Polycystic ovary syndrome; The role of androgen excess in disease pathogenesis and metabolic dysfunction

2018 ◽  
Author(s):  
Michael O Reilly
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Metabolic Dysfunction ◽  
Androgen Excess ◽  
Disease Pathogenesis ◽  
Ovary Syndrome

scholarly journals Neuroendocrine Impairments of Polycystic Ovary Syndrome

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2230-2242 ◽  
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.

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

2008 ◽  
Vol 4 (6) ◽  
pp. 583-594 ◽  
Author(s):  
Charikleia D Christakou ◽  
Evanthia Diamanti-Kandarakis
Keyword(s):  
Cardiovascular Risk ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Metabolic Abnormalities ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Major Player ◽  
Artery Disease ◽  
Androgen Levels

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.

scholarly journals What is new in the landscape of insulin-sensitizing agents for polycystic ovary syndrome treatment

2020 ◽  
Vol 14 ◽  
pp. 263349412090870 ◽  
Author(s):  
Daniela Romualdi ◽  
Valeria Versace ◽  
Antonio Lanzone
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Relevant Literature ◽  
Metabolic Dysfunction ◽  
Ovary Syndrome ◽  
New Agents ◽  
Peripheral Tissues ◽  
Open Questions

Polycystic ovary syndrome, the most common gynecological endocrinopathy, is burdened with a state of hyperinsulinemia and insulin resistance in 50–80% of affected women. Wherever the origin of these metabolic abnormalities lies, their pathogenetic role in determining, perpetuating, and worsening the clinical traits of the syndrome is ascertained. Many studies have already highlighted possible mechanisms: hyperinsulinemia and insulin resistance may contribute to hyperandrogenemia, chronic anovulation, and other comorbidities of the syndrome by differentially affecting the endocrine glands (ovaries, adrenals, and pituitary) and peripheral tissues (fat mass and skeletal muscle). Based on these evidences, in the past years, thorough research has been focused on the possible role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Many compounds were tested to verify their efficacy against polycystic ovary syndrome–related metabolic dysfunction, both relying on previous acquired experiences in the field of diabetes mellitus and experimenting new agents, in particular, those belonging to the class of nutraceuticals. We sought to summarize the most relevant aspects of insulin-sensitizing treatments in polycystic ovary syndrome, by reporting the relevant literature on this topic and by keeping an attentive eye on the newly published international guidelines on polycystic ovary syndrome 2018. This overview encompasses metformin, thiazolidinediones, inositols, alpha-lipoic acid, and GLP1-R analogues. Starting from the analysis of the mechanisms of action, we anchored to the state of the art of the use of these drugs in polycystic ovary syndrome, to the most recent evidences for clinical practice and to the remaining open questions around indications, dose, treatment schedules, and side effects.

scholarly journals Foetal Sonographic Anogenital Distance Is Longer in Polycystic Ovary Syndrome Mothers

2020 ◽  
Vol 9 (9) ◽  
pp. 2863
Author(s):  
Sharon Perlman ◽  
Yoel Toledano ◽  
Zvi Kivilevitch ◽  
Nufar Halevy ◽  
Elena Rubin ◽  
...  
Keyword(s):  
General Population ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Anogenital Distance ◽  
Appropriate For Gestational Age ◽  
2D Ultrasound ◽  
Diabetic Mothers

Anogenital distance (AGD) is a biomarker for the prenatal hormonal environment. Androgen excess is a key element in polycystic ovary syndrome (PCOS). The aim of this study was to assess the sonographic foetal AGD in a population of PCOS mothers in comparison to the general population. Foetal AGD was measured prospectively by 2D ultrasound in PCOS mothers and compared to prenatal AGD nomograms. The results were interpreted regarding maternal and foetal characteristics. The mean sonographic foetal AGD centile measurement in PCOS mothers was significantly longer in comparison to the general population (86.04% ± 18.22; p < 0.001). Estimated foetal weight and birthweight were appropriate for gestational age and did not correlate with AGD. Sonographic foetal AGD was significantly longer in PCOS diabetic mothers and in those who conceived following assisted reproduction treatments when compared to the general population (p < 0.001). Our results support the role of AGD as a biomarker of the prenatal hormonal environment and provide evidence for the hyperandrogenic effect in PCOS pregnancies on foetal androgenic status and genitalia development.

The role of vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review

2020 ◽  
pp. 1-8
Author(s):  
Daniela Menichini ◽  
Gianpiero Forte ◽  
Beatrice Orrù ◽  
Giuseppe Gullo ◽  
Vittorio Unfer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Polycystic Ovary Syndrome ◽  
Embryo Quality ◽  
Polycystic Ovary ◽  
Vitamin D Supplementation ◽  
Endometrial Receptivity ◽  
Metabolic Disturbances ◽  
Ovary Syndrome ◽  
Beneficial Role

Abstract. Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400–800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

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