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Polycystic Ovarian Syndrome [keywords]
- Cellular reprogramming for understanding and treating human disease. [REVIEW]
- Front Cell Dev Biol 2014.:67.
In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called "cellular Rosetta stones" because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging, and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease.
- Personality and Psychiatric Disorders in Women Affected by Polycystic Ovary Syndrome. [JOURNAL ARTICLE]
- Front Endocrinol (Lausanne) 2014.:185.
Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among fertile women. Studies show reduced quality of life, anxiety, depression, body dissatisfaction, eating disorder, and sexual dysfunction, but the etiology of these disturbs remains still debated. The aim of our study is to verify whether this hyperandrogenic syndrome characterizes a strong psycho(patho)logical personality. Method: Sixty PCOS subjects (mean age 25.8 ± 4.7 years) were evaluated by anthropometric, metabolic, hormonal, clinical, and psychological parameters. After the certainty of the diagnosis of PCOS, the Rorschach test, according to Exner's comprehensive system (CS) and the Millon Clinical Multiaxial Inventory-III (MCMI-III) were administered to each patient. The control group, on which the comparison was carried out, was composed by 40 healthy and aged compared women who were exclusively administered the Rorschach test according to CS. Results: MCMI-III evidenced axis II DSM-IV personality disorders [4.1% schizoid, depressive, sadistic, negativistic (passive-aggressive), and masochistic, 6.1% avoiding, 12.2% dependent, 20.4% histrionic, 16.3% narcissistic, 2.0% obsessive-compulsive], and axis I DSM-IV psychiatric disorders: 10.2% anxiety, 2.0% somatoform disorder and bipolar disorder, 16.3% major depressive disorder. Finally, we found 44.9% delusional disorder and 4.1% thought disorder. Rorschach test's results show 53.1% reduced coping abilities and social skills, 55.1% depression, 30.6% perceptual distortion and cognitive slippage, 24.5% constantly alert and worry, 8.1% at risk for suicide, and finally about 50% of our patients had chronic stress. Conclusion: PCOS women have relevant personality and psychiatric disorders, when compared with normal subjects.
- [Effects of pregnancy and changes in body weight on polycystic ovary syndrome phenotypes according to the Rotterdam criteria]. [English Abstract, Journal Article]
- Rev Med Chil 2014 Aug; 142(8):966-74.
Polycystic Ovary Syndrome (PCOS) is tightly associated with insulin resistance and obesity and characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology when fully expressed. The 2003 Rotterdam consensus proposed that two or three of these features were necessary to make the diagnosis, which generated four phenotypes. Several studies have suggested that these phenotypes could differ in their metabolic and endocrine characteristics and that they could vary in the same patient when analyzed throughout life.To determine if the initial classification of PCOS phenotypes is modified by different physiological conditions.We performed a non-concurrent prospective analysis of 88 women with PCOS according to the Rotterdam criteria. The effect of physiological conditions such as changes in body weight, pregnancy and ageing more than five years on PCOS phenotype expression was analyzed.Twenty four percent of women became pregnant, 37% decreased and 24% increased their body weight during follow up. These conditions modified significantly the proportion of the different phenotypes (c2 = 32.2, p < 0.001). For instance, weight reduction was associated with a change to a better phenotype (p = 0.047) and even a normalization of the PCOS condition in 27% of the patients. On the other hand, an increase in body weight modifying body mass index in one unit, conferred an 8% probability of changing to a worst phenotype.Pregnancy and changes in body weight significantly modify PCOS phenotypes.
- Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Nov 25.:1-5.
Abstract Aim: The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). Design: This was a retrospective study. Patients: Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Main outcome measure(s): Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Results: Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Conclusions: Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.
- MECHANISMS IN ENDOCRINOLOGY: Thyroid and polycystic ovary syndrome. [REVIEW]
- Eur J Endocrinol 2015 Jan; 172(1):R9-R21.
Thyroid disorders, especially Hashimoto's thyroiditis (HT), and polycystic ovary syndrome (PCOS) are closely associated, based on a number of studies showing a significantly higher prevalence of HT in women with PCOS than in controls. However, the mechanisms of this association are not as clear. Certainly, genetic susceptibility contributes an important part to the development of HT and PCOS. However, a common genetic background has not yet been established. Polymorphisms of the PCOS-related gene for fibrillin 3 (FBN3) could be involved in the pathogenesis of HT and PCOS. Fibrillins influence the activity of transforming growth factor beta (TGFβ). Multifunctional TGFβ is also a key regulator of immune tolerance by stimulating regulatory T cells (Tregs), which are known to inhibit excessive immune response. With lower TGFβ and Treg levels, the autoimmune processes, well known in HT and assumed in PCOS, might develop. In fact, lower levels of TGFβ1 were found in HT as well as in PCOS women carrying allele 8 of D19S884 in the FBN3 gene. Additionally, vitamin D deficiency was shown to decrease Tregs. Finally, high estrogen-to-progesterone ratio owing to anovulatory cycles in PCOS women could enhance the immune response. Harmful metabolic and reproductive effects were shown to be more pronounced in women with HT and PCOS when compared with women with HT alone or with controls. In conclusion, HT and PCOS are associated not only with respect to their prevalence, but also with regard to etiology and clinical consequences. However, a possible crosstalk of this association is yet to be elucidated.
- Association analysis between the polymorphisms of HSD17B5 and HSD17B6 and risk of polycystic ovary syndrome in Chinese population. [JOURNAL ARTICLE]
- Eur J Endocrinol 2014 Nov 24.
Objective: To assess whether single nucleotide polymorphisms of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in Chinese population. Design: Case-control study. Methods: In this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected using TaqMan method. Results and conclusions: We found that the genotypic frequencies of the rs1937845 polymorphism were different in PCOS compared with control, with the CT genotype being more commonly found in PCOS patients than in controls (P = 0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS versus the control group (adjusted OR, 1.74, 95% CI = 1.19-2.54, P = 0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47, 95% CI = 1.07-2.03, P = 0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT-carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P = 0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms of rs12529 in HSD17B5 and rs898611 in HSD17B6 between PCOS patients and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in PCOS patients. In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. The CT genotype and 'T' allele frequency influences significantly higher in PCOS patients than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.
- Does low pentraxin-3 levels associate with polycystic ovary syndrome and obesity? [JOURNAL ARTICLE]
- Int J Clin Exp Med 2014; 7(10):3512-3519.
Pentraxin-3 (PTX3) a cytokine-inducible molecule is released from various tissues. Its level increases as a response to different inflammatory conditions. Polycystic Ovary Syndrome (PCOS) is considered as a proinflammatory state. The aim of this study was to investigate the association between PTX3 and various metabolic and hormonal parameters in PCOS patients. This study included 64 new diagnosed PCOS patients who had been never treated previously with PCOS and 46 healthy controls with matched age and body mass index (BMI). PTX3, biochemical and hormonal parameters of both groups were measured. The patients were divided into obese and non-obese subgroups according to BMI (above or lower than 25 kg/m²). PTX3, HOMA-IR and high sensitive C-reactive protein (hs-CRP) levels of these subgroups were compared. Serum PTX3 (p=0.013), hs-CRP (p=0.015) and HOMA-IR (p=0.023) levels of PCOS patients were significantly higher than the control group. Serum PTX3 has been found to have negative correlations with BMI (r=-0.318, p < 0.001), waist circumference (r=-0.306, p < 0.001), HOMA-IR (r=-0.324, p < 0.001) and hs-CRP (r=-0.206, p=0.031). Subgroup analysis revealed PCOS women with obesity to have significantly higher serum PTX3 level than non-obese PCOS subjects (p=0.012), non-obese controls (p=0.015) and obese controls (p=0.002). Women with new diagnosed PCOS especially obese subjects had significantly lower serum PTX3 than the control group. PTX3 has been found to be negatively correlated with BMI and insulin resistance. Low PTX3 level may have a role in the etiology of PCOS and in the formation of atherosclerotic diseases by stimulation of chronic inflammation.
- Hyperandrogenism and phenotypes of polycystic ovary syndrome are not associated with differences in obstetric outcomes. [JOURNAL ARTICLE]
- Acta Obstet Gynecol Scand 2014 Nov 21.
To investigate obstetric outcomes in Danish women with different phenotypes of polycystic ovary syndrome (PCOS) and isolated hyperandrogenism (HA) and describe the risk of adverse obstetric outcomes in women with PCOS and HA compared to controls.Cohort study.Odense University Hospital, Denmark.Women with PCOS were identified prospectively since 1997. Singleton pregnancies in women with PCOS and HA during 2003-2011 were included (n=199). A control group was matched to the patient cohort according to date of childbirth (n= 995).Data on clinical characteristics and obstetric outcomes were collected in patients with PCOS and HA and controls. In PCOS and HA, total and free testosterone, sex hormone binding globulin, and hemoglobin A1c were measured outside pregnancy. During pregnancy, oral glucose tolerance tests were performed in 39 patients and 123 controls according to Danish national guidelines. PCOS phenotypes were based on the Rotterdam criteria.Gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, delivery by emergency cesarean section, preterm delivery and anthropometric measures in the newborn.The incidence of adverse obstetric outcomes and anthropometric measures among the newborns were comparable between different phenotypes of PCOS and patients with HA. During oral glucose tolerance test, patients had higher risk of gestational diabetes mellitus compared to controls; odds ratio (95% confidence interval) 3.3 (1.5-6.9) after adjustment for age, parity, and body mass index (p = 0.002). The incidence of other adverse obstetric outcomes was similar in patients vs. controls.Obstetric outcomes were comparable between different PCOS phenotypes. This article is protected by copyright. All rights reserved.
- Peculiarities of sexual development and reproductive function in young women with childhood onset weight problems. [Journal Article]
- Georgian Med News 2014 Oct; (235):11-6.
The risks of reproductive problems are higher in underweight and overweight or obese women, especially in case of rapid weight gain or loss. But evidence is inconsistent especially in relation to the effect of age of body weight changes. The aim of the study was detection of peculiarities of sexual development and reproductive function in underweight and overweight/obese females with childhood thinness or childhood obesity. 103 young females (48 - with low BMI, 55 - with high BMI) with different reproductive problems were examined prospectively. In all investigated patients full clinical examination was held, including body mass index (BMI), type of body fat distribution (waist-to-hip ratio), age of body weight changes, assessment of hirsutism, acne, stretch marks and hyperpigmentation, menstrual disturbances and fertility problems were recorded and gynecological ultrasound was performed. There was no difference established according to the age of menarche and types of menstrual disturbances between the groups of low BMI and high BMI females (p>.05). The correlation was established between the onset of menstrual disruption and progression of changes in body mass (R=.448, p=.005). Hirsutism, stretch marks and acantosis nigricans (hyperpigmentation) were exhibited significantly more frequently in the patients with high BMI (p<.05), whilst distribution of acne was almost the same in the study groups (p>.05). 74.5% of overweight and obese patients had upper body fat distribution (waist-to-hip ratio > 0.8), whilst underweight patients had mostly equal (66.7%) or lower body fat distribution (31.3%) (p=.000). Polycystic ovarian syndrome (PCOS) and metabolic syndrome (MS) was the most frequent in overweight and obese patients, whilst non-classical congenital adrenal hyperplasia (NCAH) and ovarian dysfunction prevailed in the underweight females (p<.05). Infertility was mostly observed in patients with high BMI (p<.05). In conclusion, the peculiarities of sexual development and menstrual function in young females with childhood thinness and obesity are related to their reproductive disorders, childhood BMI and progression of BMI changes.
- Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol. [JOURNAL ARTICLE]
- Arch Gynecol Obstet 2014 Nov 22.
To evaluate the effects of D-Chiro-Inositol in women affected by polycystic ovary syndrome (PCOS).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.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.D-Chiro-Inositol is effective in improving ovarian function and metabolism of patients affected by PCOS.