Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS

Roe, Andrea H.; Hillman, Jennifer; Butts, Samantha; Smith, M P; Rader, Daniel J.; Playford, Martin P.; Mehta, Nehal N.; Dokras, Anuja

doi:10.1210/jc.2013-3918

Cited by 53 publications

(45 citation statements)

References 30 publications

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“…7,[20][21][22] Only one report has examined both men and women. 7 Similar to our findings, the Multi-Ethnic Study of Atherosclerosis (MESA) also reported that higher SHBG levels were associated with a less atherogenic profile in both men and women.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, greater total T levels correlated with lower HDL in another report, but associations between SHBG and lipid subfractions were not reported. 20 Strengths of this report include the novel assessments of lipid subfractions and sex hormone profiles in Asian Indians, a population at high risk for atherogenesis. The cohort, while small, was also population-based rather than referral center based.…”

Section: Discussionmentioning

confidence: 99%

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Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Kim

Kong

Krauss³

et al. 2015

Metabolic Syndrome and Related Disorders

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Background: Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians. Methods: We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipidlowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity. Results: Among women, lower log SHBG levels were associated with smaller log LDL particle size and higher log triglycerides, log VLDL, and log IDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower log SHBG levels was significantly associated with lower log medium LDL and log small LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower log SHBG was also associated with smaller log LDL peak diameter size and higher log triglycerides and log VLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher log HDL and log LDL particle size, and lower log triglycerides and log VLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR. Conclusions: Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Kim

Kong

Krauss³

et al. 2015

Metabolic Syndrome and Related Disorders

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“…It can coexist with increased small low-density lipoprotein particles and an otherwise normal lipid profile (156). A study reported that cholesterol efflux capacity from macrophages, a measure of high-density lipoprotein-cholesterol function and an independent predictor of subclinical CVD, is abnormally suppressed in women with PCOS (157).…”

Section: E Cardiovascular Disease Riskmentioning

confidence: 99%

Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

et al. 2015

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Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.

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“…Recent data have shown that cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, is inversely associated with the risk of future cardiovascular events in a large population-based cohort of adults [71]. Interestingly, a recent study has reported that PCOS women have a decreased cholesterol efflux capacity and reduced atherogenic lipid particle number and size, independently of body weight [72]. Similar evaluations among NAFLD patients will be needed in the near future, because these patients, like PCOS women, are at high risk for cardiovascular disease [3-6, 47, 52, 73].…”

Section: Research Agendamentioning

confidence: 99%

Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

2015

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Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.

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Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS

Abstract: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Cited by 53 publications

References 30 publications

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

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