scholarly journals Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. R219-R227 ◽  
Author(s):  
Poli Mara Spritzer ◽  
Sheila B Lecke ◽  
Fabíola Satler ◽  
Debora M Morsch
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Lifestyle Changes ◽  
Reproductive Age ◽  
Sufficient Evidence ◽  
Low Grade ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Increased Risk

Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

scholarly journals Androgen Receptor Blocker Improves the Cardiometabolic Profile in a Rat Model of Polycystic Ovary Syndrome, but at What Cost?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A803-A804
Author(s):  
Jacob E Pruett ◽  
Steven Everman ◽  
Edgar David Torres Fernandez ◽  
Kacey Davenport ◽  
Damian G Romero ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Female Rats ◽  
Chow Diet ◽  
Model Assessment ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Glutamyl Transferase ◽  
Cardiometabolic Profile

Abstract Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by androgen excess and ovulatory dysfunction high prevalence of cardiovascular risk factors such as increased blood pressure (BP), insulin resistance (IR), and obesity. We have demonstrated previously that exposing prepubertal female rats to dihydrotestosterone (DHT) leads to increase in food intake (FI), body weight (BW), BP, and IR. We tested the hypothesis that administration of the AR blocker bicalutamide (BICA) would decrease BP, IR, and obesity in PCOS model. As there are previous reports of severe hepatotoxicity with the AR blocker flutamide, we also examined BICA effects in the liver. Methods: Four-week old female Sprague Dawley rats implanted with DHT pellets (7.5mg/90 days) or placebo (PBO) were randomized to standard chow diet with or without the AR blocker bicalutamide (BICA) at a dose of 250 mg/kg/day throughout the study (n=10/group). BW and FI were measured weekly. BP and heart rate (HR) were measured by radiotelemetry. Fasting plasma was collected for IR (Homeostatic model assessment for IR, HOMA-IR). At euthanasia, the liver was collected, as well as plasma for gamma glutamyl transferase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) quantification. Results: PCOS rats had increased BW, FI, IR, and BP compared to PBO. BICA treatment had no impact on BW (285.3 ± 7.0 vs 270 ± 8.2 g, P=0.2) as well as FI and HR in PCOS. However, in PCOS, BICA decreased HOMA-IR (5.10 ± 0.40 vs 3.33 ± 0.31, P<0.05) and BP (115.4 ± 0.7 vs 105.3 ± 0.2 mmHg, P<0.01). Compared to PBO, PCOS+BICA rats had similar IR (3.83 ± 0.28 vs 3.33 ± 0.31, P=0.7) and BP (107.4 ± 0.8 vs 105.3 ± 0.2 mmHg, P=0.9). In addition, the liver weight to tibia length ratio was drastically increased by BICA in PCOS (222.9 ± 9.5 vs 360.4 ± 16.9 mg/mm, P<0.0001) as well as GGT (0.88 ± 0.88 vs 11.67 ± 0.58 U/L, P<0.0001), though it decreased AST (60.2 ± 6.9 vs 42.4 ± 1.9 U/L, P<0.05) and had no impact on ALT. Conclusion: In summary, in a model of PCOS, BICA treatment abolished IR and BP, independent of FI, BW and HR. Prompt treatment with an AR blocker can normalize increased IR and BP triggered by androgen excess in females. Further studies need to be done to fully understand the effect of BICA in the liver in PCOS. The beneficial effect of AR blockers as a therapeutic option to improve the cardiometabolic profile in PCOS may be hampered by its liver toxicity.

scholarly journals SAT-018 Androgen Actions in Adipose Tissue and the Brain Are Key Mediators in the Development of Polycystic Ovary Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Madeleine J Cox ◽  
Melissa C Edwards ◽  
Ali Aflatounian ◽  
Valentina Rodriguez Paris ◽  
William L Ledger ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Mouse Model ◽  
Hepatic Steatosis ◽  
Polycystic Ovary ◽  
Reproductive Traits ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Adipocyte Hypertrophy ◽  
The Brain

Abstract Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.

Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome

2017 ◽  
Vol 125 (08) ◽  
pp. 522-529 ◽  
Author(s):  
Danijela Milutinović ◽  
Marina Nikolić ◽  
Nataša Veličković ◽  
Ana Djordjevic ◽  
Biljana Bursać ◽  
...  
Keyword(s):  
Animal Model ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Abdominal Obesity ◽  
Visceral Adipose Tissue ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Visceral Adipose

AbstractPolycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.

scholarly journals Polycystic ovary syndrome: reviewing diagnosis and management of metabolic disturbances

2014 ◽  
Vol 58 (2) ◽  
pp. 182-187 ◽  
Author(s):  
Poli Mara Spritzer
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Diagnostic Criteria ◽  
Polycystic Ovary ◽  
Pharmacological Therapy ◽  
Lifestyle Changes ◽  
Reproductive Age ◽  
Metabolic Dysfunction ◽  
Metabolic Disturbances ◽  
Ovary Syndrome ◽  
Individual Woman

Polycystic ovary syndrome (PCOS) is a common condition in women at reproductive age associated with reproductive and metabolic dysfunction. Proposed diagnosed criteria for PCOS include two out of three features: androgen excess, menstrual irregularity, and polycystic ovary appearance on ultrasound (PCO), after other causes of hyperandrogenism and dysovulation are excluded. Based on these diagnostic criteria, the most common phenotypes are the “classic PCOS” – hyperandrogenism and oligomenorrhea, with or without PCO; the “ovulatory phenotype” – hyperandrogenism and PCO in ovulatory women; and the “non-hyperandrogenic phenotype”, in which there is oligomenorrhea and PCO, without overt hyperandrogenism. The presence of obesity may exacerbate the metabolic and reproductive disorders associated with the syndrome. In addition, PCOS women present higher risk for type 2 diabetes and higher prevalence of cardiovascular risk factors that seems to be associated with the classic phenotype. The main interventions to minimize cardiovascular and metabolic risks in PCOS are lifestyle changes, pharmacological therapy, and bariatric surgery. Treatment with metformin has been shown to improve insulin sensitivity, lowering blood glucose and androgen levels. These effects are more potent when combined with lifestyle interventions. In conclusion, besides reproductive abnormalities, PCOS has been associated to metabolic comorbidities, most of them linked to obesity. Confounders, such as the lack of standard diagnostic criteria, heterogeneity of the clinical presentation, and presence of obesity, make management of PCOS difficult. Therefore, the approach to metabolic abnormalities should be tailored to the risks and treatment goals of each individual woman.

scholarly journals Polycystic Ovary Syndrome: It is time to change the approach in diagnosis and management

IJEDO ◽  
2021 ◽  
Vol 3 ◽  
pp. 12-14
Author(s):  
Carole Wehbe Chidiac
Keyword(s):  
Eating Disorders ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Lifestyle Changes ◽  
Reproductive Age ◽  
Evidence Based ◽  
Emotional Wellbeing ◽  
Ovary Syndrome ◽  
Communication Preferences ◽  
Evidence Based Guideline

Polycystic ovary syndrome (PCOS) is a common and very distressing condition in women of reproductive age. International evidence-based guideline for the assessment and management of polycystic ovary syndrome was published in 2018, with a governance including an international advisory board from six continents. The global guideline has provided a well-rounded and all-inclusive synopsis of all aspects of PCOS. Recommendations made are clear and should help eliminate areas of conflict. The addition of large sections addressing lifestyle and emotional wellbeing puts the prevalence of eating disorders in PCOS in the spotlight and strengthens the importance of looking at the patient as a whole rather than a collection of individual symptoms and problems to solve. This commentary focuses on the evidence against many unnecessary and even harmful practices we still frequently encounter: the diagnostic criteria in teenagers, the lack of optimal ultrasound reporting, the unnecessary recommendation for non-evidence-based diets, and the harmful effects of untimely discussions disregarding women’s priorities, communication preferences, beliefs culture and mental health. Last but not least, although screening for eating disorders has been recommended by many medical societies, especially before any triggering discussion about lifestyle changes, it is still rarely done in clinical practice.

scholarly journals Endometrium and polycystic ovary syndrome

2018 ◽  
Vol 67 (4) ◽  
pp. 60-66
Author(s):  
Pavel P Yakovlev ◽  
Igor Yu Kogan
Keyword(s):  
Endometrial Cancer ◽  
Polycystic Ovary Syndrome ◽  
Pregnancy Outcomes ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome ◽  
Endocrine Disorder ◽  
Increased Risk ◽  
Adverse Pregnancy

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Patients with PCOS present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS is inconsistently associated adverse pregnancy outcomes and an increased risk of endometrial cancer. The purpose of this review is to systematize the available data on endometrial dysfunction associated with PCOS. (For citation: Yakovlev PP, Kogan IYu. Endometrium and polycystic ovary syndrome. Journal of Obstetrics and Women’s Diseases. 2018;67(4):60-66. doi: 10.17816/JOWD67460-66).

scholarly journals A study of metabolic syndrome in women with polycystic ovary syndrome at tertiary care center

2021 ◽  
Vol 10 (6) ◽  
pp. 2427
Author(s):  
Chelsae Kuntal ◽  
Jyotsna Vyas ◽  
Asha Chaudhary ◽  
Sunita Hemani ◽  
Lata Rajoria
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Urban Areas ◽  
Polycystic Ovary ◽  
Tertiary Care ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Hormonal Profile ◽  
Increased Risk

Background: Polycystic ovary syndrome is a common endocrinopathy in women of reproductive age with prevalence of 6-10% which is characterized by hyper androgenic features and chronic oligo – anovulation and polycystic ovary morphology. Most women with polycystic ovary syndrome are also characterized by metabolic abnormalities like insulin resistance, hyperinsulinemia, dyslipidemia and abdominal obesity, these forming risk factors for metabolic syndrome. The objective of the study was to compare the clinical, biochemical and hormonal profile of polycystic ovary syndrome patients with and without metabolic syndrome.Methods: A comparative cross- sectional study was undertaken on 79 PCOS women diagnosed with PCOS according to Rotterdam criteria, in which the clinical data and hormonal profile of two groups of polycystic ovary syndrome women with and without metabolic syndrome was compared.Results: The mean age of 79 patients in this study group with and without metabolic syndrome was 26.17±3.18 and 25.57±3.41 years respectively. There were more patients from urban areas as compared to rural areas and maximum patients. Significantly higher number of PCOS women with metabolic syndrome had hirsutism and acanthosis nigricans than those without metabolic syndrome. Mean value of Waist circumference, systolic BP pressure, diastolic BP, S. Triglyceride and fasting glucose were higher and HDL levels were lower in women with metabolic syndrome than those without metabolic syndrome. Fasting insulin and HOMA-IR values were significantly higher in PCOS women with metabolic syndrome in comparison to those without metabolic syndrome.Conclusion: PCOS is not only is the most frequent cause of anovulation, but it is also associated with characteristic metabolic disturbances that may have important implications for the long term health. Metabolic syndrome is a cluster of endocrine disturbances, including insulin resistance, dyslipidemia, obesity, and hypertension. It is associated with a two-fold increased risk of cardiovascular disease and a five-fold increased risk of type 2 diabetes. This illustrates the importance of early detection of insulin resistance and metabolic syndrome with subsequent application of preventive measures in women with polycystic ovary syndrome.

scholarly journals A Narrative Review of Placental Contribution to Adverse Pregnancy Outcomes in Women With Polycystic Ovary Syndrome

2019 ◽  
Vol 104 (11) ◽  
pp. 5299-5315 ◽  
Author(s):  
Angela S Kelley ◽  
Yolanda R Smith ◽  
Vasantha Padmanabhan
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Pregnancy Complications ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Developmental Programming ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Increased Risk ◽  
Adverse Pregnancy

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. In pregnancy, women with PCOS experience increased risk of miscarriage, gestational diabetes, preeclampsia, and extremes of fetal birth weight, and their offspring are predisposed to reproductive and cardiometabolic dysfunction in adulthood. Pregnancy complications, adverse fetal outcomes, and developmental programming of long-term health risks are known to have placental origins. These findings highlight the plausibility of placental compromise in pregnancies of women with PCOS. Evidence Synthesis A comprehensive PubMed search was performed using terms “polycystic ovary syndrome,” “placenta,” “developmental programming,” “hyperandrogenism,” “androgen excess,” “insulin resistance,” “hyperinsulinemia,” “pregnancy,” and “pregnancy complications” in both human and animal experimental models. Conclusions There is limited human placental research specific to pregnancy of women with PCOS. Gestational androgen excess and insulin resistance are two clinical hallmarks of PCOS that may contribute to placental dysfunction and underlie the higher rates of maternal–fetal complications observed in pregnancies of women with PCOS. Additional research is needed to prevent adverse maternal and developmental outcomes in women with PCOS and their offspring.

Adiposity and metabolic dysfunction in polycystic ovary syndrome

2015 ◽  
Vol 21 (2) ◽  
Author(s):  
Susan Sam
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Metabolic Disorders ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Metabolic Dysfunction ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Insulin Resistant

AbstractPolycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.

scholarly journals Controversies in the diagnosis of polycystic ovary syndrome

2020 ◽  
Vol 14 ◽  
pp. 263349412091303
Author(s):  
Preetham Rao ◽  
Priya Bhide
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
Reproductive Age ◽  
Polycystic Ovaries ◽  
Women Of Reproductive Age ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Ultrasound Features

Polycystic ovary syndrome is a common endocrinological condition which is found to be prevalent in 5–10% of women of reproductive age. Historically, a combination of anovulation and androgen excess was considered a hallmark in the diagnosis of polycystic ovary syndrome. Addition of ultrasound features of polycystic ovary syndrome has improved the detection of variation in the polycystic ovary syndrome phenotype. Despite the widespread use of consensus diagnostic criteria, there remain several unresolved controversies in the diagnosis of polycystic ovary syndrome. Difficulty arises in methods of assessment and types of androgens to be measured to detect biochemical hyperandrogenism, setting a cut-off value for the diagnosis of clinical hyperandrogenism, setting an ultrasound threshold of antral follicle count to diagnose polycystic ovaries and also diagnosing this condition in adolescence where there is no clear definition for ‘irregular cycles’. This article looks at various controversies in the diagnosis of polycystic ovary syndrome.

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