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Polycystic Ovarian Syndrome [keywords]
- Enhanced insulin sensitivity and acute regulation of metabolic genes and signaling pathways after a single electrical or manual acupuncture session in female insulin-resistant rats. [JOURNAL ARTICLE]
- Acta Diabetol 2014 Sep 14.
To compare the effect of a single session of acupuncture with either low-frequency electrical or manual stimulation on insulin sensitivity and molecular pathways in the insulin-resistant dihydrotestosterone-induced rat polycystic ovary syndrome (PCOS) model. Both stimulations cause activation of afferent nerve fibers. In addition, electrical stimulation causes muscle contractions, enabling us to differentiate changes induced by activation of sensory afferents from contraction-induced changes.Control and PCOS rats were divided into no-stimulation, manual-, and electrical stimulation groups and insulin sensitivity was measured by euglycemic hyperinsulinemic clamp. Manually stimulated needles were rotated 180° ten times every 5 min, or low-frequency electrical stimulation was applied to evoke muscle twitches for 45 min. Gene and protein expression were analyzed by real-time PCR and Western blot.The glucose infusion rate (GIR) was lower in PCOS rats than in controls. Electrical stimulation was superior to manual stimulation during treatment but both methods increased GIR to the same extent in the post-stimulation period. Electrical stimulation decreased mRNA expression of Adipor2, Adrb1, Fndc5, Erk2, and Tfam in soleus muscle and increased ovarian Adrb2 and Pdf. Manual stimulation decreased ovarian mRNA expression of Erk2 and Sdnd. Electrical stimulation increased phosphorylated ERK levels in soleus muscle.One acupuncture session with electrical stimulation improves insulin sensitivity and modulates skeletal muscle gene and protein expression more than manual stimulation. Although electrical stimulation is superior to manual in enhancing insulin sensitivity during stimulation, they are equally effective after stimulation indicating that it is activation of sensory afferents rather than muscle contraction per se leading to the observed changes.
- Two follicle-stimulating hormone receptor polymorphisms and polycystic ovary syndrome risk: a meta-analysis. [REVIEW]
- Eur J Obstet Gynecol Reprod Biol 2014 Aug 15.:27-32.
The aim of this study was to explore the association between follicle stimulating hormone receptor (FSHR) Thr307Ala and Asn680Ser polymorphisms and susceptibility to polycystic ovary syndrome (PCOS). A comprehensive literature search for relevant studies was conducted on Google Scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Ten case-control studies were included in this meta-analysis. However, meta-analysis results showed no association between both FSHR Thr307Ala polymorphism and Asn680Ser polymorphism and susceptibility to PCOS. Stratified analysis of ethnicities also showed no association. In conclusion, the present study suggested that the FSHR polymorphisms were not associated with an increased risk of PCOS and larger-scale studies of populations are needed to explore the roles played by FSHR polymorphisms during the pathogenesis of PCOS.
- FTO Gene Variants Are Associated with PCOS Susceptibility and Hyperandrogenemia in Young Korean Women. [Journal Article]
- Diabetes Metab J 2014 Aug; 38(4):302-10.
The fat mass and obesity-associated (FTO) gene is associated with obesity and type 2 diabetes mellitus. Obesity and insulin resistance are also common features of polycystic ovary syndrome (PCOS). Therefore, the FTO gene might be a candidate gene for PCOS susceptibility. The aim of the present study was to evaluate the effects of FTO gene variants on PCOS susceptibility and metabolic and reproductive hormonal parameters.We recruited 432 women with PCOS (24±5 years) and 927 healthy women with regular menstrual cycles (27±5 years) and performed a case-control association study. We genotyped the single nucleotide polymorphisms rs1421085, rs17817449, and rs8050136 in the FTO gene and collected metabolic and hormonal measurements.Logistic regression revealed that the G/G genotype (rs1421085, 1.6%), the C/C genotype (rs17817449, 1.6%), and the A/A genotype (rs8050136, 1.6%) were strongly associated with an increased risk of PCOS (odds ratio, 2.551 to 2.559; all P<0.05). The strengths of these associations were attenuated after adjusting for age and BMI. The women with these genotypes were more obese and exhibited higher free androgen indices (P<0.05) and higher free testosterone levels (P=0.053 to 0.063) compared to the other genotypes. However the significant differences disappeared after adjusting for body mass index (BMI). When we analyzed the women with PCOS and the control groups separately, there were no significant differences in the metabolic and reproductive hormonal parameters according to the FTO gene variants.The rs1421085, rs17817449, and rs8050136 variants of the FTO gene were associated with PCOS susceptibility and hyperandrogenemia in young Korean women. These associations may be mediated through an effect of BMI.
- Excess of Nerve Growth Factor in the Ovary Causes a Polycystic Ovary-Like Syndrome in Mice, which Closely Resembles Both Reproductive and Metabolic Aspects of the Human Syndrome. [JOURNAL ARTICLE]
- Endocrinology 2014 Sep 11.:en20141368.
Polycystic ovarian syndrome (PCOS), the most common female endocrine disorder of unknown etiology, is characterized by reproductive abnormalities and associated metabolic conditions comprising insulin resistance, type 2 diabetes mellitus, and dyslipidemia. We previously reported that transgenic overexpression of nerve growth factor (NGF), a marker of sympathetic hyperactivity, directed to the ovary by the mouse 17α-hydroxylase/C17-20 lyase promoter (17NF) mice, results in ovarian abnormalities similar to those seen in PCOS women. To investigate whether ovarian overproduction of NGF also induces common metabolic alterations of PCOS, we assessed glucose homeostasis by glucose tolerance test, plasma insulin levels, and body composition by dual-energy x-ray absorptiometry scan in young female 17NF mice and wild-type mice. 17NF mice exhibited increased body weight and alterations in body fat distribution with a greater accumulation of visceral fat compared with sc fat (P < .01). 17NF mice also displayed glucose intolerance (P < .01), decreased insulin-mediated glucose disposal (P < .01), and hyperinsulinemia (P < .05), which, similar to PCOS patients, occurred independently of body weight. Additionally, 17NF mice exhibited increased sympathetic outflow observed as increased 24 hours of interscapular brown adipose tissue temperature. This change was evident during the dark period (7 pm to 7 am) and occurred concomitant with increased interscapular brown adipose tissue uncoupling protein 1 expression. These findings suggest that overexpression of NGF in the ovary may suffice to cause both reproductive and metabolic alterations characteristic of PCOS and support the hypothesis that sympathetic hyperactivity may contribute to the development and/or progression of PCOS.
- Polycystic ovary syndrome and chronic autoimmune thyroiditis. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Sep 11.:1-4.
Abstract Introduction: Polycystic ovary syndrome (PCOS) has been associated with an autoimmune origin, either per se or favoring the onset of autoimmune diseases, from a stimulatory action on the inflammatory response. Thus, autoimmune thyroiditis (AIT) could be more prevalent among women with PCOS. Objective: To evaluate the prevalence of AIT in women with PCOS. Study design: It was a cross-sectional study, in a tertiary center, including 65 women with PCOS and 65 women without this condition. Clinical and laboratory parameters were evaluated and a thyroid ultrasound scan was performed. Levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase (anti-TPO) antibodies, anti-thyroglobulin (anti-TG) antibodies, and thyroid ultrasound findings were evaluated. Results: The prevalence of subclinical hypothyroidism (SCH) in women with PCOS was 16.9% and 6.2% in the non-PCOS group. AIT was more common in the PCOS group compared with the non-PCOS group (43.1% versus 26.2%). But, when it was adjusted by weight and insulin resistance, the difference in the thyroiditis risk was not observed (OR 0.78, CI 0.28-2.16). Conclusion: AIT risk was similar in the PCOS and the non-PCOS group. SCH are more common in women with PCOS, highlighting a need for periodic monitoring of thyroid function.
- Obesity, insulin resistance and comorbidities ? Mechanisms of association. [Journal Article]
- Arq Bras Endocrinol Metabol 2014 Aug; 58(6):600-9.
Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. Arq Bras Endocrinol Metab. 2014;58(6):600-9.
- Immunohistochemical evaluation of proliferation, apoptosis and steroidogenic enzymes in the ovary of rats with polycystic ovary. [Journal Article]
- Rev Assoc Med Bras 2014 Jul; 60(4):349-56.
to evaluate the immunohistochemical expression of proliferative, apoptotic and steroidogenic enzyme markers in the ovaries of rats with polycystic ovary syndrome (PCOS).twenty rats were divided into two groups: GCtrl - estrous phase, and PCOS - with polycystic ovaries. The GCtrl animals were subjected to a lighting period from 7 am to 7 pm, while the animals with PCOS group remained with continuous lighting for 60 days. Subsequently, the animals were anesthetized, the ovaries were removed and fixed in 10% formaldehyde, prior to paraffin embedding. Sections were stained using H.E. or subjected to immunohistochemical methods for the detection of Ki-67, cleaved caspase-3, CYP11A1, CYP17A1 and CYP19A1. The results were analyzed using Student's t-test (p < 0,05).morphological results showed evidence of interstitial cells originating from the inner theca cells of degenerating ovarian cysts in PCOS. Immunoexpression of Ki-67 was higher in the granulosa cells in GCtrl, and the theca interna cells in PCOS, while cleaved caspase-3 was higher in granulosa cells of ovarian cysts from PCOS and in the theca interna cells of GCtrl. Immunoreactivity of CYP11A1 in the theca interna, granulosa and interstitial cells was similar between the two groups, while CYP17A1 and CYP19A1 were higher in the granulosa and interstitial cells in the PCOS group.the results indicate that the interstitial cells are derived from the theca interna and that enzymatic changes occur in the theca interna and interstitial cells in ovaries of rats with PCOS, responsible for the high levels of androgens and estradiol.
- Predictors of depression in women with polycystic ovary syndrome. [JOURNAL ARTICLE]
- Arch Womens Ment Health 2014 Sep 11.
The aim of this study is to assess the prevalence and predictors of depressive symptoms in women with polycystic ovary syndrome (PCOS). In a cross-sectional study of 114 women seeking consultation for symptoms of PCOS (menstrual irregularity, hirsutism, and/or acne), personal and family history of depression (HD and FHD respectively) were enquired. Vitamin D status (n = 104) and manifest depressive symptoms assessed by personal health questionnaire (PHQ) (MD) were evaluated in a subset (85). Relationships between HD and MD with PCOS symptoms, FHD, and vitamin D status were assessed using adjusted analyses. Thirty-five percent acknowledged a HD; MD (PHQ > 4) was apparent in 43 %. HD was associated with hirsutism (OR 2.4, 95 % CI 1.01-5.9), disturbed sleep (OR 3.0, 95 % CI 1.3-6.9), and with FHD (OR 4.8, 95 % CI 1.7-13.5). Disturbed sleep (OR 2.4, 95 % CI 1.01-5.7) and FHD (OR 3.8, 95 % CI 1.3-11.2) were independent predictors of HD adjusting for race and BMI. An inverse correlation was noted between serum 25 OH vitamin D (25OHD) levels and PHQ score, but only in those with vitamin D deficiency (25OHD ≤ 30 ng/ml, n = 57, r =-0.32, p = 0.015). 25OHD < 20 ng/ml (OR 3.5, 95 % CI 1.1-11.8) and HD (OR 12.8, 95 % CI 3.6-45.2) predicted scoring in the highest PHQ tertile after adjusting for hirsutism, BMI, and race. In women with PCOS, disturbed nocturnal sleep and FDH predicted personal HD, whereas HD and vitamin D deficiency related to the severity of MD symptoms.
- Afamin serum concentrations are associated with insulin resistance and metabolic syndrome in polycystic ovary syndrome. [JOURNAL ARTICLE]
- Reprod Biol Endocrinol 2014 Sep 10; 12(1):88.
High plasma concentrations of the vitamin E-binding protein afamin have been previously shown to be associated with insulin resistance and metabolic syndrome. We set out to determine whether the concentration of afamin in the serum of women with polycystic ovarian syndrome (PCOS) is elevated in relation to the presence and severity of insulin resistance (IR).This cross-sectional study looked at 53 patients with PCOS and 49 non-PCOS patients. IR was diagnosed as a HOMA Index >2.4 and confirmed with a three-hour glucose tolerance test. Serum concentrations of afamin were determined using enzyme-linked immunosorbent assay (ELISA). Clinical characteristics, hormone and metabolic parameters were correlated to afamin concentrations.Serum concentrations of afamin did not differ between women with PCOS and controls. When separated according to the presence of IR a significant difference in median afamin levels was seen between PCOS with IR and PCOS without IR (73.06+/-27.36 mg/L and 64.25+/-17.41 mg/L, p = 0.033). No difference in afamin levels was detected when comparing the few controls with IR and the controls without IR (76.20+/-27.96 mg/L and 60.44+/-21.03 mg/L, p = 0.235). On univariate analyses, afamin serum concentrations significantly correlated with BMI, triglycerides, HOMA Index, and AUC-Insulin. On multivariate linear regression analysis, only triglyceride concentration was seen to be an independent predictor of afamin. Subjects with metabolic syndrome had higher median afamin concentrations than did those without metabolic syndrome (77.43+/-28.60 mg/L and 65.08+/-18.03 mg/L, p = 0.010).Elevated afamin concentrations are associated with the presence of metabolic syndrome in young women and may potentially serve as an independent predictor for the development of metabolic syndrome in at-risk women, especially those with IR.
- Association of CYP17A1 gene -34T/C polymorphism with polycystic ovary syndrome in Han Chinese population. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Sep 10.:1-4.
Abstract Purpose: To investigate the influence of the cytochrome P450 17α (CYP17A1) gene -34T/C polymorphism in the pathogenesis of polycystic ovary syndrome (PCOS) in Han Chinese population. Methods: Three-hundred eighteen patients with PCOS and 306 controls were recruited and the CYP17A1 -34T/C polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Furthermore, the relationship of CYP17A1 -34T/C polymorphism and clinical feature parameters of PCOS patients was also analyzed. Results: The prevalence rates of CYP17A1 genotype TT, TC and CC were 49.69%, 43.71% and 6.6% in the case group and those were 44.77%, 46.08% and 9.15% in the control group. The frequencies of CYP17A1 T and C alleles were 71.54% and 28.46% in the case group, and those were 67.81% and 32.19% in the control group. Neither the genotypic nor the allelic distribution was significantly different between the cases and controls. However, the PCOS patients with the genotype of CC had significantly higher total testosterone levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) than those with the genotype of TT or TC. Conclusions: The CYP17A1 gene -34T/C polymorphism might not be directly correlated with the PCOS, but might influence PCOS via the association of testosterone level and the HOMA-IR.