Charikleia Christakou

Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6-6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women. Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformins targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformins cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.

Metformin in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects 6.6–6.8% of women in reproductive age. Insulin resistance and hyperinsulinemia play a critical role in the pathogenesis of PCOS and are associated with a high risk for type 2 diabetes mellitus and cardiometabolic abnormalities. Metformin has been introduced as a therapeutic option in PCOS, targeting of cardiometabolic and reproductive abnormalities on the basis of its action on the reduction of glucose levels and the attenuation of insulin resistance. The tissue‐specific actions of metformin as well as the molecular mechanisms involved in the liver, the muscle, the endothelium, and the ovary are elucidated in this review. The use of metformin in pregnant women with PCOS is another of its positive features. Overall, available data supports the therapeutic usefulness of metformin on cardiometabolic risk and reproduction assistance in PCOS women.

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 womens 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.

Phenotypes and Enviromental Factors: Their Influence in PCOS

Polycystic ovary syndrome (PCOS) is a complex syndrome of unclear etiopathogenesis characterized by heterogeneity in phenotypic manifestations. The clinical phenotype of PCOS includes reproductive and hormonal aberrations, namely anovulation and hyperandrogenism, which coexist with metabolic disturbances. Reflecting the crosstalk between the reproductive system and metabolic tissues, obesity not only deteriorates the metabolic profile but also aggravates ovulatory dysfunction and hyperandrogenism. Although the pathogenesis of PCOS remains unclear, the syndrome appears to involve environmental and genetic components. Starting from early life and extending throughout lifecycle, environmental insults may affect susceptible women who finally demonstrate the clinical phenotype of PCOS. Diet emerges as the major environmental determinant of PCOS. Overnutrition leading to obesity is widely recognized to have an aggravating impact, while another detrimental dietary factor may be the high content of food in advanced glycated end products (AGEs). Environmental exposure to industrial products, particularly Bisphenol A (BPA), may also exacerbate the clinical course of PCOS. AGEs and BPA may act as endocrine disruptors in the pathogenesis of the syndrome. PCOS appears to mirror the harmful influence of the modern environment on the reproductive and metabolic balance of inherently predisposed individuals.

Metabolic syndrome and polycystic ovary syndrome... and vice versa

The metabolic syndrome (MS) and the polycystic ovary syndrome (PCOS) appear to be interrelated, although they are distinct entities. Women with PCOS appear to be commonly affected by MS, while women with MS may display reproductive or endocrine features of PCOS. These clinical observations appear to be only partly attributable to the association of both syndromes with obesity and imply a reciprocal pathophysiologic relationship between PCOS and MS with potentially significant clinical sequelae. Adult women with MS are at a greater risk of developing cardiovascular disease; women with PCOS also appear to carry such an increased risk in their postmenopausal life. Conversely, women with MS may experience reproductive disturbances, reminiscent of PCOS, more commonly than their counterparts from the general population. This review presented the current epidemiology of MS in adults and adolescents with PCOS, as well as the limited amount of data on the prevalence of features of PCOS among women with MS or MS features. We also discuss the potential pathophysiologic mechanisms underlying the relationship between these interweaving, but distinct, syndromes.

Anxiety is associated with hormonal and metabolic profile in women with polycystic ovarian syndrome

Background  Increased prevalence of psychological morbidities, including anxiety, depression and eating disorders, has been reported in women with polycystic ovary syndrome (PCOS) in comparison with normal ovulating, nonhyperandrogenemic women.

Impact of dietary modification of advanced glycation end products (AGEs) on the hormonal and metabolic profile of women with polycystic ovary syndrome (PCOS)

OBJECTIVETo investigate the impact of dietary intervention on Advanced Glycation End products (AGEs) intake on the hormonal and metabolic profile in women with polycystic ovary syndrome (PCOS).METHODSAfter baseline evaluation, 23 women with PCOS [mean±SD, age: 23.4±5.7 years; body mass index (BMI): 26±5.7 kg/m2] underwent the following consecutive 2-month dietary regimens: a hypocaloric diet with ad-libitum AGEs content (Hypo), an isocaloric diet with high AGEs (HA) and an isocaloric diet with low AGEs (LA). Metabolic, hormonal and oxidative stress status was assessed and AGEs levels were determined in all subjects after the completion of each dietary intervention.RESULTSSerum levels of AGEs, testosterone, oxidative stress, insulin and HOMA-IR index were significantly increased on the HA compared to the Hypo diet and subsequently decreased on the LA diet (compared to HA) (p<0.05 for all parameters). BMI remained unaltered throughout the HA and LA periods compared to the Hypo period. Serum AGEs were strongly correlated with insulin, as well as with HOMA, during the LA dietary period (r = 0.53, p = 0.02 and r=0.51, p = 0.03, respectively). For the same period, dietary AGEs were correlated with insulin levels (rho = 0.49, p = 0.04).CONCLUSIONSModifications of dietary AGEs intake are associated with parallel changes in serum AGEs, metabolic, hormonal and oxidative stress biomarkers in women with PCOS. These novel findings support recommendations for a low AGEs dietary content along with lifestyle changes in women with PCOS.

The effect of pharmaceutical intervention on lipid profile in polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS), a prevalent endocrinopathy of women, has been associated with a clustering of adverse metabolic features, which co‐exist with reproductive dysfunction. Lipid abnormalities are very common in lean as well as obese women with PCOS and should be cautiously considered in the therapeutic management of the syndrome. Clinicians should also critically assess the lipidemic effect of pharmaceutical intervention, primarily aimed at hyperandrogenism, anovulation or insulin resistance. Because dyslipidemia may contribute to long‐term cardiometabolic and reproductive sequelae in PCOS, it should be considered as an additional therapeutic target when these patients are assigned to appropriate pharmaceutical treatment.

Visceral adiposity index (VAI) is related to the severity of anovulation and other clinical features in women with polycystic ovary syndrome

The clinical phenotype of polycystic ovary syndrome (PCOS) includes reproductive and hormonal aberrations. Visceral adiposity index (VAI) is an indicator which could connect hyperandrogenism and anovulation. The objective was to evaluate the relationship between VAI, menstrual disorders and hormonal, biochemical and ultrasound parameters in women with PCOS.

Polycystic ovary syndrome – Phenotypes and diagnosis

Abstract Polycystic ovary syndrome (PCOS) is a heterogeneous spectrum of symptoms lasting throughout the lifecycle. The syndrome combines reproductive as well as metabolic aberrations associated with increased cardiovascular risk. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic diversity of the syndrome. The clinical manifestations and the sequelae of PCOS vary throughout the lifecycle, partly depending on environmental factors which may affect the integral components of the syndrome, namely ovarian steroidogenesis, ovulation and insulin resistance. As the patient grows older, particularly in the postmenopausal period, the cardiovascular risk profile may translate into increased rates of cardiovascular morbidity.