Addressing the post-irradiation hypothalamic-pituitary endocrine abnormalities of brain tumors in pediatric patients.

PURPOSE: Hypothalamic-pituitary axis is susceptible to radiotherapy, causing endocrine disorders to childhood cancer survivors. We conducted a systematic review in order to assess the radiation-induced toxicity that leads to hormone secretion abnormalities and their severity in children with brain tumors. METHODS: The data were collected by relevant studies on PubMed and EMBASE. Articles up to December 2016 were included. We selected studies which focused on children patients (<18 yr old) with brain tumors treated with radiotherapy and the consequences for their endocrine system. RESULTS: Growth hormone (GH) deficiency was the most common post-irradiation abnormality among children cancer survivors, followed by gonadotrophin (GT), thyroid stimulating hormone (TSH), corticotropin (ACTH) and prolactin (PRL) disorders. CONCLUSIONS: The age of the patient, total radiotherapy dose, number of fractions, fraction size and the duration of treatment seem to determine the severity of these disturbances.

Polycystic ovary syndrome--phenotypes and diagnosis.

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.

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

OBJECTIVE: To 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). METHODS: After 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. RESULTS: Serum 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). CONCLUSIONS: Modifications 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.

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

OBJECTIVE: 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. PATIENTS: One hundred and ninety-three women with PCOS diagnosed with Rotterdam criteria. MEASUREMENTS: We correlated VAI with metabolic and clinical features of the syndrome and with indices of inflammation and insulin sensitivity. In addition, we classified the patients into four groups according to the severity of menstrual disorders: Group A (n = 42), with severe menstrual disorders, Group B (n = 83), with mild menstrual disorders, Group C (n = 58), without menstrual disorders and Group D (n = 10) with women with sychnominorroia. RESULTS: In women with PCOS studied, VAI significantly positively correlated with body weight, fasting glucose, insulin, homeostasis model assessment (HOMA) score, white blood cells, platelets, uric acid, free testosterone, oestradiol, total cholesterol, γ-GT, SGPT. Furthermore, a significant inverse correlation between VAI and SHBG, Matsuda index and menstrual cycles per year was documented. From the comparison of the four groups, PCOS women with menstrual disorders had significantly higher VAI and HOMA indices when compared to PCOS without menstrual disorders. CONCLUSIONS: Visceral adiposity index is increased in patients with PCOS in concordance with the severity of anovulation, insulin resistance and inflammation. This index could be a very easy and helpful clinical tool in daily practice to predict insulin resistance in women with PCOS.

The benefit-to-risk ratio of common treatments in PCOS: effect of oral contraceptives versus metformin on atherogenic markers.

OBJECTIVE: To compare the effects of oral contraceptives (OCPs) and metformin on atherogenic markers, including serum levels of advanced glycated end products (AGEs) and C-reactive protein (CRP), in lean women (Body Mass Index below 25 kg/m(2)) with polycystic ovary syndrome (PCOS), defined by NIH criteria. DESIGN: Prospective open-label study. RESULTS: One hundred and twenty women with PCOS were treated for 6 months with one of the following treatments: ethinylestradiol plus cyproterone acetate (OCP 1, n=40) or ethinylestradiol plus drospirenone (OCP2, n=40) or metformin (MET, n=40). The three groups were age and BMI-matched (mean age: 22 ± 0.56 yrs in group OCP1; 23.24 ± 0.64 yrs in group OCP2; 21.50 ± 0.53 yrs in group MET; mean BMI 21.80 ± 0.35 kg/m(2) in group OCP1; 22.37 ± 0.48 kg/m(2) in group OCP2; 23.03 ± 0.67 kg/m(2) in group MET). At 6 months serum AGEs were decreased in group OCP1 (P=0.005) and group MET (P=0.001), whereas these were marginally decreased in group OCP2 (P=0.069). Treatment with metformin was associated with a greater percent decrease of AGEs. CRP was decreased with metformin (P<0.001), but was increased with OCPs (P<0.001). CONCLUSIONS: This study evaluates common therapeutic options in women with PCOS by reconsidering and prioritizing the goals of treatment. OCPs and metformin appear to have differential effects on atherogenic molecules in lean PCOS patients, but metformin was superior in reducing serum AGEs and CRP. Clinicians should individualize the benefit-to-risk ratio of pharmaceutical intervention in women with PCOS in order to choose the formulation with the greatest overall efficacy as well as safety in terms of cardiovascular risk.

Structural, biochemical and non-traditional cardiovascular risk markers in PCOS.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes.

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.

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. AIM OF THE STUDY: To investigate the relationship between the degree of anxiety, depression and eating disorders via self-reported symptoms and the severity of hormonal and metabolic aberrations in women with PCOS. For this purpose, the PCOS cohort was subdivided into three subgroups according to the degree of anxiety. METHODS: One hundred and thirty women with PCOS of similar age and BMI were studied. In each subject, hormonal and metabolic status as well as psychological profile was assessed with the use of specific questionnaires. Specifically, anxiety (trait and state) was assessed with the use of STAI-T and STAI-S, while depression and eating disorders were evaluated with the use of the Beck Depression Inventory and the Eating Attitudes test, respectively. RESULTS: The subgroups did not differ in age and BMI. Subjects with the highest STAI-S compared with those with the lowest STAI-S displayed significantly higher the homeostasis assessment model-insulin resistance (HOMA-IR) and free androgen index values (P < 0·05), respectively. Regarding trait anxiety, assessed by STAI-T, HOMA-IR values were significantly elevated (P < 0·05) in the subgroup with the higher STAI-T score compared with the HOMA-IR in the group with the lower STAI-T score. CONCLUSIONS: In women with PCOS, the degree of anxiety, state and trait (STAI-S, STAI-T) appears to vary in a pattern similar to that of hyperandrogenemia and insulin resistance, independently of age and BMI. The pathophysiological mechanisms underlying the association of psychological morbidities with androgen excess and insulin resistance in PCOS remain to be elucidated.

The pluripotential effects of hypolipidemic treatment for polycystic ovary syndrome (PCOS): dyslipidemia, cardiovascular risk factors and beyond.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterized by oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenemia and polycystic ovaries. Clinical expression is determined by both genetic and environmental factors. Dyslipidemia is very common in lean as well as in obese women with PCOS and should be considered in the therapeutic management of the syndrome. Additionally to dyslipidemia, other risk factors for cardiovascular disease strongly associated with PCOS include insulin resistance, impaired glucose tolerance and metabolic syndrome. Therefore, the ideal therapeutic approach for PCOS would be multi targeted treatment ameliorating not only ovarian dysfunction but also cardiometabolic aspects, including dyslipidemia. Recently, a new era of hypolipidemic agents like statins has been initiated with regard to PCOS. The spectrum of statins' targets has been expanded and in vitro and in vivo studies have explored the specific effect of statins on androgen production, insulin resistance and inflammatory markers in PCOS. Statins are potentially promising therapeutic agents targeting hormonal and metabolic disturbances in PCOS, though conclusive results are still pending. Since several hormonal and metabolic aberrations characterizing this multifaceted syndrome cluster and interact with each other, their effects on the lipid profile are interweaving and the therapeutic modalities targeting dyslipidemia appear to have a more broad beneficial effect.

Strong and positive association of endothelin-1 with AGEs in PCOS: a causal relationship or a bystander?

OBJECTIVE: Advanced glycation end products (AGEs) activate the intracellular Nuclear Factor-κB pathway in endothelial cells, leading to production of endothelin-1 (ET-1), a peptide which causes endothelial dysfunction. The aim of the present study was to assess ΕΤ-1 and AGEs levels in women with polycystic ovary syndrome (PCOS) and controls and to investigate any potential relationship between them. DESIGN: Metabolic and hormonal data from 75 women with PCOS and 25 controls, matched for age and ΒΜΙ were analyzed and correlated to AGEs and ET-1 levels. RESULTS: Serum levels of ΕΤ-1 (1.55±0.13 vs. 0.37±0.10 pmol/l, p:0.003) and AGEs (8.34±1,81 vs. 5.77±0.78U/ml, p:0.002) were significantly higher in the PCOS group. ΕΤ-1 was correlated with AGES (r:0.54, p<0.001), Testosterone (r: 0.38, p<0.001), ΔΑ4 (r: 0.41, p<0.001) and FAI (r: 0.21, p<0.05). However, multiple linear regression analysis in the total study population showed that ΕΤ-1 was positively associated only with AGES (ß: 0.22, p<0.001). CONCLUSIONS: ET-1 levels were positively and strongly associated with AGEs in both PCOS women and controls, suggesting that the detrimental effect of AGEs on endothelial cells may involve increased ET-1 production.

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.

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 metformin's 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 metformin's 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.

In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls.

OBJECTIVE: To investigate liver enzymes in a cohort of women with Polycystic Ovary Syndrome (PCOS) and controls divided according to body mass index (BMI) and their association with features of the syndrome. DESIGN: Eighty-three PCOS women and 64 healthy women were studied. Patients and controls were subdivided into two groups, a lean subgroup (BMI <25kg/m(2)) and an overweight/obese subgroup (BMI >25kg/m(2)). Clinical history, height and weight were obtained and metabolic and hormonal parameters were determined. RESULTS: Serum fasting insulin, fasting glucose, HOMA-IR, triglycerides and total cholesterol were significantly higher (p<0.05) in women with PCOS compared to controls. No significant difference in serum liver enzymes levels between PCOS women and controls was detected. However, serum levels of alanine aminotransferase (ALT) (17.7 vs. 14.1 U/L, p<0.05) and gamma-glutamyl transpeptidase (gammaGT) (17.9 vs. 13.4 U/L, p<0.05) were significantly higher in overweight/obese PCOS women compared with overweight/obese controls. In overweight/obese PCOS patients and controls, ALT levels were positively correlated with free androgen index (FAI) (r=0.25 p<0.05) and total testosterone levels (r=0.33 p<0.01). CONCLUSIONS: The finding of elevated liver enzymes in overweight/obese PCOS women raises the question of screening for non-alcoholic fatty liver disease in this group.

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.

Metabolic syndrome and polycystic ovary syndrome... and vice versa: [review] / Síndrome metabólica e síndrome dos ovários policísticos... e vice-versa: [revisão]

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.

A síndrome metabólica (SM) e a síndrome dos ovários policísticos (SOP) parecem estar relacionadas, embora constituam duas diferentes entidades. Mulheres com SOP são comumente afetadas pela SM, enquanto mulheres com SM podem apresentar as características reprodutivas e hormonais típicas da SOP. Essas observações clínicas podem ser atribuídas apenas parcialmente à presença da obesidade em ambas as síndromes. Isso se deve a uma relação fisiopatológica recíproca com potenciais sequelas de grande significado clínico. Mulheres adultas com SM estão mais propensas ao desenvolvimento de doenças cardiovasculares; mulheres com SOP também convivem com esse risco durante a pós-menopausa. Por outro lado, as mulheres com SM podem apresentar distúrbios reprodutivos, característicos da SOP, numa frequência maior do que as mulheres não portadoras de SM da população geral. Desse modo, este artigo de revisão abordou dados epidemiológicos atuais sobre a SM em adultos e adolescentes com SOP, bem como as informações, que são limitadas, sobre a prevalência de características da SOP em mulheres com SM ou com as características desta. Também foram discutidos os mecanismos fisiopatológicos fundamentais da relação entre essas duas síndromes interligadas, mas distintas.

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.

Does polycystic ovary syndrome start in childhood?

Polycystic Ovary Syndrome (PCOS), the most frequent endocrinopathy in reproductive-aged women, represents a multifactorial nosologic entity considering its pathogenesis and clinical repercussions. PCOS is characterized mainly by hyperandrogenemia and anovulation, while insulin resistance has been established as a key player in the pathophysiology of the syndrome. The natural course of PCOS appears to originate in fetal life and factors of the intrauterine environment have been incriminated in the early pathogenesis of the syndrome. The clinical picture of PCOS becomes manifest in the peripubertal period, unfolds as patients enter later stages of life and may change over time.

Early onset adiposity: a pathway to polycystic ovary syndrome in adolescents?

Polycystic Ovary Syndrome is a heterogenous syndrome of unknown causation commonly associated with obesity. The particular timing of the onset of obesity may be important, since the earlier the onset of obesity the greater the severity of the metabolic and hormonal aberrations. Early postnatal life and peripubertal periods may be critical windows for the development of the "adiposity insult". The interaction of adiposity with genetic traits as well as with prenatal environmental factors may further aggravate the metabolic and endocrine abnormalities, which become more pronounced in adolescence.