Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

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Harmonizing research outcomes for polycystic ovary syndrome (HARP), a marathon not a sprint: current challenges and future research need

Human Reproduction ◽

10.1093/humrep/deaa331 ◽

2020 ◽

Author(s):

Bassel H Al Wattar ◽

Aurora Bueno ◽

Miguel Garcia Martin ◽

Naomi Cano Ibáñez ◽

Klejda Harasani ◽

...

Keyword(s):

Big Data ◽

Polycystic Ovary Syndrome ◽

Data Sharing ◽

Polycystic Ovary ◽

Evidence Synthesis ◽

Future Research ◽

Selective Reporting ◽

Ovary Syndrome ◽

Research Outcomes ◽

The Impact

Abstract Investing in clinical research and evidence-based medicine has helped to improve the care for women with polycystic ovary syndrome (PCOS). However, several important questions remain unanswered on the optimal prevention and management strategies for PCOS. Addressing this uncertainty is often hindered by suboptimal research conduct leading to inefficient evidence synthesis and research wastage. PCOS research is often practised by varied specialized teams in silo leading to disharmonious and fragmented efforts neglecting the lifelong impact of PCOS on women’s wellbeing. Poor engagement among key stakeholders and lay consumers continues to limit the impact and benefits of research to society. Selective reporting on surrogate outcomes with a ‘significant’ P-value is a common malpractice in PCOS outputs. Effective adoption of the harmonizing research outcomes for PCOS (HARP) core outcome set is needed to minimize heterogeneity in reporting and promote research excellence. Small single-centre studies offer limited value to assess the varied PCOS phenotypes. Efficient large scale data-sharing is needed to address complex research questions and glean the benefits of big data research. We propose a roadmap to address these challenges and remedy future research need by promoting patient and public involvement in PCOS research to guide research efforts and address real patients’ needs; engaging all key stakeholder groups to promote a multi-disciplinary lifelong approach to new research; continuously refining research needs and priorities to revise the knowledge gap and allocate resources judiciously; standardizing outcomes definitions and measurement tools to harmonize reporting and promote excellence in research; and by investing in large data-sharing infrastructure to facilitate big data research and govern ethical data sharing.

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The Impact of Obesity on Incidence of Type 2 Diabetes Mellitus (T2DM) among Women with Polycystic Ovary Syndrome (PCOS)

Diabetes ◽

10.2337/db18-1612-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1612-P

Author(s):

NADIRA SULTANA KAKOLY ◽

ARUL EARNEST ◽

HELENA TEEDE ◽

LISA MORAN ◽

DEBORAH LOXTON ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

The Impact

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Insulin Therapy in Pregnancy Hypertensive Diseases and its Effect on the Offspring and Mother Later in Life

Current Vascular Pharmacology ◽

10.2174/1570161117666181114125109 ◽

2019 ◽

Vol 17 (5) ◽

pp. 455-464 ◽

Cited By ~ 8

Author(s):

Alfonso Mate ◽

Antonio J. Blanca ◽

Rocío Salsoso ◽

Fernando Toledo ◽

Pablo Stiefel ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Insulin Therapy ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Insulin Resistant ◽

Hypertensive Disorders ◽

The Impact ◽

In Pregnancy

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.

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Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00167 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5372-5381 ◽

Cited By ~ 12

Author(s):

Nigel K Stepto ◽

Alba Moreno-Asso ◽

Luke C McIlvenna ◽

Kirsty A Walters ◽

Raymond J Rodgers

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Polycystic Ovary Syndrome ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Polycystic Ovary ◽

Evidence Synthesis ◽

Basic Research ◽

Future Research ◽

Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

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Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women

Scientific Reports ◽

10.1038/s41598-021-92265-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sairish Ashraf ◽

Shayaq Ul Abeer Rasool ◽

Mudasar Nabi ◽

Mohd Ashraf Ganie ◽

Shariq R. Masoodi ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Clinical Manifestations ◽

Additive Model ◽

Genotypic Frequency ◽

Ovary Syndrome ◽

Significant Difference ◽

Cyp19 Gene ◽

Reproductive Endocrine ◽

The Impact

AbstractPolycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in pre-menopausal women having complex pathophysiology. Several candidate genes have been shown to have association with PCOS. CYP19 gene encodes a key steroidogenic enzyme involved in conversion of androgens into estrogens. Previous studies have reported contradictory results with regard to association of SNP rs2414096 in CYP19 gene with PCOS and hyperandrogenism in different ethnic populations. Present study was aimed to investigate the impact of SNP rs2414096 polymorphism of CYP19 gene on susceptibility of PCOS and hyperandrogenism in Kashmiri women. Further we also studied the genotypic-phenotypic association for various clinical and biochemical parameters of this polymorphism. Case control study. 394 PCOS cases diagnosed on the basis of Rotterdam criteria and age matched 306 healthy women. We found a significant differences in genotypic frequency (χ2 = 18.91, p < 0.05) as well as allele frequency (OR 0.63, CI 0.51–0.78, χ2 = 17.66, p < 0.05) between PCOS women and controls. The genotype–phenotype correlation analysis showed a significant difference in FG score (p = 0.047) and alopecia (p = 0.045) between the three genotypes. Also, the androgen excess markers like DHEAS (p < 0.001), Androstenedione (p < 0.001), Testosterone (p < 0.001) and FAI (p = 0.005) were significantly elevated in GG genotype and showed a significant difference in additive model in PCOS women. rs2414096 polymorphism of CYP19 gene is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women.

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Trabecular Bone is Increased in a Rat Model of Polycystic Ovary Syndrome

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1284-5491 ◽

2020 ◽

Author(s):

Lady Katerine Serrano Mujica ◽

Werner Giehl Glanzner ◽

Amanda Luiza Prante ◽

Vitor Braga Rissi ◽

Gabrielle Rebeca Everling Correa ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Bone Formation ◽

Type I Collagen ◽

Polycystic Ovary ◽

Osteoclast Differentiation ◽

Bone Volume ◽

Negative Regulator ◽

Type I ◽

Ovary Syndrome ◽

The Impact

AbstractPolycystic ovary syndrome (PCOS) in an intricate disorder characterized by reproductive and metabolic abnormalities that may affect bone quality and strength along with the lifespan. The present study analysed the impact of postnatal androgenization (of a single dose of testosterone propionate 1.25 mg subcutaneously at day 5 of life) on bone development and markers of bone metabolism in adult female Wistar rats. Compared with healthy controls, the results of measurements of micro-computed tomography (microCT) of the distal femur of androgenized rats indicated an increased cortical bone volume voxel bone volume to total volume (VOX BV/TV) and higher trabecular number (Tb.n) with reduced trabecular separation (Tb.sp). A large magnitude effect size was observed in the levels of circulating bone formation Procollagen I N-terminal propeptide (P1NP) at day 60 of life; reabsorption cross-linked C-telopeptide of type I collagen (CTX) markers were similar between the androgenized and control rats at days 60 and 110 of life. The analysis of gene expression in bone indicated elements for an increased bone mass such as the reduction of the Dickkopf-1 factor (Dkk1) a negative regulator of osteoblast differentiation (bone formation) and the reduction of Interleukin 1-b (Il1b), an activator of osteoclast differentiation (bone reabsorption). Results from this study highlight the possible role of the developmental programming on bone microarchitecture with reference to young women with PCOS.

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The Impact of Subclinical Hypothyroidism on Patients with Polycystic Ovary Syndrome: A Meta-Analysis

Hormone and Metabolic Research ◽

10.1055/a-1463-3198 ◽

2021 ◽

Vol 53 (06) ◽

pp. 382-390

Author(s):

Yuling Xing ◽

Jinhu Chen ◽

Jing Liu ◽

Huijuan Ma

Keyword(s):

Polycystic Ovary Syndrome ◽

Subclinical Hypothyroidism ◽

Polycystic Ovary ◽

Meta Analysis ◽

Chinese Patients ◽

Cochrane Library ◽

Academic Journal ◽

Ovary Syndrome ◽

Funnel Plot ◽

The Impact

AbstractThe association between subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) has been shown in many studies. These findings are still controversial, however. It is unclear whether the co-incidence of subclinical hypothyroidism and polycystic ovary syndrome will affect the severity of metabolism. Therefore, we performed this meta-analysis to investigate the association. A comprehensive search strategy was developed to obtain all relevant studies published in PubMed, EMBASE, Cochrane Library, and Chinese Academic Journal Full-text Database (CNKI) up to 31 December 2020. We adopted the standardized mean difference (SMD) with 95% confidence intervals (CI) for evaluation, and sensitivity analysis was performed. Publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger’s test. Twenty-seven studies with 4821 participants (1300 PCOS patients with SCH, 3521 PCOS patients without SCH) were included in the present meta-analysis,among which 71.31% chinese patients out of the total. The results showed that PCOS patients with SCH had higher levels of HOMA-IR, TG, TC, LDL, FBG, FCP, PRL and lower levels of HDL, LH and T. It also recognized the limitation of the lack of a consistent definition of hypothyroidism in the 27 studies included. The results of this study indicated that SCH may aggravate lipid and glucose metabolism in patients with PCOS.

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