Elucidating the impact of obesity on hormonal and metabolic perturbations in polycystic ovary syndrome phenotypes in Indian women

Dadachanji, Roshan; Patil, Anushree; Joshi, Beena; Mukherjee, Srabani

doi:10.1371/journal.pone.0246862

Cited by 24 publications

(14 citation statements)

References 67 publications

(101 reference statements)

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“…However, PCOS is a highly heterogenic syndrome, with variable manifestations in different ethnic and age groups [8], so different cut-offs should be used for MBI, IR, hirsutism and other clinical signs [9]. Obesity, for example, is often observed in PCOS patients and known as an accentuating factor [10], albeit, for Asian ethnic groups, the connection between PCOS and obesity is less pronounced [11,12].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Dabravolski

Nikiforov

Eid

et al. 2021

IJMS

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Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Dabravolski

Nikiforov

Eid

et al. 2021

IJMS

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“…AMH was associated with the pathophysiology of reproductive dysfunction in PCOS and reflects PCOS status, therefore it may also be useful in PCOS diagnosis [40]. Dadachanji, et al [41] revealed the importance of clinicians concurrently employing Rotterdam criteria along with obesity status for ascertaining accurate disorders in the course of PCOS status.…”

Section: Discussionmentioning

confidence: 99%

Body Composition and Its Impact on the Hormonal Disturbances in Women with Polycystic Ovary Syndrome

et al. 2021

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We investigated the relationship between selected body composition (BC) parameters and included 55 women diagnosed with PCOS and 29 women in which PCOS was excluded. Hormone concentration and BC parameters were assessed during hospitalization. Women with PCOS had higher concentration of luteinizing hormones, total testosterone, androstenedione, and Anti-Müllerian hormones compared to women that were not diagnosed with PCOS. We did not observe any significant differences in the BC parameters between both groups as well as between four PCOS phenotype subgroups. Only in the group of women with PCOS was the concentration of sex hormone binding globulin and free testosterone correlated with all investigated BC parameters. Correspondence analysis did not confirm unambiguously associations between phenotypes of PCOS and the value of BC parameters, while logistic regression revealed that increased Anti-Müllerian hormone concentration and the value of body mass index could be useful parameters in differentiating women with PCOS and women with other disorders. The ROC analysis performed on the entire group of women also confirmed that the concentration of Anti-Müllerian hormones could be a powerful parameter to categorize women as suffering from PCOS.

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“…Notably, multiple MR studies revealed that obesity potentially causes PCOS, all of which exclusively used body mass index (BMI) as the surrogate anthropometric measure of obesity [ 25 – 28 ]. However, BMI is essentially a marker of general obesity whereas central obesity in particular seems to confer a formidable influence on PCOS pathogenesis [ 16 – 18 ]. Moreover, the use of multiple anthropometric traits could yield not only complementary but also exclusive information.…”

Section: Introductionmentioning

confidence: 99%

Causality of anthropometric markers associated with polycystic ovarian syndrome: Findings of a Mendelian randomization study

et al. 2022

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Introduction Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed. Objectives To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers. Methods Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables–weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling. Results Instrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69–77.05), BMI (OR: 2.90–4.06), WC (OR: 6.22–20.27), and HC (OR: 6.22–20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS. Conclusions Both and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.

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Elucidating the impact of obesity on hormonal and metabolic perturbations in polycystic ovary syndrome phenotypes in Indian women

Cited by 24 publications

References 67 publications

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Body Composition and Its Impact on the Hormonal Disturbances in Women with Polycystic Ovary Syndrome

Causality of anthropometric markers associated with polycystic ovarian syndrome: Findings of a Mendelian randomization study

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