Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001). Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

Download Full-text

Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje-09-0379 ◽

2009 ◽

Vol 161 (5) ◽

pp. 737-745 ◽

Cited By ~ 29

Author(s):

Flavia Tosi ◽

Romolo Dorizzi ◽

Roberto Castello ◽

Claudio Maffeis ◽

Giovanna Spiazzi ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Body Fat ◽

Polycystic Ovary ◽

C Reactive Protein ◽

Androgen Excess ◽

Ovary Syndrome ◽

Reactive Protein ◽

Hs Crp

ObjectiveIncreased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association.Design and methodsSerum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6±4.2 years, body mass index (BMI) 23.6±3.5 kg/m2), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance.ResultsHs-CRP concentrations were higher in PCOS women (3.43±2.01 mg/l) than in HA subjects and healthy women (2.43±1.04, P<0.005; and 2.75±0.86 mg/l, P<0.05 respectively versus PCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable.ConclusionsPCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

Download Full-text

Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause

Acta Endocrinologica ◽

10.1530/eje-12-0550 ◽

2013 ◽

Vol 168 (1) ◽

pp. 83-90 ◽

Cited By ~ 8

Author(s):

Marios C Markopoulos ◽

George Valsamakis ◽

Evangelia Kouskouni ◽

Anastassios Boutsiadis ◽

Ioannis Papassotiriou ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Waist Circumference ◽

Polycystic Ovary Syndrome ◽

Carbohydrate Metabolism ◽

Polycystic Ovary ◽

Sensitivity Index ◽

Ovary Syndrome ◽

Hs Crp

ObjectiveHyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships.Subjects and methodsBlood sampling from overweight postmenopausal women (25 PCOS and 24 age- and BMI-matched controls) at baseline and during oral glucose tolerance test for measurement of insulin and glucose levels, baseline leptin, adiponectin, visfatin, retinol-binding protein 4, lipocalin-2, androgen, and high-sensitivity C-reactive protein (hs-CRP) levels and for calculation of insulin sensitivity (glucose-to-insulin ratio (G/I), quantitative insulin sensitivity check index, and insulin sensitivity index (ISI)), resistance (homeostasis mathematical model assessment-insulin resistance (HOMA-IR)), secretion (Δ of the area under the curve of insulin (ΔAUCI), first-phase insulin secretion (1st PHIS), and second-phase insulin secretion (2nd PHIS)), and free androgen indices (FAI).ResultsPCOS women had higher insulin secretion indices, hs-CRP, androgen, and FAI levels than controls without differing in baseline glucose, insulin and adipocytokines levels, insulin sensitivity, and resistance indices. In PCOS women, FAI levels correlated positively with baseline insulin, ΔAUCI, HOMA-IR, and ΔAUCG and negatively with G/I; hs-CRP levels correlated positively with ΔAUCI and negatively with ISI. PCOS status, waist circumference, and 17-hydroxyprogesterone (17-OHP) levels were positive predictors for ΔAUCI. In all women, waist circumference was a negative predictor for ISI; 17-OHP and FAI levels were positive predictors respectively for baseline insulin levels and for 1st PHIS and 2nd PHIS.ConclusionsEarly postmenopausal PCOS women are characterized by hyperinsulinemia but attenuated insulin resistance. PCOS status and waist circumference are predictors of hyperinsulinemia while insulin sensitivity correlates negatively with FAI. The differences reported in adipocytokine levels between PCOS and non-PCOS women in reproductive years seem to disappear after menopause.

Download Full-text

Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2007.113 ◽

2007 ◽

Vol 45 (5) ◽

Cited By ~ 14

Author(s):

Jana Vrbikova ◽

Katerina Dvorakova ◽

Tereza Grimmichova ◽

Martin Hill ◽

Sona Stanicka ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Polycystic Ovary Syndrome ◽

Glucose Intolerance ◽

Polycystic Ovary ◽

Ovary Syndrome

Download Full-text

POSITION STATEMENT: Glucose Intolerance in Polycystic Ovary Syndrome—A Position Statement of the Androgen Excess Society

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1549 ◽

2007 ◽

Vol 92 (12) ◽

pp. 4546-4556 ◽

Cited By ~ 194

Author(s):

Kelsey E. S. Salley ◽

Edmond P. Wickham ◽

Kai I. Cheang ◽

Paulina A. Essah ◽

Nicole W. Karjane ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Glucose Intolerance ◽

Polycystic Ovary ◽

Position Statement ◽

Androgen Excess ◽

Ovary Syndrome

Download Full-text

Indices of insulin sensitivity, beta cell function and serum proinsulin levels in the polycystic ovary syndrome

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2005.12.016 ◽

2006 ◽

Vol 127 (1) ◽

pp. 99-105 ◽

Cited By ~ 8

Author(s):

Dimitrios Panidis ◽

Djuro Macut ◽

Dimitrios Farmakiotis ◽

David Rousso ◽

Anargyros Kourtis ◽

...

Keyword(s):

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Polycystic Ovary ◽

Ovary Syndrome

Download Full-text

Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽

10.1210/en.2015-1159 ◽

2015 ◽

Vol 156 (11) ◽

pp. 4071-4080 ◽

Cited By ~ 17

Author(s):

Amanda Hurliman ◽

Jennifer Keller Brown ◽

Nicole Maille ◽

Maurizio Mandala ◽

Peter Casson ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Insulin Sensitivity ◽

Endothelial Dysfunction ◽

Polycystic Ovary Syndrome ◽

Rat Model ◽

Polycystic Ovary ◽

Phase 1 ◽

Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

Download Full-text

SUN-010 Efficacy of High Intensity Intermittent Training for Improving Cardio-Metabolic Health in Women with Polycystic Ovary Syndrome: A Pilot Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1479 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Rhiannon Kate Patten ◽

Luke McIlvenna ◽

Alba Moreno-Asso ◽

Nigel Nigel Stepto ◽

Danielle Hiam

Keyword(s):

Body Composition ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

High Intensity ◽

Polycystic Ovary ◽

Metabolic Health ◽

Moderate Intensity ◽

Sensitivity Index ◽

Maximal Heart Rate ◽

Ovary Syndrome

Abstract Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive and metabolic manifestations, carrying a major health and economic burden. Exercise training has consistently been found improve clinical outcomes in women with PCOS, but shortfalls with exercise prescription are evident. Research suggests that high intensity intermittent exercise (HIIT) is feasible, well tolerated and enjoyable for people with or at risk of chronic disease and can address many of the shortfalls and barriers to exercise participation. To investigate the effects of high intensity exercise, twenty-four reproductive aged, overweight and obese, previously sedentary women with PCOS were recruited from the community and randomised to complete either 12 weeks of moderate intensity continuous cycling exercise (MOD; 50-60% of maximal heart rate [HRmax]; n=11) or HIIT (90-95% HRmax; n=13). All exercise was supervised by an exercise physiologist and completed 3 times per week on a cycle ergometer. Baseline and post testing measures consisted of peak oxygen consumption (VO2peak) determine by a graded maximal exercise test, insulin sensitivity determined by hyperinsulinaemic-euglycaemic clamp, body composition outcomes and anti-mullerian hormone (AMH). Enjoyment was also measured throughout the intervention using feeling scales. Significant improvements were seen for VO2peak after HIIT with an average increase of 5.6 ± 2.5 mL.kg-1.min-1 (P=0.013) and non-significant increases in the MOD group (3.4 ± 2.1 mL/kg/min; P=0.20). Body composition, fasting insulin and AMH values remained unchanged in both groups. Non-significant improvements in glucose infusion rate (3.3 ± 2.8 mg.lbmkg-1.min-1; P=0.06) and insulin sensitivity index (M-to-I ratio; 3.0 ± 3.8 mg.lbmkg-1.min-1[mU/I]-1 x 100; P=0.17) were found as a result of HIIT compared to no changes after moderate intensity exercise. Importantly, HIIT was also found to be more enjoyable than moderate intensity continuous exercise. The present study is the first to compare current exercise recommendations of moderate and vigorous intensities in women with PCOS. The results of this study provide preliminary validation of HIIT and should be considered for improving cardio-metabolic health in women with PCOS.

Download Full-text