Role of Androgen Excess on Metabolic Aberrations and Cardiovascular Risk in Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is associated with a clustering of metabolic and cardiovascular risk factors. Insulin resistance is implicated as the major player in the metabolic abnormalities and contributes to the increased cardiovascular risk associated with the syndrome. However, androgen excess appears to participate as an independent parameter, which further aggravates the cardiovascular and metabolic aberrations in affected women with PCOS. The resultant impact of hyperandrogenemia possibly acquires clinical significance for women's health in the context of PCOS, particularly since recent data support an increased incidence of coronary artery disease and of cardiovascular events directly related to androgen levels in women with the syndrome.

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The Role of Antiobesity Agents in the Management of Polycystic Ovary Syndrome

Folia Medica ◽

10.2478/folmed-2018-0036 ◽

2018 ◽

Vol 60 (4) ◽

pp. 512-520 ◽

Cited By ~ 1

Author(s):

Panagiotis Chatzis ◽

Konstantinos Tziomalos ◽

Georgios C. Pratilas ◽

Vasileios Makris ◽

Alexandros Sotiriadis ◽

...

Keyword(s):

Weight Loss ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Current Data ◽

Reproductive Age ◽

Metabolic Abnormalities ◽

Ovary Syndrome ◽

Antiobesity Agents ◽

Androgen Levels

Abstract Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. Obesity is frequently present in these patients and plays a key role in the pathogenesis of both the endocrine and metabolic abnormalities of the syndrome, particularly infertility, hyperandrogenism and insulin resistance (IR). Diet and exercise is the mainstay of management of obesity in patients with PCOS. In contrast, the eff ects of antiobesity agents on weight and on the obesityrelated characteristics of the syndrome remain unclear. The aim of the present review is to summarize the current data on the eff ects of antiobesity drugs approved in Europe (orlistat, liraglutide 3 mg od and naltrexone/bupropion) on weight loss in patients with PCOS and to discuss their impact on the endocrine, reproductive and metabolic abnormalities of this population. Several studies reported that orlistat induces weight loss, improves IR and reduces androgen levels in PCOS. In contrast, data regarding the eff ects of the dose of liraglutide that is approved for the treatment of obesity (3 mg od) are very limited. Liraglutide 1.2-1.8 mg od results in weight loss in these patients but does not aff ect IR or androgen levels. Finally, there are no studies that evaluated naltrexone/bupropion in patients with PCOS and early studies reported conflicting results regarding the eff ects of naltrexone monotherapy on weight, IR and androgen levels. In conclusion, orlistat appears to have a role in the management of overweight and obese patients with PCOS whereas more studies are needed to clarify the role of liraglutide and naltrexone/bupropion.

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Polycystic ovary syndrome and cardiovascular risk. Could trimethylamine N-oxide (TMAO) be a major player? A potential upgrade forward in the DOGMA theory

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.112171 ◽

2021 ◽

Vol 143 ◽

pp. 112171

Author(s):

Giuseppe Annunziata ◽

Roberto Ciampaglia ◽

Xavier Capò ◽

Fabrizia Guerra ◽

Antoni Sureda ◽

...

Keyword(s):

Cardiovascular Risk ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Major Player

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Androgen excess increases food intake in a rat polycystic ovary syndrome model by down-regulating hypothalamus insulin and leptin signaling pathways preceding weight gain

Neuroendocrinology ◽

10.1159/000521236 ◽

2021 ◽

Author(s):

Ying Liu ◽

Yu-chen Xu ◽

Yu-gui Cui ◽

Shi-wen Jiang ◽

Fei-yang Diao ◽

...

Keyword(s):

Weight Gain ◽

Food Intake ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Androgen Excess ◽

Ovary Syndrome ◽

Leptin Signaling ◽

Leptin Sensitivity ◽

Androgen Levels ◽

Restricted Food Intake

Background Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus, and subsequently on the food intake and obesity in females. Methods A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus, primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR respectively. The leptin levels in serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of hypothalamus. Results The excessive pre-puberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of NPY and Agouti-related peptide (Agrp) mRNAs were up-regulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. Conclusions Androgen excess increased food intake in rats and promoted obesity by down-regulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

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Contemporary approaches to the management of polycystic ovary syndrome

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018818756790 ◽

2018 ◽

Vol 9 (4) ◽

pp. 123-134 ◽

Cited By ~ 9

Author(s):

Renato Pasquali

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Ovarian Function ◽

Polycystic Ovary ◽

Review Article ◽

Metabolic Abnormalities ◽

Androgen Excess ◽

Ovary Syndrome ◽

Ovulatory Dysfunction ◽

Ovarian Morphology

Polycystic ovary syndrome (PCOS) is a common disorder in women in their reproductive years and is characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. It is also associated with several metabolic abnormalities, particularly insulin resistance and obesity, which play an important role in the pathophysiology of PCOS and, in particular, negatively influence ovarian function and fertility. This review article summarizes the available treatment for women with PCOS. Specifically, current and potentially new therapies are discussed.

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Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies

Molecular Metabolism ◽

10.1016/j.molmet.2020.01.001 ◽

2020 ◽

Vol 35 ◽

pp. 100937 ◽

Cited By ~ 9

Author(s):

Miguel A. Sanchez-Garrido ◽

Manuel Tena-Sempere

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Therapeutic Strategies ◽

Metabolic Dysfunction ◽

Pathogenic Role ◽

Androgen Excess ◽

Ovary Syndrome

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Androgen Excess as a Major Determinant of Cardiovascular Risk in Women: Evidence from the Polycystic Ovary Syndrome

Acta Endocrinologica (Bucharest) ◽

10.4183/aeb.2011.529 ◽

2011 ◽

Vol 7 (4) ◽

pp. 529-534 ◽

Cited By ~ 1

Author(s):

Carmen Gerogescu Pepene

Keyword(s):

Cardiovascular Risk ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Major Determinant ◽

Androgen Excess ◽

Ovary Syndrome

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Neuroendocrine Impairments of Polycystic Ovary Syndrome

Endocrinology ◽

10.1210/en.2019-00428 ◽

2019 ◽

Vol 160 (10) ◽

pp. 2230-2242 ◽

Cited By ~ 9

Author(s):

Amy Ruddenklau ◽

Rebecca E Campbell

Keyword(s):

Polycystic Ovary Syndrome ◽

Neuronal Network ◽

Negative Feedback ◽

Polycystic Ovary ◽

Steroid Hormone ◽

Unknown Etiology ◽

Androgen Excess ◽

Ovary Syndrome ◽

The Brain

Abstract Polycystic ovary syndrome (PCOS) is a prevalent and distressing disorder of largely unknown etiology. Although PCOS defined by ovarian dysfunction, accumulating evidence supports a critical role for the brain in the ontogeny and pathophysiology of PCOS. A critical pathological feature of PCOS is impaired gonadal steroid hormone negative feedback to the GnRH neuronal network in the brain that regulates fertility. This impairment is associated with androgen excess, a cardinal feature of PCOS. Impaired steroid hormone feedback to GnRH neurons is thought to drive hyperactivity of the neuroendocrine axis controlling fertility, leading to a vicious cycle of androgen excess and reproductive dysfunction. Decades of clinical research have been unable to uncover the mechanisms underlying this impairment, because of the extreme difficulty in studying the brain in humans. It is only recently, with the development of preclinical models of PCOS, that we have begun to unravel the role of the brain in the development and progression of PCOS. Here, we provide a succinct overview of what is known about alterations in the steroid hormone–sensitive GnRH neuronal network that may underlie the neuroendocrine defects in clinical PCOS, with a particular focus on those that may contribute to impaired progesterone negative feedback, and the likely role of androgens in driving this impairment.

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