Polycystic ovary syndrome: reviewing diagnosis and management of metabolic disturbances

Polycystic ovary syndrome (PCOS) is a common condition in women at reproductive age associated with reproductive and metabolic dysfunction. Proposed diagnosed criteria for PCOS include two out of three features: androgen excess, menstrual irregularity, and polycystic ovary appearance on ultrasound (PCO), after other causes of hyperandrogenism and dysovulation are excluded. Based on these diagnostic criteria, the most common phenotypes are the “classic PCOS” – hyperandrogenism and oligomenorrhea, with or without PCO; the “ovulatory phenotype” – hyperandrogenism and PCO in ovulatory women; and the “non-hyperandrogenic phenotype”, in which there is oligomenorrhea and PCO, without overt hyperandrogenism. The presence of obesity may exacerbate the metabolic and reproductive disorders associated with the syndrome. In addition, PCOS women present higher risk for type 2 diabetes and higher prevalence of cardiovascular risk factors that seems to be associated with the classic phenotype. The main interventions to minimize cardiovascular and metabolic risks in PCOS are lifestyle changes, pharmacological therapy, and bariatric surgery. Treatment with metformin has been shown to improve insulin sensitivity, lowering blood glucose and androgen levels. These effects are more potent when combined with lifestyle interventions. In conclusion, besides reproductive abnormalities, PCOS has been associated to metabolic comorbidities, most of them linked to obesity. Confounders, such as the lack of standard diagnostic criteria, heterogeneity of the clinical presentation, and presence of obesity, make management of PCOS difficult. Therefore, the approach to metabolic abnormalities should be tailored to the risks and treatment goals of each individual woman.

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Phenotypic clustering reveals distinct subtypes of polycystic ovary syndrome with novel genetic associations

10.1101/814210 ◽

2019 ◽

Author(s):

Matthew Dapas ◽

Frederick T. J. Lin ◽

Girish N. Nadkarni ◽

Ryan Sisk ◽

Richard S. Legro ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Diagnostic Criteria ◽

Polycystic Ovary ◽

Reproductive Age ◽

European Ancestry ◽

Sequencing Analysis ◽

Ovary Syndrome ◽

Biologically Relevant ◽

Insulin Levels ◽

Family Based

AbstractBackgroundPolycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive age women worldwide, depending on the diagnostic criteria applied. These diagnostic criteria are based on expert opinion and have been the subject of considerable controversy. The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes. We performed this study to test the hypothesis that there are biologically relevant subtypes of PCOS.Methods and FindingsUnsupervised hierarchical cluster analysis was performed on quantitative anthropometric, reproductive, and metabolic traits in a genotyped discovery cohort of 893 PCOS cases and an ungenotyped validation cohort of 263 PCOS cases. We identified two PCOS subtypes: a “reproductive” group (21-23%) characterized by higher luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels with relatively low body mass index (BMI) and insulin levels; and a “metabolic” group (37-39%), characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels. We performed a GWAS on the genotyped cohort, limiting the cases to either the reproductive or metabolic subtypes. We identified alleles in four novel loci that were associated with the reproductive subtype at genome-wide significance (PRDM2/KAZN1, P=2.2×10-10; IQCA1, P=2.8×10-9; BMPR1B/UNC5C, P=9.7×10-9; CDH10, P=1.2×10-8) and one locus that was significantly associated with the metabolic subtype (KCNH7/FIGN, P=1.0×10-8). We have previously reported that rare variants in DENND1A, a gene regulating androgen biosynthesis, were associated with PCOS quantitative traits in a family-based whole genome sequencing analysis. We classified the reproductive and metabolic subtypes in this family-based PCOS cohort and found that the subtypes tended to cluster in families and that carriers of rare DENND1A variants were significantly more likely to have the reproductive subtype of PCOS. Limitations of our study were that only PCOS cases of European ancestry diagnosed by NIH criteria were included, the sample sizes for the subtype GWAS were small, and the GWAS findings were not replicated.ConclusionsIn conclusion, we have found stable reproductive and metabolic subtypes of PCOS. Further, these subtypes were associated with novel susceptibility loci. Our results suggest that these subtypes are biologically relevant since they have distinct genetic architectures. This study demonstrates how precise phenotypic delineation can be more powerful than increases in sample size for genetic association studies.

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Promotion of reproductive and metabolic health - current trends in the treatment and prevention of polycystic ovary syndrome in different periods of life

Kwartalnik Naukowy Fides et Ratio ◽

10.34766/fetr.v47i3.895 ◽

2021 ◽

Vol 47 (3) ◽

pp. 130-149

Author(s):

Joanna Smyczyńska

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Diagnostic Criteria ◽

Polycystic Ovary ◽

Hormonal Contraception ◽

Reproductive Age ◽

Metabolic Effects ◽

Adult Women ◽

Ovary Syndrome ◽

Treatment And Prevention

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders and causes of infertility in women in reproductive age. Diagnostic criteria of PCOS in adult women include: ovulation disorders, hyperandrogenism and polycystic ovaries. According to most recommendations, 2 out of these 3 criteria are confirm the diagnosis of PCOS. In girls during puberty and in the first years after menarche, different diagnostic criteria of menstrual disorders should be taken into account (variable length of menstrual cycles, monophasic cycles) and the limited usefulness of ultrasound examination for PCOS diagnosis within 8 years after menarche. Fairly extensive differential diagnosis is also necessary, especially – exclusion of adrenal hyperandrogenism. Moreover, the diagnostic criteria of PCOS do not take into account the metabolic disorders found in most patients (obesity, insulin resistance, type 2 diabetes), which should be diagnosed as early as possible and treated appropriately. This is especially true for teenagers, in whom the unequivocal diagnosis of PCOS or its exclusion may be very difficult. Current recommendations regard hormonal contraception as the first-line therapy in PCOS, in both adult women and adolescents. Together with its beneficial effect on the reduction of hyperandrogenism and obtaining regular bleeding (which in fact are not menstruations), the unfavorable metabolic effects of hormonal contraception are emphasized, as well as the inadequacy of its use if it is expected to achieve or restore ovulation and fertility. The latest reports indicate the legitimacy of treatment aimed at correcting disorders of carbohydrate metabolism and its greater effectiveness compared to the use of oral contraceptives in both adult women and girls with PCOS. In the pharmacotherapy of insulin resistance, metformin is of fundamental importance, the use of pioglitazone, GLP-1 receptor agonists or inositols is also proposed. Adequate lifestyle and dietary modification are of major importance in the treatment and prevention of PCOS. The mechanisms of "inheritance" of PCOS and insulin resistance with the participation of epigenetic modifications are still better understood, taking into account the effects of exposure to androgen excess in utero, intrauterine growth retardation, and maternal obesity and hyperalimentation. This creates new possibilities for PCOS prophylaxis.

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Polycystic Ovary Syndrome: It is time to change the approach in diagnosis and management

IJEDO ◽

10.32044/ijedo.2021.02 ◽

2021 ◽

Vol 3 ◽

pp. 12-14

Author(s):

Carole Wehbe Chidiac

Keyword(s):

Eating Disorders ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Lifestyle Changes ◽

Reproductive Age ◽

Evidence Based ◽

Emotional Wellbeing ◽

Ovary Syndrome ◽

Communication Preferences ◽

Evidence Based Guideline

Polycystic ovary syndrome (PCOS) is a common and very distressing condition in women of reproductive age. International evidence-based guideline for the assessment and management of polycystic ovary syndrome was published in 2018, with a governance including an international advisory board from six continents. The global guideline has provided a well-rounded and all-inclusive synopsis of all aspects of PCOS. Recommendations made are clear and should help eliminate areas of conflict. The addition of large sections addressing lifestyle and emotional wellbeing puts the prevalence of eating disorders in PCOS in the spotlight and strengthens the importance of looking at the patient as a whole rather than a collection of individual symptoms and problems to solve. This commentary focuses on the evidence against many unnecessary and even harmful practices we still frequently encounter: the diagnostic criteria in teenagers, the lack of optimal ultrasound reporting, the unnecessary recommendation for non-evidence-based diets, and the harmful effects of untimely discussions disregarding women’s priorities, communication preferences, beliefs culture and mental health. Last but not least, although screening for eating disorders has been recommended by many medical societies, especially before any triggering discussion about lifestyle changes, it is still rarely done in clinical practice.

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Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Reproduction ◽

10.1530/rep-14-0435 ◽

2015 ◽

Vol 149 (5) ◽

pp. R219-R227 ◽

Cited By ~ 112

Author(s):

Poli Mara Spritzer ◽

Sheila B Lecke ◽

Fabíola Satler ◽

Debora M Morsch

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Lifestyle Changes ◽

Reproductive Age ◽

Sufficient Evidence ◽

Low Grade ◽

Androgen Excess ◽

Ovary Syndrome ◽

Increased Risk

Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

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Adiposity and metabolic dysfunction in polycystic ovary syndrome

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2015-0008 ◽

2015 ◽

Vol 21 (2) ◽

Cited By ~ 7

Author(s):

Susan Sam

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Metabolic Disorders ◽

Polycystic Ovary ◽

Reproductive Age ◽

Metabolic Dysfunction ◽

Obese Women ◽

Ovary Syndrome ◽

Insulin Resistant

AbstractPolycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.

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Evidence-Based Lifestyle and Pharmacological Management of Infertility in Women with Polycystic Ovary Syndrome

Women s Health ◽

10.2217/whe.12.14 ◽

2012 ◽

Vol 8 (3) ◽

pp. 277-290 ◽

Cited By ~ 7

Author(s):

Michael F Costello ◽

William L Ledger

Keyword(s):

Polycystic Ovary Syndrome ◽

Ovulation Induction ◽

Polycystic Ovary ◽

Pharmacological Therapy ◽

Reproductive Age ◽

First Line ◽

Ovary Syndrome ◽

Pharmacological Management ◽

Medical Treatments ◽

Laparoscopic Ovarian Drilling

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age and by far the most common cause of anovulatory infertility. Lifestyle change alone, and not in combination with pharmacological ovulation induction such as clomifene citrate or metformin, is generally considered the first-line treatment for the management of infertile anovulatory women with PCOS who are overweight or obese. Clomifene citrate should be considered as a first-line pharmacological therapy to improve fertility outcomes. Second-line medical treatments may include ovulation induction with gonadotropins (in clomifene citrate-resistant or clomifene citrate failure women) or laparoscopic ovarian drilling (in clomifene citrate-resistant women) or possibly with metformin combined with clomifene citrate (in clomifene citrate-resistant women). There is currently insufficient evidence to recommend aromatase inhibitors over that of clomifene citrate in infertile anovulatory women with PCOS in general or specifically in therapy-naive or clomifene citrate-resistant women with PCOS.

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MODERN TREATMENTS FOR PCOS (LITERATURE REVIEW)

Reproductive Medicine ◽

10.37800/rm2020-1-5 ◽

2020 ◽

pp. 27-34

Author(s):

A.I. Korkan ◽

A.D. Turekhanova ◽

Y.L. Tyugay

Keyword(s):

Endometrial Cancer ◽

Surgical Treatment ◽

Conservative Treatment ◽

Literature Review ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Reproductive Age ◽

Metabolic Dysfunction ◽

Ovary Syndrome ◽

Conservative And Surgical Treatment

According to world statistics, polycystic ovary syndrome (PCOS) is one of the most common forms of endocrinopathy in women of mainly reproductive age. PCOS can cause metabolic dysfunction, ovulatory infertility, endometrial cancer, pre- mature birth, perinatal mortality, and other serious consequences. The article discusses various methods of conservative and surgical treatment of PCOS. The main focus is on conservative treatment of infertility caused by PCOS.

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Cardiovascular Risk in Postmenopausal Women with Polycystic Ovary Syndrome

Current Vascular Pharmacology ◽

10.2174/1570161116666180828154006 ◽

2019 ◽

Vol 17 (6) ◽

pp. 579-590 ◽

Cited By ~ 3

Author(s):

Eleni Armeni ◽

Irene Lambrinoudaki

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Clinical Manifestations ◽

Reproductive Age ◽

Metabolic Disturbances ◽

Cvd Risk ◽

Ovary Syndrome ◽

Female Population ◽

Previous Diagnosis ◽

Aging Women

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age. The hormonal alterations of PCOS have been linked with a higher risk of metabolic disturbances in young, reproductively active women. However, it remains to be clarified whether the presence of PCOS increases the risk of cardiovascular disease (CVD) later in life. Aging ameliorates the clinical manifestations of PCOS; hyperandrogenaemia and metabolic abnormalities, however, persist beyond the menopause. On the other hand, aging and menopause increase CVD risk in the general female population. The results of the limited available studies in aging women with a previous diagnosis of PCOS demonstrate early atherosclerosis. However, studies addressing clinical CVD outcomes in women with PCOS report inconsistent findings. A possible explanation for this heterogeneity is the difficulty in diagnosing PCOS after the menopausal transition, due to the absence of validated diagnostic criteria for this population. Larger prospective studies of women diagnosed during their reproductive years will shed more light on the longer-term CVD implications of PCOS.

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New about the pathogenesis and treatment of polycystic ovary syndrome

Russian Journal of Woman and Child Health ◽

10.32364/2618-8430-2021-4-1-17-22 ◽

2021 ◽

Vol 4 (1) ◽

pp. 17-22

Author(s):

N.V. Artymuk ◽

◽

O.A. Tachkova ◽

Keyword(s):

Vitamin D ◽

Polycystic Ovary Syndrome ◽

Ovulation Induction ◽

Polycystic Ovary ◽

Clomiphene Citrate ◽

Lifestyle Changes ◽

Reproductive Age ◽

Therapeutic Modality ◽

Hormonal Contraceptives ◽

Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age that is characterized by reproductive and metabolic disorders. Mental issues, hypothalamic-pituitary dysfunction, ovarian dysfunction, mitochondrial dysfunction, obesity, and vitamin D deficiency account for infertility in PCOS. This paper reviews recent studies on pathogenesis and treatment approaches to this disease. Recognized therapeutic modalities for PCOS are addressed, i.e., rational diet, combined hormonal contraceptives, ovulation induction using clomiphene citrate and/or metformin, ovarian drilling, assisted reproductive technology, and alternative approaches (e.g., herbal therapy, traditional Chinese medicine, vitamin D, coenzyme Q, salubrinal, and the combination of simvastatin and metformin). Inositols are a promising therapeutic modality that improves menstrual and reproductive function (presumably via their impact on carbonic and lipid metabolism) and the quality of oocytes and embryos. KEYWORDS: polycystic ovary syndrome, pathogenesis, treatment, myo-inositol, ovulation induction, drilling, combined oral contraceptives, lifestyle changes. FOR CITATION: Artymuk N.V., Tachkova O.A. New about the pathogenesis and treatment of polycystic ovary syndrome. Russian Journal of Woman and Child Health. 2021;4(1):17–22. DOI: 10.32364/2618-8430-2021-4-1-17-22.

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5α-dihydrotestosterone treatment induces metabolic changes associated with polycystic ovary syndrome without interfering with hypothalamic leptin and glucocorticoid signaling

Archives of Biological Sciences ◽

10.2298/abs151214001n ◽

2016 ◽

Vol 68 (3) ◽

pp. 473-481

Author(s):

Marina Nikolic ◽

Natasa Velickovic ◽

Ana Djordjevic ◽

Biljana Bursac ◽

Djuro Macut ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Day Treatment ◽

Reproductive Age ◽

Female Rats ◽

Leptin Resistance ◽

Polycystic Ovaries ◽

Metabolic Disturbances ◽

Inflammatory Signaling ◽

Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogenous disorder, with hyperandrogenism, chronic anovulation and polycystic ovaries as basic characteristics, and associated metabolic syndrome features. Increased secretion of leptin and leptin resistance are common consequences of obesity. Leptin is a hormone with anorexigenic effects in the hypothalamus. Its function in the regulation of energy intake and consumption is antagonized by glucocorticoids. By modulating leptin signaling and inflammatory processes in the hypothalamus, glucocorticoids can contribute to the development of metabolic disturbances associated with central energy disbalance. The aim of the study was to examine the relationship between hypothalamic leptin, glucocorticoid and inflammatory signaling in the development of metabolic disturbances associated with PCOS. The study was conducted on an animal model of PCOS generated by a continual, 90-day treatment of female rats with 5?-dihydrotestosterone (DHT). The model exhibited all key reproductive and metabolic features of the syndrome. mRNA and/or protein levels of the key components of hypothalamic glucocorticoid, leptin and inflammatory pathways, presumably contributing to energy disbalance in DHT-treated female rats, were measured. The results indicated that DHT treatment led to the development of hyperphagia and hyperleptinemia as metabolic features associated with PCOS. However, these metabolic disturbances could not be ascribed to changes in hypothalamic leptin, glucocorticoid or inflammatory signaling pathways in DHT-treated rats.

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