Polycystic ovary syndrome (PCOS) is associated with obesity and increased risk for type 2 diabetes (T2D). However, the prospective risk of T2D in normal weight women with PCOS is debated, together with the relevant prospective screening programs for T2D in normal weight women with PCOS. Aim: To review and discuss prospective risk of T2D in normal weight women with PCOS, and to give recommendations regarding prospective screening for T2D in normal weight women with PCOS. Methods: Systematic review. Results: A systematic literature search resulted in 15 published prospective studies (10 controlled studies and 5 uncontrolled studies) regarding risk of T2D in study cohorts of PCOS, where data from normal weight women with PCOS were presented separately. In controlled studies, higher risk of T2D in normal weight women with PCOS compared to controls was reported in 4/10 studies, which included one study where T2D diagnosis was based on glucose measurement, two register-based studies, and one study where diagnosis of T2D was self-reported. Six of the 10 controlled studies reported no increased risk of T2D in normal weight women with PCOS. Four of these studies based the diagnosis of T2D on biochemical measurements, which supported the risk of surveillance bias in PCOS. In uncontrolled studies, 2/5 reported a higher risk of T2D in lean women with PCOS compared to the general population. We discuss the evidence for insulin resistance and β-cell dysfunction in normal weight women with PCOS, and aggravation in the hyperandrogenic phenotype, ageing women, and women with Asian ethnicity. Impaired glucose tolerance could be an important metabolic and vascular risk marker in PCOS. Conclusions: The risk of T2D may be increased in some normal weight women with PCOS. Individual risk markers such as hyperandrogenism, age >40 years, Asian ethnicity, and weight gain should determine prospective screening programs in normal weight women with PCOS. Full article

(This article belongs to the Special Issue Molecular Research on Polycystic Ovary Syndrome (PCOS))

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