Polycystic Ovary Syndrome

A special issue of Medical Sciences (ISSN 2076-3271). This special issue belongs to the section "Endocrinology and Metabolic Diseases".

Deadline for manuscript submissions: closed (30 May 2019) | Viewed by 77678

Special Issue Editors

Dr. Kirsty Walters
E-Mail Website
Guest Editor
Head, Ovarian Biology Laboratory, School of Women’s & Children’s Health, Discipline of Obstetrics & Gynaecology, University of New South Wales, Sydney, NSW 2052, Australia
Interests: androgens; female fertility; PCOS
Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney 2139, Australia
Interests: andrology; reproductive endocrinology, androgen physiology pharmacology & toxicology

Special Issue Information

Dear Colleagues,

Polycystic ovary syndrome (PCOS) affects >100 million women worldwide and is characterized by reproductive, metabolic, and endocrine disturbances. In addition, mounting evidence from human and animal studies implies that adverse PCOS health traits can be transferred to offspring. The high prevalence and wide range of adverse health conditions associated with PCOS brings an urgent challenge—to address not only the infertility, but also to ameliorate the metabolic disorders and intergenerational transmission of PCOS-related ill-health. Recent advances have included consensus international evidence-based guidelines for the assessment and management of PCOS aiming to unify and improve the care and health of women with PCOS. However, as the origin of PCOS remains unknown, there is neither cure nor specific treatment. Hence, there is a pressing need to develop targeted evidence-based treatments for PCOS, but this requires a much deeper knowledge of the physiological mechanisms underpinning its evolution.

This Special Issue will feature short, focused reviews discussing the distinctive features and comorbidities associates with PCOS, the modern evidence-based clinical assessment and management of PCOS, lessons learned from PCOS animal models, and the latest novel ideas in the pathophysiology of PCOS. This Special Issue aims to provide an update on advances and challenges in the field of PCOS. The goal is to provide up-to-date information on new and developing ideas on the origins, diagnosis, and management of PCOS, highlighting the latest concepts in understanding the etiology of PCOS, while also generating thought-provoking directions for future investigations and management.

Dr. Kirsty Walters
Prof. David Handelsman
Guest Editors

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Published Papers (11 papers)

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Review

26 pages, 1252 KiB  
Review
Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application
Med. Sci. 2019, 7(12), 107; https://doi.org/10.3390/medsci7120107 - 27 Nov 2019
Cited by 31 | Viewed by 3836
Abstract
Indian rhesus macaque nonhuman primate models for polycystic ovary syndrome (PCOS) implicate both female hyperandrogenism and developmental molecular origins as core components of PCOS etiopathogenesis. Establishing and exploiting macaque models for translational impact into the clinic, however, has required multi-year, integrated basic-clinical science [...] Read more.
Indian rhesus macaque nonhuman primate models for polycystic ovary syndrome (PCOS) implicate both female hyperandrogenism and developmental molecular origins as core components of PCOS etiopathogenesis. Establishing and exploiting macaque models for translational impact into the clinic, however, has required multi-year, integrated basic-clinical science collaborations. Paradigm shifting insight has accrued from such concerted investment, leading to novel mechanistic understanding of PCOS, including hyperandrogenic fetal and peripubertal origins, epigenetic programming, altered neural function, defective oocytes and embryos, adipogenic constraint enhancing progression to insulin resistance, pancreatic decompensation and type 2 diabetes, together with placental compromise, all contributing to transgenerational transmission of traits likely to manifest in adult PCOS phenotypes. Our recent demonstration of PCOS-related traits in naturally hyperandrogenic (High T) female macaques additionally creates opportunities to employ whole genome sequencing to enable exploration of gene variants within human PCOS candidate genes contributing to PCOS-related traits in macaque models. This review will therefore consider Indian macaque model contributions to various aspects of PCOS-related pathophysiology, as well as the benefits of using macaque models with compellingly close homologies to the human genome, phenotype, development and aging. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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8 pages, 232 KiB  
Review
Polycystic Ovary Syndrome in Adolescence
Med. Sci. 2019, 7(10), 101; https://doi.org/10.3390/medsci7100101 - 02 Oct 2019
Cited by 10 | Viewed by 4765
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females, and is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology based on ultrasound. Controversy surrounds the optimum diagnosis and management in the adolescent population. Many patients with adult [...] Read more.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females, and is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology based on ultrasound. Controversy surrounds the optimum diagnosis and management in the adolescent population. Many patients with adult PCOS present with pathognomonic symptoms as adolescents, and there is value in early diagnosis due to the associated long-term metabolic and reproductive health sequalae. A definitive diagnosis does not need to be made prior to implementing treatment in this group of young women. The practitioner who has an adolescent presenting with signs and symptoms of PCOS, has a unique opportunity to risk stratify, screen for co-morbidities, and implement early management strategies, many of which are lifestyle modifications, to help prevent long term morbidity associated with this disease. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
10 pages, 201 KiB  
Review
A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome
Med. Sci. 2019, 7(9), 95; https://doi.org/10.3390/medsci7090095 - 10 Sep 2019
Cited by 25 | Viewed by 5783
Abstract
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or [...] Read more.
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or obese. First line medical ovulation induction therapy to improve fertility outcomes is letrozole, whilst other less efficacious ovulation induction agents, such as clomiphene citrate, metformin, and metformin combined with clomiphene citrate, may also be considered. Metformin combined with clomiphene citrate is more effective than clomiphene citrate alone. In obese women with PCOS, clomiphene citrate could be used in preference to metformin alone whilst clomiphene citrate could be added to metformin alone in order to improve reproductive outcome in all women with PCOS. Gonadotrophins, which are more effective than clomiphene citrate in therapy naïve women with PCOS, can be considered a first line therapy in the presence of ultrasound monitoring, following counselling on the cost and the potential risk of multiple pregnancy. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
12 pages, 1246 KiB  
Review
The Mechanism of Androgen Actions in PCOS Etiology
Med. Sci. 2019, 7(9), 89; https://doi.org/10.3390/medsci7090089 - 28 Aug 2019
Cited by 76 | Viewed by 16514
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad [...] Read more.
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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8 pages, 523 KiB  
Review
Origins and Impact of Psychological Traits in Polycystic Ovary Syndrome
Med. Sci. 2019, 7(8), 86; https://doi.org/10.3390/medsci7080086 - 05 Aug 2019
Cited by 16 | Viewed by 5996
Abstract
Women with polycystic ovary syndrome (PCOS) exhibit compromised psychiatric health. Independent of obesity, women with PCOS are more susceptible to have anxiety and depression diagnoses and other neuropsychiatric disorders. During pregnancy women with PCOS display high circulating androgen levels that may cause prenatal [...] Read more.
Women with polycystic ovary syndrome (PCOS) exhibit compromised psychiatric health. Independent of obesity, women with PCOS are more susceptible to have anxiety and depression diagnoses and other neuropsychiatric disorders. During pregnancy women with PCOS display high circulating androgen levels that may cause prenatal androgen exposure affecting the growing fetus and increasing the risk of mood disorders in offspring. Increasing evidence supports a non-genetic, maternal contribution to the development of PCOS and anxiety disorders in the next generation. Prenatal androgenized rodent models reflecting the anxiety-like phenotype of PCOS in the offspring, found evidence for the altered placenta and androgen receptor function in the amygdala, together with changes in the expression of genes associated with emotional regulation and steroid receptors in the amygdala and hippocampus. These findings defined a previously unknown mechanism that may be critical in understanding how maternal androgen excess can increase the risk of developing anxiety disorders in daughters and partly in sons of PCOS mothers. Maternal obesity is another common feature of PCOS causing an unfavorable intrauterine environment which may contribute to psychiatric problems in the offspring. Whether environmental factors such as prenatal androgen exposure and obesity increase the offspring’s susceptibility to develop psychiatric ill-health will be discussed. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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16 pages, 641 KiB  
Review
The Role of the Brain in the Pathogenesis and Physiology of Polycystic Ovary Syndrome (PCOS)
Med. Sci. 2019, 7(8), 84; https://doi.org/10.3390/medsci7080084 - 02 Aug 2019
Cited by 62 | Viewed by 14454
Abstract
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, affecting at least 10% of women of reproductive age. PCOS is typically characterized by the presence of at least two of the three cardinal features of hyperandrogenemia (high circulating androgen levels), oligo- or [...] Read more.
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, affecting at least 10% of women of reproductive age. PCOS is typically characterized by the presence of at least two of the three cardinal features of hyperandrogenemia (high circulating androgen levels), oligo- or anovulation, and cystic ovaries. Hyperandrogenemia increases the severity of the condition and is driven by increased luteinizing hormone (LH) pulse secretion from the pituitary. Indeed, PCOS women display both elevated mean LH levels, as well as an elevated frequency of LH pulsatile secretion. The abnormally high LH pulse frequency, reflective of a hyperactive gonadotropin-releasing hormone (GnRH) neural circuit, suggests a neuroendocrine basis to either the etiology or phenotype of PCOS. Several studies in preclinical animal models of PCOS have demonstrated alterations in GnRH neurons and their upstream afferent neuronal circuits. Some rodent PCOS models have demonstrated an increase in GnRH neuron activity that correlates with an increase in stimulatory GABAergic innervation and postsynaptic currents onto GnRH neurons. Additional studies have identified robust increases in hypothalamic levels of kisspeptin, another potent stimulator of GnRH neurons. This review outlines the different brain and neuroendocrine changes in the reproductive axis observed in PCOS animal models, discusses how they might contribute to either the etiology or adult phenotype of PCOS, and considers parallel findings in PCOS women. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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13 pages, 623 KiB  
Review
Developmental Programming of PCOS Traits: Insights from the Sheep
Med. Sci. 2019, 7(7), 79; https://doi.org/10.3390/medsci7070079 - 11 Jul 2019
Cited by 27 | Viewed by 4624
Abstract
Polycystic ovary syndrome (PCOS) is a complex disorder that results from a combination of multiple factors, including genetic, epigenetic, and environmental influences. Evidence from clinical and preclinical studies indicates that elevated intrauterine androgen levels increase the susceptibility of the female offspring to develop [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex disorder that results from a combination of multiple factors, including genetic, epigenetic, and environmental influences. Evidence from clinical and preclinical studies indicates that elevated intrauterine androgen levels increase the susceptibility of the female offspring to develop the PCOS phenotype. Additionally, early postnatal endocrine and metabolic imbalances may act as a “second-hit”, which, through activational effects, might unmask or amplify the modifications programmed prenatally, thus culminating in the development of adult disease. Animal models provide unparalleled resources to investigate the effects of prenatal exposure to androgen excess and to elucidate the etiology and progression of disease conditions associated with this occurrence, such as PCOS. In sheep, prenatal treatment with testosterone disrupts the developmental trajectory of the fetus, culminating in adult neuroendocrine, ovarian, and metabolic perturbations that closely resemble those seen in women with PCOS. Our longitudinal studies clearly demonstrate that prenatal exposure to testosterone excess affects both the reproductive and the metabolic systems, leading to a self-perpetuating cycle with defects in one system having an impact on the other. These observations in the sheep suggest that intervention strategies targeting multiple organ systems may be required to prevent the progression of developmentally programmed disorders. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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8 pages, 218 KiB  
Review
Steroid Mass Spectrometry for the Diagnosis of PCOS
Med. Sci. 2019, 7(7), 78; https://doi.org/10.3390/medsci7070078 - 10 Jul 2019
Cited by 20 | Viewed by 3628
Abstract
The most appropriate steroids to measure for the diagnosis of hyperandrogenism in polycystic ovary syndrome (PCOS) are still open to debate but should preferably be measured using a high-quality method such as liquid chromatography tandem mass spectrometry (LC-MS/MS). Measurement of testosterone is recommended [...] Read more.
The most appropriate steroids to measure for the diagnosis of hyperandrogenism in polycystic ovary syndrome (PCOS) are still open to debate but should preferably be measured using a high-quality method such as liquid chromatography tandem mass spectrometry (LC-MS/MS). Measurement of testosterone is recommended in all of the current clinical guidelines but other steroids, such as androstenedione and dehydroepiandrosterone sulfate (DHEAS), have also been shown to be useful in diagnosing PCOS and may give additional information on metabolic risk. The 11-oxygenated steroids, and in particular 11KT derived mainly from the adrenal gland, are also increasing in prominence and have been shown to be the dominant androgens in this condition. Polycystic ovary syndrome is a complex syndrome and it is not surprising that each of the clinical phenotypes are associated with different patterns of steroid hormones; it is likely that steroid profiling with LC-MS/MS may be better at identifying hyperandrogensim in each of these phenotypes. Research into PCOS has been hampered by the small sample size of clinical studies previously undertaken and larger studies, preferably using LC-MS/MS profiling of steroids, are needed Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
18 pages, 688 KiB  
Review
Barriers and Facilitators to the Implementation of Evidence-Based Lifestyle Management in Polycystic Ovary Syndrome: A Narrative Review
Med. Sci. 2019, 7(7), 76; https://doi.org/10.3390/medsci7070076 - 27 Jun 2019
Cited by 19 | Viewed by 6612
Abstract
Polycystic ovary syndrome (PCOS) is a complex condition that involves metabolic, psychological and reproductive complications. Insulin resistance underlies much of the pathophysiology and symptomatology of the condition and contributes to long term complications including cardiovascular disease and diabetes. Women with PCOS are at [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex condition that involves metabolic, psychological and reproductive complications. Insulin resistance underlies much of the pathophysiology and symptomatology of the condition and contributes to long term complications including cardiovascular disease and diabetes. Women with PCOS are at increased risk of obesity which further compounds metabolic, reproductive and psychological risks. Lifestyle interventions including diet, exercise and behavioural management have been shown to improve PCOS presentations across the reproductive, metabolic and psychological spectrum and are recommended as first line treatment for any presentation of PCOS in women with excess weight by the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. However, there is a paucity of research on the implementation lifestyle management in women with PCOS by healthcare providers. Limited existing evidence indicates lifestyle management is not consistently provided and not meeting the needs of the patients. In this review, barriers and facilitators to the implementation of evidence-based lifestyle management in reference to PCOS are discussed in the context of a federally-funded health system. This review highlights the need for targeted research on the knowledge and practice of PCOS healthcare providers to best inform implementation strategies for the translation of the PCOS guidelines on lifestyle management in PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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11 pages, 217 KiB  
Review
A Review of Second- and Third-line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome
Med. Sci. 2019, 7(7), 75; https://doi.org/10.3390/medsci7070075 - 26 Jun 2019
Cited by 11 | Viewed by 5416
Abstract
In clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, either metformin combined with clomiphene citrate or gonadotrophins could be used as a second-line pharmacological therapy, although gonadotrophins are more effective. Gonadotrophins could also be used as a second-line [...] Read more.
In clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, either metformin combined with clomiphene citrate or gonadotrophins could be used as a second-line pharmacological therapy, although gonadotrophins are more effective. Gonadotrophins could also be used as a second-line pharmacological therapy in anovulatory women with PCOS and clomiphene-citrate-failure. Laparoscopic ovarian surgery can also be used as a second-line therapy for ovulation induction in anovulatory women with clomiphene-citrate-resistant PCOS and no other infertility factors. The usefulness of letrozole as a second-line pharmacological treatment for ovulation induction in clomiphene-citrate-resistant women with PCOS requires further research. In terms of improving fertility, both pharmacological anti-obesity agents and bariatric surgery should be considered an experimental therapy in anovulatory women with PCOS and no other infertility factors. Where first- or second-line ovulation induction therapies have failed, in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) could be offered as a third-line therapy in women with PCOS in the absence of an absolute indication for IVF/ICSI. For women with PCOS undergoing IVF/ICSI treatment, the gonadotropin-releasing hormone (GnRH) antagonist protocol is preferred and an elective frozen embryo transfer strategy could be considered. In assisted conception units with sufficient expertise, in-vitro maturation (IVM) of oocytes could be offered to women with PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
8 pages, 230 KiB  
Review
Generational Health Impact of PCOS on Women and Their Children
Med. Sci. 2019, 7(3), 49; https://doi.org/10.3390/medsci7030049 - 18 Mar 2019
Cited by 8 | Viewed by 4721
Abstract
Polycystic ovary syndrome (PCOS) is a metabolic disorder with reproductive consequences. Hence, the synergy of the dual maternal challenges of difficulties with conception, set on a background of metabolic disorder and inflammation, understandably leads to increased obstetric risk for the woman. Furthermore, she [...] Read more.
Polycystic ovary syndrome (PCOS) is a metabolic disorder with reproductive consequences. Hence, the synergy of the dual maternal challenges of difficulties with conception, set on a background of metabolic disorder and inflammation, understandably leads to increased obstetric risk for the woman. Furthermore, she is more likely than her peers to require assistance with conception, either through induction of ovulation with the attendant risk of a multiple gestation, or in vitro fertilization (IVF) with its recognized increased obstetric risk for woman and her child. The increased obstetric risk for a woman with PCOS is manifested with an increased rate of miscarriage, gestational diabetes, hypertensive disorder and premature delivery. These obstetric complications are due to impairment of placental function, systemic inflammation and metabolic disorder and are markers for the woman herself of her predisposition to cardiometabolic disorder in later life. Consequently, it is inevitable that this environment may induce changes in the fetus during pregnancy, leading to an intergenerational risk from maternal PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome)
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