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Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role in the modulating aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.

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... Insulin sensitizers are currently used for the treatment of PCOS women, with metformin being the gold standard [25], and, in recent years, different inositol isoforms have been used suggesting that they might have similar efficacy without the side effects described for metformin both in obese and lean PCOS women [26,27]. Alpha lipoic acid has also been reported to be safe and effective [28,29], and currently, it is further discussed whether diet restriction and fasting may have positive effects on insulin signaling and metabolism in PCOS [30]. The testing of new combinations of these compounds for PCOS is desirable. ...
... This study had limitations due to the reduced sample size, absence of further treatment groups with ALA or MYO alone, no treatment and/or metformin treatment, however, it sheds new light on the features of PCOS and from an exploratory point of view offers new indications and insight into the effects of combined use of MYO þ ALA. For the period of the study, no lifestyle intervention was encouraged in order to reduce confounding factors, as diet restriction and fasting have been reported to have positive effects on insulin signaling and metabolism in PCOS [30]. HMGB1, as previously described, was significantly increased in the PCOS adolescents [23,50], and the effect of the combined treatment was striking as it was reduced to levels similar to those of controls. ...
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PCOS treatment should be based on pathophysiology. High-mobility-group-box-1 (HMGB1) was shown to increase in PCOS patients as a consequence of reduced cystic-fibrosis-transmembrane-conductance-regulator (CFTR) expression in the ovary, and was associated with insulin resistance and inflammation, both features of PCOS. Inositols and ALA derivatives could have positive effects on insulin sensitivity, reduce androgens, and improve ovulation rhythm. The aim of this study was to verify changes in HMGB1, in metabolic and endocrine parameters in adolescents with PCOS compared with controls and after treatment with a combination of MYO + ALA. Twenty-three PCOS adolescents and 21 controls matched for age and BMI were enrolled. In all subjects, metabolic and hormonal parameters were assayed. Homeostatic index (HOMA-IR) and the triglyceride/HDL-cholesterol ratio were calculated. Ovarian volumes were evaluated. Patients were treated with MYO + ALA for 6 months. HMGB1 was measured using a specific ELISA assay. HMGB1 was increased in PCOS compared with controls (19.76 ± 5.99 versus 5.65 ± 1.88 ng/ml; p < .05) and normalized after treatment (2.27 ± 0.36 ng/ml, p < .05). Treatment significantly reduced insulin (24.0 ± 4.11 versus 12.13 ± 2.13 uU/ml), HOMA-IR (3.91 ± 0.41 versus 2.42 ± 0.45), and 17-hydroxyprogesterone (1.20 ± 0.15 versus 0.78 ± 0.11 ng/ml). Cholesterol, luteinizing hormone, 17-β-estradiol, delta 4-androstenedione, and testosterone were unchanged. Circulating HMGB1 was increased in PCOS adolescents, and treatment was effective in normalizing HMGB1.
... Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of childbearing age with a prevalence between 5-10% (1)(2)(3) . Its specific etiology remains largely unknown. ...
... A higher expression of insulin-like growth factor 2 (IGF2) has been showed in the oocytes belonging to PCOS hyperandrogenic women (2,18,19) . Hyperandrogenemia is associated, in PCOS women, with a more severe steatosis and with increased ALT levels, independent from obesity and insulin resistance (20)(21)(22)(23) . ...
Article
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Polycystic ovary syndrome (PCOS) is a common metabolic disorder that typically affects women of childbearing age. Several factors are involved in the genesis of this disease but a common agreement on its etiology is still far to be reached. According to Rotterdam criteria, PCOS is characterized by oligo and/ or anovulation, biochemical hyperandrogenism and polycystic ovaries on ultrasound; following main clinical features and symptoms, women with PCOS are distinguished in four different phenotypes. The combination of different medical and, in specific cases, surgical treatments is necessary to properly reduce symptoms and restore fertility. This review points out the last evidences on medical and surgical treatments for PCOS, especially it focuses on the most common assisted reproductive techniques currently performed in case of infertility due to this syndrome. We put a special attention on the possible approaches useful for sterile women who do not respond to first line medical and/or surgical treatments.
... PCOS is a complex condition that affects reproductive and metabolic function (Barber et al., 2016;Nair & Khawale, 2016). Insulin resistance is an important factor to address because it contributes to hyperandrogenism (Chiofalo et al., 2017;Williams et al., 2016). Hyperinsulinemia disrupts ovarian function and halts ovarian follicular development. ...
... In individuals with PCOS, intermittent fasting may have long-term benefits and may reduce symptoms of metabolic disorder (Nair & Khawale, 2016). Fasting can reduce chronic overactivity of the sympathetic nervous system and result in weight loss, which decreases the symptomatology involved in PCOS (Chiofalo et al., 2017;Nair & Khawale, 2016;Williams et al., 2016). ...
Article
Obesity in the United States is pervasive and associated with morbidity, mortality, and increased health care costs. For women, obesity may affect stages of life including early menarche, fertility, pregnancy, and menopause as a result of hormonal imbalances and insulin resistance. The insulin–carbohydrate model of obesity has been proposed as an explanation for growing obesity rates and can be used to target weight loss strategies by increasing insulin sensitivity. Together, low-carbohydrate dietary patterns along with intermittent fasting may help individuals with insulin resistance not only lose weight but also increase their insulin sensitivity. The purpose of this article is to review the epidemiology and physiology of obesity and the indicators for health while outlining strategies for nurses and other clinicians to use when counseling women who are following a low-carbohydrate or ketogenic diet with intermittent fasting for weight management.
... Given the high importance of insulin resistance and compensatory hyperinsulinemia in the management of PCOS [108,109], a study on the different forms of fasting, including intermittent fasting and periodic fasting, showed the significant decrease of IGF-1, IGFBP1, glucose and insulin levels, and consequently beneficial effects on ovarian function, androgen excess, and infertility in PCOS women [109]. ...
... Given the high importance of insulin resistance and compensatory hyperinsulinemia in the management of PCOS [108,109], a study on the different forms of fasting, including intermittent fasting and periodic fasting, showed the significant decrease of IGF-1, IGFBP1, glucose and insulin levels, and consequently beneficial effects on ovarian function, androgen excess, and infertility in PCOS women [109]. ...
Article
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Background: Polycystic ovary syndrome (PCOS), as one of the significant endocrine disorders, is common among women worldwide. Food insecurity (FI) and unhealthy dietary patterns can negatively affect reproductive health. The effects of the lifestyle modifications, especially dietary components, on PCOS are contradictory. The aim was the assessment of association between PCOS with food security status and dietary patterns among overweight or obese women. Methods: This case-control study was performed on 240 overweight and obese women with and without PCOS (ratio 1:1) referred to the infertility clinic of Arash Hospital, Tehran, Iran. The general and socioeconomic characteristics, anthropometrics (weight, height, body mass index (BMI), waist circumference, hip circumference), physical activity, food security status, and dietary intakes (or patterns) were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was < 0.05. Results: The prevalence of FI was 60% in women with PCOS and 30% in healthy women. PCOS risk was positively related to FI, quasi-western dietary patterns, low economic levels, waist circumference, and menstrual age and negatively with physical activity and healthy dietary patterns, even after controlling the potential confounders (P < 0.05). PCOS women had a higher intake of saturated fats, monounsaturated fats, oleic acid, fluorine, sucrose, and caffeine and a lower intake of vitamins A, B5, B6, B12, C, and D, potassium, proteins, carbohydrates, cholesterols, docosahexaenoic acid, potassium, carotenes, lutein, beta-cryptoxanthin, lycopene, calcium, iron, thiamine, riboflavin, niacin, tetra- and dihydrofolate, biotin, phosphorus, magnesium, zinc, copper, fiber (total, insoluble, and crude), glucose, galactose, fructose, and lactose compared to the healthy women (P < 0.05). Conclusions: FI, quasi-western dietary patterns, low economic levels, and waist circumference were significantly associated with the higher risk of PCOS. The lifestyle changes, especially dietary patterns, may be an essential strategy for reducing PCOS. Further studies are warranted to confirm these findings and to identify the underlying mechanisms.
... IR has inflammation and oxidative stress as major pathognomic factors. Recent reports on the effects of intermittent fasting on changes in the blood levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical, which play a key role on metabolic homeostasis (24). Also, different fasting regimens, that reducing IGF-1, IGFBP1, glucose and insulin levels, showed beneficial effects in ovarian function: and it was recently found that women with PCOS have an increased endometrial expression of IGF1 and IGFBP1, which coordinates the insulin signalling pathway (24). ...
... Recent reports on the effects of intermittent fasting on changes in the blood levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical, which play a key role on metabolic homeostasis (24). Also, different fasting regimens, that reducing IGF-1, IGFBP1, glucose and insulin levels, showed beneficial effects in ovarian function: and it was recently found that women with PCOS have an increased endometrial expression of IGF1 and IGFBP1, which coordinates the insulin signalling pathway (24). Thus, fasting may improve hyperanderogenism related symptoms. ...
Article
Context: The current study aimed to determine association of anti-TPO with LH/FSH in PCOS women. Design: Current case control study included 33 diagnosed PCOS women and 32 age matched healthy women and were analysed for body mass index (BMI) and waist to hip ratio (WHR), fasting blood glucose (FBG), free T3 (FT3), free T4 (FT4), Thyroid stimulating hormone (TSH), dehydroepiandrostenedione (DHEA-S), total testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH) and anti thyroperoxidase antibodies (anti-TPO). Data was statistically analysed by Student's t - test and Pearson's correlation analysis. Results: Of the total PCOS women, 45% were obese and 34.37% had raised anti-TPO. The biochemical profile of obese PCOS women showed significantly raised FBG (p<0.0001), LH (p<0.0001), Testosterone (p<0.0001) and DHEA-S (p=0.0021) as compared to non-obese PCOS women. The LH/FSH ratio was significantly raised in PCOS women as compared to control (p<0.0001). Pearson's correlation analysis showed a significant association of anti-TPO with FBS, testosterone, LH and LH/FSH in obese PCOS and with Testosterone and LH in non-obese PCOS women using SPSS 21. Conclusion: The current study shows a high prevalence of AITD in euthyroid PCOS women and suggests a strong link of euthyroid obese PCOS women to autoimmunity due to the hyper-anderogenism and a higher LH/FSH ratio.
... for ovulation and pregnancy rates, respectively] [36]. Recently, Chiofalo et al. [37] raised the possibility of fasting as a complementary step for the management of obese women with PCOS. Fasting can reduce Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), and glucose and insulin levels, and, consequently, has beneficial effects on ovarian function. ...
... The authors demonstrated that different forms of fasting, such as intermittent fasting (e.g., alternate day fasting, or twice weekly fasting) and periodic fasting (e.g., for several days or longer every two or more weeks) are currently under investigation. Moreover, they highlighted the need for RCTs to compare the efficacy of fasting regimens alone and in combination with common pharmacological strategies in PCOS [37]. ...
Article
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Purpose: This systematic review and meta-analysis aimed to compare the effectiveness of unilateral vs. bilateral laparoscopic ovarian drilling (ULOD vs. BLOD) for improving fertility outcomes in infertile women with clomiphene-resistant polycystic ovary syndrome (PCOS) as well as its effect on ovarian reserve. Methods: Searches were conducted on PubMed, ScienceDirect, ClinicalTrials.gov, and CENTRAL databases from January 1984 to January 2017. Only randomized trials comparing ULOD with BLOD were included. The PRISMA Statement was followed. Main outcomes were ovulation and clinical pregnancy rates per woman randomized. Secondary outcomes were; live birth and miscarriage rates as well as postoperative serum anti-mullerian hormone (AMH) concentration and antral follicle count (AFC). Quality assessment was performed by the Cochrane Collaboration risk of bias tool. Results: Eight eligible trials (484 women) were analyzed. No significant difference was found in rates of ovulation (OR 0.73; 95% CI 0.47-1.11), clinical pregnancy (OR 0.56; 95% CI 0.22-1.41), live birth (OR 0.77; 95% CI 0.28-2.10), or miscarriage (OR 0.90; 95% CI 0.33-2.84) when ULOD was compared with BLOD. The reduction in AMH was comparable between the two procedures (MD 0.64 ng/ml; 95% CI - 0.08 to 1.36). A significantly higher AFC at 6-month follow-up was found with dose-adjusted ULOD (MD 2.20; 95% CI 1.01-3.39). Conclusions: After carefully weighing up the well-known benefits of BLOD against a potential risk to ovarian reserve, clinicians could be advised to offer the fixed-dose ULOD to their infertile patients with clomiphene-resistant PCOS. This is concordant with the "primum non nocere" principal if LOD will be envisaged.
... Despite the etiology of the syndrome is still far from being elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors, and genetic background. In particular, accumulating evidence suggests that insulin resistance and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation [3]. ...
... The significant pathways involving the candidate have been associated with GCs dysfunction [43]. In addition, IL6, IL1B1 and TNF are associated with increased susceptibility to PCOS [44], and INSR plays a role in compensatory hyperinsulinemia [45]. EXD can regulate the expression of these genes via the AGE-RAGE, PCOS-related drug targets. ...
Article
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Background Polycystic ovary syndrome (PCOS) significantly affects women’s health and well-being. To explore the pharmacological basis of the Erxian decoction (EXD) action in PCOS therapy, a network interaction analysis was conducted at the molecular level. Methods The active elements of EXD were identified according to the oral bioavailability and drug-likeness filters from three databases: traditional Chinese medicine system pharmacology analysis platform, TCM@taiwan and TCMID, and their potential targets were also identified. Genes associated with PCOS and established protein–protein interaction networks were mined from the NCBI database. Finally, significant pathways and functions of these networks were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine the mechanism of action of EXD. Results Seventy active compounds were obtained from 981 ingredients present in the EXD decoction, corresponding to 247 targets. In addition, 262 genes were found to be closely related with PCOS, of which 50 overlapped with EXD and were thus considered therapeutically relevant. Pathway enrichment analysis identified PI3k-Akt, insulin resistance, Toll-like receptor, MAPK and AGE-RAGE from a total of 15 significant pathways in PCOS and its treatment. Conclusions EXD can effectively improve the symptoms of PCOS and our systemic pharmacological analysis lays the experimental foundation for further clinical applications of EXD.
... PCOS is one of the most common endocrine disorders in young women, with a prevalence of 8-18% [82][83][84]; it is the most common cause of chronic hyperandrogenic anovulation and the single most common cause of infertility in adolescent and reproductive women [85,86]. It could be also a risk factor for metabolic syndrome-related comorbidities and for impaired well-being and mortality. ...
Article
Background The use of effective contraceptive methods must be encouraged among adolescents, not only to prevent unintended pregnancies but also to promote the sexual health and well-being of these young people. In effect, hormonal contraceptives offer several benefits beyond prevention of pregnancy to every woman, in particular to adolescents (e.g., dysmenorrhea, irregular bleeding, hirsutism, acne); moreover, they can be a targeted therapy for some gynecological diseases (e.g., endometriosis, polycystic ovary syndrome), to ensure a better quality of life. Objective The purpose of this article is to review the different formulations of COCs for adolescent and young adult women, and analyze their efficacy, safety, and benefits of specific pathological conditions. Methods We screened published literature on PubMed/MEDLINE and Scopus, using as keywords “oral contraceptive” in adolescent and young adult women. We included only articles in English about the COCs, different regimens and formulations. Results Our literature analysis allows us to underline the important role of COC not only as birth control method, but also as valid treatments for gynecological disorders related to hormonal fluctuations (e.g., dysmenorrhea, irregular bleeding, hirsutism, acne) and pathological diseases, such as polycystic ovarian syndrome (PCOS), endometriosis, with a preventive role for fertility preservation and pelvic inflammatory disease. Conclusion Adequate, care and competent counseling is the key to achieve good compliance of young women with contraception. Through the “GATHER” method suggested by WHO, health care providers should first evaluate the balance between benefits and risks of hormonal treatment, create an appropriate safety profile and then recommend COC prescription in adolescent and young women.
... The changes in fasting glucose levels were associated with the changes in BMI [48]. Of note, intermittent or periodic fasting protocols have been hypothesized to improve insulin resistance in PCOS women [49]. However, there is not enough evidence to support these interventions in clinical practice. ...
Article
Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women. Insulin resistance and glucose intolerance are very prevalent metabolic complications in women with PCOS, especially in those presenting with weight excess. Therapeutic strategies targeting insulin resistance in PCOS are of interest because of their overall safety and their beneficial effects on metabolic and reproductive features. Areas covered: The authors review systematically all of the available therapeutic interventions targeting insulin resistance and/or disturbances of glucose metabolism in women with PCOS. Expert opinion: The diagnosis of glucose tolerance disorders in women with PCOS requires an oral glucose tolerance test. Strategies addressing weight excess and abdominal adiposity, from lifestyle modification to insulin sensitizers, may improve insulin resistance and glucose tolerance in women with PCOS. However, amelioration of signs and symptoms of PCOS usually requires the loss of large amounts of weight for it to be noticeable. Bariatric surgery has emerged as the most successful approach for obese patients with PCOS, because glucose intolerance, diabetes, and PCOS resolve in most cases through follow-ups. At present, the role of novel drugs targeting insulin resistance and/or diabetes such as inositols, berberine, resveratrol, and incretin-based therapies are yet to be properly established.
... However, there is no clear recommendation about the composition of the diet for PCOS women, but the reduction in daily caloric intake, adherence to low-glycaemic index (GI) dietary patterns, and consumption of nutraceuticals derived from food sources may improve insulin sensitivity and metabolic parameters [8][9][10]. Numerous pharmacological and non-pharmacological approaches have been proposed to improve InsR-related metabolic alterations in PCOS. ...
Article
Full-text available
Polycystic ovary syndrome (PCOS) is a complex disorder associated with ovarian dysfunction, infertility, menstrual irregularity, and hormonal impairments. Over the last decade, several studies have shown that some PCOS women have insulin resistance (InsR) and hyperinsulinemia, apart from being overweight or obese. Therefore, a crucial clinical aspect is that PCOS patients might develop glucose intolerance and type 2 diabetes. Insulin-sensitizing drugs have been used as first-line treatment to improve hyperinsulinemia in women with PCOS. Although reducing PCOS symptoms and signs, several used insulin-sensitizer drugs may induce side effects, which reduces compliance. D-chiro-inositol (DCI), which is a naturally occurring stereoisomer of inositol, has been classified as an insulin-sensitizer and seems to mitigate multiple InsR-related metabolic alterations in PCOS with a safe profile. However, according to a multi-targeted design, the supplementation with DCI can be synergistically integrated by combining other potential insulin-sensitizing drugs and/or nutraceuticals. The literature provides the initial support for using several unexplored nutraceutical interventions that may target relevant metabolic abnormalities associated with InsR in PCOS. With a need to promote interest in clinical research, this review aims to discuss the efficacy of DCI and the role of emerging nutraceuticals for managing InsR in PCOS.
... The polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms that are poorly understood [1,2]. Generally, PCOS affects women of childbearing age, and is accompanied by ovarian dysfunction, infertility, hyperinsulinemia, hyperandrogenism, and insulin resistance (IR) [3][4][5]. ...
Article
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Background: The polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms remain unclear. The following study investigates the ovarian hyperfibrosis forming via transforming growth factor-β (TGF-β) signaling pathway in Dehydroepiandrosterone (DHEA)- induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored whether TGF-βRI inhibitor (SB431542) decreases ovarian fibrosis by counterbalancing the expression of fibrotic biomarkers. Methods: Thirty female Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were established by subcutaneous injection of DHEA for 35 consecutive days. The 12 successful model rats were additionally divided in vehicle group (n = 6) and SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served as administration group and were intraperitoneally injected with DMSO and SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and collagen localization and expression in ovaries were detected using H&E staining, immunohistochemistry and Sirius red staining. The ovarian protein and RNA were examined using Western blot and RT-PCR. Results: In DHEA-induced ovary in rat, fibrin and collagen had significantly higher levels, while the main fibrosis markers (TGF-β, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542 significantly reduced the expression of pro-fibrotic molecules (TGF-β, Smad3, Smad2, a-SMA) and increased anti-fibrotic factor MMP2. Conclusion: TGF-βRI inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-β and upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-βRI inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes and modulating EMT mediator.
... The medical diagnosis was for a long time substantially the prerogative of forensic disciplines and has only recently assumed a more general medical and assistive character. In this regard, differential diagnosis with other conditions which may cause vaginal and/or anal bleeding, such as endometriosis [10][11][12][13][14], endocrinological diseases and hormonal dysbalance [15][16][17][18][19][20][21][22] and cancer [23][24][25][26][27][28][29], although uncommon, should be carefully taken into account. This has given the diagnosis of abuse or violence a more medical meaning, in the sense that it has become the prerequisite in commencing treatment [30,31]. ...
Article
The aim of this work is to propose a comment on the impact of different forms of child abuse. A multidisciplinary approach (gynecological, psychological and pediatric) is important for an adequate diagnosis and an early recognition of the abuse in order to minimize the serious impact of child abuse on the physical and psychological wellbeing of the victims.
... In most cases, it is not possible to identify a specific cause or a definitive treatment for the cure of CPP. In at least one-half of cases, pelvic pain is associated to other clinical conditions such as irritable bowel syndrome, interstitial cystitis/ painful bladder syndrome, uterine fibroids, ovarian cysts/polycystic ovarian syndrome, ectopic pregnancy, endometriosis, or pelvic adhesions (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) . The presence of both endometriosis and interstitial cystitis is not unusual (11,18) . ...
Article
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Chronic Pelvic Pain is a common disease, particularly in reproductive-aged women, and it is often associated with several clinical conditions such as irritable bowel syndrome, interstitial cystitis/painful bladder syndrome or gynecological cancer. Among gynecological diseases, endometriosis is the most frequently associated with chronic pelvic pain. The aim of this work is to underline the influence of psychological factors on the relationship between endometriosis and pelvic pain in order to reduce as much as possible the impact of these diseases on quality of life and psychological well-being of women affected.
... There are various fertility treatment options for the induction of ovulation in PCOS women including clomiphene citrate, metformin, gonadotrophins, inositols and laparoscopic drilling [18]. The possible benefits of different types of fasting and the addition of inositols to diet are being investigated recently as complementary therapeutic options for PCOS [19,20]. Since there are different PCOS phenotypes regarding the different combinations of the diagnostic criteria [21], drug metabolism in each of the possible phenotypes may be different. ...
Article
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Objective: To investigate whether quality of life differs between PCOS and non-PCOS infertile women. Study design: Two questionnaire forms of quality of life (PCOSQ, SF-36) were given to 238 women. Patients were asked to answer all of the questions in both of the questionnaires. Of these 238 women, only 49 infertile PCOS patients, 47 infertile non-PCOS patients and 62 fertile PCOS patients fılled the forms completely. Results: Both PCOSQ and SF-36 scores are lowest in infertile PCOS group. Although total PCOSQ score of infertile non-PCOS group was better than non-infertile PCOS and fertile PCOS groups; there was trend for lower scores when infertility is added on PCOS status. Conclusion: The quality of life is lowest among infertile PCOS women. Both PCOS and infertility as individual factors may have negative impact in quality of life of reproductive age women.
... When fasting, the metabolic imbalance typical of PCOS may improve significantly [17][18][19]. Accumulating evidence suggests that one of the most important mechanisms in PCOS pathogenesis is insulin-resistance; therefore, the efficacy of insulin-sensitizers such as inositol isoforms has gained increasing attention [20,21]. In addition, insulin-sensitizers like metformin are also utilized for the management of PCOS. ...
Article
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BACKGROUND Polycystic ovarian syndrome (PCOS) is a common endocrine disorder causing infertility among reproductive-age women. The molecular mechanisms underlying the development of PCOS are not well understood, and effective treatment options and therapeutic targets for PCOS are not available. This study was designed to investigate the role and therapeutic potential of miR-324 in PCOS. MATERIAL AND METHODS We used quantitative real time-polymerase chain reaction (qRT-PCR) to assess expression. Cell viability was determined by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Acridine orange/ethidium bromide (AO/EB) and annexin V/PI staining were performed to examine apoptosis. Western blot analysis was used to determine protein expression. RESULTS Results showed that the expression of miR-324 was aberrantly and significantly downregulated in PCOS ovarian tissues and KGN ovarian granulosa cells. Nonetheless, ectopic expression of miR-324 expression inhibited the viability of KGN cells via induction of apoptotic cell death. In silico analysis showed Wingless-Type family member 2B (WNT2B) to be the target of miR-324, which was also validated by dual-luciferase reporter assay. We also found that the expression of WNT2B was upregulated in the KGN cells, and overexpression of miR-324 inhibited WNT2B expression. Similar to WNT2B overexpression, WNT2B silencing decreased the viability of the KGN. Furthermore, overexpression of WNTB2 in KGN partially reversed the growth-inhibitory effects of miR-324 overexpression. CONCLUSIONS miR-324 regulates the proliferation of KGN cells in PCOs and be essential in the management of PCOS.
... After our three-month insulin measured in fasting state). Numerous authors also studied the influence of starvation diets and fasting on metabolic functions [28]. Various forms of fast did not have an influence on the improvement of the parameters of glucose homeostasis and lipid profile. ...
Article
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The aetiology of polycystic ovary syndrome (PCOS) remains uncertain and thus dedicated studies are still of much importance. Patients in this group are at high risk for metabolic syndrome, diabetes and ischemic heart disease. Our goal was to use a dietary intervention, facilitating the regression of the disease, through the observation of lipid and hormonal profiles, carbohydrate metabolic parameters and metabolomics of plasma fatty acids. There were 39 Caucasian women with PCOS aged 26.76 ±5.08 that qualified for this study. Fatty acid profiles were investigated using gas chromatography. The results of plasma fatty acids were compared with the initial results and the control group. A three-month caloric reduction diet with low glycemic index (GI) reduces the level of nervonic acid and is a great alternative in PCOS therapy. The introduction of rapeseed oil and olive oil to the lowered GI reduction diet caused the increase in the ratio of average length chain fatty acids (C10:0, C14:0) and the enhancement of synthesis pathways for pentadecanoic acid (C15:0) and gamma-linolenic acid (GLA, C18:3n-6), but did not inhibit the synthesis of the derivatives of arachidic acid (C20:0). Additionally, a decrease in the level of nervonic acid (C24:1) was observed. Biochemical analysis of blood showed the improvement of plasma lipid fractions, but a significant reduction of androgen levels was not observed. A reduction diet with lowered GI lead to many positive effects in the improvement of the biochemical parameters of women with PCOS. It should be continued for a prolonged period of time, until the synthesis pathways for inflammatory factors are silenced.
... Under fasting conditions, the metabolic imbalance characteristic of PCOS may show significant improvement. Different fasting regimens can reduce IGF-1, IGFBP1, glucose, and insulin levels and consequently have beneficial effects on ovarian function, androgen excess, and infertility in women with PCOS [38]. One study conducted in Iran evaluated the effects of Ramadan fasting on the metabolic statuses of women with PCOS and found that this 4-week fasting had beneficial effects on nitrous oxide and plasma glutathione levels but did not affect glucose hemostasis parameters, lipid profiles, or total antioxidant capacity [39]. ...
Article
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This study aimed to evaluate the clinical manifestations and health risks associated with polycystic ovary syndrome (PCOS) and its impact on quality of life (QOL) in Pakistan. A detailed cross-sectional study was conducted on PCOS among women of reproductive age visiting the gynecology and obstetrics and endocrinology departments at primary and tertiary care hospitals located in Abbottabad, Kohat, and Islamabad. In total, 440 patients meeting the inclusion criteria were included. A checklist was specifically designed to identify symptoms and health risks, including adverse drug reactions, complications, irrational prescription or underprescription, and drug–drug interactions. The Short Form-12 questionnaire was used to evaluate the QOL of patients with PCOS. Data collected were analyzed for descriptive and inferential statistics using chi-square test, analysis of variance, and post hoc analysis. All patients exhibited the cardinal symptoms of PCOS, including obesity (n = 352, 80%), acne (n = 296, 67.3), hirsutism (n = 299, 68%), hyperglycemia (n = 278, 63.2%), and irregular menstruation (n = 316, 71.8%). Ultrasonography confirmed that 268 (61%) patients had multiple cysts of >10 mm in diameter. Patients with untreated PCOS exhibited a high prevalence of health risks including hypertension (n = 87, 19.8%), diabetes (n = 268, 60.9%), sleep apnea (n = 11, 2.5%), infertility (n = 146, 33.2%), increased endometrial thickness (n = 21, 4.8%), miscarriages (n = 68, 15.5%), high cholesterol level (n = 85, 19.3%), and hyperandrogenism (n = 342, 77.7%). Most patients exhibited low QOL scores (n = 374, 85%), with depression being the largest contributor to low QOL. Apart from novel results, this study found an association between depression and low QOL in patients with PCOS, suggesting the need for reviewing the management guidelines and psychological health assessment of women with PCOS.
... This creates a risk of decreased fertility in these patients as well as infertility, type 2 diabetes, atherosclerosis, obesity and metabolic syndrome [51][52][53]. Moreover, limiting diet calories and various fasting models can improve metabolism in PCOS by changing the circulating levels of insulin growth factor 1 [54] and by increasing nitric oxide (NO) and glutathione [55]. As indicated by Wanders et al., patients with PCOS with accompanying deficiency of niacin may also experience reduced expression of proinflammatory cytokines as well as a low level of anti-inflammatory cytokines [56]. ...
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So far, there have been no analyses of correlations between the level of water-soluble vitamins in women with polycystic ovary syndrome (PCOS) and hormone and lipid profiles as well as carbohydrate metabolism. The unpopular concept that PCOS may also be conditioned by a chronic infection leads to a suspicion that water-soluble vitamins may be involved in the struggle against PCOS. This is why the aim of this research was to determine whether there are any indications that could confirm this hypothesis. The study included 64 women of Caucasian race: 50 patients aged 29.52 ± 7.01 years with PCOS, diagnosed according to the Rotterdam criteria. The control group consisted of 14 women aged 30.23 ± 6.3 years with correct BMI. HPLC Infinity1260 Binary LC (Agilent Technologies, Waldbronn, Germany) was used to analyze nine vitamins. The vitamins were separated using the gradient method, a buffer of 25 mM HK2PO4 with pH equal to 7.0, and 100% methanol buffer. The acquired results were compared using Statistica 12.0 (Statsoft, Tulsa, Oklahoma, USA). Non-parametric tests were used: Mann-Whitney tests for comparisons between groups (PCOS and control group, CG), in which p < 0.05 was considered statistically significant. Subsequently, we performed a correlation matrix of the biochemical parameters of blood with vitamins at p ≤ 0.05. Higher concentrations of ascorbic acid were observed in PCOS. The content of the remaining vitamins was higher in the control group, and the statistical differences were significant in reference to thiamine, riboflavin, pyridoxine and folic acid in comparison to the control group. A significant positive correlation was observed between vitamin C and testosterone/insulin, another between riboflavin and androstenedione/testosterone, next between biotin and thyrotropic hormone (TSH), between pantothenic acid and dehydroepiandrosteron (DHEA-SO4), and finally between pyridoxine and androstenedione. A negative correlation was observed in the case of niacin with sex hormone binding protein (SHBG) and high density lipoprotein (HDL). Water-soluble vitamins play an important role in the therapy of women with PCOS through the reduction of antioxidative stress and low-intensity inflammation caused by various factors, including chronic infection.
... Polycystic ovarian syndrome (PCOS), which has been renamed metabolic reproductive syndrome, is the most common but little-known reproductive endocrine dysfunction and metabolic disorder in women worldwide (1,2). It is characterized by hyperandrogenism, ovarian polycystic changes and rarity in ovulation or anovulation, and is often accompanied with obesity and insulin resistance (3)(4)(5). ...
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The present study aimed to examine the expression of FK‑506 binding protein 52 (FKBP52) in the ovary tissues of rats with polycystic ovarian syndrome (PCOS) and its action on mediating androgen receptor (AR) through the mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) pathway. PCOS model rats were established by dehydroepiandrosterone injection. Enzyme‑linked immunosorbent assay (ELISA) measured serum sex hormones. Hematoxylin and eosin (H&E) staining was used to examine histological changes of the ovarian tissues. The expression levels of FKBP52 were detected by immunohistochemical (IHC) staining, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis and western blotting (WB). In addition, RT‑qPCR analysis was used to detect the mRNA expression of AR, and WB was used to detect the protein expression levels of AR, ERK1/2 and phosphorylated (p‑)ERK1/2. In granulosa cell (GC) experiments, primary GCs were extracted and cultured. FKBP4 is the FKBP52‑encoding gene, therefore, adenovirus vectors Ad‑Oe‑FKBP4‑EGFP and Ad‑siRNA‑FKBP4‑EGFP were constructed to examine the association among the above factors using the RT‑qPCR and WB methods. In the animal experiment, the vaginal smear, H&E staining and ELISA results showed that the PCOS model was successfully established. The IHC staining revealed that the expression of FKBP52 in the GCs of the PCOS model group was higher than the remaining groups (P<0.01). The mRNA and expression levels of FKBP52 and AR in the PCOS model rats were significantly increased, when compared with levels in the other rats (P<0.05). The expression level of p‑ERK1/2 was also higher (P<0.05). In the GC experiment, following overexpression of the FKBP4 gene, the mRNA and expression levels of FKBP52 and AR were increased (P<0.05). The expression level of p‑ERK1/2 was also increased (P<0.05). Following FKBP4 gene silencing, the mRNA and expression levels of FKBP52 and AR were decreased (P<0.05). The expression level of ERK1/2 was also decreased (P<0.05). However, the expression level of p‑ERK1/2 was increased (P<0.05). In conclusion, the upregulation of co‑chaperone FKBP52 may mediate the activation of AR through the MAPK/ERK pathway.
... Fasting may also improve symptoms and signs associated with hyperandrogenemia. In addition, weight loss reduces adipose tissue and may negatively regulate androgen conversion in estrone: in this case, fasting may reduce hypothalamic and pituitary dysregulation, which underlie subfertility in women with PCOS (35). Inositol is a polyol with nine naturally occurring stereoisomers, including D-chiroinositol (DCI) and inositol (MI), which play important roles in the metabolism of glucose and free fatty acids. ...
Article
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Objective To observe the effect of metformin (MET) monotherapy versus MET plus liraglutide (LIRA) on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome (PCOS).Methods Sixty overweight patients with PCOS were recruited from January 2021 to January 2022 in Shengjing Hospital of China Medical University and were randomly assigned to the MET or combination (COM) group to receive 12 weeks of MET monotherapy or MET plus LIRA therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and oral glucose tolerance tests (OGTT) were conducted at baseline and after the 12-week treatment.ResultsFifty-two subjects completed the trial while eight were lost during the follow-up. Both MET and COM improved menstrual cycles, anthropometric parameters, and glucose metabolism after the 12-week treatment; however, there was no statistical difference between the two groups. MET plus LIRA therapy improved hyperandrogenemia, including TT (total testosterone), SHBG (sex hormone binding globulin) and FAI (free androgen index), whereas MET monotherapy only improved SHBG and FAI when compared with baseline. Furthermore, both MET monotherapy and MET plus LIRA therapy improved E2 (estradiol) while only MET plus LIRA therapy improved LH (luteinizing hormone), FSH (follicle stimulating hormone) and Prog (progesterone) more effectively than baseline. Additionally, MET plus LIRA therapy may improve TT, SHBG, FAI, LH and Prog more effectively than MET monotherapy; however, there were no significant differences on E2, FSH and LH/FSH between the two groups.Conclusions In overweight patients with PCOS, both MET monotherapy and MET plus LIRA therapy improved glucose metabolism and relieved insulin resistance (IR). Additionally, MET plus LIRA therapy was more effective than MET monotherapy in improving reproductive abnormalities and hyperandrogenemia, potentially by modulating the hypothalamic-pituitary-ovarian axis.
... Because insulin plays an important role in PCOS and its metabolic features, controlling the disease with diet is the best step for people who want to manage PCOS and its associated symptoms [46,47]. Approximately, 50% of people with PCOS develop diabetes or pre-diabetes before turning 40 years age [48]; therefore, following a special lifestyle and diets that maintain body weight and eventually increases good insulin levels, reduces the risk of the disease and its associated adverse events [49][50][51][52][53][54]. ...
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Background Treatment for polycystic ovary syndrome (PCOS) usually initiates with a series of lifestyle modifications such as diet, weight loss, and exercise. Aims We, therefore, conducted this meta-analysis to systematically review and evaluate the possible benefits of LGD on a range of anthropometric, clinical, and biochemical parameters in women with PCOS. Methods We performed a systematic search through major indexing databases, including Scopus, Pubmed/Medline, ISI web of science, Embase, Cochrane central, and CINAHL (1966–April 30, 2021) using key concepts of PCOS. Results Of 935 initial publications, 542 remain after duplicates removal. Then, 141 records were removed at the title and abstract screening level. After excluding 392 literatures, we finally included 8 articles. The final selected studies included 412 overweight and obese individuals with PCOS (207 cases in LGID group and 205 patients in comparators) with a mean age of 21–32 years. Measured emotional health (3 studies, 132 participants, SMD: -1.97; 95%CI:-3.54, -0.40, P=0.01, I²=89%) and body hair (3 studies, 132 participants, SMD: -0.40; 95%CI:-0.46, -0.35, P<0.0001, I²=0%), were found to be significantly lower in women in LGD vs control diet groups. Moreover, infertility (3 studies, 132 participants, SMD: 1.45; 95%CI: 0.30, 2.61, P=0.01, I²=79%) was significantly higher in women in LGD vs control diet groups. Conclusion The present meta-analysis has shown that LGD may play a significant role in reducing the risk and improving the clinical and biochemical features of PCOS. So far the evidences for choosing the best dietary modalities for PCOS are not strong to make a definite recommendation.
... Various studies regarding fasting, have gained popularity in terms of PCOS. The recent study by chiofalo et al., have reported ameliorative effects of fasting on metabolic and hormonal dysfunctions in PCOS [143]. ...
Article
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Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.
... In addition, although the sample size of this study is larger than that of the previous studies (14,15), the sample size is still relatively small considering the incidence of precocious puberty. The clinical manifestations of polycystic ovary syndrome (PCOS) patients mostly start in puberty and the main clinical features are particularly similar to physiological changes in puberty, such as insulin resistance (30,31). CPP has been shown to be the rst appearance of PCOS (32). ...
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Background: To date, the gonadotropin-releasing hormone (GnRH) stimulation test is still the gold standard for precocious puberty (PP) diagnosis. However, it has many disadvantages, including low sensitivity, high cost, and invasive operation. This study aims to evaluate whether magnetic resonance imaging (MRI)-derived variables, including pituitary volume (PV), could be used as diagnostic factors for PP in girls, providing a non-invasive diagnostic approach for PP. Methods: A total of 288 young female patients who presented to the Clinic of Pediatric Endocrinology for evaluation of PP from January 2015 to December 2017 were enrolled. The sample included 90 girls diagnosed with premature thelarche (PT), 133 girls determined as idiopathic central precocious puberty (ICPP), 35 early pubertal girls, and 30 normal girls. All patients received pituitary MRI examinations. Results: The largest PV and pituitary height were shown in the ICPP and pubertal groups, followed by the PT group. The receiver operating characteristic (ROC) curve analysis showed that PV is a predictive marker for ICPP, with a sensitivity of 54.10% and a specificity of 72.20% at the cutoff value of 196.01 mm³. By univariate analysis, PV was positively associated with peak luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), age, bone age, and body mass index (BMI) (all P < 0.05). However, bone age and peak LH were the only significant predictors of PV as demonstrated by the stepwise multivariate regression analysis (Model: PV = 9.431 * bone age + 1.230 * peak LH + 92.625 [P = 0.000, R² = 0.159]). Conclusions: The PV in the ICPP group was significantly higher than in PT and control groups, but there was no reliable cutoff value to distinguish ICPP from PT. Pituitary MRI should be combined with clinical and laboratory tests to improve the diagnostic value of PV for PP.
... Polycystic ovary syndrome (PCOS) is one of the endocrine diseases that associated with metabolic derangement in women of the reproductive age. The characteristic metabolic features of PCOS are obesity, dyslipidemia, and insulin resistance (InsR) and the later involved in the hyperandrogenism of the PCOS phenotype [1] . The percentage of PCOS among obese adolescents is varied according to the criteria, and guidelines of PCOS diagnosis which ranged from 18.4% to 26.4% [2] . ...
... In addition, although the sample size of this study is larger than that of the previous studies [12,13], the sample size is still relatively small considering the incidence of precocious puberty. The clinical manifestations of polycystic ovary syndrome (PCOS) patients mostly start in puberty and the main clinical features are particularly similar to physiological changes in puberty, such as insulin resistance [28,29]. CPP has been shown to be the first appearance of PCOS [30]. ...
Article
Full-text available
Background: To date, the gonadotropin-releasing hormone (GnRH) stimulation test is still the gold standard for precocious puberty (PP) diagnosis. However, it has many disadvantages, including low sensitivity, high cost, and invasive operation. This study aims to evaluate whether magnetic resonance imaging (MRI)-derived variables, including pituitary volume (PV), could be used as diagnostic factors for PP in girls, providing a non-invasive diagnostic approach for PP. Methods: A total of 288 young female patients who presented to the Clinic of Pediatric Endocrinology for evaluation of PP from January 2015 to December 2017 were enrolled. The sample included 90 girls diagnosed with premature thelarche (PT), 133 girls determined as idiopathic central precocious puberty (ICPP), 35 early pubertal girls, and 30 normal girls. All patients received pituitary MRI examinations. Results: The largest PV and pituitary height were shown in the ICPP and pubertal groups, followed by the PT group. The receiver operating characteristic (ROC) curve analysis showed that PV is a predictive marker for ICPP, with a sensitivity of 54.10% and a specificity of 72.20% at the cutoff value of 196.01 mm3. By univariate analysis, PV was positively associated with peak luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), age, bone age, and body mass index (BMI) (all P < 0.05). However, bone age and peak LH were the only significant predictors of PV as demonstrated by the stepwise multivariate regression analysis (Model: PV = 9.431 * bone age + 1.230 * peak LH + 92.625 [P = 0.000, R2 = 0.159]). Conclusions: The PV in the ICPP group was significantly higher than in PT and control groups, but there was no reliable cutoff value to distinguish ICPP from PT. Pituitary MRI should be combined with clinical and laboratory tests to improve the diagnostic value of PV for PP.
... Even small changes in diet and physical activity can improve insulin resistance which leads to ameliorate the complications of PCOS [6,10]. Also, diet restriction and fasting might improve the metabolic imbalance typical of PCOS [11,12]. ...
Article
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Background Patients with Polycystic ovary syndrome (PCOS) are predisposed to the development of several mental comorbidities such as depression. According to several studies, PCOS can be managed by improving insulin sensitivity. The insulin-sensitizing effect of vitamin K has been reported in recent studies. Therefore, in the current trial, we assessed the effect of administrating vitamin K2 (Menaquinone-7) on depression status in women afflicted with PCOS. Methods Eighty-four PCOS women were allocated into the intervention and comparison groups; the intervention group (n = 42) administered 90 µg/day Menaquinone-7, and the comparison group (n = 42) consumed placebo capsules (containing avesil) for 8 weeks. In this randomized, double blind, placebo-controlled clinical trial, depression status was measured by BECK depression inventory-II (BDI-II) before and after 8 weeks of intervention. Results Consumption of Menaquinone-7 in comparison with the placebo capsules significantly improved depression status ( P = 0.012). Conclusion This clinical study reported the advantageous effect of Menaquinone-7 administration on depression status in PCOS patients. Trial registration The present study was registered at http://www.IRCT.ir on 06/06/2018 (registration number: IRCT20170916036204N5).
... This finding could be the consequence of adopting a healthy dietary pattern after having been diagnosed with PCOS. Dietary interventions that, for example, involve intermittent periods of fasting [54] and/or the use of insulin sensitizers (e.g., inositol isoforms) [55], can lead to improvements of PCOS features, substantiating the hypothesis that diet can indeed affect neuroendocrine pathways that regulate metabolic and reproductive functions [50,56,57]. Yet, the composition of the ideal weight-loss diet leading to improved PCOS features, such as hyperandrogenism, cycle regularity and metabolic and psychiatric outcomes, remains to be elucidated, as study outcomes to date have been conflicting [51,[58][59][60][61][62][63]. ...
Article
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Polycystic ovary syndrome (PCOS) is an endocrine condition associated with reproductive and psychiatric disorders, and with obesity. Eating disorders, such as bulimia and recurrent dieting, are also linked to PCOS. They can lead to the epigenetic dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, thereby impacting on ovarian folliculogenesis. We postulate that PCOS is induced by psychological distress and episodes of overeating and/or dieting during puberty and adolescence, when body dissatisfaction and emotional distress are often present. We propose that upregulated activation of the central HPG axis during this period can be epigenetically altered by psychological stressors and by bulimia/recurrent dieting, which are common during adolescence and which can lead to PCOS. This hypothesis is based on events that occur during a largely neglected stage of female reproductive development. To date, most research into the origins of PCOS has focused on the prenatal induction of this disorder, particularly in utero androgenization and the role of anti-Müllerian hormone. Establishing causality in our peripubertal model requires prospective cohort studies from infancy. Mechanistic studies should consider the role of the gut microbiota in addition to the epigenetic regulation of (neuro) hormones. Finally, clinicians should consider the importance of underlying chronic psychological distress and eating disorders in PCOS.
... According to the World Health Organization, it is estimated that the 13% of the world population is obese, with a higher predominance of women as compared to men (37% vs 27.4%) (2). In this regard, obesity represents a significant risk factor for many gynecological diseases, of which some have a hysterectomy as the primary therapeutic approach (3)(4)(5)(6)(7)(8)(9). Laparoscopic hysterectomy (LH) was introduced in 1989 by Reich et al. and underwent a progressive technical development allowing surgeons to perform even more complex procedures with this minimally invasive approach. ...
Article
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In the last decades, obesity has reached epidemic proportions in the world (40% in certain countries). It predisposes to many diseases and morbidities in both males and females. In the latter, obesity predisposes to multiple gynecological conditions requiring hysterectomy such as endometrial cancer. Over the years, technical im provements have allowed surgeons to perform a hysterectomy in a minimally invasive approach (laparoscopically) with clear benefits, safety and better outcomes compared to the abdominal approach. The aim of this review is to provide an overview of the effec ts of obesity on the outcomes of laparoscopic hysterectomy performed both for benign and malignant gynecological pathologies. We performed literature research on the electronic database PubMed from the database inception through June 29, 2019. Obesity does not seem to increase adverse outcomes in laparoscopic hysterectomy as compared to the increased postoperative complication rate after open surgery. Therefore, laparoscopic hysterectomy can be performed safely in this population and represent the approach of choice. © 2021, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.
... Nowadays, there is not a definitive treatment for PCOS. Diet and regular physical activity represent the first thera-peutic target [11,21,65,66]. Several studies showed a tailored effect on insulin and sex hormone pathways, reducing inflammatory markers and testosterone levels [21,67,68]. ...
Article
Polycystic ovary syndrome (PCOS) is a condition that affects about 15% of women of reproductive age and is correlated with infertility, insulin resistance, and obesity. The etiology of PCOS is multifactorial and genetic, endocrine, and metabolic causes are involved. New evidence suggests a link between microorganisms residing in the digestive tracts of humans and the development of PCOS. Moreover, an imbalance in the gut microbial community could be a possible factor for the onset of insulin resistance and obesity. Hyperandrogenism, a key feature of PCOS, could also play a critical role in shaping the microbiome community. Probiotics could modify the gut microbiota and serve as a potential treatment for PCOS. Here we disclose the association between PCOS and intestinal microbiota and the possible role of probiotics as a new treatment approach.
... Fasting can help preserve energy levels [97], thereby providing the body time to regenerate and heal. Increased hormonal modulation, reduced inflammation [98], and increased stress resistance are ways in which fasting may help reduce chronic pain severity. ...
Article
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Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and monosaccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and welldesigned randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.
... New research on fasting for PCOS has gained attention. It has been found that fasting can improve the metabolic and hormonal dysfunctions associated with PCOS in a recent study by Chiofalo et al [29]. Metabolism and reproductive health are addressed by MNT in PCOS patients through the use of a personalized diet that addresses insulin resistance and metabolic and reproductive functions. ...
Article
PCOS (Polycystic Ovary Syndrome) is an endocrine condition that affects women of reproductive age: it can have catastrophic consequences, as it is accompanied by anovulation, androgen excess, infertility, insulin resistance, depression, and amenorrhea. Women who have a hereditary tendency are more likely to be affected. Other environmental variables such as a sedentary lifestyle, bad eating habits, inactivity, and obesity have frequently been implicated in the development of this illness. Each year, more women are diagnosed with PCOS as a result of an increasingly unhealthy lifestyle. When PCOS is detected early and treated correctly, the accompanying reproductive, metabolic, and cardiovascular problems can be effectively managed or predicted. PCOS is becoming a growing source of worry, as it primarily affects women of reproductive age. PCOS is also prevalent in many teenage girls during puberty. Despite being one of the most frequent reproductive health issues among women, doctors face a tremendous obstacle in providing appropriate medical therapy. PCOS is known to cause anxiety and despair, particularly when exacerbated by excessive facial hair growth, obesity, and infertility, anxiety and despair. Thus, PCOS can have a negative effect on an individual’s quality of life if it is not treated promptly. The best first-line treatment for PCOS is a lifestyle intervention that includes a healthy diet with caloric restriction, exercise to aid in weight loss and to avoid future weight gain, and support for behaviour modification. Future studies should focus on the gaps in our understanding of PCOS. Patients will receive the best care if those physicians are followed. To date, there has been no effective treatment for PCOS, and most patients receive only symptomatic treatment with hormones and insulin sensitizers, which leads to long-term medication dependency.
... Considering the importance of InsR and compensatory hyperinsulinemia in inducing androgen excess in PCOS women, fasting may improve hyperandrogenism-related symptoms and signs. Although several studies evaluated the correlation between insulin signaling pathways and fasting, there is no adequate data to suggest a clear fasting regime for PCOS patients (31). It seems that more studies should be conducted to prove the above claim. ...
Article
Objective. Polycystic ovary syndrome is a disorder in women of reproductive age and it is one of the pathological factors that play a role in the failure of laboratory fertilization (IVF). The aim of this study was to determine the effect of inofolic supplementation on women with polycystic ovary syndrome (PCOS). Material and methods. This clinical trial study was performed on 70 infertile women aged 20 to 40 years with polycystic ovary syndrome referred to the Sanandaj Besat Hospital infertility center in 2019. Patients were randomly divided into intervention and control groups. Patients in the intervention group took Clomiphene and inofolic supplement for 3 months and patients in the control group received only Clomiphene for 3 months. Various parameters such as fasting sugar, LDL, HDL, cholesterol, triglyceride and testosterone level were also measured. Results. LDL (96.6 ± 19.4 vs 105.2 ± 10.1, p = 0.02), cholesterol (158.2 ± 10.4 vs 79.8 ± 14.4, p = 0.0001) and triglycerides levels (140.1 ± 30.3 vs 160.3 ± 22.0, p = 0.002) was significantly lower in the intervention group than in the control group. The mean HDL level in the intervention group was higher than the control group (47.3 ± 7.5 vs 43.2 ± 5.1, p = 0.009). The frequency of follicles (+ 2) in the intervention group (85.7%) was higher than in the control group (37.1%) (p = 0.001). The frequency of clinical pregnancies, pregnancies leading to live births, miscarriages, and preterm births in the two groups did not differ significantly and were almost similar (P > .05). Conclusions. Inofolic supplementation improved fat profile status, fetal quality and reduced miscarriage and also increased follicles in women with polycystic ovary syndrome
... Most of the research work carried out in this field in recent times also highlighted the prime importance of insulin in the development of PCOS and our study also reinforced the role of insulin. Regarding the importance of insulin resistance and the resultant hyperinsulinemia, various dieting routines could decrease growth factors and receptors specific to insulin and thus have positive results in improving hormonal variations and irregularities in ovulation (18). Research works based on insulin sensitizer drugs like D-Dhiro-inositol (DCI) and myo-inositol [MI] received more attention due to their effectiveness in improving ovarian function and metabolism in subjects with PCOS. ...
Article
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Context: Polycystic ovary syndrome (PCOS) or disease (PCOD) is one of the most common causes of female infertility. Objective: The objective of this study was to find out the influence of insulin on LH, testosterone and SHBG in diffrent PCOS categories. Experimental design: A total of 800 women who were subjected to infertility treatment at infertility clinics were selected. About 60 healthy females with regular menstrual cycles were considered as control. The data were collected from hospital records using subject's consent. Results: Relationship of insulin to LH and testosterone was positive and significant (p<0.05) in the entire PCOS group and in five PCOS subcategories with increased LH rise (i.e. 1.3, 2, 3, 4 & 5 times of LH rise in relation to FSH levels in each group respectively). The correlation pattern showed an increasing trend from lower to increased rise of LH compared to FSH. The relationship between insulin and SHBG was negative and significant (p<0.05) in all PCOS subcategories, except for the group having similar LH and FSH levels and also in another group with FSH levels higher than LH levels. A strong positive correlation was established between insulin and SHBG in normal subjects. The percentage of negative correlation was strong in PCOD subcategories with elevated rises of LH. Conclusion: This study established the influence of insulin on other marker hormones (LH, testosterone an SHBG) in various PCOS categories in view of their percentage of relationship.
Article
Excess adiposity is a hallmark of obesity, which is caused due to an imbalance between energy intake and energy consumed. Obesity is often associated with several metabolic disorders like dyslipidemia, cardiovascular diseases and type 2 diabetes. Earlier, our group had reported natural product Aegeline (amino-alcohol) isolated from the plant Aegle marmelos as an anti-diabetic and anti-dyslipidemic compound. With this background, we synthesized a series of novel amino alcohol and thiazolidinedione hybrid molecules and studied their antiadipogenic activity. As a result, we have identified a potent hybrid compound 12c as an inhibitor of adipocyte differentiation. The compound 12c inhibits lipid accumulation and adipogenesis in 3T3-L1 preadipocyte cell line. Exposure of compound 12c blocks mitotic clonal expansion and arrests cells in S-phase of cell cycle. Detailed analysis showed that compound 12c decreases expression of two major transcription factors that are involved in adipocyte differentiation, PPARγ, C/EBPα, and other adipogenesis associated genes like aP2 and FAS. Thus, we concluded that compound 12c shows potential ability to inhibit adipocyte differentiation which can be used therapeutically for the treatment of obesity and its associated metabolic disorders.
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ABSTRACT Otocephaly is characterized by agenesis or severe hypogenesis of the mandible or agnathia, synotia (the external ears horizontally placed and/or fused), microstomia (“small mouth”), aglossia (congenital absence of the tongue). This anomaly is often associated with other malformations as; Holoprosencephaly, anencephaly, congenital heart disease, tracheoesophageal fistula etc. The etiology is unknown. The pathogenetic mechanism seems to be related to a complete failure of the mandibular development, possibly associated with inhibited or arrested migration of neural crest cells. Threedimensional ultrasound is often the only way to obtain an overall idea of the anomaly. The virtually all views of the fetal face are abnormal, due to the complete distortion of the facial anatomy. Otocephaly has been always lethal, so when detected, an accurate counseling of pregnancy should be offered at parents with also the possibility to offer termination of pregnancy. We report the case of a fetus, who was born on the 30th week of pregnancy, and was diagnosed with otocephaly, after birth.
Article
Background: Obesity is an important public health issue with an increasing prevalence in Turkey as well as throughout the world. Aims: The purpose of this study is to identify the prevalence of obesity in women of reproductive age group living in Adıyaman which is located in southeastern Turkey and the factors related to it. Patients and methods: This descriptive study was carried out with 1,100 women registered at Family Health Centers in the Adıyaman city center. Data were collected through a face-to-face survey method and evaluated on a computer. Chi-square and logistic regression evaluations were used in comparisons and P < 0.05 was considered statistically significant. Results: The mean age of the women was 32.94 ± 8.65; 78.3% of them were homemakers, and half were elementary school graduates or less educated; 57.6% of the women were overweight with 24.1% being obese. It was observed that women's body mass index increased with their age and decreased with higher levels of education. Also, the study showed that the risk of being overweight increased 3,2 times for married women and 2,0 times for unemployed women. Additionally, the rate of women being overweight was higher among the women with more number of previous pregnancies. Conclusion: Prevalence of obesity among women of reproductive age was high in the Adıyaman city center. Specific training should be planned, especially for women with low education levels, for fighting obesity.
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Adnexal masses are a common finding in women, with 20% of them developing at least one pelvic mass during their lifetime. There are more than 30 different subtypes of adnexal tumours, with multiple different subcategories, and the correct characterisation of the pelvic masses is of paramount importance to guide the correct management. On that basis, different algorithms and scoring systems have been developed to guide the clinical assessment. The first scoring system implemented into the clinical practice was the Risk of Malignancy Index, which combines ultrasound evaluation, menopausal status, and serum CA-125 levels. Today, current guidelines regarding female patients with adnexal masses include the application of International Ovarian Tumours Analysis simple rules, logistic regression model 1 (LR1) and LR2, OVERA, cancer ovarii non-invasive assessment of treating strategy, and assessment of Different Neoplasias in the adnexa. In this scenario, the choice of the scoring system for the discrimination between benign and malignant ovarian tumours can be complex when approaching patients with adnexal masses. This review aims to summarise the available evidence regarding the different scoring systems to provide a complete overview of the topic.
Article
Polycystic ovary syndrome (PCOS) is one of the most common disorders among women of reproductive age and can be diagnosed when at least two of the following criteria are present: chronic ovulatory disorder, clinical and/or biochemical hyperandrogenism, and polycystic ovaries. Diet and lifestyle modifications are the main therapeutic intervention and they can fully restore ovary function and avoid PCOS consequences in a certain number of patients. However, prescription of medications or dietary supplements is often needed. The literature has confirmed the significant role of inositol therapy in PCOS, with particular reference to Myo-inositol and D-chiro-Inositol. The aim of this review is to clarify the use of inositols for the treatment of PCOS and the recent scientific theories about D-Chiro-Inositol properties as an ovarian aromatase inhibitor.
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To evaluate the effects of the combination of d-chiro inositol and alpha lipoic acid on menstrual cycles and insulin sensitivity in women with polycystic ovary syndrome (PCOS). Forty-one women with PCOS and 31 controls have been enrolled in the study. The menstrual cycle, BMI, homeostasis model assessment index (HOMA-I), and insulin secretion in response to an OGTT were evaluated before and after 6 months of treatment. During the observation period, the patients have been asked to not modify their diet and physical activity. The menstrual cycle length improved in 76.7% of the women. Ovulation was restored in 40%. During treatment, BMI significantly decreased (p<.002). The HOMA-I and insulin secretion were unchanged by treatment. However, when women were divided according to the presence of insulin resistance (IR; HOMA-I > 2.5), in those with IR the HOMA-I and the insulin secretion significantly decreased (p<.05 and p<.006). The association of d-chiro-inositol and alpha lipoic acid improves menstrual cycle length, restoring ovulation in the majority of women. Insulin sensitivity improved in women with IR only, confirming that in presence of IR the d-chiro-inositol has a role in restoring the insulin action overcoming the inactivity of epimerase in transforming myo-inositol to d-chiro inositol.
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Polycystic ovarian syndrome (PCOS) is an endocrine disorder that commonly affects women of reproductive age. Its prevalence varies quite significantly and its clinical presentation includes: reproductive, metabolic and psychological issues. PCOS develops due to a variety of factors some of which are not yet fully understood. Due to the complexity in the development and presentation of this condition, the management of PCOS in most instances is complicated and involves the combination of pharmacological, non-pharmacological and surgical interventions. This review discusses the pathogenesis and management of PCOS as means of providing information that would enhance understanding and control of this disease.
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Polycystic ovary syndrome (PCOS), a multisystem disease, is a major reason for female infertility around the world. It is no longer considered simply as a disease of ovary. Now researchers growing awareness of the multisystem features of this disease. PCOS has a higher relationship with metabolic disturbance and hypothalamic-pituitary-ovarian axis (HPOA)function disorders. This syndrome results in hyperandrogenemia (HA), hyperinsulinemia/insulin resistance (IR), increased estrone, luteinizing hormone (LH)and follicle-stimulating hormone (FSH)ratio imbalance, infertility, cardiovascular diseases, endometrial dysfunction, obesity, and including a litany of other health issues. Furthermore, PCOS has been garnered in recent times. Interventions like metformin, orlistat, hormonal contraceptives, GLP1 agonists, and VitD have been applied to ameliorate or reverse the pathological characterization of PCOS. Moreover, drug-combined therapy of PCOS is superior to single drug administration. This review will focus on the recent progress in pathogenesis and therapy of PCOS.
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Background: Laparoscopic ovarian drilling (LOD) is one of the common modes of treatment for women with polycystic ovary syndrome (PCOS) who are resistant to clomiphene citrate. The data related to the effect of LOD on sex hormones are limited. Aim: The objective of the study was to investigate the effect of LOD on hormonal parameters and clinical outcomes in women with PCOS. Settings and design: This study was conducted in a tertiary care hospital. Materials and methods: Fifty PCOS patients who were admitted for LOD were enrolled in the study. Serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were estimated in all the patients before and after LOD. Statistical analysis: Paired t-test was used to assess the differences in hormonal parameters before and after LOD. Results: LOD reduces testosterone (P < 0.001), LH (P < 0.001), and LH/FSH ratio (P < 0.001), increases FSH (P < 0.001) levels, and improves the rate of ovulation (38/50) and clinical pregnancy (21/50) in PCOS. When subgroup analysis was done, LOD significantly reduced testosterone and LH/FSH ratio in ovulatory and conceived groups. Furthermore, the menstrual cycle became regular, and hirsutism and acne were reduced after LOD in women with PCOS. Conclusions: LOD reduces testosterone and LH/FSH ratio and improves clinical outcome in PCOS.
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Research question: Polycystic ovary syndrome (PCOS) is a complex disease and its pathophysiology is still unclear. This polygenic study may provide some clues. Design: A polygenic, functionome-based study with the ovarian gene expression profiles downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, including 48 PCOS and 181 normal control samples. These profiles were converted to the gene set regularity (GSR) indices, which were computed by the modified differential rank conversion algorithm and were defined by the gene ontology terms. Results: Machine learning could accurately recognize the patterns of functional regularities between PCOS and normal controls. The significantly aberrant functions in PCOS included transporter activity, catalytic activity, the receptor signalling pathway via signal transducer and activator of transcription (STAT), the cellular metabolic process, and immune response. Conclusion: This study provided a comprehensive view of the dysregulated functions and information for further studies on the management of PCOS.
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Aim of the study was to asses and compare serum anti-Mullerian harmone (AMH) levels after laparoscopic ovarian drilling (LOD) and transvaginal hydrolaparoscopy (THL) ovarian drilling in clomifene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients; secondary outcome was to evaluate postoperative pain to estimate the acceptability of procedures. A total of 246 patients with CC-resistant PCOS were randomized into two groups: 123 underwent LOD and 123 underwent THL ovarian drilling. AMH serum levels were evaluated before and after the procedure; moreover, women were asked to rate pain on a visual analog scale (VAS) from 0 (no pain, perfectly acceptable) to 10 (unbearable pain, completely unacceptable). In both groups, postoperative serum AMH levels were significantly reduced compared to preoperative levels (6.06 ± 1.18 and 5.84 ± 1.16 versus 5.00 ± 1.29 and 4.83 ± 1.10; p < 0.0001). Comparing postoperative serum AMH levels, no statistically significant difference was observed between the two surgical technique. After the procedure, mean pain VAS score was significantly higher for women who underwent LOD ovarian drilling in comparison to THL (3.26 ± 1.1 versus 1.11 ± 0.5; p < 0.0001). In conclusion, THL ovarian drilling is comparable to the LOD in terms of reduction in AMH, but it is preferred by patients in terms of acceptability. These results could support to use of THL ovarian drilling in the treatment of patients with CC- resistant PCOS.
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The present study was designed to evaluate the effects of metformin on metabolic and endocrine parameters in patients with polycystic ovary syndrome (PCOS). The study included 40 patients with PCOS. Patients were divided into 2 groups based on whether they will receive metformin (500 mg 3 times a day, n=20) or placebo (n=20) for 3 consecutive months. Serum concentrations of fasting blood glucose, insulin, HOMA-IR, INSL-3, visfatin, FSH, and LH were measured at baseline and after 3 months of therapy. The key endocrine and metabolic parameters significantly changed after metformin treatment. The systolic and diastolic blood pressures were significantly reduced in the metformin group after treatment compared to placebo (p<0.001). A significant reduction in the size of the right ovary was observed after metformin treatment (p=0.05), while no change was found in the size of left ovary (p>0.12). Moreover, a significant reduction was observed in the serum levels of FSH (p>0.01), LH (p>0.001), and visfatin (p>0.001) after metformin treatment. However, HOMA-IR (which is used to assess insulin resistance) failed to reach the statistical significance (p=0.20). We conclude that metformin treatment in females with PCOS showed significant improvement in systolic and diastolic blood pressures. In addition, an improvement in the hormonal profile in the form of reduction in LH, FSH, and visfatin levels was observed. Thus, therapeutic intervention with metformin could be of clinical importance in high-risk group of young females with PCOS.
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Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers. We evaluated the effect of IGF-1 on the phenotype and chemoresistance of B16-F10 cells. IGF-1 inhibition in these cells prevented malignant cell proliferation, migration and invasion, and lung colony formation in immunodeficient mice. IGF-1 downregulation also markedly inhibited EMT, with low levels of ZEB1 and mesenchymal markers (N-cadherin, CD44, CD29, CD105) associated with high levels of E-cadherin and MITF, the major regulator of melanocyte differentiation. IGF-1 inhibition greatly reduced stemness features, including the expression of key stem markers (SOX2, Oct-3/4, CD24 and CD133), and the functional characteristics of MICs (melanosphere formation, aldehyde dehydrogenase activity, side population). These features were associated with a high degree of sensitivity to mitoxantrone treatment. In this study, we deciphered new connections between IGF-1 and stemness features and identified IGF-1 as instrumental for maintaining the MIC phenotype. The IGF1/IGF1-R nexus could be targeted for the development of more efficient anti-melanoma treatments. Blocking the IGF-1 pathway would improve the immune response, decrease the metastatic potential of tumor cells and sensitize melanoma cells to conventional treatments.
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Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.
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A growing body of research is currently focused on the role of inositol isomers and in particular myo-inositol (MYO-INS) and D-chiroinositol (DCI) in the treatment of insulin resistance states. Both isomers have been shown to exert insulin-mimetic action and to lower postprandial glucose. Further, insulin resistance-related diseases were associated to derangements in inositol metabolism. Thus, the aim of this review is to provide current evidence on the potential benefits of inositol isomers (MYO-INS and DCI) in the treatment of disease associated to insulin resistance such as polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic syndrome. Finally, molecular insights into inositol insulin-sensitizing effects will be covered focusing on the possible role of inositol glycans as insulin second messengers.
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Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women and is characterized by two of the following three features: oligoovulation or anovulation, clinical and/or biochemical signs of hyperandrogenism, or polycystic ovaries. Summary: It has been demonstrated that PCOS includes a complex number of systemic symptoms in addition to symptoms related to the reproductive apparatus. It has been associated with obesity, metabolic syndrome, type 2 diabetes and an increased risk of cardiovascular disease. Several clinical and basic studies have investigated the link between PCOS and the cardiovascular disease risk, which seems to be due to blunted lipid/glucose metabolism, hypertension, and systemic inflammatory and coagulation disorders. Therefore, the current manuscript aims to review the main findings on PCOS and obesity/obesity-related disease (glucose derangements and cardiovascular disease risk factors). Key message: Although there are no long-term data on the morbidity and mortality for cardiovascular disease in PCOS, it is advisable to perform a careful metabolic and cardiovascular assessment in women with PCOS in order to tailor the most suitable strategy to prevent cardiovascular disease.
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Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.
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Background: Polycystic ovary syndrome (PCOS) is a complex syndrome characterized by reproductive and metabolic implications. Lifestyle changes, such as diet and exercise, are considered first-line treatment for women affected by PCOS. Pharmacologic treatments target the hormonal and metabolic dysregulations associated to the disease such as insulin resistance, anovulation, hirsutism and menstrual irregularities. Objective: To focus on the role of inositol isoforms, as well as Mediterranean and ketogenic diets, as possible therapeutic strategies in PCOS women. Method: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Results: Accumulating evidence suggests that two inositol isoforms, myo- and D-chiro-, may play a pivotal role in re-addressing both hormonal and metabolic parameters toward homeostasis, counteracting the symptoms and signs typical of this syndrome. In addition, studies focused on Mediterranean and ketogenic diet provided positive results in patients affected by obesity and type 2 diabetes, so these dietetic regimens could represent a fascinating dietetic treatment for the management of PCOS Conclusion: Both the isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS. In spite of accumulating evidence, it is currently not possible to draw firm conclusion(s) about the efficacy of these interventions considering the severe bias due to different samples size, dose, and duration of intervention among the published studies on this topic. Furthermore, future longitudinal cohort studies along with prospective interventional trials may contribute to better clarify the role of Mediterranean and ketogenic diets in the treatment of PCOS.
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The incidence of metabolic syndrome (MetS), type II diabetes (T2D) and polycystic ovarian syndrome (PCOS) has been progressively increasing. Insulin resistance (InsR) seems to play a key role in a majority of phenotypes of these conditions, altering metabolic homeostasis, within muscle, liver, adipose and other tissues. Hyperinsulinemia is often associated with InsR and causes hormonal imbalances especially within ovaries and adrenals. Inositol is a polyalcohol, naturally occurring as nine stereoisomers, including D-chiro-inositol (DCI) and myo-inositol (MI), which have prominent roles in the metabolism of glucose and free fatty acids. MI and DCI have been classified as insulin-sensitizers and seem to adequately counteract several InsR-related metabolic alterations with a safe nutraceutical profile. Based on our analysis of selected studies that investigated MI and/or DCI, we conclude that supplementation with MI and/or DCI complement each other in their metabolic actions and act in synergy with other insulin sensitizing drugs and/or nutraceuticals. Nevertheless, considering the possible severe bias due to different methodologies across published studies, we conclude that there is a need for further studies on larger cohorts and with greater statistical power. These should further clarify outcomes and suitable therapeutic dosages of MI and DCI, possibly based on each patient's clinical status.
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PURPOSE: To evaluate the effects of D-Chiro-Inositol in women affected by polycystic ovary syndrome (PCOS). METHODS: We enrolled 48 patients, with homogeneous bio-physical characteristics, affected by PCOS and menstrual irregularities. These patients underwent treatment with 1 gr of D-Chiro-Inositol/die plus 400 mcg of Folic Acid/die orally for 6 months. We analyzed pre-treatment and post-treatment BMI, Systolic and Diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, DHEA-S, Δ-4-androstenedione, SHBG, prolactin, glucose/IRI ratio, HOMA index, and resumption of regular menstrual cycles. RESULTS: We evidenced a statistically significant reduction of systolic blood pressure, Ferriman-Gallwey score, LH, LH/FSH ratio, total Testosterone, free Testosterone, ∆-4-Androstenedione, Prolactin, and HOMA Index; in the same patients, we noticed a statistically significant increase of SHBG and Glycemia/IRI ratio. Moreover, we observed statistically significant (62.5%; p < 0.05) post-treatment menstrual cycle regularization. CONCLUSIONS: D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.
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Many aging theories and their related molecular mechanisms have been proposed. Simple model organisms such as yeasts, worms, fruit flies and others have massively contributed to their clarification, and many genes and pathways have been associated with longevity regulation. Among them, insulin/IGF-1 plays a key and evolutionary conserved role. Interestingly, dietary interventions can modulate this pathway. Calorie restriction (CR), intermittent fasting, and protein and amino acid restriction prolong the lifespan of mammals by IGF-1 regulation. However, some recent findings support the hypothesis that the long-term effects of diet also involve epigenetic mechanisms. In this review, we describe the best characterized aging pathways and highlight the role of epigenetics in diet-mediated longevity.
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Context: Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized. Objective: Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels. Design, setting and participants: IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy. Main outcome measures: Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated. Results: Fasting insulin and C-peptide levels and glucose Ra were reduced (all P < .05) in low-IGF compared with high-IGF subjects, indicating increased hepatic IS. Acute insulin and C-peptide responses were lower (both P < .05), but similar peripheral IS resulted in reduced insulin secretion adjusted for IS in low-IGF subjects (P = 0.044). Low-IGF subjects had higher overnight levels of free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. Conclusions: These data suggest that serum IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting.
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Polycystic ovary syndrome (PCOS) constitutes a continuum spectrum of symptoms starting from the early prepubertal years and continuing after menopause. The phenotypic expression varies through time, depending on several internal (e.g. ovarian/adrenal steroidogenesis, insulin resistance) and external factors (e.g. quality and quantity of food, exercise). Moreover, the emergence of new definitions with the use of ovarian morphology, besides chronic anovulation and hyperandrogenism, as diagnostic criteria, increased the phenotypic variety of PCOS presentation. In this review, the clinician is provided with useful information regarding grey zones in assessing anovulation, hyperandrogenism, ovarian morphology and the difficulties in differential diagnosis of PCOS. Furthermore, the lack of substantial data characterizing metabolic/hormonal profile and the potential cardiovascular risk in newer PCOS phenotypes, as well as the absence of longitudinal data questioning a possible shift from one phenotype to another are underlined. These notions indicate that despite the initial presentation of a patient with PCOS, close follow-up and therapeutic interventions aiming to reduce long-term cardiovascular risk are warranted.
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Background. Metabolic risk factors like insulin resistance and dyslipidemia are frequently observed in severly obese children. We investigated the hypothesis that moderate weight reduction by a low-threshold intervention is already able to reduce insulin resistance and cardiovascular risk factors in severely obese children. Methods. A group of 58 severely obese children and adolescents between 8 and 17 years participating in a six-month-long outpatient program was studied before and after treatment. The program included behavioral treatment, dietary education and specific physical training. Metabolic parameters were measured in the fasting state, insulin resistance was evaluated in an oral glucose tolerance test. Results. Mean standard deviation score of the body mass index (SDS-BMI) in the study group dropped significantly from +2.5 ± 0.5 to 2.3 ± 0.6 (P < 0.0001) after participation in the program. A significant decrease was observed in HOMA (6.3 ± 4.2 versus 4.9 ± 2.4, P < 0.03, and in peak insulin levels (232.7 ± 132.4 versus 179.2 ± 73.3 μU/mL, P < 0.006). Significant reductions were also observed in mean levels of hemoglobin A(1c), total cholesterol and LDL cholesterol. Conclusions. These data demonstrate that already moderate weight reduction is able to decrease insulin resistance and dyslipidemia in severely obese children and adolescents.
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Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL6 mice are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid beta-peptide (Abeta) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD (3xTgAD mice). Groups of 3xTgAD mice were maintained on an ad libitum control diet, or CR or IF diets, beginning at 3 months of age. Half of the mice in each diet group were subjected to behavioral testing (Morris swim task and open field apparatus) at 10 months of age and the other half at 17 months of age. At 10 months 3xTgAD mice on the control diet exhibited reduced exploratory activity compared to non-transgenic mice and to 3xTgAD mice on CR and IF diets. Overall, there were no major differences in performance in the water maze among genotypes or diets in 10-month-old mice. In 17-month-old 3xTgAD mice the CR and IF groups exhibited higher levels of exploratory behavior, and performed better in both the goal latency and probe trials of the swim task, compared to 3xTgAD mice on the control diet. 3xTgAD mice in the CR group showed lower levels of Abeta1-40, Abeta1-42 and phospho-tau in the hippocampus compared to the control diet group, whereas Abeta and phospho-tau levels were not decreased in 3xTgAD mice in the IF group. IF may therefore protect neurons against adverse effects of Abeta and tau pathologies on synaptic function. We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies.
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The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.
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Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans.
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Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case-control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 − IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026–0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 − IGF1) may be inversely associated with the incidence of hepatoma.
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Background: Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (EC) risk compared to women without PCOS, the precise molecular mechanisms which link between PCOS and EC remain unclear. It has been suggested that insulin resistance may contribute to the increased risk of EC in PCOS. The specific expression of genes related to the insulin-signalling pathway including the IGF system in the endometrium of women with PCOS has however never been measured and compared to that in women with EC without PCOS and control women without EC or PCOS. . Objectives: To test the hypothesis that insulin signalling plays a key role in the development of EC in women with PCOS by measuring and comparing the expression of three key genes involved in the insulin signalling pathway (IGF1, PTEN and IGFBP1) in endometrial tissue obtained from three groups of women; PCOS without EC, women with EC without PCOS and non-PCOS women without EC (controls). We also aimed to determine the correlation between the gene expressions to various clinical variables among participants. Methods: This was a cross-sectional study of 102 women in 3 groups (PCOS, EC and controls) at a University teaching hospital in the United Kingdom. Clinical assessment (blood pressure, body mass index (BMI) and waist-hip-circumference ratio), venepuntures (fasting blood sugar, insulin, lipid profile, hormones) and endometrial tissue biopsies were taken in all participants. Endometrial tissue RNA extraction was performed before real time polymerase-chain-reaction for the genes of interest (IGF1, IGFBP1 and PTEN) was carried out. To compare the baseline characteristics of the study population, One-Way-ANOVA test or the Independent t-test was used. For variables that were not normally distributed, the Spearman correlation test was used to calculate the r value. A "p" value of <0.05 was considered statistically significant. Results: IGF1, IGFBP1 and PTEN gene expression were significantly up-regulated in the endometrium of PCOS and EC women compared to controls. However there was no significant difference in the expression of these genes in PCOS compared to EC endometrium. The BMI of women with PCOS and controls, were not significantly different (29.28 (± 2.91) vs 28.58 (± 2.62) kg/m(2)) respectively, women with EC however had a higher mean BMI (32.22 (± 5.70) kg/m(2)). PCOS women were younger (31.8 (± 5.97) years) than women with EC (63.44 (± 10.07) years) and controls (43.68 (± 13.12) years). The changes in gene expression were independent of BMI, waist hip ratio, estradiol and androgen levels. Protein validation test in the serum samples in the three groups were consistent with the gene findings. Conclusion: Women with PCOS and EC have an increased endometrial expression of genes (IGF1, IGFBP1 and PTEN) involved in the insulin signalling pathway compared with control women. This may explain the increased risk of EC in PCOS women. This study provides a strong basis for clinical trials aiming to prevent EC in women with PCOS by investigating drugs targeting the insulin signalling pathway. This panel of genes may also serve as clinically useful early biomarkers which predict which women with PCOS will go on to develop EC.
Article
BACKGROUND: To our knowledge, no reports are available indicating the effects of Ramadan fasting on metabolic parameters, inflammatory factors and oxidative stress in polycystic ovary syndrome (PCOS). The current study was designed to evaluate the effects of Ramadan fasting on metabolic status among women with PCOS. METHODS: This cross-sectional study was conducted on twenty seven PCOS patients who had fasted for a mean period of 16.5 hours a day during the 29 days of the month of Ramadan in Kashan, Iran. Fasting blood samples were collected at the beginning of the study and after 29 days of the study to quantify related variables. To identify within-group differences (before and after Ramadan), paired-samples t-tests were used. RESULTS: Plasma nitric oxide (NO) levels in PCOS women after Ramadan fasting were significantly higher compared to the baseline values (70.63 ± 15.78 vs. 59.94 ± 13.87 μmol/L, P = 0.003). Post-Ramadan levels of plasma glutathione (GSH) increased significantly in comparison with pre-Ramadan (974.95 ± 414.20 vs. 746.96 ± 205.93 μmol/L, P = 0.011). In addition, a trend toward a significant effect of Ramadan fasting on reducing serum high sensitivity C-reactive protein (hs-CRP) concentrations (2001.07 ± 1686.08 vs. 2962.72 ± 2845.21 ng/mL, P = 0.072) was seen. We did not observe any significant effect of Ramadan fasting on glucose hemostasis parameters, lipid profiles or total antioxidant capacity (TAC). CONCLUSION: In conclusion, Ramadan fasting in women with PCOS for 4 weeks had beneficial effects on NO and GSH levels, but did not affect glucose hemostasis parameters, lipid profiles or TAC. © 2015, Academy of Medical Sciences of the I.R. Iran. All rights reserved.
Article
Dear Editor, We appreciate Vitagliano and Colleagues’ interest in our recent article [1] about ovarian function and metabolic factors in women affected by polycystic ovary syndrome (PCOS) after treatment with d-chiro-inositol. We are grateful for their insightful comments [2] and the opportunity to clarify a number of elements from our work.As evidenced by Vitagliano et al., despite the plethora of published papers about the treatment of PCOS with Inositol isoforms (for systematic reviews, see Unfer et al. [3] and Galazis et al. [4]), very few of them focused on lean patients (BMI Accumulating evidence suggests that pre-treatment BMI may play a key role in the effect of inositol treatment of PCOS: Genazzani et al. [5] recently showed d-chiro-inositol administration is effective in restoring better insulin sensitivity and an improved hormonal pattern in obese hyperinsulinemic PCOS patients, in particular, in hyperinsulinemic PCOS patients who have diabetic relatives. In our previo ...
Article
BACKGROUND Extravasation is a critical step in cancer metastasis, in which adhesion of intravascular cancer cells to the vascular endothelial cells is controlled by cell surface adhesion molecules. The role of interleukin-17 (IL-17), insulin, and insulin-like growth factor 1 (IGF1) in adhesion of prostate cancer cells to the vascular endothelial cells is unknown, which is the subject of the present study.METHODS Human umbilical vein endothelial cells (HUVECs) and human prostate cancer cell lines (PC-3, DU-145, LNCaP, and C4–2B) were analyzed for expression of vascular cell adhesion molecule 1 (VCAM-1), integrins, and cluster of differentiation 44 (CD44) using flow cytometry and Western blot analysis. The effects of IL-17, insulin, and IGF1 on VCAM-1 expression and adhesion of prostate cancer cells to HUVECs were examined. The interaction of VCAM-1 and CD44 was assessed using immunoprecipitation assays.RESULTSInsulin and IGF1 acted with IL-17 to increase VCAM-1 expression in HUVECs. PC-3, DU-145, LNCaP, and C4–2B cells expressed β1 integrin but not α4 integrin. CD44 was expressed by PC-3 and DU-145 cells but not by LNCaP or C4–2B cells. When HUVECs were treated with IL-17, insulin or IGF1, particularly with a combination of IL-17 and insulin (or IGF1), adhesion of PC-3 and DU-145 cells to HUVECs was significantly increased. In contrast, adhesion of LNCaP and C4–2B cells to HUVECs was not affected by treatment of HUVECs with IL-17 and/or insulin/IGF1. CD44 expressed in PC-3 cells physically bound to VCAM-1 expressed in HUVECs.CONCLUSIONSCD44-VCAM-1 interaction mediates the adhesion between prostate cancer cells and HUVECs. IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through increasing VCAM-1 expression in the vascular endothelial cells. These findings suggest that IL-17 may act with insulin/IGF1 to promote prostate cancer metastasis. Prostate © 2015 Wiley Periodicals, Inc.
The purpose of this systematic review was to evaluate, synthesize, and interpret findings from recent randomized controlled trials (RCTs) of dietary and lifestyle weight loss interventions examining the effects of (1) diet composition, (2) use of food provision, and (3) modality of treatment delivery on weight loss. Trials comparing different dietary approaches indicated that reducing carbohydrate intake promoted greater initial weight loss than other approaches but did not appear to significantly improve long-term outcomes. Food provision appears to enhance adherence to reduction in energy intake and produce greater initial weight losses. The long-term benefits of food provision are less clear. Trials comparing alternative treatment modalities suggest that phone-based treatment produce short- and long-term weight reductions equivalent to face-to-face interventions. The use of Internet and mobile technologies are associated with smaller reductions in body weight than face-to-face interventions. Based on this review, clinical implications and future research directions are provided.
Conference Paper
Background and aim. The Polycystic Ovary Syndrome (PCOS) has multifactorial pathogenesis, and is defined by the identification of two out of following parameters: oligo-anovulation, hyperandrogenism, polycystic ovaries. Emerging evidences support the opinion for which the Inositol isoforms seems to increase insulin action and, in this way, improve the ovulatory function and inhibit or limit the production of circulating androgens. The aim of this work is to evaluate the effects of D-Chiro-inositol, one of the Inositol isoforms, in women affected by PCOS. Materials and methods. We enrolled 25 patients, with homogeneous bio-physical characteristics, affected by PCOS and menstrual irregularities. We analyzed the following pre-treatment (T0) parameters: BMI, Systolic and Diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free Testosterone, DHEA-S, Δ-4-Androstenedione, SHBG, Prolactin, Glucose/IRI ratio, HOMA index. Then, the enrolled patients underwent treatment with 1 gr of D-Chiro-Inositol/die plus 400 mcg of Folic Acid/die orally for 6 months. We checked in the post-treatment (T1) the same parameters analyzed in the pre-treatment phase, in order to evaluate if any variation occurred. Moreover, we evaluate the post-treatment rate of resumption of regular menstrual cycles. Results. We evidenced a statistically significant reduction of the Systolic blood pressure, Gallwey-Ferriman Score, LH, LH/FSH ratio, total Testosterone, free Testosterone, ∆-4-Androstenedione, Prolactin and HOMA Index; in the same patients we noticed a statistically significant increase of SHBG and Glycemia/IRI ratio. Moreover, we observed statistically significant (64%; p<0.05) post-treatment menstrual cycle regularization. Conclusion. D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.
Article
Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.
Article
Abstract Myo-inositol and d-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and d-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of d-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas d-chiro-inositol reduced hyperandrogenism better.
Article
Objective: Recently, it has been debated whether the new polycystic ovary syndrome (PCOS) phenotypes, according to the Rotterdam criteria, share the same metabolic risk with the classic ones (National Institutes of Health 1990). Our study sought to compare the prevalence of metabolic syndrome (MS) and glucose homeostasis disorders in Greek women with classic and new PCOS phenotypes. Materials and methods: Two hundred and sixty-six Greek PCOS women were recruited and divided into groups according to two of the three Rotterdam criteria that they fulfilled. Two subgroups were formed; the first represented the classic phenotypes and the second the new phenotypes. The clinical, biochemical, and ultrasound characteristics of both groups were explored. All subjects were evaluated for MS and underwent a 2-h glucose tolerance test to assess insulin resistance (IR) as measured by the homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MATSUDA indices. Results: 62.4% of PCOS women were classified as classic NIH phenotypes of which 32 women had MS (prevalence 19.6%). Only 4 patients categorized in the newer phenotypic groups had MS (prevalence 4.1%). Among the subjects with classic phenotypes, 11.7% exhibited impaired glucose tolerance (3-fold higher percentage compared to patients with newer phenotypes). Regarding IR indices, HOMA-IR was significantly higher and QUICKI significantly lower for classic phenotypes. Conclusions: Greek PCOS women with classic phenotypes are at increased risk for MS and impaired glucose homeostasis compared to women with newer phenotypes. A subclassification of PCOS permits the earlier recognition and closer surveillance of women whose metabolic profile indicates potential risks for adverse health outcomes.
Article
Caloric restriction in rodents is well known to retard the rate of aging, increase mean and maximum life-spans, and inhibit the occurrence of many age-associated diseases. However, little is known about the influence of short-term repeated fasting on longevity. In this study, female (NZB×NZW)F1 mice were used to test the physiological effect of short-term repeated fasting (4 consecutive days, every 2 weeks). The results showed that fasting mice survived significantly longer than the full-fed mice, in spite of the fasting group having a heavier body weight than the control group. Mean survival times for fasting and control mice were 64.0±15.3 and 47.9±9.4 weeks, respectively. Short-term repeated fasting manipulation was also effective on the prolongation of life-span in autoimmune-prone mice.
Article
Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15-60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4-8%, 11-16%, respectively) and daily CR (5-8%, 10-20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.
Article
Previously we found that intermittent calorie restriction (ICR) delayed the age of prostate tumor detection and death in TRAMP mice in comparison to chronic calorie restricted (CCR) and ad libitum fed (AL) TRAMP mice. In the present study the same protocol was used in a cross-sectional experiment whereby mice were either ad libitum fed, intermittently calorie restricted at 50% of the consumption of AL mice for 2 weeks followed by 2 weeks of refeeding matched to AL intake or were pair-fed to the ICR. Both ICR and CCR protocols resulted in a 25% reduction in caloric intake. Mice were enrolled in the study at 7 weeks of age to be euthanized at designated time points in cycles 3, 6, and 9 with mice euthanized at the end of restriction and refeeding. At the youngest time point in cycle 3 ICR impacted body weight, fat pad weights and serum factors the most. Additionally, the incidence of detectable prostate cancer pathology was reduced for ICR mice compared to AL and CCR mice. However, by cycle 5 when the mice were 28-30 weeks of age all mice except one ICR mouse had pathologically confirmed prostate cancer. Furthermore, at the two older time points many of the mice assigned to the study did not survive to reach their designated endpoints. Overall these findings are consistent with other studies indicating protective effects of various interventions on the development of prostate cancer in young TRAMP mice.
Article
The objective of this study was to elucidate the relationship and role of insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), insulin and luteinizing hormone (LH) in the pathogenesis of polycystic ovary syndrome (PCOS). In a pilot study, serum concentrations of IGF-1 were determined in women with PCOS (n = 10), hypopituitarism (n = 12) and normal controls (n = 10). In the main study, serum concentrations of IGF-1, IGFBP-1, insulin and LH in women with anovulation associated (n = 23) and not associated (n = 47) with PCOS were determined. Serum concentrations of IGF-1 were not different in women with PCOS, anovulatory non-PCOS and healthy women but were low in those with hypopituitarism. Mean serum IGFBP-1 in PCOS (33.8 +/- 21.2 micrograms/l) was decreased compared with anovulatory non-PCOS (60.0 +/- 22 micrograms/l) (P = 0.0001), and correlated negatively with insulin concentrations (r = -0.67, P = 0.0006). Patients with PCOS could be separated into those with high LH and those with high insulin levels. It was concluded that women with PCOS have normal serum IGF-1 concentrations but IGFBP-1 levels, regulated by insulin, are low. Hyperinsulinaemia and raised LH are independently capable of stimulating ovarian androgen production. Growth factors may have an important role in the pathogenesis of PCOS.
Article
Heterozygous p53-deficient (p53(+/-)) mice, a potential model for human Li-Fraumeni Syndrome, have one functional allele of the p53 tumor suppressor gene. These mice are prone to spontaneous neoplasms, most commonly sarcoma and lymphoma; the median time to death of p53+/- mice is 18 months. We have shown previously that juvenile-onset calorie restriction (CR) to 60% of