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Effects of distinct Polycystic Ovary Syndrome phenotypes on bone health.

ABSTRACT: Polycystic Ovary Syndrome (PCOS) is a highly prevalent and heterogenous endocrinopathy affecting 5-18% of women. Although its cardinal features include androgen excess, ovulatory dysfunction, and/or polycystic ovarian morphology, women often display related metabolic manifestations, including hyperinsulinaemia, insulin resistance, and obesity. Emerging data reveal that the hormonal alterations associated with PCOS also impact bone metabolism. However, inconsistent evidence exists as to whether PCOS is a bone-protective or bone-hindering disorder with an accumulating body of clinical data indicating that hyperandrogenism, hyperinsulinaemia, insulin resistance, and obesity may have a relative protective influence on bone, whereas chronic low-grade inflammation and vitamin D deficiency may adversely affect bone health. Herein, we provide a comprehensive assessment of the endocrine and metabolic manifestations associated with PCOS and their relative effects on bone metabolism. We focus principally on clinical studies in women investigating their contribution to the alterations in bone turnover markers, bone mineral density, and ultimately fracture risk in PCOS. A thorough understanding in this regard will indicate whether women with PCOS require enhanced surveillance of bone health in routine clinical practice.

SUBMITTER: Mills EG

PROVIDER: S-EPMC10213631 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Effects of distinct Polycystic Ovary Syndrome phenotypes on bone health.

Mills Edouard G EG Abbara Ali A Dhillo Waljit S WS Comninos Alexander N AN

Frontiers in endocrinology 20230512

Polycystic Ovary Syndrome (PCOS) is a highly prevalent and heterogenous endocrinopathy affecting 5-18% of women. Although its cardinal features include androgen excess, ovulatory dysfunction, and/or polycystic ovarian morphology, women often display related metabolic manifestations, including hyperinsulinaemia, insulin resistance, and obesity. Emerging data reveal that the hormonal alterations associated with PCOS also impact bone metabolism. However, inconsistent evidence exists as to whether P ...[more]

PMID: 37251667

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Project description:ImportanceThe prevalence of polycystic ovary syndrome (PCOS) varies across the globe. Indian studies on PCOS are limited by poor design, small sizes, regional representations, and varying methods.ObjectivesTo estimate the nationwide prevalence of PCOS in India, examine the phenotypic spectrum, and assess the magnitude of comorbidities associated with PCOS.Design, setting, and participantsThis cross-sectional study recruited 9824 women aged 18 to 40 years from November 1, 2018, to July 31, 2022, across 5 zones of the country. A prevalidated questionnaire dichotomized women into screen-positive and screen-negative groups. Relevant clinical, hormonal, and sonographic assessments categorized women as either women with criteria-based PCOS (ie, National Institutes of Health [NIH] 1990 criteria, Rotterdam 2003 criteria, or Androgen Excess and Polycystic Ovary Syndrome Society [AE-PCOS] criteria), women with partial phenotypes (hyperandrogenism, oligomenorrhea, or polycystic morphology labeled as pre-PCOS), or healthy women, in addition to quantitating various comorbidities.Main outcomes and measuresThe prevalence and phenotypes of PCOS among women of reproductive age and the burden of comorbidities associated with PCOS.ResultsA total of 8993 women (mean [SD] age, 29.5 [6.2] years) were enrolled in this study; 196 women were already diagnosed with PCOS, 2251 were categorized as screen positive, and 6546 were categorized as screen negative. The mean (SD) age of screen-positive women (28.1 [6.4] years) was lower than that of screen-negative women (29.7 [6.1] years) (P < .001), and the mean (SD) age at menarche was higher in the former group (13.2 [1.3] vs 13.1 [1.2] years; P < .001). The national prevalence of PCOS was 7.2% (95% CI, 4.8%-10.8%) by NIH 1990 criteria, 19.6% (95% CI, 12.7%-29.2%) by Rotterdam 2003 criteria, and 13.6% (95% CI, 8.4%-21.6%) by AE-PCOS criteria. Overall, PCOS phenotypes C (501 [40.8%]) and D (301 [24.6%]) were the most common, and 492 women (pre-PCOS subgroup) had oligomenorrhea (n = 75), hyperandrogenism (n = 257), or polycystic ovarian morphology (n = 160) only. Among women with PCOS (n = 1224), obesity was present in 529 (43.2%), dyslipidemia in 1126 (91.9%), nonalcoholic fatty liver disease in 403 (32.9%), metabolic syndrome in 305 (24.9%), impaired glucose tolerance in 111 (9.1%), diabetes in 41 (3.3%), and hypertension in 101 (8.3%). The pre-PCOS subgroup (n = 492) displayed similar metabolic aberrations (dyslipidemia: 390 [79.3%]; metabolic syndrome: 78 [15.9%]; nonalcoholic fatty liver disease: 163 [33.1%]; impaired glucose tolerance: 62 [12.6%]; diabetes: 7 [1.4%]; and hypertension: 26 [5.3%]).Conclusions and relevanceIn this cross-sectional study of reproductive-age women recruited across India, the prevalence of PCOS was high, with phenotype C being predominant. Most of these women had metabolic abnormalities. These findings are crucial for developing preventive and therapeutic strategies, potentially integrating PCOS management into national health programs.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications.MethodsA total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS).ResultsOur results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity.ConclusionsOur results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin sensitivity and could be considered as the potential biomarkers for long-term risk assessment of diabetes mellitus.

Project description:ContextPolycystic ovary syndrome (PCOS) has a largely unknown etiology and presents with a clinical heterogeneous patient group. Small noncoding microRNA (miRNA) might prove promising as biomarker candidates for PCOS patient stratification. Altered miRNA expression profiles have been observed in few studies.ObjectiveThe aim was to assess the miRNA expression profile in follicular fluid from PCOS patients and healthy, regularly cycling, matched controls.Design and settingExperimental case-control study including 49 PCOS women (19 of which were hyperandrogenic and 30 normo-androgenic) and 21 healthy matched women all undergoing in vitro fertilization treatment.Interventions and main outcomeAnthropometric and relevant clinical baseline measurements were obtained. Relative expression of miRNA levels were estimated using miRNA quantitative PCR arrays and validated by quantitative RT-PCR. Correlation between miRNAs and clinical relevant measurements was estimated.ResultsPCOS women, both normo-androgenic and hyperandrogenic, had decreased levels of miR-24-3p, -29a, -151-3p, and -574-3p compared with controls. Furthermore, miR-518f-3p was differentially expressed within the PCOS group with high levels observed in the hyperandrogenic group compared with the normo-androgenic PCOS patients. Serum levels of total and free T were positively correlated with miR-518f-3p in PCOS subjects (P = .001). Distinction between PCOS and controls could be made using miR-151-3p alone with an area under the curve of 0.91 or a combination of four selected miRNAs (area under the curve, 0.93). Bioinformatic target analysis points to an involvement of these miRNAs in biological pathways involving regulation of cell proliferation, extracellular matrix, and processes in intermediary metabolism.ConclusionOur study provides evidence that the miRNA expression profile in follicular fluid is altered in PCOS and indicates that specific follicular fluid miRNAs are associated with phenotypical traits of PCOS. An altered miRNA profile holds potentials for new methods of PCOS patient stratification and may contribute to and in part explain the heterogeneous nature found within PCOS women.

Dataset Information

Effects of distinct Polycystic Ovary Syndrome phenotypes on bone health.

Publications

Effects of distinct Polycystic Ovary Syndrome phenotypes on bone health.

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