Distinctive Reproductive Phenotypes in Peripubertal Girls at Risk for Polycystic Ovary Syndrome

Torchen, Laura; Legro, Richard S.; Dunaif, Andrea

doi:10.1210/jc.2018-02313

Cited by 39 publications

(23 citation statements)

References 41 publications

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“…Infants born to mothers with PCOS, and thus likely to exhibit PCOS themselves [17,18], demonstrate elongated anogenital distance [29] and facial sebum [30], both indicative of gestational exposure to T; they also have elevated circulating levels of ovarian antimullerian hormone (AMH) [31,32], indicative of exaggerated antral follicle numbers typical of polycystic ovaries. Peripubertal daughters of PCOS women similarly exhibit elevated AMH levels [18,33], in addition to increased circulating LH levels [18], potentially from accelerated hypothalamic gonadotropin-releasing hormone (GnRH) pulsatile release (a trait programmed in rhesus macaques by gestational T exposure or prepubertal androgen excess [34,35]), and increased proclivity for synthesizing the highly biopotent androgen, dihydrotestosterone (DHT) [36], suggesting enhanced androgen action within target tissues. Not surprisingly, therefore, a major goal of pediatric medicine includes identifying girls at risk of PCOS from reliable prepubertal characteristics [37], in order to initiate early preventive therapy and/or treatment [37,38].…”

Section: Pcos and Its Potential Originsmentioning

confidence: 99%

“…Infant daughters of women with PCOS exhibit elongated anogenital distance [29], as do adult women with PCOS [59][60][61]. Prepubertal daughters of women with PCOS exhibit increased whole body 5alpha-reductase activity [36], enhancing target organ exposure to androgen action before menarche, while pre-and peripubertal daughters exhibit hyperandrogenism [18,33,124], including elevated 'free' T (not bound to sex hormone binding globulin, SHBG) [33], along with consistently elevated ovarian AMH levels from infancy [18,31,32] and LH hypergonadotropism during adolescence [18]. Peripubertal hyperandrogenism can persist into adulthood, associated with reduced fecundity [125], and persistent adolescent menstrual irregularities progress to a PCOS diagnosis in~57% of cases [126].…”

Section: Infant and Peripubertal Reproduction-related Endocrine And Omentioning

confidence: 99%

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Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

et al. 2019

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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.

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Section: Pcos and Its Potential Originsmentioning

confidence: 99%

Section: Infant and Peripubertal Reproduction-related Endocrine And Omentioning

confidence: 99%

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

et al. 2019

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“…PCOS has diverse phenotypes [15][16][17] and thus requires individualized treatment. The European Society of Endocrinology [2] proposed four phenotypes, including a type without hyperandrogenemia.…”

Section: Introductionmentioning

confidence: 99%

Improving the accuracy and efficacy of diagnosing polycystic ovary syndrome by integrating metabolomics with clinical characteristics: study protocol for a randomized controlled trial

Huang

Jiang

et al. 2020

Trials

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Background: Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics.Methods: This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 1:1 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment. Discussion: The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy.

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“…Due to its heterogeneity of clinical manifestations and complex pathogenesis, the strategy of diagnosis is mainly aimed to exclude other diseases. It is well recognized that there are diverse phenotypes of PCOS [15][16][17] and each one ought to take a separate and precise therapy. European Society of Endocrinology [2] proposed a statement that there were four phenotypes of PCOS, including a type without hyperandrogenemia which is contrary to popular belief.…”

Section: Introductionmentioning

confidence: 99%

Accuracy and efficacy of diagnosis via integrated with metabolomics in patients with PCOS: study protocol for a randomized controlled trial

Huang

Jiang

et al. 2019

Preprint

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Background Polycystic ovary syndrome (PCOS) is defined as a complex endocrine syndrome and the mechanisms underlying its various clinical signs and symptoms are still poorly understood, brings huge difficulties for clinical diagnosis and treatment. General agreement based on several clinical guideline[1, 2] suggest that it is critical to precisely diagnose the phenotypes of PCOS and give them an individual therapy. However, the criteria for different phenotypes remains unclear, mostly based on symptoms, physical examination and laboratory evaluation. The aim of this study is to compare the accuracy and preciseness of metabolomics markers with common clinical characteristics to find a more effective way to diagnose and treat these two subgroups (based on our basic study[3]) of PCOS patients. What’s more, the effects of different interventions according to two subgroups will also be observed. Methods/design This is a prospective, multicenter, analyst-blinded and randomized controlled trial. One healthy control group and two parallel experiment arms will be proposed in this study: (1) people without PCOS (health control group); (2) PCOS patients diagnosed mainly based on clinical indexes (group one); (3) PCOS patients diagnosed mainly based on metabolomics indexes (group two). A total of 276 eligible people will be recruited, which includes 60 healthy people and 216 PCOS patients, which will be randomly assigned to different diagnosis groups in a 1:1 ratio. Patients in two different diagnosis groups will be divided into two different subgroups according to their clinical characteristics (group one based on clinical indexes, group two based on metabolomics indexes) and receive a 6-month corresponding treatment. The primary outcome for experiment groups will be the condition of PCOS. All data will be analyzed periodically. This trial will help us to clarify the value of metabolomics integrated with clinical characteristics in diagnosis and treatment of two PCOS subgroups. It will also highlight any differences in the accuracy and efficacy of these two techniques and it may provide a new specific direction of integrated method for the PCOS therapy. Discussion The purpose of this trial is to determine whether integrated metabolomics indexes is more accuracy and effective than clinical characteristics in diagnose the phenotypes of reproductive females with PCOS. This trial will, therefore, contribute to providing a solid foundation for clinical precise diagnosis of two PCOS subgroups, as well as future research in PCOS individual therapy.

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Distinctive Reproductive Phenotypes in Peripubertal Girls at Risk for Polycystic Ovary Syndrome

Cited by 39 publications

References 41 publications

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

Improving the accuracy and efficacy of diagnosing polycystic ovary syndrome by integrating metabolomics with clinical characteristics: study protocol for a randomized controlled trial

Accuracy and efficacy of diagnosis via integrated with metabolomics in patients with PCOS: study protocol for a randomized controlled trial

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