Hyperglycemia Alters Tumor Necrosis Factor-α Release from Mononuclear Cells in Women with Polycystic Ovary Syndrome

Abstract Context: Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. Objective: The purpose of this study was to determine the effects of hyperglycemia on lipopolysaccharide (LPS)-stimulated TNFα release from mononuclear cells (MNC) in PCOS. Design: The study was designed as a prospective controlled study. Setting: The study was carried out at an academic medical center. Patients: Sixteen reproductive age women with PCOS (eight lean, eight obese) and 14 age-matched controls (eight lean, six obese) participated in the study. Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Percentage of truncal fat was determined by dual-energy absorptiometry. TNFα release was measured from MNC cultured in the presence of LPS from blood samples drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in women with PCOS compared with controls (3.9 ± 0.4 vs. 6.3 ± 1.0; P < 0.03) and was negatively correlated with percentage of truncal fat (r = 0.56; P < 0.002). Truncal fat was greater in lean women with PCOS compared with lean controls (29.8 ± 2.6 vs. 23.8 ± 2.5%; P < 0.04). The TNFα response was different between obese and lean controls (−96.9 ± 21.2 vs. 24.4 ± 21.6 pg/ml; P < 0.03) and obese and lean women with PCOS (−94.1 ± 34.5 vs. 30.4 ± 17.6 pg/ml; P < 0.002). Fasting plasma C-reactive protein was elevated (P < 0.003) in obese PCOS and obese controls compared with lean controls. Conclusion: An increase in abdominal adiposity and increased TNFα release from MNC after hyperglycemia may contribute to insulin resistance in lean PCOS patients. In contrast, obese PCOS patients have more profound chronic inflammation, and thus may have LPS tolerance that protects them from relatively mild excursions in blood glucose.

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Increased Activation of Nuclear Factor κB Triggers Inflammation and Insulin Resistance in Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-2327 ◽

2006 ◽

Vol 91 (4) ◽

pp. 1508-1512 ◽

Cited By ~ 107

Author(s):

Frank González ◽

Neal S. Rote ◽

Judi Minium ◽

John P. Kirwan

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Nuclear Factor Κb ◽

Controlled Study ◽

Plasma Testosterone ◽

Nuclear Factor ◽

Ovary Syndrome ◽

Percent Change ◽

Glucose Ingestion

Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS. Design and Setting: This was a prospective controlled study conducted at an academic medical center. Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P < 0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. −14.1 ± 10.9, P < 0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P < 0.04) and plasma testosterone (r = 0.49; P < 0.006) and correlated negatively with ISOGTT (r = 0.39; P < 0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (−22.3 ± 3.2 and −17.0 ± 5.0 vs. 8.4 ± 11.8, P < 0.02). Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

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Polycystic ovary syndrome and increased risk of psychiatric disorders

Endocrinology&Metabolism International Journal ◽

10.15406/emij.2020.08.00296 ◽

2020 ◽

Vol 8 (6) ◽

pp. 133-137

Author(s):

Mohadetheh Moulana PhD ◽

Anju P Sukumaran MD

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Medical Center ◽

Psychological Disorders ◽

Well Being ◽

Reproductive Age ◽

Physical And Mental Health ◽

Ovary Syndrome ◽

Increased Risk ◽

First Time

Aim: This study is aimed to assess, for the first time the prevalence of polycystic ovary syndrome (PCOS) and associated psychological disorders among women at reproductive age in Mississippi. Methods: The data was collected through “the Patient Cohort Explorer” system at the University of Mississippi Medical Center (UMMC) from January 2013 to December 2018. De-identified patients were searched with diagnosis code for PCOS, age, ethnicity, and associated diagnosis including weight gain, anxiety, depression, attention-deficit/hyperactivity disorder (ADHD), and other psychological concerns. Results: Collected data from 166,748 females (19-45 years) showed 1.4% (95% CI: 1.32 – 1.44) prevalence of PCOS in women seen in UMMC clinics during the period of study. Almost 51% of patients with PCOS suffered from one or more psychological disorders; anxiety 21% (95% CI: 19.3 – 22.6), depression 20% (95% CI: 18.9 – 22.1), ADHD 3.2% (95% CI: 2.6 – 4.0), and bipolar disorder 2.5% (95% CI: 1.9 – 3.2). In addition, prevalence values suggest a positive correlation between obesity, anxiety, and depression in PCOS patients. Conclusion: Results from this study provide 1) for the first time an estimate regarding the prevalence of PCOS and associated psychological disorders in women with PCOS in a Mississippi, 2) associated psychological disorders in PCOS women may be diverse based on race and ethnicity. Our data clearly highlight that the psychological well-being of women with PCOS are affected. Therefore, it is critical for the primary care and specialty clinics to use appropriate psychological screenings. Left undiagnosed and/or untreated, chronic psychological disorders may exacerbate physical and mental health conditions.

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Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00491.2012 ◽

2013 ◽

Vol 304 (4) ◽

pp. E375-E383 ◽

Cited By ~ 14

Author(s):

Frank González ◽

John P. Kirwan ◽

Neal S. Rote ◽

Judi Minium

Keyword(s):

Polycystic Ovary Syndrome ◽

Protein Content ◽

Mononuclear Cells ◽

Polycystic Ovary ◽

Cross Sectional Study ◽

Low Grade ◽

Obese Women ◽

Ovary Syndrome ◽

Cross Sectional ◽

Glucose Ingestion

Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation that can increase the risk of atherothrombosis. We performed a cross-sectional study to examine the effect of glucose ingestion on markers of atherothrombotic inflammation in mononuclear cells (MNC) of 16 women with PCOS (8 lean, 8 obese) and 16 weight-matched controls. Activator protein-1 (AP-1) activation and the protein content of early growth response-1 (EGR-1), matrix matalloproteinases-2 (MMP2), and tissue factor (TF) were quantified from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Plasma MMP9 and C-reactive protein (CRP) were measured from fasting blood samples. Truncal fat was determined by DEXA. Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls. Obese women with PCOS exhibited greater EGR-1 and TF protein content after glucose ingestion, and plasma CRP levels were even higher compared with lean subjects regardless of PCOS status. Truncal fat correlated with MMP9 and CRP levels and glucose-stimulated increases in AP-1 activation and EGR-1 and TF protein content. Testosterone correlated with glucose-stimulated AP-1 activation, and androstenedione correlated with MMP9 and CRP levels and glucose-stimulated AP-1 activation. Thus, both PCOS and obesity contribute to an atherothrombotic state in which excess abdominal adiposity and hyperandrogenism may be specific risk factors for developing atherothrombosis.

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Prevalence of Psychological Disorders in Women with Polycystic Ovary Syndrome in Mississippi

Women Health Care and Issues ◽

10.31579/2642-9756/029 ◽

2020 ◽

Vol 3 (3) ◽

pp. 01-07

Author(s):

Mohadetheh Moulana

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Medical Center ◽

Psychological Disorders ◽

Well Being ◽

Reproductive Age ◽

Physical And Mental Health ◽

Ovary Syndrome ◽

Southeastern Us ◽

First Time

Aim: This study is aimed to assess, for the first time the prevalence of polycystic ovary syndrome (PCOS) and associated psychological disorders among women at reproductive age from a state in southeastern US. Methods: The data was collected through “the Patient Cohort Explorer” system at the University of Mississippi Medical Center (UMMC) from January 2013 to December 2018. De-identified patients were searched with diagnosis code for PCOS, age, ethnicity, and associated diagnosis including weight gain, anxiety, depression, attention-deficit/hyperactivity disorder (ADHD), and other psychological concerns. Results: Collected data from 166,748 females (19-45 years) showed 1.4% (95% CI: 1.32 – 1.44) prevalence of PCOS in women seen in UMMC clinics during the period of study. Almost 51% of patients with PCOS suffered from one or more psychological disorders; anxiety 21% (95% CI: 19.3 – 22.6), depression 20% (95% CI: 18.9 – 22.1), ADHD 3.2% (95% CI: 2.6 – 4.0), bipolar disorder 2.5% (95% CI: 1.9 – 3.2). In addition, prevalence values suggest a positive correlation between obesity, anxiety, and depression in PCOS Patients. Conclusions: Results from this study provide 1) for the first time an estimate regarding the prevalence of PCOS and associated psychological disorders in women with PCOS in a southern state, 2) associated psychological disorders in PCOS women may be diverse based on race and ethnicity. Our data clearly highlight that the psychological well-being of women with PCOS are affected. Therefore, it is critical for the primary care and specialty clinics to use appropriate psychological screenings. Left undiagnosed and/or untreated, chronic psychological disorders may exacerbate physical and mental health conditions.

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Indexes of Insulin Resistance in Hyperinsulinemic Polycystic Ovary Syndrome in a Macedonian Cohort of Women of Reproductive Age: A Cross-Sectional Study

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2016.107 ◽

2016 ◽

Vol 4 (4) ◽

pp. 607-612

Author(s):

Sasha Jovanovska-Mishevska ◽

Aleksandra Atanasova-Boshku ◽

Iskra Bitoska ◽

Irfan Ahmeti ◽

Biljana Todorova ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Cross Sectional Study ◽

Reproductive Age ◽

Control Group ◽

Oral Glucose ◽

Sectional Study ◽

Ovary Syndrome ◽

Cross Sectional

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex hormonal, metabolic and reproductive disorder and is a leading cause of female infertility. Hyperinsulinemia secondary to insulin resistance plays important role in the pathogenesis of PCOS.AIM: To assess the sensitivity of different indices of insulin resistance and their relevance in a clinical setting.MATERIAL AND METHODS: A cross-sectional study of 43 patients with PCOS and 29 noromo ovulatory women as a control group was conducted. Standard clinical, anthropometrical and hormonal testing for hyperandrogenism was conducted, as well as oral glucose tolerance test with determination of basal and stimulated glucose and insulin values.RESULTS: The dynamic I/G index showed the highest sensitivity and specificity, but the static indexes HOMA-IR and QUICKI, although based on only basal glycemic and insulinemic values, showed good sensitivity, 90.38% and 94.01% respectively. HOMA-IR showed significant positive correlation with the stimulated insulin values.CONCLUSIONS: Our results support the use of static indexes in the evaluation of insulin resistance in women with PCOS in a clinical setting, offering a simple assessment of insulin resistance in PCOS, which holds great prognostic and treatment implications.

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Increased Androgen Response to Follicle-Stimulating Hormone Administration in Women with Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2664 ◽

2008 ◽

Vol 93 (5) ◽

pp. 1827-1833 ◽

Cited By ~ 25

Author(s):

Deborah S. Wachs ◽

Mickey S. Coffler ◽

Pamela J. Malcom ◽

Shunichi Shimasaki ◽

R. Jeffrey Chang

Keyword(s):

Polycystic Ovary Syndrome ◽

Outcome Measures ◽

Polycystic Ovary ◽

Medical Center ◽

Academic Medical Center ◽

Theca Cell ◽

Ovary Syndrome ◽

Enhanced Production ◽

Normal Women ◽

17 Hydroxyprogesterone

Abstract Context: In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. Objective: The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. Design: A prospective study was conducted to compare androgen production in response to FSH in two groups of women. Setting: The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Patients: Women with PCOS, 18–35 yr (n = 20), and normal ovulatory controls, 18–35 yr (n = 10), were recruited for study. Interventions: Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). Main Outcome Measures: The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Results: Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. Conclusions: These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

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Clinical Evidence for Predominance of Delta-5 Steroid Production in Women with Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2200 ◽

2011 ◽

Vol 96 (4) ◽

pp. 1106-1113 ◽

Cited By ~ 15

Author(s):

Marcus A. Rosencrantz ◽

Mickey S. Coffler ◽

Annette Haggan ◽

Kimberly B. Duke ◽

Michael C. Donohue ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Medical Center ◽

Academic Medical Center ◽

Ovary Syndrome ◽

Clinical Research Center ◽

Normal Women ◽

17 Hydroxyprogesterone ◽

A Prospective Study

Abstract Context: In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway. Objective: This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women. Design: We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women. Setting: The study was conducted in a General Clinical Research Center in an academic medical center. Participants: Women with PCOS (age, 18–37 yr; n = 10) and normal ovulatory controls (age, 18–37 yr; n = 11) were recruited. Interventions: For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 μg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 μg of recombinant hCG. Main Outcome Measure(s): We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration. Results: In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women. Conclusion: In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.

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