Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls

Journal of the Endocrine Society, Год журнала: 2019, Номер 3(8), С. 1545 - 1573

Опубликована: Июнь 14, 2019

Abstract Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hyperandrogenism and chronic anovulation. Depending on diagnostic criteria, 6% to 20% of reproductive aged women are affected. Symptoms PCOS arise during the early pubertal years. Both normal female development irregular menstrual cycles, anovulation, acne. Owing complicated interwoven pathophysiology, discerning inciting causes challenging. Most available clinical data communicate findings outcomes in adult women. Whereas Rotterdam criteria accepted for women, different adolescent girls have been delineated. Diagnostic features irregularity, hyperandrogenism, and/or hyperandrogenemia. Pelvic ultrasound not needed diagnosis girls. Even before definitive PCOS, adolescents with signs androgen excess oligomenorrhea/amenorrhea, can be regarded as being “at risk PCOS.” Management both those at confirmed includes education, healthy lifestyle interventions, therapeutic interventions targeting their symptoms. Interventions include metformin, combined oral contraceptive pills, spironolactone, local treatments hirsutism In addition ascertaining associated comorbidities, management should also regular follow-up visits planned transition care providers. Comprehensive knowledge regarding pathogenesis will enable earlier identification high propensity develop PCOS. Timely implementation individualized improve overall adolescence, prevent quality life.

Язык: Английский

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Polycystic ovary syndrome and cardiometabolic risk: Opportunities for cardiovascular disease prevention

Trends in Cardiovascular Medicine, Год журнала: 2019, Номер 30(7), С. 399 - 404

Опубликована: Сен. 4, 2019

Although polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women, its etiology not entirely understood. Clinical symptoms PCOS include acne, amenorrhea or oligomenorrhea, hirsutism, infertility, and mood disorders, which tend to be primary focus clinical management. However, impact on future cardiovascular disease (CVD) risk should overlooked, opportunities implement CVD prevention strategies in these women given high priority. The pathogenesis commonly involves insulin resistance leads several cardiometabolic abnormalities (e.g., dyslipidemia, hypertension, glucose intolerance, diabetes, metabolic syndrome), thereby putting at an increased for CVD. Prior studies have found that subclinical markers such as coronary artery calcium scores, C-reactive protein, carotid intima-media thickness, endothelial dysfunction are more likely with PCOS. While associations between been well established, whether associated CVD, independently factors, clear. Lifestyle interventions weight management may mitigate some risks encouraged. This review summarizes literature factors provides recommendations would aid clinicians factors.

Язык: Английский

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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome

Nature Medicine, Год журнала: 2019, Номер 25(12), С. 1894 - 1904

Опубликована: Дек. 1, 2019

Язык: Английский

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Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome

Endocrine Reviews, Год журнала: 2020, Номер 41(4)

Опубликована: Апрель 20, 2020

Abstract More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS accompanying morbidities likely underdiagnosed, averaging > 2 years 3 physicians before diagnosed. Although it has been intensively researched, underlying cause(s) have yet to be defined. In order understand pathophysiology, developmental origins, how predict prevent onset, there is an urgent need for safe effective markers treatments. this review, we detail which animal models more suitable contributing our understanding etiology pathophysiology PCOS. We summarize highlight advantages limitations hormonal or genetic manipulation models, as well naturally occurring PCOS-like females.

Язык: Английский

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Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis

PLoS Medicine, Год журнала: 2020, Номер 17(6), С. e1003132 - e1003132

Опубликована: Июнь 23, 2020

Background Polycystic 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 are based expert opinion and have been subject considerable controversy. The phenotypic variation observed in PCOS suggestive an underlying heterogeneity, but recent meta-analysis European ancestry cases found that architecture defined by different was generally similar, suggesting do not identify biologically distinct disease subtypes. We performed this study test hypothesis there relevant subtypes PCOS. Methods findings Using biochemical genotype data from previously published genome-wide association (GWAS), we investigated whether were reproducible with subtype-specific associations. Unsupervised hierarchical cluster analysis quantitative anthropometric, reproductive, metabolic traits genotyped cohort 893 (median interquartile range [IQR]: age = 28 [25–32], body mass index [BMI] 35.4 [28.2–41.5]). clusters replicated independent, ungenotyped 263 IQR: [24–33], BMI 35.7 [28.4–42.3]). clustering revealed 2 subtypes: "reproductive" group (21%–23%), characterized higher luteinizing hormone (LH) sex binding globulin (SHBG) levels relatively low insulin levels, "metabolic" (37%–39%), BMI, glucose, lower SHBG LH levels. GWAS cohort, limiting either reproductive or identified alleles 4 loci associated subtype at significance (PRDM2/KAZN, P 2.2 × 10−10; IQCA1, 2.8 10−9; BMPR1B/UNC5C, 9.7 CDH10, 1.2 10−8) one locus significantly (KCNH7/FIGN, 1.0 10−8). developed predictive model classify separate, family-based 73 [25–33], 34.3 [27.8–42.3]) tended families carriers reported rare variants DENND1A, gene regulates androgen biosynthesis, more likely Limitations our only diagnosed National Institutes Health (NIH) included, sample sizes for small, replicated. Conclusions In conclusion, Furthermore, these novel, knowledge, susceptibility loci. Our results suggest because they appear architecture. This demonstrates how subtyping can be used gain additional insights data.

Язык: Английский

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Deconstructing a Syndrome: Genomic Insights Into PCOS Causal Mechanisms and Classification

Endocrine Reviews, Год журнала: 2022, Номер 43(6), С. 927 - 965

Опубликована: Янв. 13, 2022

Polycystic ovary syndrome (PCOS) is among the most common disorders in women of reproductive age, affecting up to 15% worldwide, depending on diagnostic criteria. PCOS characterized by a constellation interrelated abnormalities, including disordered gonadotropin secretion, increased androgen production, chronic anovulation, and polycystic ovarian morphology. It frequently associated with insulin resistance obesity. These metabolic derangements cause major morbidities across lifespan, anovulatory infertility type 2 diabetes (T2D). Despite decades investigative effort, etiology remains unknown. Familial clustering cases has indicated genetic contribution PCOS. There are rare Mendelian forms extreme phenotypes, but typically follows non-Mendelian pattern inheritance consistent complex architecture, analogous T2D obesity, that reflects interaction susceptibility genes environmental factors. Genomic studies have provided important insights into disease pathways current criteria do not capture underlying differences biology different We provide state-of-the-science review analyses PCOS, an overview genomic methodologies aimed at general audience non-geneticists clinicians. Applications will be discussed, strengths limitations each study. The contributions factors, developmental origins, reviewed. Insights pathogenesis architecture summarized. Future directions for outlined.

Язык: Английский

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The Genetics of Polycystic Ovary Syndrome: An Overview of Candidate Gene Systematic Reviews and Genome-Wide Association Studies

Journal of Clinical Medicine, Год журнала: 2019, Номер 8(10), С. 1606 - 1606

Опубликована: Окт. 3, 2019

Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms well documented, providing evidence for genetic contribution condition. This overview aims firstly systematically summarise current literature surrounding PCOS, secondly, assess methodological quality systematic reviews identify limitations. Four databases were searched candidate gene reviews, was assessed AMSTAR tool. Genome-wide association studies (GWAS) identified by semi structured search. Of 17 high moderate four low quality. A total 19 loci have been associated risk in GWAS, 11 these replicated across two different ancestries. Gene located neuroendocrine, metabolic, reproductive pathways. Overall, most robust findings THADA, FSHR, INS-VNTR, DENND1A, that now require validation. also limitations important considerations future studies. Much work remains causal variants functional relevance genes PCOS.

Язык: Английский

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The Role of Genetics, Epigenetics and Lifestyle in Polycystic Ovary Syndrome Development: the State of the Art

Reproductive Sciences, Год журнала: 2021, Номер 29(3), С. 668 - 679

Опубликована: Март 11, 2021

Язык: Английский

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Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation

Reproductive Biology and Endocrinology, Год журнала: 2022, Номер 20(1)

Опубликована: Янв. 10, 2022

Abstract As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and ovarian morphology. It linked with insulin resistance through preferential abdominal fat accumulation that worsened obesity. Over the past two millennia, menstrual irregularity, male-type habitus sub-infertility have been described in women confirm these clinical features PCOS were antiquity. Recent findings normal-weight hyperandrogenic show exaggerated lipid subcutaneous (SC) stem cells during development to adipocytes vitro occurs combination reduced sensitivity highly-lipolytic intra-abdominal vivo. This phenotype may be an evolutionary metabolic adaptation balance energy storage glucose availability fatty acid oxidation for optimal use reproduction. review integrates fundamental endocrine-metabolic changes healthy, similar PCOS-like traits present animal models which tissue differentiation completed fetal life as humans support concept has ancestral developmental origins.

Язык: Английский

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Family-Based Quantitative Trait Meta-Analysis Implicates Rare Noncoding Variants in DENND1A in Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2019, Номер 104(9), С. 3835 - 3850

Опубликована: Апрель 30, 2019

Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% this population depending on diagnostic criteria applied. It characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS highly heritable, but only a small proportion heritability can be accounted for genetic susceptibility variants identified to date.

Язык: Английский

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