The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women

AbstractContextPolycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date.ObjectiveThe objective of this study was to test whether rare genetic variants contribute to PCOS pathogenesis.Design, Patients, and MethodsWe performed whole-genome sequencing on DNA from 261 individuals from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis.ResultsWe found rare variants in DENND1A (P = 5.31 × 10−5, adjusted P = 0.039) that were significantly associated with reproductive and metabolic traits in PCOS families.ConclusionsCommon variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.

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Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

International Journal of Endocrinology ◽

10.1155/2016/9545239 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Tommy Kyaw Tun ◽

Anne McGowan ◽

Niamh Phelan ◽

Neuman Correia ◽

Gerard Boran ◽

...

Keyword(s):

Insulin Resistance ◽

Cardiovascular Risk ◽

Polycystic Ovary Syndrome ◽

Apolipoprotein B ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Premenopausal Women ◽

Postprandial Glucose ◽

Ovary Syndrome ◽

Mixed Meal

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age30.4±1.2years (mean ± SEM), body mass index (BMI)36.8±1.5 kg/m2) and 26 non-PCOS subjects (age34.1±0.9years, BMI31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.

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Serum Concentrations of Fibroblast Growth Factors 19 and 21 in Women with Gestational Diabetes Mellitus: Association with Insulin Resistance, Adiponectin, and Polycystic Ovary Syndrome History

PLoS ONE ◽

10.1371/journal.pone.0081190 ◽

2013 ◽

Vol 8 (11) ◽

pp. e81190 ◽

Cited By ~ 26

Author(s):

Dongyu Wang ◽

Wenjing Zhu ◽

Jieming Li ◽

Chongyou An ◽

Zilian Wang

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Growth Factors ◽

Gestational Diabetes ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Fibroblast Growth Factors ◽

Fibroblast Growth ◽

Serum Concentrations ◽

Ovary Syndrome

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Increased Anti-Müllerian Hormone Serum Concentrations during Late Reproductive Age in Women with Polycystic Ovary Syndrome

10.1210/endo-meetings.2011.part2.p32.p2-232 ◽

2011 ◽

pp. P2-232-P2-232

Author(s):

Teresa Sir-Petermann ◽

Amanda Ladron de Guevara ◽

Jessica Preisler ◽

Barbara Echiburu ◽

Manuel Maliqueo ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Reproductive Age ◽

Serum Concentrations ◽

Ovary Syndrome

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Family-based quantitative trait meta-analysis implicates rare noncoding variants in DENND1A in pathogenesis of polycystic ovary syndrome

10.1101/460972 ◽

2018 ◽

Cited By ~ 1

Author(s):

Matthew Dapas ◽

Ryan Sisk ◽

Richard S. Legro ◽

Margrit Urbanek ◽

Andrea Dunaif ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Quantitative Trait ◽

Rare Variants ◽

Polycystic Ovary ◽

Association Studies ◽

Meta Analysis ◽

Premenopausal Women ◽

Endocrine Disorders ◽

Genome Wide Association Studies ◽

Ovary Syndrome

ABSTRACTPolycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS is a leading risk factor for type 2 diabetes in young women. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date. To test the hypothesis that rare genetic variants contribute to PCOS pathogenesis, we performed whole-genome sequencing on DNA from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis. We found rare variants in DENND1A (P=5.31×10−5, Padj=0.019) that were significantly associated with reproductive and metabolic traits in PCOS families. Common variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.

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Fertility and Pregnancy Outcomes in Women with Polycystic Ovary Syndrome Following Bariatric Surgery

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa439 ◽

2020 ◽

Vol 105 (9) ◽

pp. e3384-e3391

Author(s):

Estela Benito ◽

Jesús M Gómez-Martin ◽

Belén Vega-Piñero ◽

Pablo Priego ◽

Julio Galindo ◽

...

Keyword(s):

Bariatric Surgery ◽

Birth Weight ◽

Polycystic Ovary Syndrome ◽

Live Birth ◽

Polycystic Ovary ◽

Premenopausal Women ◽

Obese Women ◽

Ovary Syndrome ◽

Birth Rates ◽

Live Birth Rates

Abstract Context Restoration of ovulation is quite common in women with polycystic ovary syndrome (PCOS) after surgically induced weight loss. Whether or not this results in an improvement of PCOS-associated infertility is uncertain. Objective To study fertility and gestational outcomes in women with PCOS after bariatric surgery. Design Unicenter cohort study. Setting Academic hospital. Patients Two hundred and sixteen premenopausal women were screened for PCOS before bariatric surgery. Women were followed-up after the intervention until mid-2019 regardless of having or not PCOS. Interventions All participants underwent bariatric surgery from 2005 to 2015. Main outcome measures Pregnancy and live birth rates in the PCOS and control groups. Results In women seeking fertility, pregnancy rates were 95.2% in PCOS and 76.9% in controls (P = 0.096) and live birth rates were 81.0% and 69.2%, respectively (P = 0.403). The time to achieve the first pregnancy after surgery was 34 ± 28 months in women with PCOS and 32 ± 25 months in controls. Albeit the mean birth weight was lower (P = 0.040) in newborns from women with PCOS (2763 ± 618 g) compared with those from controls (3155 ± 586 g), the number of newborns with low birth weight was similar in both groups (3 in the PCOS group and 1 in the controls, P = 0.137). Maternal (17.6% in PCOS and 22.2% in controls, P = 0.843) and neonatal (23.5% in PCOS and 14.8% in controls, P = 0.466) complications were rare, showing no differences between groups. Conclusions Pregnancy and fertility rates in very obese women with PCOS after bariatric surgery were high, with few maternal and neonatal complications.

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