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Polycystic Ovarian Syndrome [keywords]
- Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles. [JOURNAL ARTICLE]
- Hum Reprod 2014 Oct 21.
Are circulating microparticles (MPs) altered in young women with polycystic ovary syndrome (PCOS)?Women with PCOS have elevated concentrations of circulating platelet-derived MPs, which exhibit increased annexin V binding and altered microRNA (miR) profiles compared with healthy volunteers.Some studies have shown that cardiovascular risk is increased in young women with PCOS but the mechanisms by which this occurs are uncertain. Circulating MPs are elevated in patients with cardiovascular disease but the characteristics of MPs in patients with PCOS are unclear.Case-control study comprising 17 women with PCOS (mean ± SD; age 31 ± 7 years, BMI 29 ± 6 kg/m(2)) and 18 healthy volunteers (age 31 ± 6 years, BMI 30 ± 6 kg/m(2)).The study was conducted in a University hospital. Nanoparticle tracking analysis (NTA) and flow cytometry (CD41 platelet, CD11b monocyte, CD144 endothelial) were used to determine MP size, concentration, cellular origin and annexin V positivity (reflecting phosphatidylserine exposure). Fatty acid analysis was performed by gas chromatography and MP miR expression profiles were compared by microarray.PCOS subjects showed increased MP concentrations compared with healthy volunteers (mean ± SD; 11.5 ± 5 × 10(12)/ml versus 10.0 ± 4 × 10(12)/ml, respectively; P = 0.03), which correlated with the homeostasis model of insulin resistance (r = 0.53, P = 0.03). This difference was predominantly seen in MPs whose size was in the small exosomal range (<150 nm in diameter, P< 0.05). PCOS patients showed a greater percentage of annexin V(+) MPs compared with healthy volunteers (84 ± 18 versus 74 ± 24%, respectively, P = 0.05) but the cellular origin of MPs, which were predominantly platelet-derived (PCOS: 99 ± 0.9%; controls: 99 ± 2.5%), did not differ. MP fatty acid concentration and composition was similar between groups but 16 miRs were differentially expressed (P < 0.05).Patients with PCOS were classified by the Rotterdam criteria, which describes a less severe metabolic phenotype than other definitions of the syndrome. Our findings may thus not be generalizable to all patients with PCOS. MicroRNA expression analysis was only undertaken in an exploratory subset of the overall study population hence, validation of our findings in a larger cohort is mandatory. Furthermore, miR levels were unaltered for the highly expressed miRs and it is unclear whether differences in the lowly expressed miRs carries pathological relevance.This study suggests that women with PCOS have an altered MP profile but further studies are needed to confirm this, to explore the mechanisms by which these alterations develop and to establish whether therapies that improve insulin sensitivity are able to reduce circulating MP concentrations.The study was funded by grants from the Wales Heart Research Institute and Mrs John Nixon Scholarship. The authors have no conflicts of interest to declare.
- Evidence for gonadotrophin secretory and steroidogenic abnormalities in brothers of women with polycystic ovary syndrome. [JOURNAL ARTICLE]
- Hum Reprod 2014 Oct 21.
Are there abnormalities in gonadotrophin secretion, adrenal steroidogenesis and/or testicular steroidogenesis in brothers of women with polycystic ovary syndrome (PCOS)?Brothers of women with PCOS have increased gonadotrophin responses to gonadotrophin releasing hormone (GnRH) agonist stimulation and alterations in adrenal and gonadal steroidogenesis.PCOS is a complex genetic disease. Male as well as female first-degree relatives have reproductive features of the syndrome. We previously reported that brothers of affected women have elevated circulating dehydroepiandrosterone sulfate levels.This was a case-control study performed in 29 non-Hispanic white brothers of 22 women with PCOS and 18 control men.PCOS brothers and control men were of comparable age, weight and ethnicity. Adrenocorticotrophic hormone (ACTH) and GnRH agonist stimulation tests were performed. Gonadotrophin responses to GnRH agonist as well as changes in precursor-product steroid pairs (delta, Δ) across steroidogenic pathways in response to ACTH and GnRH agonist were examined.Basal total (T) levels did not differ, but dehydroepiandrosterone (DHEA) levels (0.13 ± 0.08 brothers versus 0.22 ± 0.09 controls, nmol/l, P = 0.03) were lower in brothers compared with control men. ACTH-stimulated Δ17-hydroxypregnenolone (17Preg)/Δ17-hydroxyprogesterone (17Prog) (7.8 ± 24.2 brothers versus 18.9 ± 21.3 controls, P = 0.04) and ΔDHEA/Δandrostenedione (AD) (0.10 ± 0.05 brothers versus 0.14 ± 0.08 controls, P = 0.04) were lower in brothers than in the controls. GnRH agonist-stimulated Δ17Prog/ΔAD (0.28 ± 8.47 brothers versus 4.79 ± 10.28 controls, P = 0.003) was decreased and luteinizing hormone (38.6 ± 20.6 brothers versus 26.0 ± 9.8 controls, IU/l, P = 0.02), follicle-stimulating hormone (10.2 ± 7.5 brothers versus 4.8 ± 4.1 controls, IU/l P = 0.002), AD (1.7 ± 1.4 brothers versus 0.9 ± 1.5 controls, nmol/l, P = 0.02) and ΔAD/ΔT (0.16 ± 0.14 brothers versus 0.08 ± 0.12 controls, P = 0.005) responses were increased in brothers compared with controls.The modest sample size may have limited our ability to observe other possible differences in steroidogenesis between PCOS brothers and control men.Decreased ACTH-stimulated Δ17Preg/Δ17Prog and ΔDHEA/ΔAD responses suggested increased adrenal 3β-hydroxysteroid dehydrogenase activity in the brothers. Decreased Δ17Prog/ΔAD and increased ΔAD/ΔT responses to GnRH agonist stimulation suggested increased gonadal 17,20-lyase and decreased gonadal 17β-hydroxysteroid dehydrogenase activity in the brothers. Increased LH and FSH responses to GnRH agonist stimulation suggested neuroendocrine alterations in the regulation of gonadotrophin secretion similar to those in their proband sisters. These changes in PCOS brothers may reflect the impact of PCOS susceptibility genes and/or programming effects of the intrauterine environment.This research was supported by P50 HD044405 (A.D.), K12 HD055884 (L.C.T.), U54 HD034449 (A.D., R.S.L.) from the National Institute of Child Health and Development. Some hormone assays were performed at the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core that is supported by U54 HD28934 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Partial support for some of the clinical studies was provided by UL1 RR025741 and UL1 TR000150 (Northwestern University Clinical and Translational Sciences Institute) from the National Center for Research Resources, National Institutes of Health, which is now the National Center for Advancing Translational Sciences. The authors have no conflict of interest to declare.
- Serum zonulin is elevated in women with polycystic ovary syndrome, and correlates with insulin resistance and severity of anovulation. [JOURNAL ARTICLE]
- Eur J Endocrinol 2014 Oct 21.
Objective: Evidence suggests that increased gut permeability may be associated with polycystic ovary syndrome (PCOS). Human zonulin is currently the only physiological mediator known to regulate gut permeability reversibly by disassembling intestinal tight junctions. So far, no data on serum zonulin levels in patients with PCOS is available. This study aimed to determine circulating serum zonulin levels in women with PCOS, and discuss the relationship between zonulin, insulin resistance and menstrual disorders in this group. Design: Case-control study. Methods: Seventy-eight women recently diagnosed with PCOS, and 63 age matched healthy controls were recruited for this study. Serum zonulin levels were determined by ELISA. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda and DeFronzo's insulin sensitivity index (ISI). Results: PCOS women had higher serum zonulin (p=0.022). After adjustment for age and body mass index, zonulin levels significantly correlated with HOMA-IR and ISI. Furthermore, PCOS women with more severe menstrual disorders had significantly higher zonulin levels and displayed an inverse correlation between zonulin and the number of menstrual cycles per year (r=-0.398, p<0.001). Conclusions: Serum zonulin, a biomarker for gut permeability, is increased in PCOS women, and correlates with insulin resistance and severity of menstrual disorders. It suggests that alterations of gut permeability may play a role in the patho-physiology of PCOS, and serum zonulin might be used as a biomarker for both risk stratification and therapeutic outcomes in PCOS women.
- Classification of ovary abnormality using the probabilistic neural network (PNN). [JOURNAL ARTICLE]
- Technol Health Care 2014 Oct 20.
In recent times there has been a significant change in lifestyle in many parts of the world, with most people experiencing a more sedentary existence combined with an abundance of food. This has resulted in the modern epidemic of obesity and consequent hyperinsulinemia - situations which in women may precipitate expression of fertility problems; effective methods to evaluate the fertility status are required. Ultrasonographic imaging is an effective, easy to use, safe, and readily available noninvasive means to evaluate fertility potential.OBJECTIVE: Manual recognition of the follicles in terms of area measurement and counting the number of follicles is laborious; often fatigue may lead to error-prone conclusions. The paper attempts an automated classification of the ovaries based on the biomarking done by the physician. Also, biomarked data correlates with the hormones values such as androgen, testosterone and leutinizing hormone.METHODS: Despeckled images are segmented by improved active contour with split-Bregman optimization. The features are extracted from images using geometric and intensity method. The significant features selected by particle swarm optimization and dimension reduction by principal component analysis and classification by probabilistic neural network.Proposed probabilistic neural network achieves maximum efficiency of 97% compared to SVM 92% and RBF 88%.The results obtained show that using a very large number of features combined with a feature selection approach allows us to achieve high classification rates.
- Metformin use in women with polycystic ovary syndrome. [Journal Article, Review]
- Ann Transl Med 2014 Jun; 2(6):56.
Polycystic ovary syndrome (PCOS) is an endocrinopathy characterised by increased resistance to insulin. Metformin is one of the longest established oral insulin sensitising agents. For decades its use was restricted to management of type 2 diabetes. However, in the past two decades, its properties as an insulin sensitising agent have been explored in relation to its applicability for women with PCOS. Metformin is an effective ovulation induction agent for non-obese women with PCOS and offers some advantages over other first line treatments for anovulatory infertility such as clomiphene. For clomiphene-resistant women, metformin alone or in combination with clomiphene is an effective next step. Women with PCOS undergoing in vitro fertilisation should be offered metformin to reduce their risk of ovarian hyperstimulation syndrome. Limited evidence suggests that metformin may be a suitable alternative to the oral contraceptive pill (OCP) for treating hyperandrogenic symptoms of PCOS including hirsutism and acne. More research is required to define whether metformin has a role in improving long term health outcomes for women with PCOS, including the prevention of diabetes, cardiovascular disease and endometrial cancer.
- Impact of metformin on reproductive tissues: an overview from gametogenesis to gestation. [Journal Article, Review]
- Ann Transl Med 2014 Jun; 2(6):55.
Metformin is an oral anti-hyperglycemic drug that acts as an insulin sensitizer in the treatment of diabetes mellitus type 2. It has also been widely used in the treatment of polycystic ovary syndrome (PCOS) and gestational diabetes. This drug has been shown to activate a protein kinase called 5' AMP-activated protein kinase or AMPK. AMPK is present in many tissues making metformin's effect multi factorial. However as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus. The majority of reports suggest no significant adverse effects or teratogenicity. However, disconcerting reports of male mouse offspring that were exposed to metformin in utero that present with a reduction in testis size, seminiferous tubule size and in Sertoli cell number suggest that we do not understand the full suite of effects of metformin. In addition, recent molecular evidence is suggesting an epigenetic effect of metformin which could explain some of the long-term effects reported. Nevertheless, the data are still insufficient to completely confirm or disprove negative effects of metformin. The aims of this review are to provide a summary of the safety of metformin in various aspects of sexual reproduction, the use of metformin by gestating mothers, and its possible side-effects on offspring from women who are administered metformin during pregnancy.
- Role of the combination spironolactone-norgestimate-estrogen in Hirsute women with polycystic ovary syndrome. [Journal Article]
- J Reprod Med 2014 Sep-Oct; 59(9-10):455-63.
To compare the combination spironolactone-norgestimate-ethinyl estradiol in hirsutism with other protocols including the same dose of estrogen.In this open prospective study, 167 women with hirsutism due to polycystic ovary syndrome (PCOS) were randomly assigned to the following treatment protocols: Group A (n = 72): spironolactone 100 mg-norgestimate 250 mcg-ethinyl estradiol 35 microg; Group B (n = 70): cyproterone acetate 12 mg-ethinyl estradiol 35 microg; Group C (n = 25): norgestimate 250 microg-ethinyl estradiol 35 microg.The decrease in the hirsutism score was higher in group A than in the other groups (p < 0.001) and comparable in groups B and C. The decrease in acne score, androgen and estradiol levels, and ovary volume was similar in groups A and B. C-reactive protein increase was similar in all groups, but the augmentation of fibrinogen (p = 0.04), triglycerides (p < 0.01), monocyte count (p = 0.04), platelet number (p < 0.001) and mean volume (p = 0.01) was more pronounced in group B than in group A. Low-density lipoprotein/high-density lipoprotein cholesterol ratio decreased in groups A and C.Spironolactone-norgestimate-ethinyl estradiol is an effective and well-tolerated combination for the treatment of hirsutism in PCOS, with a favorable influence on lipids and indices of low-grade inflammation.
- Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome. [JOURNAL ARTICLE]
- Endocr Res 2014 Oct 20.:1-6.
Abstract Aim: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) stimulate satiety leading to reductions in food intake and body weight. The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet. Methods: Thirty-six obese women with PCOS (mean ± SD, aged 31.2 ± 7.8 years, with BMI 38.7 ± 0.1 kg/m(2)), pretreated with metformin (1000 mg BID) were switched to liraglutide 1.2 mg QD sc for 12 weeks. Adiposity parameters and eating behavior as assessed by Three-Factor Eating Questionnaire (TFEQ-R18) were examined at baseline and after 12 weeks. Results: Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg (p < 0.001). Significant reductions of waist circumference and visceral adipose tissue (VAT) mass, volume and area were demonstrated from liraglutide induction to the end of the study. TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention. After treatment with liraglutide the uncontrolled eating (UE) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 (p < 0.001) and emotional eating (EE) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 (p < 0.001). Scores for cognitive restraint (CR) were not changed. Conclusions: Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS.
- The relationship between serum anti-Müllerian hormone levels and the follicular arrest for women with polycystic ovary syndrome. [JOURNAL ARTICLE]
- Syst Biol Reprod Med 2014 Oct 20.:1-7.
Abstract The aim of this study was to ascertain whether higher levels of serum anti-Müllerian hormone (AMH) are associated with the ovarian follicular arrest in women with polycystic ovary syndrome (PCOS). This prospective study compared AMH levels between serum and dominant follicular fluid (FF) in ovulatory polycystic ovary (PCO) women and anovulatory (menstrual cycle ≥60 days.) PCOS women. All 102 women provided a baseline hormone profile and underwent controlled ovarian hyperstimulation (COH). The anovulatory PCO women had a similar body mass index (BMI), antral follicle count (AFC), and baseline serum AMH levels as the ovulatory PCO women except that their median luteinizing hormone (LH; 10.0 mIU/ml), testosterone (T) (0.61 ng/l), and androstenedione (A) (3.47 ng/l) levels were significantly higher than ovulatory PCO women (4.9 mIU/m; 0.43 ng/l and 2.09 ng/l, respectively). The ovarian response to gonadotropin stimulation during COH including serum AMH on the day of HCG administration and dominant FF AMH at 36 hours after HCG administration, total follicle stimulating hormone (FSH) dose administrated, peak E2, (estrogen) levels and number of occytes retrieved were all similar between women with anovulatory and ovulatory PCO. Using multiple regression analysis it was found that an important independent determinant affecting AMH was AFC, as opposed to LH and T. Logistic regression analysis showed that the two most important factors affecting ovulation were serum LH and T, whereas serum AMH and AFC were not selected for inclusion in the model. The reduction in AMH during COH occurs as a consequence of dominant follicles with a corresponding reduction in small antral follicle number. Elevated serum AMH levels in PCO women seem to be related only to follicular excess and not follicular arrest.
- [Multisystemic involvement in obstructive sleep apnea]. [English Abstract, Journal Article]
- Rev Med Chil 2014 Jun; 142(6):748-57.
Obstructive Sleep Apnea (OSA) is characterized by repetitive upper airway collapse with apnea/hypopnea and recurrent hypoxia during sleep, which results in fragmented sleep and intermittent drops in arterial blood oxygen saturation (hypoxemia). Several dysfunctions of neurocognitive, endocrine, cardiovascular, and metabolic systems are recognized in patients with OSA. The most commonly reported associations are with obesity, increased cardiovascular risk, dyslipidemia, diabetes mellitus 2 and liver damage. However, there is a proven relationship between OSA and other diseases, such as polycystic ovary syndrome, gastroesophageal reflux, and chronic kidney disease. The aim of this review is to analyze clinical and experimental evidence linking OSA with other diseases.