... Health Topics > Polycystic ovary syndrome Polycystic ovary syndrome Polycystic ovary syndrome Polycystic ovary syndrome (PCOS) is a health problem ... of infertility. Expand all | Collapse all What is polycystic ovary syndrome (PCOS)? Polycystic (pah-lee-SIS-tik) ovary syndrome ( ...
f AQ FREQUENTLY ASKED QUESTIONS FAQ121 GYNECOLOGIC PROBLEMS Polycystic Ovary Syndrome (PCOS) • What are common signs and symptoms of polycystic ovary syndrome (PCOS)? • What causes PCOS? • What is insulin resistance? • ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Polycystic Ovary Syndrome KidsHealth > For Teens > Polycystic Ovary Syndrome A A ... condition called polycystic ovary sydrome (PCOS) . What Is Polycystic Ovary Syndrome? Polycystic (pronounced: pol-ee-SISS-tik) ovary syndrome ...
Viswanathan, Lakshminarayanapuram G.; Satishchandra, Parthasarathy; Bhimani, Bipin C.; Reddy, Janardhan YC; Rama Murthy, Batchu S.; Subbakrishna, Doddaballapura K.; Sinha, Sanjib
Objective: This study aims to discuss the prevalence of polycystic ovary (PCO) and Polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) on valproate (VPA), carbamazepine (CBZ), or phenobarbitone (PB), drug naive WWE and women with bipolar affective disorder (BPAD) on VPA. Materials and Methods: This prospective study included 190 women aged 18–45 years, who had epilepsy or BPAD (on VPA), and consented for study. Patients were grouped as Group 1 (n = 40): WWE on VPA, Group 2 (n = 50): WWE on CBZ, Group 3 (n = 50): WWE on PB, Group 4 (n = 30): drug naïve WWE, and Group 5 (n = 20): women with BPAD on VPA. All women were interviewed for medical, menstrual, drug and treatment history, nature of epilepsy, and seizure control. Chi-square test and Fisher's exact test were done to compare results between the groups. Results: Fifty-two women (52/190; 27.4%) had menstrual disturbances, in which oligomenorrhea was the most common (55.8%). There was a significant difference in the occurrence of PCOS in patients on VPA versus normal population (P = 0.05) and patients on other antiepileptic drugs (AEDs) (P = 0.02). There was, however, no significant difference in the occurrence of PCO between patients on VPA and the untreated epileptic women. VPA group (Epilepsy + BPAD) had a significantly higher occurrence of obesity than other treatment groups (P = 0.043, OR = 2.11). Conclusions: The study observed significantly higher occurrence of PCO in patients on VPA compared to other AEDs and the normal population. The importance of proper clinical evaluation before initiating VPA is highlighted. PMID:27570385
Kiyak Caglayan, Emel; Engin-Ustun, Yaprak; Gocmen, Ayse Yesim; Polat, Muhammet Fevzi; Aktulay, Ayla
Objective of the study is to determine the human nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 level in women with polycystic ovary syndrome (PCOS). This cross-sectional study included 24 patients aged 20-38 years, who were diagnosed to have PCOS (patient group). The control group included 16 age- and body mass index-matched healthy female volunteers. The patients and controls were compared in terms of pre-prandial blood glucose, the homoeostatic model assessment for insulin resistance (HOMA-IR) index, and cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein (CRP) and sirtuin 1 levels. The mean sirtuin 1 level in the patient group (6.67 ± 2.29 ng mL(-1)) was significantly higher than that in the control group (4.69 ± 1.85 ng mL(-1)) (P = 0.007). Correlation analysis showed that there were no significant differences between the groups in fasting blood glucose, HOMA-IR index or cholesterol, triglyceride, HD, LDL and CRP levels. The sirtuin 1 level, which is associated with inflammation, the immune system and insulin metabolism, was higher in the PCOS patients than in the healthy controls.
Tirgar-Tabari, Soudabeh; Sharbatdaran, Majid; Manafi-Afkham, Sara; Montazeri, Mohammad
Background: Hirsutism is one of the most important diseases that lead women to refer to dermatology clinic. Hyperprolactinemia is one of the causes of hirsutism. The aim of this study was to determine prolactin (PRL) levels in hirsute women. Materials and Methods: In this cross-sectional study, hirsute patients were evaluated. For all of the patients, 2 or 3 days after mense starting, hormone level tests were performed, and 200 patients that had not polycystic ovary syndrome enrolled to the study. A questionnaire of history and physical examination were performed. Data have been analyzed with SPSS version 21. Results: Hyperprolactinemia were seen in 25 patients (12.5%). There was no significant relation between marital statuses, galactorrhoea, positive family history, and infertility with hyperprolactinemia. But significant relation was seen between irregular mense and hyperprolactinemia. Conclusion: Although hyperprolactinemia is the rare cause of hirsutism, the prevalence of hyperprolactinemia was high in our study. Thus, PRL level in hirsute patients should be evaluate. PMID:27625565
Jayasena, Channa N; Franks, Stephen
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. The syndrome is typified by its heterogeneous presentation, which includes hirsutism (a function of hypersecretion of ovarian androgens), menstrual irregularity and infertility (that is due to infrequent or absent ovulation). Furthermore, PCOS predisposes patients to metabolic dysfunction and an increased risk of type 2 diabetes mellitus (T2DM). The aetiology of the syndrome has a major genetic component. Obesity exacerbates the insulin resistance that is a feature of PCOS in many women and amplifies the clinical and biochemical abnormalities. In clinical practice, the choice of investigations to be done depends mainly on the presenting symptoms. The approach to management is likewise dependent on the presenting complaint. Symptoms of androgen excess (hirsutism, acne and alopecia) require cosmetic measures, suppression of ovarian androgen function and anti-androgen therapy, alone or in combination. Ovulation rate is improved by diet and lifestyle intervention in overweight individuals but induction of ovulation by, in the first instance, anti-estrogens is usually required. Monitoring of glucose is important in overweight women and/or those with a family history of T2DM. Metformin is indicated for women with impaired glucose tolerance but whether this drug is otherwise useful in women with PCOS remains debatable.
BALIKCI, Adem; ERDEM, Murat; KESKIN, Uğur; BOZKURT ZINCIR, Selma; GÜLSÜN, Murat; ÖZÇELIK, Fatih; AKGÜL, Emin Özgür; AKARSU, Süleyman; ÖZTOSUN, Muzaffer; ERGÜN, Ali
Introduction Polycystic Ovary Syndrome (PCOS) is a syndrome of heterogeneous nature, affecting multiple systems, particularly the endocrine system. We propose to investigate the possible relationships among hormonal changes, levels of anxiety, depression, and anger in patients with PCOS. Method Forty-four female patients with PCOS and 44 body mass index (BMI )-matched healthy women participated in this study. We measured the sociodemographic features, some serum hormonal levels (insulin, gonadotropins, prolactin, dehydroepiandrosterone sulfate (DHEAS), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), 17 OH-progesterone, and total and free testosterone), and some other biochemical parameters of the participants. Also, all participants completed the Trait Anger-Anger Expression Scale (STAS), Beck Depression, and Beck Anxiety Inventories. We evaluated the psychiatric scale scores obtained from PCOS patients and control subjects. We used the independent-samples t-test for parametric data to evaluate normal distribution, and Mann-Whitney U-test was used for both abnormally distributed and nonparametric data. We used Pearson correlation analysis to evaluate the potential connection between the two groups’ data. Results The mean ages of the patients with PCOS and control subjects who participated in this study were 27.3±5.6 and 27.4±6.1 years, respectively. The measures of BMI, insulin, luteinizing hormone (LH), DHEAS, and total testosterone serum levels in the patient group were significantly higher than in the control group (p<.05). There was a statistically significant positive correlation between Beck anxiety scores and serum DHEAS levels (Pearson r=.4366, P=.0001). We found significant differences between the two groups in terms of trait anger, anger control, outward and inward anger, anxiety level, and depression scores (P<.05). Conclusion Anxiety symptoms indicate a stronger relationship compared to depression with DHEAS serum levels
Dewailly, D; Hieronimus, S; Mirakian, P; Hugues, J-N
1. The Rotterdam classification should be used to define PCOS in the event of: menstrual cycle anomalies; amenorrhoea, oligomenorrhoea or long cycles, clinical and/or biochemical hyperandrogenism and ultrasound appearance of polycystic ovaries. 2. The presence of two of these three criteria is sufficient once all other diagnoses have been ruled out. 3. Diagnosis of hirsutism should not be based on the Ferriman-Gallway score. 4. The ultrasound definition of PCOS contains precise criteria that must be included in the report: presence of at least 12 follicles in each ovary measuring 2-9 mm in diameter, and/or increase in ovary size>10 ml. 5. Screening for elevated plasma LH no longer necessary. Testing for GnRH serves no purpose. 6. Routine screening for metabolic abnormalities should be carried out systematically based on weight, height and BMI, waist circumference, blood pressure and laboratory parameters: plasma glucose, triglycerides, HDL cholesterol. 7. In the case of obesity (BMI>30 kg/m(2)), oral glucose tolerance testing (OGTT) is recommended where fasting serum glucose is normal. 8. Clomiphene citrate (CC) remains the first-line therapy for ovulation induction. In patients with BMI>30, it should be preceded by improvement of metabolic status through appropriate lifestyle modifications.
McCormick, Betsy A; Wilburn, Rochelle D; Thomas, Michael A; Williams, Daniel B; Maxwell, Rose; Aubuchon, Mira
Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10).
Norman, Robert J; Wu, Ruijin; Stankiewicz, Marcin T
Polycystic ovary syndrome (PCOS) is a common condition characterised by menstrual abnormalities and clinical or biochemical features of hyperandrogenism. Features of PCOS may manifest at any age, ranging from childhood (premature puberty), teenage years (hirsutism, menstrual abnormalities), early adulthood and middle life (infertility, glucose intolerance) to later life (diabetes mellitus and cardiovascular disease). While pelvic ultrasound examination is useful, many women without PCOS have polycystic ovaries; ultrasound evidence is not necessary for the diagnosis. Testing for glucose intolerance and hyperlipidaemia is wise, especially in obese women, as diabetes mellitus is common in PCOS. Lifestyle changes as recommended in diabetes are fundamental for treatment; addition of insulin-sensitising agents (eg, metformin) may be valuable in circumstances such as anovulatory infertility. Infertility can be treated successfully in most women by diet and exercise, clomiphene citrate with or without metformin, ovarian drilling, or ovulation induction with gonadotrophins; in-vitro fertilisation should be avoided unless there are other indications.
Mortada, Rami; Williams, Tracy
Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy.
Chuan, Sandy S; Chang, R Jeffrey
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. It is typically characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. Women with PCOS often experience dermatologic manifestations of hyperandrogenism, including hirsutism, acne vulgaris, and androgenic alopecia. This article will review the treatments for acne due to androgen excess in PCOS women.
Belosi, C; Giuliani, M; Suriano, R; Sagnella, F; Lanzone, A
Polycystic ovary syndrome (PCOS) is the most common endocrine disorders among women in reproductive age, but diagnostic criteria used in clinical practice are still controversial. In 1990 the National Institute of HEALTH (NIH) conference on PCOS recommended that diagnostic criteria should include biochemical evidence of hyperandrogenism and ovarian dysfunction (in the absence of non-classical adrenal hyperplasia) without considering the morphological diagnosis of polycystic ovary by ultrasound as an essential part of the diagnosis. In the Rotterdam PCOS workshop of May 2003, however, PCOS is diagnosed when 2 of the following criteria are recognized: oligomenorrhea and/or anovulation, clinical or biochemical signs of hyperandrogenism, ultrasound findings of polycystic ovary. Further-more, it is underlined that the metabolic study is not necessary for PCOS diagnosis, while it is suggested for "at risk patients" (obesity, diabetes, familiar and obstetrical history) with an oral glucose tolerance test (OGTT). A recent study carried out by our group underlined the role of ultrasound parameter, in particular suggesting a ratio between ovarian stroma area and total area of the ovarian section (S/A), with a cut-off of 0.34, as "gold parameter" for PCOS diagnosis, because it shows high sensitivity and specificity (96.3%, 97.0% for the S/A).
Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy, affecting 5-10% of the female population. It involves overproduction of ovarian androgens leading to a heterogeneous range of symptoms including hirsutism, acne, anovulation and infertility. Hyperinsulinaemia, exacerbated by obesity, is often a key feature. Treatment depends on the presenting symptoms, which may often be ameliorated by weight loss where relevant. Anti-androgen preparations are used for hyperandrogenic symptoms, and clomiphene citrate (CC) is the first-line treatment for anovulation and infertility. Aromatase inhibitors are being investigated as an alternative to CC. Failure to conceive with CC can be treated in a number of ways, including the addition of insulin-lowering agents (mainly metformin), low-dose gonadotrophin therapy or surgically by laparoscopic ovarian drilling. Although the exact aetiology of PCOS is not known, the therapeutic alternatives provide reasonably successful symptomatic treatment.
Kong, Wen; Niu, Xun; Zeng, Tianshu; Lu, Meixia; Chen, Lulu
Background Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported. To provide high-quality evidence about the effect of metformin treatment on adipocytokines in patients with polycystic ovary syndrome, relevant studies that assessed the levels of adipocytokines (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving treatment with metformin administration were reviewed and analyzed. Methods A literature search was conducted in the SCI, PUBMED, EMBASE, and Elsevier databases, and personal contact was made with the authors. Standard mean differences and 95% confidence intervals were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. Results A total of 34 data sets were included in 4 different outcomes, involving 744 women with polycystic ovary syndrome and adipocytokine levels measured both before and after metformin administration. Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], −0.43 [−0.75 to −0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (−0.01 [−0.49 to 0.45]) or visfatin level (−0.04 [−1.55 to 1.46]) was found. Conclusions Metformin administration was associated with increased serum adiponectin concentrations and decreased serum leptin levels. Further study is needed to elucidate whether this apparent effect decreases the incidence of type 2 diabetes and other metabolic diseases in patients with polycystic ovary syndrome later in life. PMID:26473366
Whitaker, Kristin Nadine
Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. It affects 6% to 7% of the population and is characterized by hyperandrogenism and ovarian dysfunction. Women with the disorder often present with insulin resistance and obesity, making it importance for health care providers to monitor closely for signs and symptoms of metabolic syndrome and type 2 diabetes. Treatments are targeted toward improving insulin tolerance, reducing signs and symptoms of hyperandrogenism (hirsutism, anovulation, etc), restoring normal menstrual cycle function, and restoring fertility. Major treatment should include weight management through diet and exercise, regardless of body mass index and might include concurrent drug therapy. It is important that pharmacists understand the underlying pathophysiology of the disease and the available treatments, in addition to the importance of reducing risk of metabolic syndrome/type 2 diabetes, and cardiovascular disease in these patients.
Kolahi, Leila; Asemi, Neda; Mirzaei, Mohammadreza; Adibi, Neda; Beiraghdar, Mina; Mehr, Asieh Maghami
Background: There are many factors that affect the quality of life, for example, stress and the coping strategies. Polycystic ovary syndrome is a common hormonal disorder leading to menstrual disorders, hirsutism, acne, obesity, infertility and abortion. In such cases, the patients suffer from a variety of stresses and face problems in their coping strategies with life's problems which can affect the quality of life and cause psychological distress and low the quality of life. The quality of life is a descriptive term which points to health and emotional, social and physical promotion of individuals as well as their ability to perform daily living tasks. The purpose of this study was to investigate the relationship between quality of life and coping strategies in patients with polycystic ovary syndrome. Materials and Methods: To perform this study, randomly 200 women who had inclusion criteria and were referred to Ali Shariati Hospital in Isfahan were selected and responded DLQI questionnaire and Carver coping strategies and form of demographic characteristics. Results: The mean score of quality of life in the patients was 4.14 ± 5.57. It was shown that acne has no effective role on quality of life and coping strategies in contrast in hirsute and non-hirsute patients; there was a significant difference in quality of life P value < 0.001). Also there is a significant relationship between the quality of life and coping strategies (problem solving, cognitive, emotional and social support) (P < 0.05) and quality of life has the highest correlation with emotional strategies (r = 0.46). Conclusion: According to results of this study, patients with PCOS are at risk pcychologicla disorders that may be led to decrease of quality of life. Thus this patients need to support by oppositions strategies. Also not only physical treatment but also psychological surveillance especially social support must be done for them. PMID:26436082
Long, Xiaoyu; Li, Rong; Yang, Yan; Qiao, Jie
Women with polycystic ovary syndrome (PCOS) exhibit low implantation rate and high abortion rate. To explore the effect of low-grade chronic inflammation on endometrium of women with PCOS, we investigated the expression of interleukin 18 (IL-18) in the endometrium of 23 women with PCOS and 20 healthy women. Endometrial tissue samples were obtained during hysteroscopic surgery. We found that IL-18 was significantly increased in the endometrium of women with PCOS compared with normal groups. In overweight women, IL-18 was obviously overexpressed in the PCOS group compared to the healthy group. However, in normal-weight women, there was no statistically significant difference between the 2 groups, and there was no significant difference in IL-18 expression in patients having PCOS with or without insulin resistance. We conclude that IL-18 protein and messenger RNA levels are increased in the endometrium of patients with PCOS, and this effect is correlated with body mass index.
... ovaries that contain small collections of fluid — called follicles — located in each ovary as seen during an ultrasound exam. Infrequent or prolonged menstrual periods, excess hair growth, acne, and obesity can all occur in ...
Yildiz, Yunus; Ozaksit, Gülnur; Serdar Unlu, Bekir; Ozgu, Emre; Energin, Hasan; Kaba, Metin; Ugur, Mustafa
Background: To investigate the relationship between adiponectin, metabolic and hor- monal parameters, and insulin resistance in patients with non-treated polycystic ovary syndrome. Materials and Methods: In this cross-sectional observational study, 81 patients admitted to out-patient clinic with complaints of menstrual irregularity, hirsutism and obesity were enrolled. Serum adiponectin, biochemical and hormonal parameters, and 75 gram oral glu- cose tolerance test (OGTT) were measured. Spearman’s correlation coefficient was used for statistical analysis. Results: We observed inverse correlations between serum adiponectin level and body mass index, homeostasis model assessment insulin-resistance score, insulin level, fast- ing glucose level, and prolactin level (p=0.001, p=0.02, p=0.04, p=0.02, and p=0.005, respectively). No significant correlations were found between serum adiponectin level and age, height, weight, Ferriman-Gallwey score, 2 hours OGTT test value and free tes- tosterone level (p=0.3, p=0.6, p=0.2, p=0.8, p=0.9, and p=0.01, respectively). Conclusion: The present study demonstrated that in polycystic ovary syndrome patients, when serum adiponectin level decreased, degree of insulin resistance increased. Our find- ings indicate that serum adiponectin level is likely to be an adequate marker for deter- mination of the degree of insulin resistance, and may be a predictor of diseases, such as type 2 diabetes mellitus (T2DM) and metabolic syndrome, which develop on the basis of insulin resistance. PMID:24520503
Emekçi Özay, Özlen; Özay, Ali Cenk; Çağlıyan, Erkan; Okyay, Recep Emre; Gülekli, Bülent
Objectıve: The aim of the study is to investigate the effect of myo-inositol (MYO) on pregnancy rates of patients diagnosed with polycystic ovary syndrome (PCOS) who undergone controlled ovulation induction and intrauterine insemination (IUI).
Zahra, M; Shah, M; Ali, A; Rahim, R
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.
Sang, Qing; Zhang, Shaozhen; Zou, Shien; Wang, Huan; Feng, Ruizhi; Li, Qiaoli; Jin, Li; He, Lin; Xing, Qinghe; Wang, Lei
Epigenetic mechanisms may contribute to polycystic ovary syndrome (PCOS). To date, however, no studies have associated CpG methylation levels of any candidate gene with PCOS susceptibility. Follistatin (FST), an activin-binding protein, is expressed in numerous tissues and is shown to have linkage with PCOS. However, results from case-control association analyses between this gene and PCOS are inconsistent. Thus, this study investigated possible association of methylation levels in the promoter and 5'-untranscribed region (UTR) of the FST gene with PCOS incidence in peripheral blood leukocytes and endometrial tissue. Using mass array quantitative methylation analysis, first the 5'-UTR methylation in FST was analysed in 130 PCOS patients and 120 controls. The methylation level of the FST gene was further studied in endometrium from 24 controls and 24 PCOS patients. This study demonstrates that methylation levels of CpG sites in the FST promoter and 5'-UTR are not associated with PCOS. Nonetheless, this was the first study to quantitatively evaluate the methylation levels of a candidate gene in association with PCOS. Further studies should be performed to examine methylation in other candidate genes. Understanding the epigenetic mechanisms involved in PCOS may yield new insights into the pathophysiology of the disorder. Animal models demonstrate that epigenetic reprogramming may contribute to polycystic ovary syndrome (PCOS). To date, however, no studies have associated CpG methylation levels of any candidate gene with PCOS susceptibility. Follistatin (FST), an activin-binding protein, is expressed in numerous tissues and is a PCOS candidate gene. However, results from association analyses between this gene and PCOS are inconsistent. Thus, we investigated possible association of methylation levels in the promoter and 5'-UTR of the FST gene with PCOS incidence in peripheral blood leukocytes and endometrial tissue. Using mass array quantitative methylation analysis, we
Omran, Maha Yousef Soliman
The polycystic ovary syndrome (PCOS), one of the most common causes of infertility due to anovulation, affects 4–7% of women). Etiology of PCOS remains largely unknown, familial aggregation of cases suggests genetic susceptibility to the disorder. Though genes involved remain unknown, recent evidence points to a gene of the insulin receptor. Genes implicated in ovarian follicular development may also play a role. A fundamental aspect of the syndrome seems to be a defect in insulin metabolism. There is consistent evidence that increase of body weight may favour a more severe hyperandrogenism. Treatment of PCOS has been mostly symptomatic. Only recently has the use of insulinomimetic or insulin sensitizing agents provided an option to treat the presumed underlying cause of this disorder, which is insulin resistance. Metformin appears to improve risk factors for cardiovascular disease in diabetic and non-diabetic patients, indicating that its use could be associated with a reduction in coronary heart disease in patients with PCOS. The use of metformin in hyperinsulinemic women with PCOS improved the lipid profile, including decreases in total cholesterol, low density lipoprotein cholesterol, and triglyceride concentration. PMID:21475454
Eftekhar, Tahereh; Sohrabvand, Farnaz; Zabandan, Neda; Shariat, Mamak; Haghollahi, Fedyeh; Ghahghaei-Nezamabadi, Akram
Background: Polycystic Ovary Syndrome (PCOS) is presented with characteristic complications such as chronic an ovulation, obesity, and hyperandrogenism which can affect sexual function in women of reproductive age. Objective: Herein we evaluated the frequency and predisposing factors of sexual dysfunction in infertile PCOS patients. Materials and Methods: In this cross-sectional study, 130 married women with a definite diagnosis of PCOS who were referred due to infertility were recruited. They were evaluated concerning their sexual function in the domains of desire, arousal, lubrication, orgasm, satisfaction and pain with the female sexual function index (FSFI) questionnaire. Results: The frequency of sexual dysfunction was verified 57.7% in PCOS patients with the domains of desire and arousal being commonly affected in 99.2% and 98.5%of cases respectively. BMI had a significant effect on sexual desire and arousal (p=0.02) while the effect of hirsutism was significant on all domains (p<0.001 for total FSFI score) except for dyspareunia. Conclusion: PCOS patients markedly suffer from sexual dysfunction as comorbidity. It seems appropriate to screen all PCOS patients for sexual function with a simple short questionnaire such as FSFI. Targeted interventions could be considered to help improve their quality of life along with other treatments. PMID:25408703
Driscoll, Deborah A
Polycystic ovary syndrome (PCOS) is a relatively common disorder among adolescent women. The typical clinical features including menstrual irregularities and hirsutism are usually not apparent until middle to late adolescence. Yet studies suggest that PCOS may begin in early puberty. Young women with premature pubarche, a family history of PCOS, Caribbean Hispanic and African American ancestry, and/or obesity are more likely to develop PCOS. Adolescents with PCOS may have elevated total or free testosterone, androstenedione, and luteinizing hormone levels; insulin resistance; and hyperinsulinemia. The laboratory evaluation and management of the adolescent with suspected PCOS should be individualized on the basis of the clinical features and symptoms. The cornerstone of most treatment strategies includes either a combination oral contraceptive or progestin to decrease testosterone levels and regulate the menstrual cycle. Consideration of insulin-sensitizing agents, antiandrogens, topical treatments for acne and excess facial hair, and hair removal is dependent on the patient's symptoms and concerns. A healthy approach to eating, in some cases weight loss, and exercise is encouraged to reduce the risk of cardiovascular disease and type 2 diabetes mellitus. Management of the adolescent with PCOS is challenging and often requires a supportive, multidisciplinary team approach for optimal results.
Li, Li; Zhang, Jiangyu; Deng, Qingshan; Li, Jieming; Li, Zhengfen; Xiao, Yao; Hu, Shuiwang; Li, Tiantian; Tan, Qiuxiao; Li, Xiaofang; Luo, Bingshu; Mo, Hui
Objectives To identify differential protein expression pattern associated with polycystic ovary syndrome (PCOS). Methods Twenty women were recruited for the study, ten with PCOS as a test group and ten without PCOS as a control group. Differential in-gel electrophoresis (DIGE) analysis and mass spectroscopy were employed to identify proteins that were differentially expressed between the PCOS and normal ovaries. The differentially expressed proteins were further validated by western blot (WB) and immunohistochemistry (IHC). Results DIGE analysis revealed eighteen differentially expressed proteins in the PCOS ovaries of which thirteen were upregulated, and five downregulated. WB and IHC confirmed the differential expression of membrane-associated progesterone receptor component 1 (PGRMC1), retinol-binding protein 1 (RBP1), heat shock protein 90B1, calmodulin 1, annexin A6, and tropomyosin 2. Also, WB analysis revealed significantly (P<0.05) higher expression of PGRMC1 and RBP1 in PCOS ovaries as compared to the normal ovaries. The differential expression of the proteins was also validated by IHC. Conclusions The present study identified novel differentially expressed proteins in the ovarian tissues of women with PCOS that can serve as potential biomarkers for the diagnosis and development of novel therapeutics for the treatment of PCOS using molecular interventions. PMID:27846214
Espinós, Juan J; Calaf, Joaquim; Estadella, Josep; Checa, Miguel A
In a clinical series of 68 women with polycystic ovary syndrome in which the reason for consultation was hirsutism, the mean (standard error of the mean) hirsutism score of the modified Ferriman-Gallwey method was 15.1 (6.8), compared with 12.0 (4.4) for clinicians' scoring. In the multivariable analysis, clinicians' scoring of hirsutism was the only independent variable significantly associated with increased testosterone free index levels.
Qu, Qinglan; Zhao, Dongmei; Zhang, Fengrong; Bao, Hongchu; Yang, Qiuhua
Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.
To study and critically analyze the published evidence on correlation of hormonal abnormalities and endothelial dysfunction (ED) in polycystic ovary syndrome (PCOS) through a systematic review. The databases including MEDLINE, PubMed, Up-To-Date, and Science Direct were searched using Medical subject handling terms and free text term keywords such as endocrine abnormalities in PCOS, ED assessment in PCOS, ED in combination with insulin resistance (IR), hyperandrogenism (HA), increased free testosterone, free androgen index (FAI), gonadotrophin levels, luteinizing hormone (LH), prolactin, estrogen, adipocytokines to search trials, and observational studies published from January 1987 to September 2015. Authors of original studies were contacted for additional data when necessary. PCOS increases the risk of cardiovascular disease in women. ED, which is a reliable indicator of cardiovascular risk in general population, is seen in most (but not all) women with PCOS. IR, seen in 70% patients with PCOS, is associated with ED in these women, but patients can have normal endothelial function even in the presence of IR. Free testosterone and FAI are consistently associated with ED, but endothelial function can be normal despite HA. Estradiol (not estrone) appears to be protective against ED though estrone is the predominant estrogen produced in PCOS. Increased levels of adipocytokines (visfatin) are promising in predicting ED and cardiovascular risk. However, more studies are required focusing on direct correlation of levels of prolactin, LH, estrone, and visfatin with ED in PCOS. PMID:27843797
Palacio, J R; Iborra, A; Ulcova-Gallova, Z; Badia, R; Martínez, P
Polycystic ovary syndrome (PCOS) affects 5–10% of women of reproductive age. Free radicals, as a product of oxidative stress, impair cells and tissue properties related to human fertility. These free radicals, together with the oxidized molecules, may have a cytotoxic or deleterious effects on sperm and oocytes, on early embryo development or on the endometrium. Aldehyde-modified proteins are highly immunogenic and circulating autoantibodies to new epitopes, such as malondialdehyde (MDA), may affect the reproductive system. Autoantibodies or elevated reactive oxygen species (ROS) in serum are often associated with inflammatory response. The purpose of this work is to investigate whether PCOS women show increased levels of oxidized proteins (protein–MDA) and anti-endometrial antibodies (AEA) in their sera, compared with control patients, and to determine whether AEA specificity is related to oxidized protein derivatives. Sera from 31 women [10 patients with PCOS (PCOS group) and 21 women with male factor of infertility (control group)] were chosen from patients attending for infertility. Anti-endometrial antibodies were determined by enzyme-linked immunosorbent assay (ELISA) with an endometrial cell line (RL-95). Antibodies against MDA modified human serum albumin (HSA–MDA) were also determined by ELISA. Oxidized proteins (protein–MDA) in serum were determined by a colorimetric assay. Patients with PCOS have significantly higher levels of AEA and anti-HSA–MDA, as well as oxidized proteins (protein–MDA) in serum than control patients. For the first time, we describe an autoimmune response in PCOS patients, in terms of AEA. The evidence of protein–MDA in the serum of these patients, together with the increased antibody reactivity to MDA-modified proteins (HSA–MDA) in vitro, supports the conclusion that oxidative stress may be one of the important causes for abnormal endometrial environment with poor embryo receptivity in PCOS patients. PMID:16634794
Mioni, Roberto; Cà, Anna Dalla; Turra, Jenni; Azzolini, Sara; Xamin, Nadia; Bleve, Luigi; Maffei, Pietro; Vettor, Roberto; Fallo, Francesco
To differentiate the impact of insulin levels/resistance per se from that of excess weight on blood pressure (BP) daily changes, we evaluated, using 24-h ambulatory blood pressure monitoring (ABPM), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a cohort of young normotensive patients affected by polycystic ovary syndrome (PCOS). A cross-sectional study was performed. Fifty-four patients were studied according to (a) insulinemic state: 32 hyperinsulinemic and/or insulin-resistant (h-INS) and 22 normoinsulinemic (n-INS) patients; and (b) body mass index (BMI): 22 obese (BMI > 30) and 32 lean (18.0 < BMI < 24.9) patients. Each subject's SBP and DBP and heart rate (HR) were measured by ABPM. Supine and upright plasma renin activity (PRA), and aldosterone levels were also assayed. Patients in the h-INS group showed higher 24-h, daytime, and nighttime diastolic blood pressure (DBP), higher nighttime systolic blood pressure (SBP) levels, as well as an increased 24-h, daytime and nighttime HR, compared to both obese and lean patients in the n-INS group. In relation to BMI, only 24-h, daytime, and nighttime DBP were higher in obese than in lean patients. At variance, when both h-INS and obesity were considered, 24-h SBP and DBP were higher in h-INS obese subjects than in the other groups. In multivariate analysis, insulin (max peak), area under the curve of insulin and insulin sensitivity index was independently associated with SBP. (1) Within a normotensive range, hyperinsulinemia and/or insulin resistance influence daily BP variation more than obesity does, suggesting a pivotal role of insulin on BP control in PCOS; (2) altered insulinemic state and ABPM-derived higher nighttime BP and HR may represent early markers to identify PCOS subjects prone to high cardiovascular risk.
Hajishafiha, Masomeh; Dehghan, Meisam; Kiarang, Nazila; Sadegh-Asadi, Nahideh; Shayegh, Seyed Navid; Ghasemi-Rad, Mohammad
Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age (6.8%–18%), is among the most common causes of infertility due to ovulation factors, and accounts for 55%–70% of infertility cases caused by chronic anovulation. In this study, we used a combination of letrozole and clomiphene in patients resistant to both drugs individually, and studied the effects of this combination in ovulation and pregnancy in resistant PCOS patients. Methods The study population included infertile couples diagnosed as PCOS in the wife. The women used clomiphene for at least six cycles in order to ovulate after failure to form the dominant follicle, and were then put on letrozole for four cycles. Patients who were unable to form the dominant follicle were enrolled on letrozole and clomiphene combination therapy. Results One hundred enrolled patients underwent 257 cycles of a combination of letrozole and clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44 were unable to do so (17.1%). The number of mature follicles was 2.3±1.1. The mean endometrial thickness in patients on the day of human chorionic gonadotropin administration was 8.17±1.3 mm. The pregnancy rate was 42%. Conclusion According to the results of this study, it can be proposed that in PCOS patients resistant to clomiphene and letrozole used as single agents, a combination of the two drugs can be administered before using more aggressive treatment that may have severe complications or surgery. This combination may also be used as a first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense. PMID:24348019
Jensterle, Mojca; Janez, Andrej; Vrtovec, Bojan; Meden-Vrtovec, Helena; Pfeifer, Marija; Prezelj, Janez; Kocjan, Tomaz
We describe 4 consecutive hypertensive women with polycystic ovary syndrome, classified according to the National Institute of Child Health and Human Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months. Blood pressure, menstrual pattern, body mass index (BMI), homeostasis model assessment of insulin resistance, testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were recorded and measured before and after telmisartan treatment. Obese hypertensive polycystic ovary syndrome patients had a decrease in systolic blood pressure. Marked drop-off in serum androgen concentrations was observed in all four patients. Three patients improved their menstrual cyclicity. The improvements were independent of changes in weight. The reduction of androgen concentrations and improvement in menstrual pattern was achieved despite a non-significant change of fasting insulin levels in patients, who were not considered severely insulin resistant at baseline. These findings may provide a new basis for a proper choice of the antihypertensive drug in hypertensive women with polycystic ovary syndrome. PMID:18074422
Jensterle, Mojca; Janez, Andrej; Vrtovec, Bojan; Meden-Vrtovec, Helena; Pfeifer, Marija; Prezelj, Janez; Kocjan, Tomaz
We describe 4 consecutive hypertensive women with polycystic ovary syndrome, classified according to the National Institute of Child Health and Human Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months. Blood pressure, menstrual pattern, body mass index (BMI), homeostasis model assessment of insulin resistance, testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were recorded and measured before and after telmisartan treatment. Obese hypertensive polycystic ovary syndrome patients had a decrease in systolic blood pressure. Marked drop-off in serum androgen concentrations was observed in all four patients. Three patients improved their menstrual cyclicity. The improvements were independent of changes in weight. The reduction of androgen concentrations and improvement in menstrual pattern was achieved despite a non-significant change of fasting insulin levels in patients, who were not considered severely insulin resistant at baseline. These findings may provide a new basis for a proper choice of the antihypertensive drug in hypertensive women with polycystic ovary syndrome.
Wang, Bo; Yan, Wei; Hou, Li-hui; Wu, Xiao-ke
Traditional Chinese medicine (TCM) usually views polycystic ovary syndrome (PCOS) as a menstrual disease or infertility disease. Reproductive dysfunction in PCOS is characterized by ovarian androgen excess and disturbance of follicular development, and its main clinical manifestations include delayed menstruation, scant menstruation, amenorrhea or infertility. Insulin resistance is a key pathological mechanism of PCOS. "Tiangui" (kidney essence) as a sex-stimulating essence in female in TCM theory, is essential to the menstruation and pregnancy of women. The disturbance of Tiangui (including time, status and rhythm) would result in female reproductive problems. Current studies of Tiangui indicate that ovary is the target organ of PCOS treatment, and its functional characteristics are consistent with the properties of Tiangui in time frame, state form and rhythm cycle. It is then concluded that ovarian dysfunction in PCOS can be expressed as disorder of Tiangui.
Moura, Heloisa Helena Gonçalves de; Costa, Dailana Louvain Marinho; Bagatin, Ediléia; Sodré, Celso Tavares; Manela-Azulay, Mônica
Polycystic ovary syndrome (POS) is one of the most common endocrine abnormalities affecting women of reproductive age. It is a cause of significant social embarrassment and emotional distress. The pathogenesis of the disease is not yet fully understood, but it is thought to be a complex multigenic disorder, including abnormalities in the hypothalamic-pituitary axis, steroidogenesis, and insulin resistance. The main diagnostic findings of the syndrome are: hyperandrogenism, chronic anovulation and polycystic ovarian morphology seen on ultrasound. Hyperandrogenism is generally manifested as hirsutism, acne, seborrhea, androgenic alopecia and, in severe cases, signs of virilization. Treatment may improve the clinical manifestations of excess androgen production, normalize menses and ameliorate metabolic syndrome and cardiovascular complications. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. Early diagnosis and the consequent early treatment may prevent metabolic complications and emotional distress that negatively impact the patients' quality of life.
Huang, Shuo; Pang, Yanli; Yan, Jie; Lin, Shengli; Zhao, Yue; Lei, Li; Yan, Liying; Li, Rong; Ma, Caihong; Qiao, Jie
Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS. PMID:27386819
Skampardonis, N; Kouskoukis, A; Karpouzis, A; Maroulis, G
PCOS represents the commonest endocrinopathy among women of reproductive age. We conducted this study to evaluate the association between polycystic ovaries and clinical and biochemical features of the syndrome. TVS was performed in 74 women with the clinical diagnosis of PCOS. The findings were compared to biochemical, hormonal and clinical features of the syndrome. Statistical analysis revealed a significantly higher prevalence of acne, LH/FSH ratios and testosterone levels in women with PCO compared to those with normal ovarian morphology. In the subgroup analysis, total ovarian volume correlated significantly with hirsutism scores. Our study revealed a great prevalence of polycystic ovaries in Greek women with PCOS, and emphasizes the significance of transvaginal ultrasound in establishment of the diagnosis of the syndrome. The presence of PCO may not be clinically important when present alone without clinical manifestations but reflects the underlying hyperandrogenemia in PCOS women, representing a useful tool in the management of these patients.
Ozegowska, Katarzyna E; Pawelczyk, Leszek A
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is manifested by hyperandrogenism, polycystic ovaries on ultrasound, oligomenorrhoea and anovulation. PCOS patients are more vulnerable to metabolic disorders: insulin resistance, obesity endothelium dysfunction, atherosclerosis, and activation of proinflammatory factors. This association shows that PCOS might be an ovarian manifestation of a metabolic syndrome. Insulin resistance is also strongly correlated with reproductive failure. Approximately 100 factors, secreted in adipose tissue, are responsible for its regulation. Adipocytokines have been found to play an important role in regulating insulin sensitivity Abnormal levels of adipokines are detected in patients with insulin resistance. Studies indicate that these factors, and their different activity in PCOS women, may affect changes observed in their metabolism and, especially may participate in the development of insulin resistance. There are several adipokines whose role has been thoroughly investigated and many that we still know very little about, for example apein and visfatin. Counseling PCOS patients about the possibility of developing metabolic syndrome, diabetes mellitus, and cardiovascular diseases should be a standard of care.
Lazúrová, Ivica; Figurová, Jana; Dravecká, Ingrid
Currently there is growing evidence on possible influence of vitamin D (VD) on reproductive function in both females and males. The relationship between VD and clinical or laboratory manifestations of polycystic ovary syndrome (PCOS) seems to be mostly evaluated. Patients with PCOS have been demonstrated to have significantly lower levels of serum VD and they also have the higher prevalence of vitamin D deficiency as compared to controls. Some studies documented the relation of VD to serum androgen levels, other found that VD correlated with metabolic parameters (body weight, insulin resistance and lipid profile) only. Several interventional studies demonstrated that VD replacement improved these metabolic parameters in PCOS women with VD deficiency. On the other hand some studies also documented improvement of ovarian function and androgen levels. Also vitamin D replacement may represent an additional treatment in VD deficient PCOS women with the aim to improve phenotypic manifestations. It requires further randomized interventional studies on larger groups of patients.Key words: metabolic syndrome - polycystic ovary syndrome - vitamin D.
Lanham, M S M; Lebovic, D I; Domino, S E
Polycystic ovary syndrome is a multi-system endocrinopathy with long-term metabolic and cardiovascular health consequences. Patients typically present due to symptoms of irregular menstruation, hair growth, or infertility; however, recent management options are aimed at further treating underlying glucose-insulin abnormalities as well as androgen excess for proactive control of symptoms. By a 2003 international consensus conference, diagnosis is made by two out of three criteria: chronic oligoovulation or anovulation after excluding secondary causes, clinical or biochemical evidence of hyperandrogenism (but not necessarily hirsutism due to inter-patient variability in hair follicle sensitivity), and radiological evidence of polycystic ovaries. Traditional medical treatment options include oral contraceptive pills, cyclic progestins, ovulation induction, and anti-androgenic medications (aldosterone antagonist, 5alpha-reductase antagonist, and follicle ornithine decarboxylase inhibitor). Recent pharmacotherapies include insulin-sensitizing medications metformin and two thiazolidinediones (rosiglitazone/Avandia and pioglitazone/Actos), a CYP19 aromatase inhibitor (letrozole/Femara), and statins to potentially lower testosterone levels.
Introduction Polycystic ovary syndrome (PCOS) is classically characterised by an accumulation of incompletely developed follicles in the ovaries due to anovulation. However, since the publication of the Rotterdam criteria, there is acceptance that menstrual cycle and endocrine dysfunction with hyperandrogenism is more important in reaching the diagnosis than ultrasound findings. It is diagnosed in up to 10% of women attending gynaecology clinics, but the prevalence in the population as a whole varies from 10% to 20%, depending on which diagnostic criteria are used. PCOS has been associated with hirsutism, infertility, acne, weight gain, type 2 diabetes, cardiovascular disease (CVD), and endometrial hyperplasia. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of metformin on hirsutism and menstrual frequency in women with PCOS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 14 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: metformin compared with placebo/no treatment, metformin compared with weight loss intervention, or metformin compared with cyproterone acetate-ethinylestradiol. PMID:25814168
Tasali, Esra; Van Cauter, Eve; Ehrmann, David A.
Synopsis Polycystic ovary syndrome (PCOS), the most common endocrine disorder of pre-menopausal women, is characterized by chronic hyperandrogenism, oligoanovulation, obesity and insulin resistance. Importantly, PCOS women are at increased risk for glucose intolerance, type 2 diabetes and cardiovascular disorders. Recent reports indicate an unexpectedly high prevalence of obstructive sleep apnea (OSA) in PCOS. Alterations in sex steroids (i.e. high androgen and low estrogen levels) and increased visceral adiposity in PCOS could potentially contribute to the increased prevalence of OSA in this disorder. There is some evidence to suggest that there may be strong associations between the presence and severity of OSA and the metabolic disturbances that characterize PCOS. Causal mechanisms in the link between PCOS and OSA remain to be elucidated. Clinicians who manage PCOS patients should be aware of the high prevalence of OSA in these patients and systematically evaluate these women for sleep disturbances. PMID:19255602
Taghavi, Seyed Abdolvahab; Bazarganipour, Fatemeh; Montazeri, Ali; Kazemnejad, Anoshirvan; Chaman, Reza; Khosravi, Ahmad
Background: Increasing attention to the concept of polycystic ovary syndrome (PCOS) health-related quality of life has led to the development of tool that aims to measure this concept. Objective: The purpose of this study was to conduct a systematic review of psychometric properties of the PCOS health-related quality of life questionnaire. Materials and Methods: A search of database (Pubmed, PsychInfo, CINAHL, CENTRAL, Scopus and SID) from January1998 to December 2013 yielded 6152 references of which 27 papers remained after review of the titles and abstracts. The reviewers used structural tools to analyze the articles, critically appraise papers, and extract the data. Finally, eight papers met the full inclusion criteria. Results: Studies suggested that the PCOS health-related quality of life questionnaire (PCOSQ)/or its modified version (MPCOSQ) have partial known groups validity. The convergent/divergent validity of the questionnaire also was found to be relatively acceptable. The PCOSQ/MPCOSQ reached acceptable benchmarks for its reliability coefficients. Regarding structural validity, some studies suggested that the PCOSQ/MPCOSQ have an extra dimension (related to menstruation) in addition to its existing dimensions for original or modified versions. Conclusion: The PCOSQ/MPCOSQ showed acceptable content and construct validity, reliability and internal consistency. However, some other properties, particularly those related to factor and longitudinal validity, absolute error of measurement, minimal clinically important difference and responsiveness still need to be evaluated. PMID:26568749
Archer, Johanna S; Chang, R Jeffrey
Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality affecting reproductive age women. Population-based studies estimate a prevalence of 5-10% [Obstet Gynecol 101 (2003) 995; Aust N Z J Obstet Gynaecol 41 (2001) 202]. The clinical characteristics of PCOS include hyperandrogenism, chronic anovulation, insulin resistance and infertility. Hyperandrogenism is generally manifested as hirsutism and acne. Both these clinical symptoms are treated with similar drug therapies, including oral contraceptive pills (OCPs), topical medications or antiandrogens such as spironolactone, flutamide and finasteride, as well as topical medications. Recent studies have shown that lower doses of these medications are as efficacious as high doses and have the advantage of decreased cost and an improved side-effect profile. Although hirsutism and acne can be considered cosmetic in nature, they cause significant social embarrassment and emotional distress. Physicians should be sensitive to these issues and approach patients in a caring and sympathetic manner.
Polycystic ovary syndrome (PCOS) results in the greatest single cause of anovulatory infertility in reproductive age women (affecting 5-10%). Previously, research groups have created animal models utilizing non-human primates and sheep to better understand the mechanisms involved in PCOS. However, c...
Pereira, Katherine; Kreider, Kathryn Evans
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting reproductive-age women. PCOS causes hyperandrogenism and anovulation and increases the risk of multiple health conditions including infertility, diabetes mellitus, and cardiovascular disease. This article outlines current recommendations for diagnostic testing, treatment options, and holistic care of the woman with PCOS.
Abali, Remzi; Temel Yuksel, Ilkbal; Yuksel, Mehmet Aytac; Bulut, Berk; Imamoglu, Metehan; Emirdar, Volkan; Unal, Fehmi; Guzel, Savas; Celik, Cem
The aim of the study was to evaluate the fatty acid-binding protein-4 (FABP4) and irisin concentrations in women with polycystic ovary syndrome (PCOS). Forty-nine women with PCOS, diagnosed according to Rotterdam criteria and 39 healthy women matched for body mass index (BMI) and age. Serum irisin and plasma FABP4 concentrations were measured in both groups. The association of irisin and FABP4 concentrations with metabolic parameters were also tested. Women with PCOS had significantly lower mean serum irisin concentrations than control subjects (158.5 ± 123.3 versus 222.9 ± 152.2 ng/ml, p < 0.05). Concentrations of FABP4 in PCOS and control groups were not significantly different (10.5 ± 4.4 versus 10.9 ± 4.2 ng/ml, p > 0.05). FABP4 concentrations were correlated with BMI, waist-hip ratio (WHR) and HOMA-IR (r = 0.57, p = 0.001; r = 0.26, p = 0.03; r = 0.26, p = 0.03, respectively). No associations between irisin and all the others parameters except serum levels of LH were found. Serum irisin concentrations of women with PCOS were lower compared to the controls. Moreover, there were no difference in plasma FABP4 concentrations between women with PCOS and controls.
Li, Muyan; Tang, Yuanyuan; Lin, Chunlei; Huang, Qiaoying; Lei, Danqing; Hu, Yanling
Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases. However, its pathogenesis is unclear. We aim to explore the potential relationships between serum macroelements/microelements and PCOS. A total of 1137 women were involved in the current study. PCOS was defined according to ESHRE/ASRM, and complete blood samples were collected. Serum macroelements (calcium and magnesium) and microelements (copper, zinc, and iron) were assayed through atomic absorption spectrophotometry. PCOS patients had significantly higher copper concentrations than patients without PCOS (P < 0.001). By contrast, PCOS patients had lower serum calcium levels than patients without PCOS (P < 0.001). No significant differences were observed in the levels of serum zinc, magnesium, and iron between PCOS and non-PCOS patients. PCOS patients with acne had higher magnesium levels than those without acne (P = 0.020), and PCOS patients with hirsutism had lower magnesium levels than those without hirsutism (P = 0.037). High serum copper and low calcium levels may be correlated with PCOS. Magnesium concentrations are correlated with acne and hirsutism in PCOS patients. These results provide clues to explore the mechanism of PCOS and guidance for element treatments in PCOS patients.
Yuan, Chun; Liu, Xiaoqiang; Mao, Yundong; Diao, Feiyang; Cui, Yugui; Liu, Jiayin
Abstract Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome (PCOS). There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index (BMI), total testosterone (TT), modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin (SHBG), homeostasis model assessment-estimated insulin resistance (HOMA-IR) and free androgen index (FAI) between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyperandrogenism had significantly higher BMI (P < 0.05), but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong predictor of hyperandrogenism in PCOS. PMID:27526961
Wang, Fang; Dai, Wei; Yang, Xin-hong; Guo, Yi-hong; Sun, Ying-pu
We observed the effect of body mass index (BMI) on pregnancy outcomes in Chinese patients undergoing assisted reproductive treatment (ART). All the patients were divided into polycystic ovary syndrome (PCOS) group and non-PCOS group, and then according to BMI, each group was subdivided into 6 subgroups: group 1 (BMI < 18 kg/m2), group 2 (18–20 kg/m2), group 3 (20–22 kg/m2), group 4 (22–24 kg/m2), group 5 (24–26 kg/m2) and group 6 (BMI > 26.0 kg/m2). We found that in 20 to 25-year-old patients, the pregnancy rate was not significantly correlated with BMI in PCOS patients; while in non-POCS patients, the pregnancy rate significantly decreased at the BMI cut-off point value of 24–26 kg/m2. The pregnancy rate significantly declined at the BMI cut-off point values of 22–24 kg/m2 and 18–20 kg/m2, respectively in 25 to 35-year-old and in over 35-year-old PCOS patients; while in over 25-year-old non-PCOS patients, no significant correlation between pregnancy rate and BMI was observed. We conclude that for under 25-year-old non-PCOS patients, ART should be performed after BMI is controlled under 26 kg/m2. For PCOS patients, if age is 25 to 35 years or over 35 years, BMI should be controlled below 24 kg/m2 or below 20 kg/m2, respectively. PMID:27686055
Knebel, Birgit; Lehr, Stefan; Janssen, Onno E; Hahn, Susanne; Jacob, Sylvia; Nitzgen, Ulrike; Müller-Wieland, Dirk; Kotzka, Jorg
Polygenic diseases with a broad phenotypic spectrum, such as polycystic ovary syndrome (PCOS), present a particular challenge in terms of identifying the underlying genetic mechanisms, nevertheless genetic variants have impact on the individual phenotype. We aimed to determine if next to genetic variations like SNPs further mechanisms might play a role in the pathogenesis of PCOS. We examined the effect of copy-number variations (CNVs) on metabolic phenotypes in PCOS. The intragenic rs1244979, rs2815752 in NEGR1 gene, and rs780094 in GCKR gene were genotyped and CNVs were determined by droplet digital polymerase chain reaction (ddPCR) in PCOS patients (n = 153) and controls without metabolic syndrome (n = 142). The study indicated that SNPs are not associated with the pathogenesis of PCOS but affect metabolic phenotypes. The CNVs investigated show a lower variability in PCOS than in CON. Furthermore, we provided direct evidence that the copy number, but not the genotype of the CNV in the genomic regions of rs780094(GCKR) is associated with low level of high-density lipoprotein cholesterol in PCOS. This study supports the hypothesis that not only genetic variants, but also CNVs in metabolically relevant genes, have an effect on metabolic phenotypes in our group of PCOS patients.
Churchill, S J; Wang, E T; Pisarska, M D
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and the leading cause of anovulatory infertility. The prevalence of the syndrome ranges between 6 to 15% based on broader Rotterdam diagnostic criteria verses strict NIH diagnostic criteria.1 The condition is characterized by a combination of ovulatory dysfunction, hyperandrogenism and the presence of polycystic ovaries. PCOS has been associated with multiple metabolic alterations and consequences including impaired glucose tolerance, insulin resistance, hyperinsulinemia, type II diabetes, dyslipidemia, metabolic syndrome, obesity and subclinical cardiovascular disease. It remains unclear however if these associations lead to an increased risk of clinically significant long-term cardiovascular disease. Large prospective studies to date have not detected significant differences in overall cardiovascular morbidity and mortality in PCOS. The phenotypical variability in PCOS has made researching each of these associations challenging as different aspects of the syndrome may be contributing, opposing or confounding factors. The ability to detect significant differences in long-term cardiovascular outcomes may also be due to the variable nature of the syndrome. In this review, we attempt to describe a summary of the current literature concerning the metabolic alterations and cardiovascular consequences of polycystic ovary syndrome.
Ali, Aus Tariq
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, where the main clinical features include menstrual irregularities, sub-fertility, hyperandrogenism, and hirsutism. The prevalence of PCOS depends on ethnicity, environmental and genetic factors, as well as the criteria used to define it. On the other hand, metabolic syndrome is a constellation of metabolic disorders which include mainly abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. These associated disorders directly increase the risk of Type 2 diabetes mellitus (DMT2), coronary heart disease (CHD), cardiovascular diseases (CVD) and endometrial cancer. Many patients with PCOS have features of metabolic syndrome such as visceral obesity, hyperinsulinaemia and insulin resistance. These place patients with PCOS under high risk of developing cardiovascular disease (CVD), Type 2 diabetes (DMT2) and gynecological cancer, in particular, endometrial cancer. Metabolic syndrome is also increased in infertile women with PCOS. The aim of this review is to provide clear and up to date information about PCOS and its relationship with metabolic syndrome, and the possible interaction between different metabolic disorders.
Agacayak, Elif; Tunc, Senem Yaman; Sak, Sibel; Basaranoglu, Serdar; Yüksel, Hatice; Turgut, Abdulkadir; Gul, Talip
Background We aimed to measure the levels of inflammatory markers and neopterin in obese and non-obese patients with PCOS by using 2 separate control groups with matching body mass index (BMI). Material/Methods A total of 60 women of reproductive age with (n=30) and without (n=30) PCOS were included in this study. Based on their BMI, patients with PCOS were divided into 2 groups as obese (n=15) and non-obese (n=15) PCOS groups. In addition, 2 BMI-matched control groups were formed. Neopterin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (N/L ratio), and vitamin B12 were assessed by complete blood count. Results No significant difference was found between patients with PCOS and control subjects in neopterin, IL-6, TNF-α, and CRP levels. However, N/L ratio levels were significantly higher (p 0.045) and vitamin B12 levels were significantly lower (p 0.033) in patients with PCOS compared to control subjects. No statistically significant difference was found between obese and non-obese patients with PCOS and control subjects in neopterin, IL-6, TNF-α, and N/L ratio levels. However, CRP levels were significantly higher in obese patients with PCOS compared to obese control subjects (p 0.007). Conclusions It can be concluded that inflammatory activity is increased in patients with PCOS, can lead to an increased risk for atherosclerosis, and this increase is not caused by obesity but rather by the polycystic ovary syndrome itself. However, studies with larger sample sizes are needed in this area. PMID:26292090
Brady, Christine; Mousa, Shaymaa S; Mousa, Shaker A
In the past, polycystic ovary syndrome has been looked at primarily as an endocrine disorder. Studies now show that polycystic ovary syndrome is a metabolic, hormonal, and psychosocial disorder that impacts a patient’s quality of life. It is extremely important to holistically treat these patients early on to help them deal with the emotional stress that is often overlooked with polycystic ovary syndrome. Early diagnosis and long term management can help control polycystic ovary syndrome so that women can still live a healthy active life and avoid long-term complications such as metabolic syndrome and cardiovascular diseases. PMID:21701605
Albu, Alice; Radian, Serban; Fica, Simona; Barbu, Carmen Gabriela
The aim of the study was to determine whether Romanian polycystic ovary syndrome (PCOS) patients have an increased prevalence of metabolic syndrome (MetS) and to study the involvement of adiposity, insulin resistance and hyperandrogenism in the pathogenesis of MetS in PCOS. A total of 398 PCOS patients and 126 controls were evaluated between January 2006 and December 2012. MetS was defined by National Cholesterol Education Program, Adult Treatment Panel III criteria. Principal component analysis (PCA) was used to analyze the correlations among variables of interest by grouping them in few components, and principal component (PCs) scores were saved and used as independent variables in logistic regression. The prevalence of MetS was higher among patients with PCOS (20.4 %) than in controls (11.1 %, p < 0.05). In PCOS patients, PCA extracted three PCs from the analyzed variables. First PC aggregated variables related to adiposity and insulin resistance, with factor loadings showing strong relationship between these parameters. The second PC included markers of hyperandrogenemia and was best represented by free androgen index (FAI) which correlated strongly and exclusively with this PC. The third component was best represented by hirsutism. Logistic regression analysis revealed that in PCOS patients, the first and the second PCs were independently associated with MetS, whereas the third component was not. Romanian PCOS patients have an increased risk for MetS; adiposity, insulin resistance and hyperandrogenemia, but not hirsutism, are independent predictors of MetS presence. Our data also suggest that insulin resistance is only secondary to increased adiposity and FAI is a good marker of biochemical hyperandrogenism with little influences from the metabolic component.
Lee, Amy T; Zane, Lee T
Polycystic ovary syndrome (PCOS) affects 5-10% of reproductive-aged women and is one of the most common endocrine disorders in women. The disorder is commonly characterized by elevated levels of androgen and insulin. Women with PCOS may present with a range of signs and symptoms, and face increased risks of reproductive, metabolic, cardiovascular, psychologic, and neoplastic sequelae, particularly if the condition is left unrecognized or untreated. The clinical definition of PCOS has changed in recent years and includes as one of its cardinal criteria the dermatologic manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, and androgenetic alopecia. Acanthosis nigricans, a cutaneous sign of hyperinsulinemia, may also be present. These dermatologic features may provide early clinical clues to recognition of PCOS, and treatment of these cutaneous conditions may improve the patient's quality of life and psychologic well-being. The effects of androgen on pilosebaceous units in the skin can vary by anatomic location, producing pathophysiologic effects on hair growth and differentiation, sebaceous gland size and activity, and follicular keratinization. Treatment modalities may include hormonal therapy intended to modulate androgen production and action as well as non-hormonal therapies directed toward specific dermatologic conditions.
BALDANI, DINKA PAVICIC; SKRGATIC, LANA; CERNE, JASMINA Z.; FERK, POLONCA; SIMUNIC, VELIMIR; GERSAK, KSENIJA
Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity. PMID:24649096
Li, Hang Wun Raymond; Brereton, Rebecca E; Anderson, Richard A; Wallace, A Michael; Ho, Clement K M
Both vitamin D deficiency and polycystic ovary syndrome (PCOS) are associated with aspects of metabolic syndrome, but it is unclear whether vitamin D deficiency contributes to the metabolic disturbances commonly found in women with PCOS. This study sought to investigate (1) the prevalence of vitamin D deficiency in PCOS women in Scotland and (2) the relationship between vitamin D status and metabolic risk factors. This was an observational study on 52 women (25 in PCOS group and 27 in control group). Serum 25-hydroxyvitamin D concentrations less than 25 nmol/L were classified as severe vitamin D deficiency and were found in 44.0% and 11.2% of subjects in the PCOS and control groups, respectively (P = .047). Among the PCOS subjects, 25-hydroxyvitamin D concentrations were negatively correlated with body mass index (P = .033), C-reactive protein (P = .027), and free androgen index (P = .025) and positively correlated with quantitative insulin sensitivity check index (P = .035), high-density lipoprotein cholesterol (HDL-C) (P = .033), and sex hormone binding globulin (P = .038). Associations of vitamin D deficiency with quantitative insulin sensitivity check index and HDL-C were independent of body mass index and waist-to-hip ratio. Vitamin D deficiency is highly prevalent in PCOS women in Scotland, and a larger proportion of PCOS patients than control women were found to be vitamin D deficient. We also demonstrate correlations of vitamin D status with insulin sensitivity, HDL-C, and C-reactive protein in PCOS patients, which support the increasing evidence that vitamin D deficiency is associated with multiple metabolic risk factors in PCOS women.
Barber, T M; Franks, S
Polycystic Ovary Syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including insulin resistance. There is a clear association between obesity, the development of PCOS and the severity of its phenotypic, biochemical and metabolic features. Evidence to support this link includes data from epidemiological, pathophysiological and genetic studies. Given the importance of obesity in the development and manifestation of PCOS, ongoing research into the many facets of adipocyte biology in women with the condition is important and should continue to be a priority. In this review article, we discuss the existing literature on fat distribution, adipokines, adipocyte hypertrophy and adipocyte steroid metabolism in women with PCOS.
Kiałka, Marta; Milewicz, Tomasz; Klocek, Marek
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder occurring in women of childbearing age. The literature describes the relationship between PCOS and high blood pressure levels and increased risk of arterial hypertension development, which is an important and strong risk factor for adverse cardiovascular events in the future. Among the main causes of hypertension in PCOS women insulin resistance, hyperandrogenism, greater sympathetic nerve activity and concomitance of obesity are stressed. Because PCOS may contribute to earlier development of hypertension, as well as pre-hypertension, therefore it is advisable to monitor blood pressure systematically, to control known risk factors, and to initiate the treatment of hypertension when the disease occur.
Kalra, Bharti; Kalra, Sanjay; Sharma, J. B.
This review describes the rationale, biochemical, and clinical data related to the use of inositols in polycystic ovary syndrome (PCOS). It covers studies related to the mechanism of action of myo-inositol and D-chiro-inositol (MDI), with randomized controlled trials conducted in women with PCOS, and utilizes these data to suggest pragmatic indications and methods for using MDI combination in PCOS. Rationally crafted inositol combinations have a potential role to play in maintaining metabolic, endocrine, and reproductive health in women with PCOS. PMID:27730087
Kim, Jin Ju; Choi, Young Min
Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.
Ajossa, S; Guerriero, S; Paoletti, A M; Orrù, M; Melis, G B
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women in reproductive age. As for the treatment of this disease the lack of a clear etiology for PCOS has led to a symptom-orientated treatment. However, the overall aims of treatment are to induce ovulation for women desiring conception, to reduce androgen levels, to reduce body weight and to reduce long-term health risks of diabetes mellitus and cardiovascular disease. Clomiphene citrate (CC) is recommended as first line treatment for induction of ovulation in patients with PCOS by virtue of its efficacy, safety, and ease of administration. Alternatives for CC-resistant patients include gonadotrophin therapy (better with low-dose step-up protocol) and laparoscopic ovarian diathermy. Recently, recombinant FSH (rFSH) has been introduced in clinical practice and it seems more effective than urinary FSH as demonstrated by a significantly higher number of follicles recruited and embryos obtained with a shorter treatment period. The addition of GnRH-agonist to the stimulation protocol for women affected by PCOS could reduce premature luteinization and increase cycle fecundity. Other drugs under investigation are metformin and cabergoline. Hirsutism is the manifestation of hyperandrogenemia in PCOS. The primary goal of the treatment of hirsutim is central or peripheral androgen suppression using 3 groups of drugs: inhibitors of androgen production (oral contraceptives, GnRH analogues), peripheral androgen blockers (cyproterone acetate, flutamide, finasteride and spironolactone), and insulin-sensitizing agents (metformin). Weight reduction and exercise could also improve not only menstrual disturbances and infertility, but also insulin resistance and its adverse metabolic con-sequences.
Tsikouras, P; Spyros, L; Manav, B; Zervoudis, S; Poiana, C; Nikolaos, T; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, GF
Rationale: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman’s life. Objective: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. Methods and Results: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. Discussion:The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. Abbreviations: PCOS = Polycystic Ovary Syndrome PMID:26351529
Marciniak, Aleksandra; Nawrocka Rutkowska, Jolanta; Brodowska, Agnieszka; Wiśniewska, Berenika; Starczewski, Andrzej
Polycystic ovary syndrome is a disorder which affects 5-10% of women in reproductive age. PCOS is a cause of hyperandrogenism, menstrual disorders and infertility. The most common clinical symptoms are hirsutism, acne and obesity. Patients often suffer from metabolic disorders: insulin resistance, hyperinsulinemia, dislipidemia, leading to atherosclerosis and others irregularities of the metabolic syndrome. Patients are in the high risk group for cardiovascular diseases (CVD) development because of the metabolic abnormalities. Obesity is observed in 35-60% of women with PCOS. Lean women with PCOS are also exposed to a greater risk of glucose intolerance development and abnormalities in lipid profile than women without PCOS with comparable BMI. Adipocytes are the source of many compounds of the paracrine and endocrine activity. Some of them are also markers and mediators of inflammation. Increased levels of proinflammatory cytokines in blood can promote atherosclerosis and cardiovascular disease. Markers: IL-18, TNF, IL-6 and hs-CRP are often elevated in patients with polycystic ovary syndrome. An increase in inflammatory markers may be an early indicator of the risk of developing insulin resistance and atherosclerosis, and may become a useful prognostic and therapeutic tool for monitoring patients with PCOS: lean and those with overweight and obesity. Assessment of the concentrations of inflammatory markers may become a very useful test in evaluating the risk of developing atherosclerosis and cardiovascular disease, long before their clinical manifestation. It will also allow for the appropriate prophylaxis.
Xu, Xiaohui; Lai, Yerui; Yang, Gangyi; Yang, Mengliu; Li, Ling; Zhang, Qin; Liu, Hua; Zheng, Hongting; Zhu, Danping
Abstract The euglycemic–hyperinsulinemic clamp is not available in most clinical settings. An accessible and inexpensive measurement for identifying insulin resistance (IR) is necessary. Our aim is to assess whether the adiponectin (ADI) index (ADI/[FBG × FIns]) is a better surrogate index for the assessment of IR or metabolic syndrome (MetS). A population-based cross-sectional study was conducted including 100 healthy women and 99 polycystic ovary syndrome patients. The euglycemic–hyperinsulinemic clamp was performed. Circulating ADI levels were determined by ELISA. Polycystic ovary syndrome and polycystic ovary syndrome plus MetS subjects had higher products of fasting triglycerides and glucose (TyG), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), increased ratios of the area under the curve for insulin/the area under the curve for glucose (AUCi/AUCg), but lower ADI index as compared with healthy subjects. Partial correlation analysis in all populations showed that the M-value was significantly negatively correlated with HOMA-IR, TyG, TG/HDL, and AUCi/AUCg, and correlated positively with the ADI index. The r value of Pearson correlation between the ADI index and M-value was greater than that of the correlation between HOMA-IR, TyG, TG/HDL-C, and AUCi/AUCg. The optimal cut-off value of the ADI index for detection of IR was 0.67, with a sensitivity of 89.4% and a specificity of 88.1%, whereas for detection of MetS, it was 0.32, with a sensitivity of 88.7% and a specificity of 71.0%. The ADI index may be a surrogate marker in detecting IR and MetS. PMID:27930544
Lujan, Marla E.; Chizen, Donna R.; Pierson, Roger A.
It is estimated that as many as 1.4 million Canadian women may be afflicted with polycystic ovary syndrome (PCOS). Although PCOS is heralded as one of the most common endocrine disorders occurring in women, its diagnosis, management, and associated long-term health risks remain controversial. Historically, the combination of androgen excess and anovulation has been considered the hallmark of PCOS. To date, while these symptoms remain the most prevalent among PCOS patients, neither is considered an absolute requisite for the syndrome. Inclusion of ultrasonographic evidence of polycystic ovaries as a diagnostic marker has substantially broadened the phenotypic spectrum of PCOS, yet much debate surrounds the validity of these newly identified milder variants of the syndrome. Difficulty in resolving the spectrum of PCOS stems from the continued use of inconsistent and inaccurate methods of evaluating androgen excess, anovulation, and polycystic ovaries on ultrasound. At present, there is no clear-cut definition of biochemical hyperandrogenemia, particularly since we depend on poor laboratory standards for measuring androgens in women. Clinical signs of hyperandrogenism are ill-defined in women with PCOS, and the diagnosis of both hirsutism and polycystic ovarian morphology remains alarmingly subjective. Lastly, there is an inappropriate tendency to assign ovulatory status solely on the basis of menstrual cycle history or poorly timed endocrine measurements. In this review, we elaborate on these limitations and propose possible resolutions for clinical and research settings. By stimulating awareness of these limitations, we hope to generate a dialogue aimed at solidifying the evaluation of PCOS in Canadian women. PMID:18786289
Samraj, George P N; Kuritzky, Louis
Polycystic ovary syndrome is a common premenopausal endocrino-metabolic disorder. In addition to hyperandrogenism, menstrual abnormalities, ovulatory disturbances and infertility, insulin resistance, dyslipidemia, and obesity may eventuate in long-term cardiovascular consequences.
Legro, R S
Our understanding of Polycystic Ovary Syndrome (PCOS) has been hampered by varying diagnostic criteria, and ignorance of the etiology of the syndrome. PCOS women are uniquely insulin resistant and obesity aggravates this underlying predisposition to insulin resistance. Diagnostic criteria which focus on hyperandrogenism and/or menstrual irregularity are more likely to identify insulin resistant women, than such criteria as abnormal gonadotropin secretion or ovarian morphology. The lack of a clear etiologic mechanism to the syndrome has led to a multitude of symptom-oriented treatments with few therapies improving all aspects of the endocrine syndrome of PCOS. Improving insulin sensitivity has become established as a baseline treatment strategy in PCOS. There are, however, few randomized controlled trials of adequate power to provide an evidence based guide to treatment in PCOS.
Alemzadeh, R; Kansra, A R
Polycystic ovary syndrome (PCOS) is a common but heterogeneous disorder that usually arises during puberty. This endocrine disorder is associated with chronic anovulation and hyperandrogenemia with clinical manifestation of oligomenorrhea, hirsutism and acne. While the underlying etiology of PCOS remains unknown, it is commonly associated with obesity and insulin resistance leading to increased risk of cardiovascular disease, dyslipidemia and type 2 diabetes mellitus in hyperandrogenemic phenotypes. Menstrual irregularities and insulin resistance in obese adolescents are usually indistinguishable from the clinical manifestations of PCOS and pose a diagnostic dilemma due to higher circulating androgens during puberty. Consequently, a universal consensus on the definition of hyperandrogenemia in adolescents has been elusive. Nevertheless, hyperandrogenemia, independent of obesity, in postmenarchal adolescents is associated with increased risk of cardiometabolic syndrome. Therefore, treatment strategies including lifestyle changes and/or use of insulin-sensitizers, hormone replacement and antiandrogens should be utilized in order to delay long-term cardiovascular and metabolic complications of this endocrinopathy.
Berent-Spillson, Alison; Love, Tiffany; Pop-Busui, Rodica; Sowers, MaryFran; Persad, Carol C; Pennington, Kathryn P; Eyvazaddeh, Aimee D; Padmanabhan, Vasantha; Zubieta, Jon-Kar; Smith, Yolanda R
This pilot study describes a relationship between insulin resistance and μ-opioid neurotransmission in limbic appetite and mood-regulating regions in women with polycystic ovary syndrome (PCOS), suggesting that insulin-opioid interactions may contribute to behavioral and reproductive pathologies of PCOS. We found that  patients with PCOS who are insulin-resistant (n = 7) had greater limbic μ-opioid receptor availability (nondisplaceable binding potential) than controls (n = 5);  receptor availability was correlated with severity of insulin resistance; and  receptor availability normalized after insulin-regulating treatment.
Palomba, Stefano; Daolio, Jessica; La Sala, Giovanni Battista
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and affects fertility and pregnancy in cases of oligoanovulation. Ovulation induction is often used to treat anovulatory patients with PCOS, but many of these women fail to conceive and resort to assisted reproductive technologies. Alterations in oocyte competence (OC) are considered potential causative factors for subfertility in women with PCOS. In this review we present and critically assess all recent clinical and experimental data regarding OC in women with PCOS. Our analysis demonstrates that the contribution of OC to reproductive potential in women with PCOS varies and largely depends on the PCOS phenotype and comorbidities associated with PCOS.
Celik, Fatih; Kose, Mesut; Yilmazer, Mehmet; Köken, Gülengül N; Arioz, Dagistan Tolga; Kanat Pektas, Mine
It is well-known that plasma L-carnitine concentrations are significantly decreased in obese individuals. A study showed that L-carnitine concentrations are significantly lower in lean PCOS patients than in lean healthy women. Thus, it has been suggested that lowered L-carnitine is associated with PCOS. This study also showed that the women with PCOS had significantly lower L-carnitine levels than those of the healthy controls. In addition, this study hypothesised that low L-carnitine levels in PCOS patients were associated with obesity and/or insulin resistance. Moreover, plasma L-carnitine concentrations were found to be statistically similar in PCOS patients and healthy controls, when controlled for obesity. This study implied that L-carnitine could be used as an adjunctive therapy in the management of insulin resistance or obesity in women who have PCOS. Further research might be planned to clarify the clinical effects of L-carnitine administration in PCOS patients with insulin resistance and/or obesity.
Terán Dávila, J; Teppa-Garrán, A D
An established fact in the polycystic ovarian syndrome (POS) is an abnormal ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the syndrome could also be influenced by factors outside the ovaries. Although of unknown etiology, the POS is one of the most frequent endocrine disorders in the gynecologic practice. The disorder is characterized by ultrasound findings of enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and including the appearance of infertility. There are a series of mechanisms involved in the extraovarian androgen increase in patients with POS. Among these mechanisms are implicated those of central and peripheral origin, genetic factors and adrenocortical dysfunction. In the same way, the alterations produced could imply genetic, molecular biological, biochemical, physiological and endocrinological factors. Sometimes all these factors could interact at the same time. The high serum androgen level could stop the pituitary gonadotropin production, either as a direct mechanism or as a result of its peripheral conversion. The increased androgens also explain the manifestations of clinical acne, hirsutism, and the detention in follicular ovarian maturation. All these manifestations are related with the menstrual disorders, anovulation, and infertility that these patients develop. The characteristics of the extraovarian POS include the 17-hydroxyprogesterone elevation in response to the ACTH test and the dexamethasone suppression of adrenal androgens. It is possible to improve the ovarian function in some patients with POS. This could be achieved with clomiphene citrate associated with glucocorticoids to induce ovulation.
Glintborg, Dorte; Andersen, Marianne
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance. Available data from register-based and data linkage studies support that metabolic-vascular and thyroid diseases, asthma, migraine, depression and cancer are diagnosed more frequently in PCOS, whereas fracture risk is decreased. Drug prescriptions are significantly more common in PCOS than controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long-term morbidity could be worsened by obesity, sedentary way of life, Western-style diet and smoking, whereas lifestyle intervention including weight loss may partly or fully resolve the symptoms of PCOS and could improve the long-term prognosis. In this review, the possible implications of increased morbidity for the clinical and biochemical evaluation of patients with PCOS at diagnosis and follow-up is further discussed along with possible modifying effects of medical treatment.
Zabuliene, Lina; Tutkuviene, Janina
Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders of reproductive age women. The main signs of PCOS are as follows: androgen excess, menstrual dysfunction, infertility, obesity, and other numerous health problems. By different authors, the disorder affects 2-28% of reproductive age women. Polycystic ovary syndrome is characterized by presence of hyperandrogenism, anovulation, menstrual cycle disturbances, also by the other metabolic changes. The lack of well-defined and universally accepted diagnostic criteria makes identification of this syndrome confusing to many clinicians. There are only few studies concerning the correlations between phenotypic expression, body composition and PCOS, and relationship with the processes of growth and sexual maturation and various environmental factors (nutrition, physical activity, stress, and other factors). There is a lack of knowledge about further PCOS development and prognosis, considering the individual and environmental factors. Variation in human body composition and shape ranges considerably: many body size and shape indices (height, weight, body composition, and proportions) are the result of long evolution process and adaptation to environment. Obviously, the morphological body parameters, physiological and biochemical indices are complex and compound the interdependent system. By current literature, more than 50% of women are overweight or obese. If waist circumference and waist-to-hip ratio of women with PCOS increase, reproductive function and metabolic state of a woman is altered more than in cases when there are no changes in these parameters. The investigations of the strongest sexual dimorphism sign--the subcutaneous and visceral fat topography--showed that women with PCOS have greater adipose tissue mass in the areas of the abdomen, waist, and upper arms than control women. It is known that some indices of sexual dimorphism may be considered as the morphological signs of
Polak, K; Czyzyk, A; Simoncini, T; Meczekalski, B
Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. The diagnostic criteria include two out of three features: hyperandrogenism, polycystic ovaries on ultrasound and menstrual irregularities (Rotterdam Criteria 2003). PCOS patients are more vulnerable to develop diabetes, cardiovascular diseases and metabolic syndrome. Insulin resistance (IR) is prevalent in women with PCOS independently of obesity and is critically involved in reproductive and metabolic complications of the syndrome. Several tests have been developed to measure IR, some very reliable but complex like the hyperinsulinemic euglycemic glucose clamp and others less precise but easier and less invasive like HOMA-IR. New markers are needed to reach a more reliable assessment of insulin resistance. To date, several surrogate markers have been proposed in the literature to facilitate and improve the determination of IR. Many new proteins are strongly involved with PCOS physiopathology and IR, such as some adipocytokines (adiponectin, visfatin, vaspin and apelin), copeptin, irisin, PAI-1 and zonulin. Many other proteins have been proposed as potential new markers of IR in PCOS, such as resistin, leptin, RBP4, kisspetin and ghrelin, but their role is still controversial. In this review, we provide a short characterization of these new markers, recently studied as indicators of metabolic state.
Sirmans, Susan M; Pate, Kristen A
Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%–70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications. PMID:24379699
Although the aetiology of polycystic ovary syndrome (PCOS) is still not known and the search for causative genes is proving elusive, it is generally agreed that hyperandrogenism is at the heart of the syndrome. Here, it is proposed that excess androgens are the root cause of PCOS starting from their influence on the female fetus in programming gene expression, producing the characteristic signs and symptoms which are then exacerbated by a propagation of excess ovarian androgen production from multiple small follicles, anovulation and insulin resistance in the reproductive life-span, thus setting up a vicious perpetual circle of androgen excess. This opinion paper, rather than being a full-scale review, is intentionally biased in support of this hypothesis that androgen excess is the 'root of all evil' in PCOS; in the hope that its acceptance could lead to more direct treatment of the syndrome in all its facets rather than the symptomatic treatment of side effects of androgen excess that we are addressing today.
Butterworth, James; Deguara, Jean
Background. Polycystic ovary syndrome (PCOS) is the commonest cause of female infertility. Visceral obesity and insulin resistance are key pathophysiological mechanisms behind PCOS. Women suffering from this syndrome and infertility often seek bariatric surgery hoping that they would be able to conceive postoperatively. Objective. At present, there is no consensus on the role of bariatric surgery in the management of PCOS-associated infertility within the medical community, making it difficult to give specific advice to these women, so a review of the literature was necessary. Results. A detailed review of the literature was performed. Only 6 manuscripts were relevant and contained quantitative data. They demonstrated that bariatric surgery results in postoperative conception rates varying from 33% to 100%. Surgery is also associated with amelioration of menstrual irregularities, hormonal abnormalities, and hirsutism that are associated with PCOS. These studies were retrospective and only had a small number of participants with infertility. Conclusions. Bariatric surgery has been shown to conclusively improve life expectancy, quality of life, and comorbidities like type 2 diabetes and obstructive sleep apnea. However, further research is required to identify whether weight loss surgery results in significant improvement in fertility of women with PCOS and to investigate which operation has the best results. PMID:27965894
Barnard, L; Balen, A H; Ferriday, D; Tiplady, B; Dye, L
To date there have been no published studies of cognitive functioning in polycystic ovary syndrome (PCOS). This large internet-based study compared neuropsychological functioning in right-handed women with (minimum n=135) and without PCOS (minimum n=322), stratified according to use of anti-androgen medication and level of depression. Women with PCOS are thought to have hyperandrogenism and hyperestrogenism which was hypothesized to differentially influence cognitive function across cognitive domains. Performance did not differ according to diagnosis on mental rotation and spatial location tasks. Hence, no evidence to support the view that women with PCOS display a more masculine cognitive profile due to hyperandrogenism. Despite presumed hyperestrogenism, women with PCOS demonstrated impaired performance in terms of speed and accuracy, on reaction time and word recognition tasks. These findings are intriguing given the well-documented roles of estrogen and testosterone in cognitive function. Overall, these findings suggest that PCOS is not associated with masculinized cognitive functioning, and, although associated with impaired performance on tasks considered to demonstrate female-advantage, such impairments are subtle and are unlikely to affect daily functioning.
Abstract Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a “two-hit” hypothesis has been proposed: (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic–pituitary–ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptom-directed treatment. PMID:20939704
Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the “thrifty” phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS. PMID:26185601
Tan, Bee K.; Weickert, Martin O.; Lois, Konstantinos; Nestler, John E.; Sattar, Naveed; Lehnert, Hendrik
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic perturbations, in addition to chronic anovulation and factors related to androgen excess. In general, women live longer than men and develop cardiovascular disease at an older age. However, women with PCOS, as compared with age- and body mass index-matched women without the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical atherosclerosis, vascular dysfunction, and finally cardiovascular disease and mortality. Further alterations in PCOS include an increased prevalence of sleep apnea, as well as various changes in the secretion and/or function of adipokines, adipose tissue-derived proinflammatory factors and gut hormones, all of them with direct or indirect influences on the complex signaling network that regulates metabolism, insulin sensitivity, and energy homeostasis. Reviews on the cardiometabolic aspects of PCOS are rare, and our knowledge from recent studies is expanding rapidly. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge, focusing on the alterations of cardiometabolic factors in women with PCOS. Further insight into this network of factors may facilitate finding therapeutic targets that should ameliorate not only ovarian dysfunction but also the various cardiometabolic alterations related to the syndrome. PMID:22829562
Brawer, J.; Richard, M.; Farookhi, R. )
The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.
Williams, Sophie; Sheffield, David; Knibb, Rebecca C
Polycystic ovary syndrome affects 6 percent of women. Symptoms include hirsutism, acne, and infertility. This research explores the impact of polycystic ovary syndrome on women's lives using photovoice. Nine participants photographed objects related to their quality of life and made diary entries explaining each photograph. Three themes emerged from thematic analysis of the diaries: control (of symptoms and polycystic ovary syndrome controlling their lives), perception (of self, others, and their situation), and support (from relationships, health care systems, and education). These findings illuminate positive aspects of living with polycystic ovary syndrome and the role pets and social networking sites play in providing support for women with polycystic ovary syndrome.
Herczeg, Zita; Vanya, Melinda; Szili, Károly; Dézsi, Csilla; Nagy, Zsolt; Szabó, János
The development of polycystic ovary syndrome and its exact pathophysiological mechanism is still unclear, but environmental and genetic factors likely play a role. Exposition to teratogenic effects during the prenatal development can lead to chronic diseases in the postnatal period. This finding confirms the common familial aggregation as well. A literature search was conducted up to January 1, 2016 for articles dealing with the genetic or epigenetic factors of polycystic ovary syndrome. This review will discuss the current understanding of the genetic basis and clinical presentation of this disease. Orv. Hetil., 2016, 157(32), 1275-1281.
Casarini, Livio; Simoni, Manuela; Brigante, Giulia
Several studies have attempted to explain the high overall prevalence of polycystic ovary syndrome among women worldwide (about 4-10%) despite its link to subfertile phenotypes. For this reason, it is considered an evolutionary paradox. In this review, we show that several genetic loci associated with the disease differently modulate the reproductive parameters of men and women. This observation suggests that such genetic variants lead to opposite effects in the two sexes in reproductive success. Intralocus sexual conflict as a cause of the persistence polycystic ovary syndrome genotypes among humans is supported.
Dumesic, Daniel A.; Abbott, David H.; Padmanabhan, Vasantha
The prenatal testosterone (T)-treated adult female rhesus monkey is one animal model of polycystic ovary syndrome (PCOS) in women, with early prenatal T excess programming a permanent PCOS–like phenotype characterized by luteinizing hormone (LH) hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess from increased abdominal adiposity. These combined reproductive and metabolic abnormalities are associated with ovarian hyperandrogenism and follicular arrest in adulthood, as well as premature follicle differentiation and impaired embryo development during gonadotropin therapy for in vitro fertilization (IVF). A second animal model for PCOS, the prenatal T-treated sheep also is characterized by LH hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback, persistent follicles and insulin resistance, but also is associated with intrauterine growth retardation and compensatory growth after birth. The ability of prenatal T excess in both species to alter the developmental trajectory of multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programs target tissue differentiation, raising the possibility that T excess in human fetal development promotes PCOS in adulthood. Such a hypothesis must include data from clinical studies of PCOS women to clarify the homology between these PCOS-like animal models and PCOS per se in reproductive and metabolic function. Future studies should develop new clinical strategies that improve pregnancy outcome and minimize pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus as well as minimize transgenerational susceptibility to adult PCOS and its metabolic derangements in male close relatives. PMID:17659447
Carvalho, L M L; Ferreira, C N; Sóter, M O; Sales, M F; Rodrigues, K F; Martins, S R; Candido, A L; Reis, F M; Silva, I F O; Campos, F M F; Gomes, K B
Polycystic Ovary Syndrome (PCOS) is associated with a chronic low-grade inflammation and predisposition to hemostatic and atherosclerotic complications. This case-control study evaluated the microparticles (MPs) profile in patients with the PCOS and related these MPs to clinical and biochemical parameters. MPs derived from platelets (PMPs), leuckocytes (LMPs) and endothelial cells (EMPs) were evaluated, as well as MPs expressing tissue factor (TFMPs), by flow cytometry, comparing women with PCOS (n = 50) and a healthy control group (n = 50). PCOS women presented increased total MPs, PMPs, LMPs and EMPs levels when compared to control group (all p < 0.05). TFMPs was similar between the groups (p = 0.379). In conclusion, these MPs populations could be useful biomarkers for association with thrombosis and cardiovascular disease in PCOS women.
Lanzo, Erin; Monge, Maria; Trent, Maria
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in adolescent girls that has both reproductive and metabolic implications. Patients with PCOS typically present to their pediatrician for evaluation of menstrual irregularity and/or signs of hyperandrogenism, such as hirsutism and acne. The diagnosis of PCOS is made by clinical symptoms and laboratory evaluation. Because of the long-term health consequences that can accompany the disorder, pediatricians should consider PCOS in their initial evaluation of menstrual irregularity. Lifestyle modification is the cornerstone of treatment for girls with PCOS; however, hormonal medication such as oral contraceptive pills and insulin-sensitizing agents are useful and effective adjuncts to therapy. The goals of treatment for girls with PCOS are to improve clinical manifestations of the disorder, health-related quality of life, and long-term health outcomes.
Wang, Fangfang; Pan, Jiexue; Liu, Ye; Meng, Qing; Lv, Pingping; Qu, Fan; Ding, Guo-Lian; Klausen, Christian; Leung, Peter C. K.; Chan, Hsiao Chang; Yao, Weimiao; Zhou, Cai-Yun; Shi, Biwei; Zhang, Junyu; Sheng, Jianzhong; Huang, Hefeng
Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in ∼62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgen-induced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS. PMID:25825716
Heim, S C; De Geyter, C; Siegrist, W; Bilz, S; Keller, U
The Polycystic Ovary Disease (PCOD) is one of the most common endocrine disorders in women with a prevalence of 5%. Affected women often consult a gynecologist because of menstrual irregularities, fertility problems or problems of androgen excess. However, PCOD is a metabolic disorder affecting multiple organs. Studies suggest that those women are at risk for developing several complications such as type II diabetes mellitus, hypertension, dyslipidemia and myocardial infarction. The risk to develop endometrial carcinoma is also elevated. To give adequate treatment to women with PCOD, an interdisciplinary approach of gynecologists together with endocrinologists specialized in metabolic and nutritional disorders at the University of Basel is presented. The work-up for diagnosis and assessment of risk factors is outlined. Goal of this interdisciplinary approach is an adequate evaluation of affected patients and their long-term follow-up to test if proposed interventions as weight loss, treatment of hyperinsulinemia, regulation of menstrual cycle and others can avoid long-term sequelae.
... Fertility and Sterility , 92, 1966–1982. [top] Legro, R. S. (2007). Pregnancy considerations in women with polycystic ovary syndrome. Clinical Obstetrics and Gynecology , 50, 295–304. [top] Kiddy, D.S., Hamilton-Fairley, D., Bush, A., Short, F., Anyaoku, V., Reed, ...
Herguner, Sabri; Harmanci, Hatice; Hergner, Arzu; Toy, Harun
Several studies suggested that prenatal androgen exposure might contribute to development of polycystic ovary syndrome (PCOS). The androgen theory of autism proposes that autism spectrum conditions (ASC) are in part due to elevated fetal testosterone levels. Furthermore, higher rates of androgen-related conditions including PCOS are reported in…
... PDF - 273 KB) [top] Moran, L. J., Pasquali, R., Teede, H. J., Hoeger, K. M., & Norman, R. J. (2009). Treatment of obesity in polycystic ovary ... htm [top] Moran, L. J., Hutchison, S. K., Norman, R. J., & Teede, H. J. (2011). Lifestyle changes in ...
Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying
Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.
Yang, Mei; Du, Juan; Lu, Danyu; Ren, Caixia; Shen, Huan; Qiao, Jie; Zhang, Hongquan
Hyperandrogenemia is the leading defect in patients with polycystic ovary syndrome (PCOS) and considered to be involved in the ovulation dysfunction of PCOS. During the process of ovulation, granulosa cells (GCs) undergo epithelial–mesenchymal transition (EMT), and integrin-interacting protein kindlin 2 is a well-known regulator in EMT. Therefore, our objective here was to compare the expression levels of kindlin 2 in luteinized GCs between patients with PCOS and control women and the relationship between kindlin 2 and PCOS pathogenesis. In this study, kindlin 2 expression was significantly increased in luteinized GCs from patients with PCOS, and kindlin 2 could be induced by testosterone both in vitro and in vivo. Meanwhile, kindlin 2 was positively correlated with androgen receptor (AR) in PCOS GCs. Taken together, kindlin 2 may play a role in luteinized GCs, especially in the case of excess androgen. Further studies are required to assess the specific role of kindlin 2 in follicular development and PCOS pathogenesis. PMID:24336678
Mazloomi, Sahar; Alizadeh, Narges; Aminzare, Majid; Niroomand, Soudabeh; Mousavi, Seyedeh Neda
Previous studies have shown that serum zinc and adiponectin levels are associated with insulin resistance in the polycystic ovary syndrome (PCOS) patients. But there is no study to evaluate serum zinc and adiponectin levels as predictor markers of PCOS, adjusted for anthropometric, biochemical, dietary intake, and physical activity measures. Ninety-one new PCOS cases (based on the Rotterdam criteria) and 85 healthy control women participated and individually matched based on age. Food intake of all participants obtained by the food frequency and physical activity level was assessed by the International Physical Activity Questionnaires. Serum glucose, lipid profile, androgens, insulin, adiponectin, and zinc concentrations were measured at the fasting state. Weight, BMI, waist circumference, and body fat, as well as serum levels of DHEAS, insulin, TG, LDL cholesterol (LDL.C), homeostasis model assessment of insulin resistance (HOMA-IR), and LH/FSH ratio, were significantly higher in the PCOS compared with those of the healthy control women. Serum levels of zinc and adiponectin were significantly lower in the PCOS than those of the healthy control women. Results of the logistic regression model showed significant effects of adiponectin, zinc, and LH/FSH ratio on the PCOS, adjusted for anthropometric and biochemical measures (p < 0.05). In the present study, serum level of zinc had significant correlation with adiponectin in the PCOS patients, and serum levels of zinc, adiponectin, and LH/FSH ratio had significant effects on the PCOS occurrence.
Seok, Hyun Ha; Song, Haengseok; Kim, You Shin; Lee, Dong Ryul; Lee, Woo Sik; Yoon, Tae Ki
Objective The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. Methods A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. Results Through logistic regression analyses, we arrived at the novel finding that serum anti-Müllerian hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005–1.164; p=0.037) and 0.113 (95% CI, 1.038–1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels ≥8.5 ng/mL showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. Conclusion Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels. PMID:27358832
Shayan, Arezoo; Masoumi, Seyedeh Zahra; Tohidi, Shahin; Khalili, Arash
Introduction Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy and cause of oligomenorrhea in women. Aim The present study was conducted with the aim to compare the effect of Agnugol and Metformin drugs on oligomenorrhea in patients with PCOS. Materials and Methods This study was a clinical trial on 120 women with PCOS and had oligomenorrhea, referring to a gynaecology clinic Fatemieh, Hamadan city, Iran, 2015. Women were randomly divided into 2 groups using permutation blocks (getting the medications Agnugol and Metformin) and were treated with drugs Agnugol and Metformin for 3 months. Data collection included demographic questionnaire and check list was designed and completed before and at the end of interventions, by both groups. To analyse the data, descriptive statistics, chi-square tests, t-test, ANOVA with repeated measures was used. Results The mean and SD of age was 39.45±4.60 for women taking Agnugol and 38.466±0.84 for those taking Metformin. Based on the results between the subjects, the two groups were not significantly different in terms of menstruation length, cycle intervals, or the number of pads, meaning that the two drugs had similar effects on menstrual cycle regulation, menstruation length and the number of pads. More side effects were reported in the group using Metformin. Conclusion Agnugol and Metformin drugs in the treatment of oligomenorrhea patients with PCOS have the same effect. Since Metformin is a chemical drug with side effects, Agnugol can be presented as its herbal alternative to treat oligomenorrhea. PMID:28208942
Hashim, Zainab Hasan; Hamdan, Farqad Bader; Al-Salihi, Anam Rashid
Background: Central obesity and hyperinsulinaemia of polycystic ovary syndrome (PCOS) are associated with chronic sympathetic over activity. Objective: To evaluate the autonomic functions and to indicate the superiority, if any, for those functions in the diagnosis of sympathetic over activity in PCOS women. Materials and Methods: Sixty-four PCOS patients and 40 women served as the control group were studied. The two groups were subdivided according to the body mass index (BMI) into two obese and non-obese groups. Waist:hip ratio (WHR), plasma epinephrine level was estimated, sympathetic skin response (SSR); postural orthostatic tachycardia syndrome, heart rate variability (HRV), and valsalva ratio were measured in both groups. Results: Compared to the control group, obese PCOS patients demonstrated higher BMI and WHR, reduced palmar SSR latency and higher amplitude, altered HRV, higher plasma epinephrine level, and rapid pulse rate. Moreover, non-obese patients show reduced palmar SSR latency and higher amplitude, higher plasma epinephrine level, and higher pulse rate. BMI and WHR of the patients were positively correlated with plasma epinephrine level; while the HRV was negatively correlated WHR. Conclusion: Women with PCOS exhibits altered autonomic function and sympathoexcitation is more pronounced in obese than non-obese patients; therefor the SSR could be useful auxiliary electrophysiological test to predict autonomic dysfunction in those patients. Receiver operating characteristics curve demonstrate the pulse rate in standing position as the autonomic function test that is superior to others in predicting sympathetic over activity in those patients. PMID:25653673
Rezaee, Mohsen; Asadi, Nasrin; Pouralborz, Yasna; Ghodrat, Mahshid; Habibi, Shaghayegh
Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders among women of reproductive age, with a variety of complications and consequences mostly due to hyperandrogenism and insulin resistance (IR). PCOS patients with IR are at risk for metabolic syndrome and diabetes mellitus (DM) along with its complications such as cardiovascular events. There are several methods for screening IR in patients with PCOS to predict DM and other complications. Fasting plasma glucose test, oral glucose tolerance test, and insulin and glycosylated hemoglobin (HbA1c) levels are some available screening tools for IR. The American Diabetes Association recommended HbA1c to screen for DM because HbA1c is not affected by day-to-day plasma glucose levels and reflects the plasma glucose status during 2-3 months before measurement. Some studies have evaluated the role of HbA1c as a screening method to predict DM in PCOS patients, however, there are still controversies in this matter. Also some studies reported that HbA1c has a correlation with complications of PCOS such as metabolic syndrome and cardiovascular events. We found that HbA1c could be a suitable screening test for IR in PCOS patients but more studies are recommended, omitting confounding factors that could affect IR in patients with PCOS, such as antihyperglycemic agents like metformin, or lifestyle modification, which can be effective in reducing IR in patients with PCOS.
Wasinarom, Artisa; Sereepapong, Wisan; Sirayapiwat, Porntip; Rattanatanyong, Prakasit; Mutirangura, Apiwat
Objective The long interspersed elements (LINE-1, L1s) are a group of genetic elements found in large numbers in the human genome that can translate into phenotype by controlling genes. Growing evidence supports the role of epigenetic in polycystic ovary syndrome (PCOS). The purpose of this study is to evaluate the DNA methylation levels in LINE-1 in a tissue-specific manner using cumulus cells from patients with PCOS compared with normal controls. Methods The study included 19 patients with PCOS and 22 control patients who were undergoing controlled ovarian hyperstimulation. After oocyte retrieval, cumulus cells were extracted. LINE-1 DNA methylation levels were analysed by bisulfite treatment, polymerase chain reaction, and restriction enzyme digestion. The Connection Up- and Down-Regulation Expression Analysis of Microarrays software package was used to compare the gene regulatory functions of intragenic LINE-1. Results The results showed higher LINE-1 DNA methylation levels in the cumulus cells of mature oocytes in PCOS patients, 79.14 (±2.66) vs. 75.40 (±4.92); p=0.004, but no difference in the methylation of cumulus cells in immature oocytes between PCOS and control patients, 70.33 (±4.79) vs. 67.79 (±5.17); p=0.155. However, LINE-1 DNA methylation levels were found to be higher in the cumulus cells of mature oocytes than in those of immature oocytes in both PCOS and control patients. Conclusion These findings suggest that the epigenetic modification of LINE-1 DNA may play a role in regulating multiple gene expression that affects the pathophysiology and development of mature oocytes in PCOS. PMID:27358825
Bazarganipour, Fatemeh; Ziaei, Saeideh; Montazeri, Ali; Foroozanfard, Fatemeh; Kazemnejad, Anoshirvan; Faghihzadeh, Soghrat
Background This study aimed to assess sexual functioning among women with polycystic ovary syndrome (PCOS) in Iran. Materials and Methods A cross-sectional study was conducted to ascertain factors re- lated to sexual functioning in 300 PCOS patients attending to the private practice centers in Kashan, Isfahan Province, Iran, from May to October 2012. The Female Sexual Function Index (FSFI) was used to measure sexual functioning. Moreover, the socio-demo-graphic details and clinical information of PCOS including obesity, hirsutism, acne, mestrual cycle disturbances, infertility and endocrine profile were recorded for each patient. Results Overall the prevalence of female sexual dysfunction (FSD) was 16.6%. In particular patients indicated poorer sexual functioning for the desire (48.3%) and the arousal (44.7%) subscales. Multiple logistic regression analysis suggested patients with lower educational level (OR: 2.94; 95% CI: 1.46-5.92) and irregular menstrual status (OR: 4.61; 95% CI: 1.93-11) were more likely to report sexual dysfunction. Conclusion The findings suggest that desire and arousal were the most prevalent sexual disorders reported in this patient population. In addition, findings suggested that women with limited or no formal education and a history of menstrual irregularities were the most likely to report female sexual dysfunction. Further investigations are needed to examine female sexual functioning among women with PCOS, to educate their health care providers, and to develop therapeutic interventions. PMID:25379156
Gődény, Sándor; Csenteri, Orsolya
Polycystic ovary syndrome is recognized as the most common hormonal and metabolic disorder of women. This heterogeneous endocrinopathy characterized by clinical and/or biochemical hyperandrogenism, oligo- or amenorrhoea, anovulatory infertility, and polycystic ovarian morphology. The prevalence, clinical feature and the risk of co-morbidity vary depending on the accuracy of the diagnosis and the criteria used. Evidence suggests that those women are at high risk who fulfil the criteria based on National Institute of Health. The complex feature of the syndrome and the considerable practice heterogeneity that is present with regards to diagnostic testing of patients who are suspected to have polycystic ovary syndrome require an interdisciplinary, evidence-based diagnostic approach. Such a method can ensure the patient safety and the effectiveness and efficiency of the diagnosis. This paper summarises the highest available evidence provided by well-designed studies, meta-analysis and systematic reviews of the clinical feature and the clinical implications of the diagnostic criteria of polycystic ovary syndrome.
Zahiri Sorouri, Ziba; Sharami, Seyede Hajar; Tahersima, Zinab; Salamat, Fatemeh
Background Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in polycystic ovary syndrome (PCOS) patients with clomiphene citrate (CC) resistant instead of gonadotropins. This study aimed to compare the efficacy of unilateral LOD (ULOD) versus bilateral LOD (BLOD) in CC resistance PCOS patients in terms of ovulation and pregnancy rates. Materials and Methods In a prospective randomized clinical trial study, we included 100 PCOS patients with CC resistance attending to Al-Zahra Hospital in Rasht, Guilan Province, Iran, from June 2011 to July 2012. Patients were randomly divided into two ULOD and BLOD groups with equal numbers. The clinical and biochemical responses on ovulation and pregnancy rates were assessed over a 6-month follow-up period. Results Differences in baseline characteristics of patients between two groups prior to laparoscopy were not significant (p>0.05). There were no significant differences between the two groups in terms of clinical and biochemical responses, spontaneous menstruation (66.1 vs. 71.1%), spontaneous ovulation rate (60 vs. 64.4%), and pregnancy rate (33.1 vs. 40%) (p>0.05). Following drilling, there was a significant decrease in mean serum concentrations of luteinizing hormone (LH) (p=0.001) and testosterone (p=0.001) in both the groups. Mean decrease in serum LH (p=0.322) and testosterone concentrations (p=0.079) were not statistically significant between two groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in two groups after LOD (p>0.05). Conclusion Based on results of this study, ULOD seems to be equally efficacious as BLOD in terms of ovulation and pregnancy rates (Registration Number: IRCT138903291306N2). PMID:25918587
Özler, Sibel; Öztaş, Efser; Tokmak, Aytekin; Ergin, Merve; Kuru Pekcan, Meryem; Gümüş Güler, Başak; Yakut, Halil İbrahim; Yılmaz, Nafiye
Objective: ADAMTS-1 is a matrix metalloproteinase which cleaves versican in the cumulus oocyte complex under the effect of luteinizing hormone surge in the periovulatory period. Altered levels may have a role in the pathogenesis of polycystic ovary syndrome (PCOS). We aimed to determine the serum versican and ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif-1) levels in PCOS patients and compare the results with healthy controls. Methods: Thirty-eight patients with PCOS and forty healthy controls aged between 15 and 22 years were included in the study. They were sampled according to their basal hormone, serum versican, and ADAMTS-1 levels. Serum versican and ADAMTS-1 levels were measured by enzyme-linked immunosorbent assay. A multivariate logistic regression model was used to identify the independent risk factors of PCOS. Results: Serum versican levels were significantly decreased in the PCOS group when compared with the controls. The best versican cut-off value for PCOS was calculated to be 33.65 with 76.74% sensitivity and 52.94% specificity. Serum versican levels, homeostasis model assessment of insulin resistance index, a Ferriman-Gallwey score higher than 8, and oligomenorrhea were the strongest predictors of PCOS. Serum versican levels were significantly decreased in PCOS patients. Besides, serum ADAMTS-1 and versican levels were significantly and positively correlated with each other. Conclusion: Serum versican levels were significantly decreased in patients with PCOS. This suggests a possible role of versican in ovulatory dysfunction and in the pathogenesis of PCOS. PMID:27908842
Chen, Zhihua; Zhang, Mengzhen; Qiao, Yuhuan; Yang, Junjuan
Objective: To explore the effects of letrozole (LE) in combination with low-dose intramuscular injection of human menopausal gonadotropin (HMG) on the ovulation induction and pregnancy of patients with polycystic ovary syndrome (PCOS). Methods: A total of 156 patients with PCOS infertility were randomly divided into an LE group, a clomiphene citrate (CC) group and an LE + HMG group (n= 52). LE and CC were orally taken according to the prescribed dosage on the 3rd-5th days of menstruation respectively, and 75 IU HMG was given through intramuscular injection. The ovulation induction parameters and pregnancy outcomes were observed. Results: The number of ovulation cycle of LE + HMG group was significantly higher than that of LE group (χ2=8.451, P<0.001). After injection of human chorionic gonadotropin, both endometrial thickness and number of mature follicles of LE + HMG group were significantly higher than those of other two groups (P<0.001), and the daily estradiol (E2) level was also higher (q=4.531, P<0.05). The pregnancy rate of LE + HMG group was 55.7%, which exceeded those of other two groups (compared to LE group, χ2=4.012, P<0.05). In LE + HMG group, the average medication cycle of clinically pregnant patients was (2.9 ± 0.3) weeks, which was significantly shorter than those of CC and LE groups (F=17.241, P<0.001). Conclusion: The regimen using LE in combination with low-dose intramuscular injection of HMG has satisfactory therapeutic effects on ovulation induction, short medication cycle and high clinical pregnancy rate, which is promising for treating patients with PCOS infertility. PMID:28083040
Deniz, Rulin; Gurates, Bilgin; Aydin, Suleyman; Celik, Husnu; Sahin, Ibrahim; Baykus, Yakup; Catak, Zekiye; Aksoy, Aziz; Citil, Cihan; Gungor, Sami
Polycystic ovary syndrome (PCOS) is commonly characterised by obesity, insulin resistance (IR), hyperandrogenemia and hirsutism. Nesfatin-1 a recently discovered hormone, acts upon energy balance, glucose metabolism, obesity and probably gonadal functions. This study was to evaluate the circulating levels of nesfatin-1 in patients with PCOS (n = 30) and in age and body mass index (BMI)-matched controls (n = 30). PCOS patients had significantly lower levels of nesfatin-1 (0.88 ± 0.36 ng/mL) than healthy controls (2.22 ± 1.14 ng/mL). PCOS patients also had higher gonadotropin and androgen plasma concentrations, Ferriman-Gallwey scores, blood glucose levels and a homeostasis model of assessment-IR index (HOMA-IR) index than in healthy women. Correlation tests in PCOS subjects detected a negative correlation between nesfatin-1 levels and BMI, fasting blood glucose, insulin levels and a HOMA-IR index. Lower nesfatin-1 concentration may plays a very important role in the development of PCOS.
Sills, E Scott; Perloe, Mark; Tucker, Michael J; Kaplan, Carolyn R; Genton, Marc Georges; Schattman, Glenn L
BACKGROUND: This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age. METHODS: Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions. RESULTS: From 657 participants, the majority (63%) were between 26-34 years old; mean BMI was 30.4 kg/m2. 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648). CONCLUSIONS: In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women.
Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang
Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641
Wojtkiewicz, Joanna; Jana, Barbara; Kozłowska, Anna; Crayton, Robert; Majewski, Mariusz; Zalecki, Michał; Baranowski, Włodzimierz; Radziszewski, Piotr
The aim of the present study was to determine the changes in both the distribution pattern and density of nerve fibers containing dopamine β-hydroxylase (DβH), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), substance P (SP), calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (SOM), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the human polycystic ovaries. In the polycystic ovaries, when compared to the immunoreactions pattern observed in the control gonads, following changes were revealed: (1) an increase in the number of DβH-, VAChT-, VIP- or GAL-immunoreactive (IR) nerve fibers within the stroma as well as in the number of DβH-IR fibers near primordial follicles and medullar veins and venules; (2) a reduction in the number of nerve fibers containing nNOS, CGRP, SOM, PACAP within the stroma and in the numbers of CGRP-IR fibers around arteries; (3) an appearance of SP- and GAL-IR fibers around medullar and cortical arteries, arterioles, veins and venules, with except of GAL-IR fibers supplying medullar veins; and (4) the lack of nNOS-IR nerve fibers near primordial follicles and VIP-IR nerves around medullar arteries and arterioles. In conclusion, our results suggest that the changes in the innervation pattern of the polycystic ovaries in human may play an important role in the pathogenesis and/or course of this disorder.
Beltadze, K; Barbakadze, L
The problem of Polycystic Ovary Syndrome (PCOS) is of a special importance due to its connection with not only medical but with psychosocial factors. PCOS is the most common endocrine cause of anovulatory infertility. It is a major factor for the metabolic syndrome, cardiovascular disease, type 2 diabetes mellitus (T2DM). Clinical symptoms of PCOS such as acne, hirsutism, obesity, alopecia represent psychological problem, especially for the adolescents. Many women who have PCOS have the onset of symptoms during adolescence. Early diagnosis and treatment of PCOS are important for preventing of the above mentioned long-term consequences associated with this condition. Adolescent patients often have diagnostic problems because the features of normal puberty are similar with symptoms of PCOS. This article reviews the diagnostic and differential diagnostic characteristics of PCOS in adolescents. In conclusion, consensus statement in adolescent patients is still awaiting. Our data suggest that it may be prudent to define adolescent PCOS according to the Carmina modified Rotterdam criteria. The increase rate of metabolic syndrome in adolescents with PCOS emphasize the importance of regular screening due to the high cardiometabolic disorders risk.
Palomba, Stefano; Santagni, Susanna; Falbo, Angela; La Sala, Giovanni Battista
Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up. PMID:26261426
Cai, Guoqing; Ma, Xiangdong; Chen, Biliang; Huang, Yanhong; Liu, Shujuan; Yang, Hong; Zou, Wei
Polycystic ovary syndrome (PCOS) is a complex, heterogeneous endocrine and metabolic disorder affecting 5% to 10% of reproductive-age women. A high rate of granulosa cell (GC) proliferation contributes to the abnormal folliculogenesis in patients with PCOS. Evidence has proved that dysregulation of microRNAs is involved in the pathogenesis of PCOS. In this study, we investigated the effect of miR-145 on cell proliferation and the underlying mechanism of miR-145 in isolated human GCs from the aspirated follicular fluid in women with PCOS. Our findings showed that miR-145 is downregulated in human GCs from PCOS. The miR-145 mimics suppress cell proliferation and promoted cell apoptosis in human GCs from PCOS. However, miR-145 inhibitor promotes cell proliferation and inhibited cell apoptosis. Moreover, using a dual-luciferase reporter assay, we confirmed that the insulin receptor substrate 1 (IRS1) gene is a direct target of miR-145. The miR-145 mimics inhibited messenger RNA and protein IRS1 expression levels, and silencing of IRS1 by small interfering RNA inhibits human GC proliferation, but IRS1 overexpression abrogates the suppressive effect of miR-145 mimics. Furthermore, miR-145 mimics can inhibit the activation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK). The IRS1 overexpression abrogates the suppressive effect of miR-145 mimics on MAPK/ERK signaling pathways. Together, miR-145 mimics suppress cell proliferation by targeting and inhibiting IRS1 expression to inhibit MAPK/ERK signaling pathways. Our study further found that high concentrations of insulin decreases the miR-145 expression, upregulates IRS1, and promotes cell proliferation. These observations showed that miR-145 is a novel and promising molecular target for improving the dysfunction of GCs in PCOS.
Chen, Yen-Hao; Heneidi, Saleh; Lee, Jung-Min; Layman, Lawrence C; Stepp, David W; Gamboa, Gloria Mabel; Chen, Bo-Shiun; Chazenbalk, Gregorio; Azziz, Ricardo
Approximately 70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR) above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT). In AT, analysis of the IRS/PI3-K/AKT pathway signaling components identified only GLUT4 expression to be significantly lower in PCOS patients and in control subjects with IR. We examined the role of miRNAs, particularly in the regulation of GLUT4, the insulin-sensitive glucose transporter, in the AT of PCOS and matched control subjects. PCOS AT was determined to have a differentially expressed miRNA profile, including upregulated miR-93, -133, and -223. GLUT4 is a highly predicted target for miR-93, while miR-133 and miR-223 have been demonstrated to regulate GLUT4 expression in cardiomyocytes. Expression of miR-93 revealed a strong correlation between the homeostasis model assessment of IR in vivo values and GLUT4 and miR-93 but not miR-133 and -223 expression in human AT. Overexpression of miR-93 resulted in downregulation of GLUT4 gene expression in adipocytes through direct targeting of the GLUT4 3'UTR, while inhibition of miR-93 activity led to increased GLUT4 expression. These results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93 and demonstrate upregulated miR-93 expression in all PCOS, and in non-PCOS women with IR, possibly accounting for the IR of the syndrome. In contrast, miR-133 and miR-223 may have a different, although yet to be defined, role in the IR of PCOS.
Cheraghi, Ebrahim; Mehranjani, Malek Soleimani; Shariatzadeh, Mohammad Ali; Esfahani, Mohammad Hossein Nasr; Ebrahimi, Zahra
Polycystic ovary syndrome (PCOS) is associated with low-quality oocytes. The aim of the present study was to investigate the effects of metformin (MET), N-acetylcysteine (NAC) and their combination on follicular fluid parameters, oocytes and embryo quality in PCOS patients. A prospective randomised placebo-controlled pilot study on 60 Iranian women with PCOS (aged 25-35 years) undergoing intracytoplasmic sperm injection (ICSI) was designed. Women were divided into four groups (n=15 in each): (1) an MET, administered 1500mg day(-1) MET; (2) an NAC group, administered 1800mg day(-1) NAC; (3) an NAC + MET group; and (4) a placebo group. Drugs were administered from the 3rd day of previous cycle until the day of oocyte aspiration (6 weeks treatment in total). Data were analysed by one-way ANOVA, with significance set at P<0.05. The number of immature and abnormal oocytes decreased significantly in the NAC compared with placebo group, with a concomitant increase in the number of good-quality embryos in the NAC group (P<0.05). Malondialdehyde levels decreased significantly in the NAC and NAC + MET groups compared with the placebo-treated group (P<0.02). In addition, there were significant decreases in leptin levels in the NAC, MET and NAC + MET groups compared with the placebo group (P<0.001). Insulin and LH levels were significantly lower in the MET and NAC groups compared with the placebo-treated group (P<0.02). We concluded that NAC improves oocyte and embryo quality and could be administered as an alternative to MET.
The complex mechanisms linking fat excess to metabolic syndrome are not well understood, but several experimental studies have shown that altered production of adipokines plays a main role in development and progression of this disorder. In particular, reduced secretion of adiponectin has a crucial role in inducing insulin resistance but also in determining the clustering of elevated triglycerides and small, dense LDL particles. Increased leptin secretion may be responsible for sympathetic nervous system overactivity and hypertension, while reduced omentin may have an important permissive role in the development of atherogenic processes. Finally, cytokines and other adipokines (resistin, visfatin) determine and modulate the inflammatory process that is an essential component of this condition of cardiovascular risk. Because obesity is prevalent in polycystic ovary syndrome (PCOS), it is not surprising that patients with PCOS present altered adipokine levels and increased prevalence of metabolic syndrome. However, because of the presence of other CV risk factors (androgen excess), in PCOS adipokine dysfunction is particularly severe. Understanding and treating adipokine dysfunction in young women with PCOS is an essential component of any politics of prevention of CV diseases in the general population.
Su, Hung-wen; Chen, Ching-min; Chou, Szu-yuan; Liang, So-jung; Hsu, Chun-sen; Hsu, Ming-i
Polycystic ovary syndrome (PCOS) and hyperprolactinaemia are both common causes of secondary amenorrhoea in reproductive women. The relationship between PCOS and hyperprolactinaemia has been reported with controversial results. To evaluate the clinical and laboratory features of women with mild hyperprolactinaemia and PCOS, we studied 474 Taiwan Chinese women: 101 had mild hyperprolactinaemia, 266 had PCOS and 107 were the control group. In this study, we found that 64% of the women with mild hyperprolactinaemia fulfilled the PCOS diagnostic criteria, regardless of their prolactin levels. Obese women with PCOS had significantly lower luteinising hormone (LH) and LH-to-FSH ratios than non-obese women with PCOS. Obese hyperprolactinaemic women had significantly lower follicle-stimulating hormone (FSH), but higher LH-to-FSH ratios than the non-obese hyperprolactinaemic women. For women with PCOS, the BMIs were significantly negative with LH (γ = -0.253, p < 0.001), but not with FSH (γ = -0.061, p = 0.319). For the hyperprolactinaemic women, the BMIs were significantly negative with FSH (γ = -0.353, p < 0.001), but not with LH (γ = -0.021, p = 0.837). Although PCOS-related syndrome was very prevalent in women with hyperprolactinaemia, the patterns of disturbance in gonadotropin secretion were different between the PCOS and the hyperprolactinaemia patients.
Bozdag, Gurkan; Yildiz, Bulent O
Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances including obesity, insulin resistance, diabetes and dyslipidemia. Cardiometabolic risk should be assessed at regular intervals starting from diagnosis. A comprehensive clinical evaluation includes determination of body mass index, waist circumference, blood pressure and measurement of serum lipid and glucose levels in all women with PCOS. A standard 2-h 75g oral glucose tolerance test is required for women with a body mass index over 25kg/m(2) and with other risk factors for glucose intolerance. No long-term data are available for the risk or benefit of any medical intervention for metabolic dysfunction of PCOS. For the initial management of metabolic dysfunction in PCOS, available guidelines recommend lifestyle intervention which improves androgen excess and insulin resistance without significant effect on glucose intolerance or dyslipidemia. Pharmacological interventions include insulin sensitizing agents and statins. Metformin is the most commonly prescribed insulin sensitizer in PCOS. Available randomized controlled trials suggest that metformin improves insulin resistance without any effect on body mass index, fasting glucose or lipid levels. Short term use of statins alone or in combination with metformin decreases total cholesterol, low-density lipoprotein-cholesterol and triglycerides in PCOS patients with dyslipidemia. Low dose oral contraception in PCOS appears not to be associated with clinically significant metabolic dysfunction.
Janssen, Onno E; Hahn, Susanne; Tan, Susanne; Benson, Sven; Elsenbruch, Sigrid
Women with polycystic ovary syndrome (PCOS) fail to conform with societal norms for outer appearance. Many PCOS patients thus feel stigmatized in the sense of a loss of "feminine identity." In addition to somatic impairment, mood disturbances such as depression and limitations in emotional well-being, quality of life, and life satisfaction, the diagnosis of PCOS also has a negative impact on sexual self-worth and sexual satisfaction. Both obesity and hirsutism are major determinants of the physical component of quality of life in affected women. However, its psychological aspect appears to be inherent and specific for PCOS. Confirmation of the diagnosis and provision of detailed information to affected women, together with the availability of interdisciplinary treatment aimed at improving PCOS-related symptoms, such as hirsutism, obesity, menstrual irregularity, and infertility, will also reduce psychological distress and improve sexual self-worth. New treatment options, including insulin sensitizers, psychological counseling, and participation in a PCOS support group, are likely to further improve life satisfaction and coping of affected women.
Bozdag, Gurkan; Yildiz, Bulent Okan
Combined oral contraceptive pills (OCPs) have been used in women with polycystic ovary syndrome (PCOS) for the treatment of menstrual disorders, acne and hirsutism. Despite years of their use and broad clinical experience, there are still ongoing doubts concerning their implications for the cardiovascular system and carbohydrate metabolism both in the general population and women with PCOS. In the general population, the risk of venous thromboembolism is reported to be increased. However, arterial thrombotic events seem to require concomitant risk factors to appear during administration of OCPs. In terms of carbohydrate metabolism, available data do not consistently suggest an increased risk of impaired glucose tolerance (IGT) or conversion of IGT to type 2 diabetes mellitus, in spite of some subtle fluctuations in glucose and insulin levels. In subgroup analyses of epidemiological studies in the general population, there is no finding indicating an increased risk of cardiovascular disease and related mortality in premenopausal women with PCOS. There is no significant alteration in carbohydrate and lipid metabolism after use of OCP in PCOS either. The absence of further cardiometabolic risk with OCP use in PCOS might suggest some unproven preventive alterations in this patient population.
Zuo, Tao; Zhu, Minghui; Xu, Wenming
Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%–12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic. PMID:26770659
Zuo, Tao; Zhu, Minghui; Xu, Wenming
Oxidative stress (OS) has received extensive attention in the last two decades, because of the discovery that abnormal oxidation status was related to patients with chronic diseases, such as diabetes, cardiovascular, polycystic ovary syndrome (PCOS), cancer, and neurological diseases. OS is considered as a potential inducing factor in the pathogenesis of PCOS, which is one of the most common complex endocrine disorders and a leading cause of female infertility, affecting 4%-12% of women in the world, as OS has close interactions with PCOS characteristics, just as insulin resistance (IR), hyperandrogenemia, and chronic inflammation. It has also been shown that DNA mutations and alterations induced by OS are involved in cancer pathogenesis, tumor cell survival, proliferation, invasion, angiogenesis, and so on. Furthermore, recent studies show that the females with PCOS are reported to have an increasing risk of cancers. As a result, the more serious OS in PCOS is regarded as an important potential incentive for the increasing risk of cancers, and this study aims to analyze the possibility and potential pathogenic mechanism of the above process, providing insightful thoughts and evidences for preventing cancer potentially caused by PCOS in clinic.
Zhang, Fan; Liu, Xiao-Ling; Rong, Nan; Huang, Xiao-Wen
The present study aimed to investigate the clinical value of serum anti-mullerian hormone (AMH) and inhibin B (INHB) in predicting the ovarian response of patients with polycystic ovary syndrome (PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group (n=36), a normal-response group (n=44), and a high-response group (n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay (ELISA). The follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic (ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index (BMI), FSH, total gonadotropin-releasing hormone (GnRH), LH, E2, and antral follicle counts (AFCs) between the groups (P<0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing (P<0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels (P<0.05). They were positively correlated with the LH levels and AFCs (P<0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve (AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/mL. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/mL, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/mL, and
Himelein, Melissa J; Thatcher, Samuel S
Common features of polycystic ovary syndrome (PCOS), including hyperandrogenism, ovarian dysfunction and obesity, can be highly distressing. We compared 40 women with PCOS to women with infertility but not PCOS, and to women with neither PCOS nor infertility, on measures of depression and body image. Women with PCOS reported higher depression scores and greater body dissatisfaction (p < .001) than comparison group women. Body image was strongly associated with depression overall, even after controlling body mass. Among women with PCOS, body dissatisfaction measures and education explained 66 percent of the variance in depression, suggesting explanations of the PCOS-depression link should consider the role of potentially mediating psychosocial variables.
Buzney, Elizabeth; Sheu, Johanna; Buzney, Catherine; Reynolds, Rachel V
Dermatologists are in a key position to treat the manifestations of polycystic ovary syndrome (PCOS). The management of PCOS should be tailored to each woman's specific goals, reproductive interests, and particular constellation of symptoms. Therefore, a multidisciplinary approach is recommended. In part II of this continuing medical education article, we present the available safety and efficacy data regarding treatments for women with acne, hirsutism, and androgenetic alopecia. Therapies discussed include lifestyle modification, topical therapies, combined oral contraceptives, antiandrogen agents, and insulin-sensitizing drugs. Treatment recommendations are made based on the current available evidence.
The objective of this study was to investigate adrenal steroid regulation in Polycystic Ovary Syndrome (PCOS). A 5-h oral glucose tolerance test (OGTT) and a 3-h frequently sampled-intravenous glucose tolerance test (FSIVGTT) were administered to 30 patients with PCOS. Anthropometric parameters (hei...
Ott, Johannes; Aust, Stefanie; Kurz, Christine; Nouri, Kazem; Wirth, Stefan; Huber, Johannes C; Mayerhofer, Klaus
In infertile women suffering from polycystic ovary syndrome (PCOS), anti-thyroid peroxidase antibodies values exceeding the upper level of normal were found in significantly more clomiphene citrate resistant patients compared clomiphene citrate responders and metformin responders. Thus, elevated antiTPO levels are associated with poor treatment response in infertile women who suffer from PCOS.
Karaca Adıyeke, Seda; Karaca, Ibrahim; Yıldırım, Suna; Adıyeke, Mehmet; Uyar, İbrahim; Türe, Gamze
Objectives: This study aimed to investigate the anterior segment in women with polycystic ovary syndrome (PCOS) and to compare them with those of healthy reproductive-age female volunteers. Materials and Methods: The study included 50 right eyes of 50 women with PCOS (group 1) and 50 right eyes of 50 healthy women (group 2). Intraocular pressure, Schirmer’s test, tear film break-up time and central corneal thickness were evaluated in all subjects. Correlations between serum hormone (estradiol and testosterone) levels and observed findings were also investigated. Results: Mean central corneal thickness values were significantly higher in the PCOS group (p=0.001). The mean intraocular pressures values were similar between the two groups (p=0.560). Schirmer’s test results and tear film break-up time values were significantly lower in the PCOS group (p=0.001 and p=0.001 respectively). Serum estradiol levels were moderately positively correlated with mean central corneal thickness (r=0.552), weakly positively correlated with intraocular pressure (r=0.351) and weakly negatively correlated with tear film break-up time (r=-0.393). Serum free testosterone levels were weakly correlated with intraocular pressure (r=0.342) and central corneal thickness (r=0.303), and showed weak negative correlations with Schirmer’s test results (r=-0.562) and tear film break-up time (r=-0.502). Conclusion: PCOS leads to physiological and structural changes in the eye. Dry eye symptoms were more severe and central corneal thickness measurements were greater in patients with PCOS. Those are correlated serum testosterone and estradiol levels. PMID:28182154
Spritzer, Poli Mara
Polycystic ovary syndrome (PCOS) is a common condition in women at reproductive age associated with reproductive and metabolic dysfunction. Proposed diagnosed criteria for PCOS include two out of three features: androgen excess, menstrual irregularity, and polycystic ovary appearance on ultrasound (PCO), after other causes of hyperandrogenism and dysovulation are excluded. Based on these diagnostic criteria, the most common phenotypes are the "classic PCOS"--hyperandrogenism and oligomenorrhea, with or without PCO; the "ovulatory phenotype"--hyperandrogenism and PCO in ovulatory women; and the "non-hyperandrogenic phenotype", in which there is oligomenorrhea and PCO, without overt hyperandrogenism. The presence of obesity may exacerbate the metabolic and reproductive disorders associated with the syndrome. In addition, PCOS women present higher risk for type 2 diabetes and higher prevalence of cardiovascular risk factors that seems to be associated with the classic phenotype. The main interventions to minimize cardiovascular and metabolic risks in PCOS are lifestyle changes, pharmacological therapy, and bariatric surgery. Treatment with metformin has been shown to improve insulin sensitivity, lowering blood glucose and androgen levels. These effects are more potent when combined with lifestyle interventions. In conclusion, besides reproductive abnormalities, PCOS has been associated to metabolic comorbidities, most of them linked to obesity. Confounders, such as the lack of standard diagnostic criteria, heterogeneity of the clinical presentation, and presence of obesity, make management of PCOS difficult. Therefore, the approach to metabolic abnormalities should be tailored to the risks and treatment goals of each individual woman.
Amjadi, Fatemehsadat; Aflatoonian, Reza; Javanmard, Shaghayegh Haghjoo; Saifi, Bita; Ashrafi, Mahnaz; Mehdizadeh, Mehdi
Background: Women with polycystic ovary syndrome have lower pregnancy rates, possibly due to the decreased uterine receptivity. Successful implantation depends on protein networks that are essential for cross-talk between the embryo and endometrium. Apolipoprotein A1 has been proposed as a putative anti-implantation factor. In this study, we evaluated apolipoprotein A1 expression in human endometrial tissues. Materials and Methods: Endometrial apolipoprotein A1 messenger RNA (mRNA) and protein expression were investigated using quantitative real-time polymerase chain reaction (PCR) and Western blot. The distribution of apolipoprotein A1 was also detected by immunostaining. Samples were obtained from 10 patients with polycystic ovary syndrome and 15 healthy fertile women in the proliferative (on day 2 or day 3 before ovulation, n = 7) and secretory (on days 3-5 after ovulation, n = 8) phases. Results: Endometrial apolipoprotein A1 expression was upregulated in patients with polycystic ovary syndrome compared to normal subjects. However, apolipoprotein A1 expression in the proliferative phase was significantly higher than in the luteal phase (P value < 0.05). Conclusion: It seems that differentially expressed apolipoprotein A1 negatively affects endometrial receptivity in patients with polycystic ovary syndrome. The results showed that apolipoprotein A1 level significantly changes in the human endometrium during the menstrual cycle with minimum expression in the secretory phase, coincident with the receptive phase (window of implantation). Further studies are required to clarify the clinical application of this protein. PMID:26941806
Hirsutism affects 5-25% women, and the condition is most often caused by polycystic ovary syndrome (PCOS). The initial evaluation of hirsute patients should include a thorough medical history, clinical evaluation, and standardized blood samples to diagnose the 5% hirsute patients with rare endocrine disorders. The majority of these examinations can be performed by the patient's general practitioner. PCOS is a diagnosis of exclusion and is a multiorgan disease affecting most endocrine organs including ovaries, adrenals, pituitary, fat cells, and endocrine pancreas. The manifestations of PCOS are diverse, and up to 50% patients are normal weight. In most cases, however, the severity of symptoms can be related to abdominal obesity. Increased inflammation in PCOS can be measured as decreased adiponectin levels and increased levels of adipokines, chemokines, and interleukins. In the present thesis the use of these inflammatory markers is reviewed, but more data including hard end points are needed to determine which of these markers that should be introduced to the daily clinic. Abdominal obesity and insulin resistance stimulates ovarian and adrenal androgen production, whereas SHBG levels are decreased. Increased testosterone levels may further increase abdominal obesity and inflammation, therefore describing PCOS as a vicious cycle. Abdominal obesity and increased activation of the inflammatory system is seen in both normal weight and obese PCOS patients leading to an increased risk of dyslipidemia, diabetes, and possibly cardiovascular disease. Patients diagnosed with PCOS therefore should be screened for elements in the metabolic syndrome including weight, waist, blood pressure, HbA1c, and lipid status. Our data supported that prolactin and HbA1c levels could be markers of cardiovascular risk and should be confirmed by prospective studies. PCOS is a life-long condition and treatment modalities involve lifestyle modification, insulin sensitizers such as metformin, or
Kahyaoglu, Serkan; Yumuşak, Omer Hamid; Ozyer, Sebnem; Pekcan, Meryem Kuru; Erel, Merve; Cicek, Mahmut Nedim; Erkaya, Salim; Tasci, Yasemin
Background Polycystic ovary syndrome (PCOS) is highly associated with an ovulatory infertility, features of the metabolic syndrome, including obesity, insulin resistance and dyslipidemia. Serum concentrations of high sensitive C-reactive protein (hs-CRP) were significantly higher in obese than in non-obese PCOS patients at baseline, suggesting a relationship between elevated hs-CRP levels and obesity. The aim of this study was to evaluate whether cycle day 3 hs-CRP levels before clomiphene citrate (CC) treatment would predict cycle outcomes in women with PCOS. Materials and Methods This cross-sectional study was conducted among 84 infertile women with PCOS who were treated with CC at Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey, between January 2014 and January 2015. Based on the exclusion criteria, cycle outcomes of remaining 66 infertile women with PCOS treated with CC were analyzed. The hs-CRP levels and insulin resistance indexes were evaluated on day 3 of the CC treatment cycle. The primary outcome measures were number of preovulatory follicles measuring≥17 mm and pregnancy rates. Results The mean ± SD age of the patients was 24.0 ± 3.8 years (range 18-36). The mean ± SD body mass index (BMI) of the patients was 25.7 ± 4.9 (range 17-43). Fifty patients developed dominant follicle (75%) and 5 patients established clinical pregnancy during the study (clinical pregnancy rate: 7%). The mean ± SD baseline hs-CRP, fasting insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values of the patients with and without dominant follicle generation during treatment cycle were 6.42 ± 7.05 and 4.41 ± 2.95 (P=0.27), 11.61 ± 6.94 and 10.95 ± 5.65 (P=0.73), 2.68 ± 1.79 and 2.41 ± 1.30 (P=0.58), respectively. The mean ± SD baseline hs-CRP, fasting insulin and HOMA-IR values of the patients with and without clinical pregnancy establishment following treatment cycle were 6.30 ± 2.56 and 5.90 ± 6.57 (P=0.89), 11
Wang, Xuefeng; Yang, Yue; Huang, Yanbing; Wang, Qiongyao
Objective: To study the distribution of polymorphism of FXIIIVal34Leu gene in patients with polycystic ovary syndrome and to explore its relationship with polycystic ovary syndrome. Methods: FXIIIVal34Leu genotype of 120 patients with polycystic ovary syndrome (PCOS) and 90 controls was detected, and the endocrine and metabolic conditions of PCOS patients and the control group were analyzed. Results: Body mass index (BMI) of PCOS patients (26.45±5.81) kg/m2 was higher than the control group (22.33±5.58) kg/m2, (p=0.00); the androgen level of PCOS group was (0.67±0.85) ng/mL higher than the control group (0.42±0.22) ng/mL, (p=0.02), and the luteinizing hormone (LH) (16.8±3.61 IU/L) level is higher than the control group (9.23±4.67) IU/L, (p=0.01). Frequency of Val34Leu allele in PCOS group was 1.25%, which was not statistically significant compared to the control group (P=0.56). BMI of patients with the genotype of FXIIIVal34Leu was relatively higher (with the average 34±1 kg/m2), and serum HDL level was significantly lower (0.23±0.11 mmol/L). Polymorphism of FXIIIVal34Leu gene had no correlation with susceptibility of PCOS. Conclusion: Polymorphism of FXIIIA1 gene may be related to metabolism of PCOS patients; the mutation of FXIIIAVal34Leu is not at the common site for PCOS; polymorphism of FXIIIVal34Leu gene may not have correlation with PCOS. PMID:25550970
Unlu, Ebru; Unlu, Bekir Serdar; Turamanlar, Ozan; Acay, Mehtap Beker; Kacar, Emre; Yıldız, Yunus; Verim, Ozgur; Okur, Nazan; Balcik, Cinar; Tasgetiren, Suleyman; Yucel, Aylin
The purpose of this prospectively designed cross-sectional observational study was to evaluate the effect of polycystic ovary syndrome (PCOS) on pituitary gland volume (PGV) under the hypothesis that endocrinologic changes may lead to morphologic changes of the pituitary gland. Twenty-six PCOS patients and 31 control subjects underwent magnetic resonance imaging (MRI) of the pituitary. Informed consent was obtained from all subjects. PGV was significantly larger in PCOS patients than in control subjects. Luteinizing hormone/follicle-stimulating hormone ratio was the only predictor of PGV. The association between pituitary gland enlargement and PCOS should be kept in mind when pituitary hypertrophy is detected on MRI.
Steiner, Charles A.; Janez, Andrej; Jensterle, Mojca; Reisinger, Katrin; Forst, Thomas; Pfützner, Andreas
Background There is increasing evidence that insulin resistance (IR) has an important implication in the pathogenesis of polycystic ovary syndrome (PCOS), a common endocrinopathy in women. This study was performed to investigate the impact of different treatments for IR on five currently discussed markers for insulin resistance: intact proinsulin, adiponectin, retinol-binding protein 4 (RBP4), resistin, and visfatin in patients with PCOS. Methods Thirty-five women with clinically confirmed PCOS diagnosis were included in the study [age (mean±SD): 24.7±4.8 years; body mass index: 27.4±6.0 kg/m2]. They were randomized to receive either metformin (850 mg twice a day) or rosiglitazone (4 mg once a day). Blood samples for measurement of the HOMAIR score, visfatin, RBP4, intact proinsulin, resisitin, and adiponectin were taken at baseline and after 6 months of treatment. Results Both drugs improved ovulation, and an increase in insulin sensitivity was observed, especially in the rosiglitazone arm. Adiponectin levels increased in both treatment arms (metformin: 8.6±3.3 to 16.7±7.2 mg/liter, p < 0.001; rosiglitazone: 8.2±3.5 to 26.2±9.5 mg/liter, p < 0.001), but the increase was more pronounced with rosiglitazone (p < 0.001). While no changes of visfatin concentrations were observed during rosiglitazone therapy (15.4±6.9 ng/ml vs 17.4±4.8 ng/ml, n.s.), there was an increase in the metformin treatment arm (11.9±4.0 to 21.8±8.3 ng/ml, p < 0.001). Significant increases demonstrated for RBP4 in both treatment arms were more pronounced in the metformin group (metformin: +66%, rosiglitazone: +33%). All patients were in stage I or II of ß-cell dysfunction and none of them showed increased intact proinsulin levels or changes in resisitin at baseline or end point. Conclusions Both drugs slightly improved ovulation in our PCOS patient population during 6 months of therapy, which was accompanied by improved insulin sensitivity and an increase in adiponectin levels
Blumenfeld, Zeev; Kaidar, Gabi; Zuckerman-Levin, Nehama; Dumin, Elena; Knopf, Carlos; Hochberg, Ze’ev
OBJECTIVE The aim of this study was to assess the activity of cortisol-metabolizing enzymes in women with polycystic ovary syndrome (PCOS), using a fully quantitative gas chromatography/mass spectrometry (GCMS) method. DESIGN We investigated the glucocorticoid degradation pathways that include 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1, 5α-reductase (5α-R) and 5β-reductase (5β-R), 3α-hydroxysteroid dehydrogenase, and 20α- and 20β-hydroxysteroid dehydrogenase (20α-HSD and 20β-HSD, respectively) in young nonobese women with PCOS, using a fully quantitative GCMS method. SETTING This study was conducted in a tertiary referral hospital in Israel. PATIENTS This study group consisted of 13 young women, aged 20.1 ± 2.8 years (mean ± SD), with the body mass index (BMI) of 22.6 ± 3.7 kg/m2, diagnosed with PCOS according to the Rotterdam criteria. The control group consisted of 14 healthy young women matched for weight, height, and BMI. INTERVENTIONS Urine samples were analyzed using GCMS. We measured urinary steroid metabolites that represent the products and substrates of the study enzymes and calculated the product/substrate ratios to represent enzyme activity. MAIN OUTCOME MEASURES The calculation of enzymatic activity, based on glucocorticoid degradation metabolites, was done by GCMS in PCOS vs. controls. RESULTS All glucocorticoid degradation metabolites were higher in the PCOS group than in controls. Of the adrenal enzymes, the activities of 21-hydroxylase and 17α-hydroxylase were reduced, whereas the activity of 17,20-lyase was enhanced in PCOS. Of the degradation enzymes, the activity of 11β-HSD type 1 was reduced in women with PCOS only when calculated from cortoles and cortolones ratios. The activities of 5α-R/5β-R were increased only when calculating the 11-hydroxy metabolites of androgens. The activity of 20α-HSD was elevated in the patients with PCOS and its relation with the substrate levels was lost. CONCLUSIONS We confirm PCOS
Raja-Khan, Nazia; Urbanek, Margrit; Rodgers, Raymond J; Legro, Richard S
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligoanovulation and hyperandrogenism and associated with insulin resistance, type 2 diabetes, and cardiovascular risk. In recent years, genetic studies have linked PCOS to a dinucleotide marker D19S884 in the fibrillin 3 gene. Fibrillins make up the major component of microfibrils in the extracellular matrix (ECM) and interact with molecules in the ECM to regulate transforming growth factor β (TGF-β) signaling. Therefore, variations in fibrillin 3 and subsequent dysregulation of TGF-β may contribute to the pathogenesis of PCOS. Here, we review the evidence from genetic studies supporting the role of TGF-β in PCOS and describe how TGF-β dysregulation may contribute to (1) the fetal origins of PCOS, (2) reproductive abnormalities in PCOS, and (3) cardiovascular and metabolic abnormalities in PCOS.
The etiology of the polycystic ovary syndrome (PCOS) remains unclear, despite its high prevalence among infertility disorders in women of reproductive age. Although there is evidence for a genetic component of the disorder, other causes, such as prenatal insults are considered among the potential factors that may contribute to the development of the syndrome. Over the past few decades, several animal models have been developed in an attempt to understand the potential contribution of exposure to excess steroids on the development of this syndrome. The current review summarizes the phenotypes of current animal models exposed to excess steroid during the prenatal and early postnatal period and how they compare with the phenotype seen in women with PCOS. PMID:23701728
Palioura, Eleni; Diamanti-Kandarakis, Evanthia
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure.
Polycystic ovary syndrome (PCOS) is a major public health problem in the US. Worldwide, the public is largely unaware of the condition and health care providers do not seem to fully understand it. Research on PCOS has primarily focused on its etiology and clinical characteristics and less on the psychosocial aspects of human development associated with PCOS. This paper posits that a life course perspective provides a framework for further understanding the psychosocial experiences of women with PCOS and the contexts in which they live. The paper discusses how life course principles of human development, constraints on agency, interdependence of lives, time and place, and timing of events and experiences are relevant to the management of PCOS and prevention of its complications.
Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age.
Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age. PMID:26473107
Feichtinger, Michael; Stopp, Tina; Göbl, Christian
Polycystic ovarian syndrome represents the most common endocrine disease of women of reproductive age. Symptoms include metabolic, gynecologic and cosmetic features. Genetic factors seem to contribute to the disease, affecting not only women but also male relatives of patients with similar symptoms. Besides, lifestyle factors play a central role impacting clinical PCOS appearance. Following we present an overview of the syndrome, its epidemiology, metabolic and gynecological aspects, gender and genetic factors and its therapy.
Inan, Cihan; Karadag, Cihan
Objective: To determine the biochemical and hormonal differences in polycystic ovary syndrome (PCOS) patients with and without polycystic ovary (PCO) morphology and to evaluate the outcomes resulting from those differences. Methods: The study included a total of 83 patients with PCOS; 43 of them had PCO morphology (Group-I) and 40 did not (Group-II). Serum LDL, HDL, total cholesterol, triglyceride (TG), total testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17b-estradiol (E2), prolactin (PRL), thyroid stimulating hormone (TSH), sex hormone binding globulin (SHBG), glucose and insulin levels were determined. Homoeostatic model assessment insulin resistance (HOMA-IR) index was calculated. Results: The two groups were similar with respect to BMI. The systolic and diastolic blood pressure measurements of Group-I were significantly lower (p<0.01). Serum mean level of LH (p=0.026) and the mean LH/FSH (p=0.001) level of Group-I were significantly higher than Group-II. The total cholesterol and triglyceride levels of Group-I were significantly lower (p<0.05, p<0.01). The mean HOMA-IR level of Group-I was significantly lower than Group-II (p=0.004). Conclusions: The group without PCO morphology had a higher risk than the other group in terms of increased insulin resistance, dyslipidemia and cardiovascular diseases due to effects of hyperandrogenism. PMID:27375725
Montezuma, Thais; Antônio, Flávia Ignácio; de Sá Rosa e Silva, Ana Carolina Japur; de Sá, Marcos Felipe Silva; Ferriani, Rui Alberto; Ferreira, Cristine Homsi Jorge
OBJECTIVES: The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. METHODS: One hundred thirteen 18- to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls) were recruited at the University Hospital of School Medicine of São Paulo University at Ribeirão Preto City, Brazil. The subjects were not taking any hormonal medication, had not undergone previous pelvic surgery and did not exercise their pelvic floor muscles. The women were divided into the following four groups: I- polycystic ovary syndrome with normal body mass index (n = 18), II- polycystic ovary syndrome with body mass index ≥25 (n = 32), III- controls with normal body mass index (n = 29), and IV- controls with Body Mass Index ≥25 (n = 34). Quality of life was evaluated using the SF-36 questionnaire, and the subjects with urinary complaints also completed the International Consultation on Incontinence Questionnaire Short Form to evaluate the severity of their urinary incontinence. RESULTS: The replies to the International Consultation on Incontinence Questionnaire Short Form revealed a significant difference in urinary function between groups, with 24% of the subjects in group IV reporting urinary incontinence. The mean scores for the SF-36 questionnaire revealed that group II had the lowest quality of life. CONCLUSIONS: The control obese group (IV) reported a higher prevalence of urinary incontinence. There was no difference in the reported frequency of urine loss between the polycystic ovary syndrome and control groups with normal body mass index or between the polycystic ovary syndrome and control groups with body mass index ≥25. PMID:22086521
Nasri, Khadijeh; Hantoushzadeh, Sedigheh; Aghadavod, Esmat; Taghizadeh, Mohsen; Asemi, Zatollah
Limited data are available evaluating the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid-signaling pathway in women with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid signaling pathway in women with PCOS. This randomized double blind, placebo-controlled trial was done among 60 women aged 18-40 years old and diagnosed with PCOS according to the Rotterdam criteria. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid (n=30) or placebo (n=30) twice a day for 12 weeks. Gene expressions involved in the insulin and lipid-signaling pathway were quantified in blood samples of PCOS women with RT-PCR method. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) mRNA (p=0.005) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo, omega-3 fatty acids supplementation downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA (p=0.002) in peripheral blood mononuclear cells of women with PCOS. We did not observe any significant effect of omega-3 fatty acids supplementation on expressed levels of glucose transporter 1 (GLUT-1) and lipoprotein(a) [Lp(a)] genes in peripheral blood mononuclear cells. Overall, omega-3 fatty acids supplementation for 12 weeks in PCOS women significantly improved gene expression of PPAR-γ and LDLR.
Context: Polycystic ovary syndrome (PCOS) is a common complex genetic disease. It is characterized by hyperandrogenism, gonadotropin secretory changes, polycystic ovarian morphology, and insulin resistance. The etiology of PCOS remains unknown, but modern genetic approaches, such as genome-wide association studies (GWAS), Mendelian randomization, and next-generation sequencing, promise to identify the pathways that are primarily disrupted. Evidence Acquisition: The literature on PCOS, including the author's research, is discussed. Evidence Synthesis: Recent genetic analyses are reviewed. Conclusions: Considerable progress has been made mapping PCOS susceptibility genes. GWAS have implicated gonadotropin secretion and action as important primary defects in disease pathogenesis in European and Han Chinese PCOS cohorts, respectively. European women with the National Institutes of Health and Rotterdam phenotypes as well as those with self-reported PCOS have some gene regions in common, such as chromosome 11p14.1 region containing the FSH B polypeptide (FSHB) gene, suggesting shared genetic susceptibility. Several chromosomal signals are significant in both Han Chinese and European PCOS cohorts, suggesting that the susceptibility genes in these regions are evolutionarily conserved. In addition, GWAS have suggested that DENND1A, epidermal growth factor signaling, and DNA repair pathways play a role in PCOS pathogenesis. Only a small amount of the heritability of PCOS is accounted for by the common susceptibility variants mapped so far. Future studies should clarify the contribution of rare genetic variants and epigenetic factors to the PCOS phenotype. Furthermore, Mendelian randomization can be used to clarify causal relationships, and phenome-wide association studies can provide insight into health risks associated with PCOS susceptibility variants. PMID:26908109
Rosenfield, Robert L; Ehrmann, David A
Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity
Akpinar, Funda; Dilbaz, Berna; Cirik, Derya A.; Yılmaz, Saynur; Kıykac, Sadıman; Karahanoglu, Ertugrul; Mollamahmutoglu, Leyla
Objectives: To investigate factors associated with the response to ovarian stimulation in patients with polycystic ovary syndrome. Methods: The records of patients with polycystic ovary syndrome and infertility who underwent ovulation induction with clomiphene citrate were reviwed between January 2011 and December 2014 in Etlik Zübeyde Hanim Women’s Health Training and Research Hospital Ankara, Turkey. The anthropometric and endocrine factors of patients who were resistant to treatment at a dose of 150 mg/day (n=84) were compared with those who responded with growth of at least one graaffian follicle at a dose of 50 mg/day (n=342). Results: Of the parameters examined, body mass index, luteinizing hormone level, and luteinizing hormone/follicle stimulating hormone ratio were significantly higher in the clomiphene citrate-resistant group compared with the responsive group. Conclusion: Reproductive treatment in patients with polycystic ovary syndrome show different outcomes. Significantly higher body mass index, luteinizing hormone level, and luteinizing hormone/follicle stimulating hormone ratio observed in clomiphene citrate resistant group can be a possible explanation for this impedance. PMID:27761570
Falsetti, L; Gambera, A; Andrico, S; Sartori, E
The aim of this study was to investigate whether the absence or presence of acne or hirsutism in 248 women with polycystic ovary syndrome was associated with different clinical, endocrine, metabolic and ultrasonographic factors. Patients were divided into three groups: 96 (38.7%) without any androgenic symptoms; 94 (37.9%) with only hirsutism; and 58 (23.4%) with only acne. The cycle alterations (oligomenorrhea or amenorrhea) and the echographic ovarian morphology (polycystic or multifollicular ovaries) showed no significant differences between the three groups. Hirsutism was associated with a greater incidence of obesity and insulin resistance, with an increase of 17-hydroxyprogesterone, ovarian and adrenal androgens, 3alpha-androstanediol glucuronide, insulin, insulin-like growth factor-I and low luteinizing hormone, sex hormone binding globulins and insulin-like growth factor binding protein-1 levels. Acne was associated only with the lowest 3alpha-androstanediol glucuronide levels. Therefore, two different pathogenetic mechanisms may play a role in the onset of acne and hirsutism.
Arain, Farzana; Arif, Nesreen; Halepota, Hafeez
Background: Infertility is defined as inability of couple to conceive after one year of unprotected intercourse. The prevalence of infertility in Pakistan is 21.9%. The most common cause of medically treatable infertility is polycystic ovarian syndrome (PCO). This study was conducted to see the frequency and outcome of treatment in PCOs related infertility in infertile couples coming to Mohammad Medical College Hospital, Mirpurkhas, Sindh. Methods: This prospective observational study was conducted at Muhammad Medical College for three years from 2005 to 2008. Total 1289 infertile couples were included in this study. Result: The frequency of PCOs in female related infertility was 38.5%. Other causes of female infertility were in the frequency of 44% pelvic inflammatory disease, 12.3% endometriosis, 2.9% hyperprolactenemia, and 1.35% hypothyroidism. Patients with PCOS were given different treatment modalities. One hundred fifty patients with PCO were given ovulation induction with clomephene citrate and out of them 109 (72%) conceived. Sixty three women were given combination of clomephene citrate and Metformin. Out of them 50 (79%) conceived. Five patients were given gonadotrophins, Out of them 2 (40%) patients conceived. Five patients had laparoscopic drilling out of them 3 (60%) conceived. Conclusion: In contrast to the literature review Polycystic Ovarian Syndrome turned out to be the second most common cause of female related infertility. But as the international literature shows it had very good out come after medical and /or surgical treatment. PMID:26150870
Mahalingaiah, Shruthi; Diamanti-Kandarakis, Evanthia
Introduction Metabolic syndrome is comprised of a combination of the following states: increased insulin resistance, dyslipidemia, cardiovascular disease, and increased abdominal obesity. Women with polycystic ovary syndrome (PCOS) have an increased risk of developing metabolic syndrome over the course of their lives. Metabolic syndrome increases risk of major cardiovascular events, morbidity, quality of life, and overall health care costs. Though metabolic syndrome in women with PCOS is an area of great concern, there is no effective individual medical therapeutic to adequately treat this issue. Areas Covered This article will review key aspects of metabolic syndrome in PCOS. We will discuss classic and novel therapeutics to address metabolic syndrome in women with PCOS. We will conclude with the importance of developing strategic interventions to increase the compliance to lifestyle and dietary modification, in addition to appreciation of the emerging pharmaceutical therapeutics available. Expert Opinion Innovation in lifestyle modification, including diet, exercise, with and without dedicated stress reduction techniques is the future in treatment of metabolic syndrome in PCOS. Application of novel interventions, such as group medical care, may improve future adherence to lifestyle modification recommendations, in addition to or in combination with pharmaceutical therapeutics. PMID:26488852
Boomsma, Carolien M; Fauser, Bart C J M; Macklon, Nick S
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. There is an increasing body of evidence indicating that PCOS may have significant implications for pregnancy outcomes and long-term health of a woman and her offspring. Whether or not PCOS itself or the symptoms that coincide with PCOS, like obesity and fertility treatment, are responsible for these increased risks is a continuing matter of debate. Miscarriage rates among women with PCOS are believed to be increased compared with normal fertile women, although supporting evidence is limited. Pregnant women with PCOS experience a higher incidence of perinatal morbidity from gestational diabetes, pregnancy-induced hypertension, and preeclampsia. Their babies are at an increased risk of neonatal complications, such as preterm birth and admission at a neonatal intensive care unit. Pre-pregnancy, antenatal, and intrapartum care should be aimed at reducing these risks. The use of insulin sensitizing drugs to decrease hyperinsulinemic insulin resistance has been proposed during pregnancy to reduce the risk of developing preeclampsia or gestational diabetes. Although metformin appears to be safe, there are too few data from prospective, randomized controlled trials to support treatment during pregnancy.
Vélez, Leandro Martín; Motta, Alicia Beatriz
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder affecting women in reproductive age. Although the etiology of PCOS remains unclear, it is believed to result from genetic, environmental and behavioral interactions. Women with PCOS have higher lifetime risk for cardiovascular disease (CVR) than healthy women at the same age and tend to display insulin resistance (IR). IR has traditionally been defined as a decreased ability of insulin to mediate the metabolic actions on glucose uptake, glucose production, and/or lipolysis. This results in a requirement for increased amounts of insulin to achieve a given metabolic action. Metabolic syndrome (MS) includes hyperinsulinemia, dyslipidemia, increased CVR and hyperleptinemia and metabolic disorders such as hypertension, IR, gestational diabetes, type 2 diabetes mellitus, systemic inflammation and endothelial dysfunction. The prevalence of MS in women is around 50 %. In addition, it has been recently suggested that women with MS show increased circulating androgens. The present review discusses the main alterations and features of PCOS and MS and the most important treatments.
Caserta, Donatella; Adducchio, Gloria; Picchia, Simona; Ralli, Eleonora; Matteucci, Eleonora; Moscarini, Massimo
Metabolic syndrome is an increasing pathology in adults and in children, due to a parallel rise of obesity. Sedentary lifestyle, food habits, cultural influences and also a genetic predisposition can cause dyslipidemia, hypertension, abdominal obesity and insulin resistance which are the two main features of metabolic syndrome. Polycystic ovary syndrome (PCOS) is a condition directly associated with obesity, insulin resistance (HOMA index) and metabolic syndrome, and it is very interesting for its relationship and overlap with the metabolic syndrome. The relationship between the two syndromes is mutual: PCOS women have a higher prevalence of metabolic syndrome and also women with metabolic syndrome commonly present the reproductive/endocrine trait of PCOS. Prevention and treatment of metabolic syndrome and PCOS are similar for various aspects. It is necessary to treat excess adiposity and insulin resistance, with the overall goals of preventing cardiovascular disease and type 2 diabetes and improving reproductive failure in young women with PCOS. First of all, lifestyle changes, then pharmacological therapy, bariatric surgery and laparoscopic ovarian surgery represent the pillars for PCOS treatment.
Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.
Guo, Yanjie; Qi, Yane; Yang, Xuefei; Zhao, Lihui; Wen, Shu; Liu, Yinhui; Tang, Li
Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats. PMID:27093642
Agapova, Sophia E.; Cameo, Tamara; Sopher, Aviva B.; Oberfield, Sharon E.
Although the diagnostic criteria for polycystic ovary syndrome (PCOS) have become less stringent over the years, determination of the minimum diagnostic features in adolescents is still an area of controversy. Of particular concern is that many of the features considered to be diagnostic for PCOS may evolve over time and change during the first few years after menarche. Nonetheless, attempts to define young women who may be at risk for development of PCOS is pertinent since associated morbidity such as obesity, insulin resistance, and dyslipidemia may benefit from early intervention. The relative utility of diagnostic tools such as persistence of anovulatory cycles, hyperandrogenemia, hyperandrogenism (hirsutism, acne, or alopecia), or ovarian findings on ultrasound is not established in adolescents. Some suggest that even using the strictest criteria, the diagnosis of PCOS may not valid in adolescents younger than 18 years. In addition, evidence does not necessarily support that lack of treatment of PCOS in younger adolescents will result in untoward outcomes since features consistent with PCOS often resolve with time. The presented data will help determine if it is possible to establish firm criteria which may be used to reliably diagnose PCOS in adolescents. PMID:24715514
Barrett, Emily S.; Sobolewski, Marissa
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by multiple endocrine disturbances and its underlying causes, although uncertain, are likely to be both genetic and environmental. Recently, there has been interest in whether endocrine disrupting chemicals (EDCs) in the environment, particularly Bisphenol A (BPA), may contribute to the disorder. In animal models, exposure to BPA during the perinatal period, dramatically disrupts ovarian and reproductive function in females, often at doses similar to typical levels of human exposure. BPA also appears to have obesogenic properties, disrupting normal metabolic activity and making the body prone to overweight. In humans, cross-sectional data suggests that BPA concentrations are higher in women with PCOS than in reproductively healthy women, but the direction of causality has not been established. As this research is in its infancy, additional work is needed to understand the mechanisms by which EDCs may contribute to PCOS as well as the critical periods of exposure, which may even be transgenerational. Future research should also focus on translating the promising work in animal models into longitudinal human studies and determining whether additional EDCs, beyond BPA, may be important to consider. PMID:24715511
Saha, Lekha; Kaur, Sharonjeet; Saha, Pradip Kumar
Polycystic ovary syndrome (PCOS) is a persisting challenge to clinical and basic research scientists as none of the presently available medications have been fully able to combat these consequences. The aim of the present review is to summarize the different lines of treatment available for the different symptomologies that women with PCOS presents. In this comprehensive review, search was made for various treatment options available for PCOS by using Cochrane library, Pubmed, Medline, in addition to the relevant printed medical journals and periodicals. The search results revealed that oral contraceptives containing oestrogen and progesterone regularize the menstruation, antiandrogens like spironolactone and drosperinone have proven to be effective in hirsutism and acne, clomiphene is the gold standard for ovulation induction, but multiple pregnancies and clomiphene failure add to its limitation. Hence, aromatase inhibitors like letrozole, low-dose gondotropins, and ovarian drilling procedure have shown to be beneficial effect in clomiphene-resistant cases. Insulin sensitizers such as metformin, thiazolidinediones, and d-chiro-inositol increase insulin sensitivity and improve ovulation rate. Recently, melatonin, N-acetyl cysteine, acarbose, and statins have shown positive results in different symptomologies of PCOS. The results show that PCOS treatment constitutes varied line of treatment depending upon the clinical features with which a woman is presenting. Still, unfortunately, none of the treatments are fully able to combat the PCOS.
Jiang, Li-Le; Xie, Juan-Ke; Cui, Jin-Quan; Wei, Duo; Yin, Bao-Li; Zhang, Ya-Nan; Chen, Yuan-Hui; Han, Xiao; Wang, Qian; Zhang, Cui-Lian
Abstract Background: DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS. Methods: Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR. Results: Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (−443, −431, −403, −371, −331, −120, −49, −5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose–dependent relation. Conclusion: Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS. PMID:28079802
Leptin concentrations in patients with polycystic ovary syndrome before and after met-formin treatment depending on insulin resistance, body mass index and androgen con-centrations--introductory report.
Marciniak, Aleksandra; Nawrocka-Rutkowska, Jolanta; Brodowska, Agnieszka; Sienkiewicz, Robert; Szydłowska, Iwona; Starczewski, Andrzej
Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder which may concern about 3-8% of women. Some PCOS women have the increased leptin concentration in blood serum. Leptin concentration is higher in patients with high body mass index (BMI) and impaired tissue sensitivity to insulin. The aim of this study was to determine leptin concentrations in PCOS patients before and after metformin treatment depending on BMI, insulin resistance calculated on the basis of the Homeostasis Model Assessment (HOMA) index, as well as concentrations of androgens: testosterone and androstendion. Such values as BMI, insulin resistance according to the HOMA index, and concentrations of androstendion, testosterone and leptin were determined in 35 patients with PCOS before and after 3-month metformin treatment administered in daily doses of 2 x 850 mg. Increased leptin levels before the therapy were observed in 91.3% (21 out of 23) of obese patients, in 75% (9 out of 12) non-obese patients, in 100% (8 patients) insulin resistance women, in 81.5% (22 out of 27) insulin sensitive patients, in 94.7% (18 out of 19) women with elevated androstendion concentration and in 75% (12 out of 16) with normal androstendion concentration, in 93.7% (15 out of 16) patients with increased testosterone concentration and in 78.9% (15 out of 19) patients with testosterone concentrations within the normal range. After treatment statistically significant decrease in leptin concentration was obtained in the patients with BMI
Panico, Annalisa; Messina, Giovanni; Lupoli, Gelsy Arianna; Lupoli, Roberta; Cacciapuoti, Marianna; Moscatelli, Fiorenzo; Esposito, Teresa; Villano, Ines; Valenzano, Anna; Monda, Vincenzo; Messina, Antonietta; Precenzano, Francesco; Cibelli, Giuseppe; Monda, Marcellino; Lupoli, Giovanni
Objective Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are overweight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients’ quality of life and to what extent obesity contributes to worsen this disease. Design To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) >25 kg/m2 (group A1) and 50 with BMI <25 kg/m2 (group A2), were recruited. They were evaluated with a specific combination of standardized psychometric questionnaires: the Symptom Checklist-90 Revised, the 36-Item Short-Form Health Survey, and the Polycystic Ovary Syndrome Questionnaire. The patients were compared with a normal-weight healthy control group of 40 subjects (group B). Another control group of 40 obese healthy women (group C) was used to make a comparison with PCOS obese patients (A1). Results Our results showed a considerable worsening of HRQoL in PCOS patients (A) compared with controls (B). In addition, patients with PCOS and BMI >25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). Conclusion PCOS is a complex disease that alone determines a deterioration of HRQoL. The innovative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress. PMID:28280314
Upadhya, Krishna; Trent, Maria
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5-10% of women of reproductive age. The health risks associated with PCOS include infertility, diabetes, metabolic syndrome and endometrial cancer. In this article, we review the tools used to assess health-related quality of life (HRQL) and the current state of knowledge of the effects of PCOS on HRQL in adult women and adolescent girls. A significant body of evidence consistently demonstrates that PCOS has a negative impact on women's HRQL. This impact does not necessarily correlate with clinical measures of disease severity. There is evidence that the effect on HRQL may be mediated by obesity, infertility concerns and menstrual dysfunction. Cross-cultural studies suggest that the effect of PCOS on the HRQL of an individual patient may be specific to the perception, values and culture of that patient.
Patients who have polycystic ovary syndrome (PCOS) present with infertility, recurrent miscarriages, menstrual irregularities, hirsutism, and acne. Many also have metabolic and hormonal abnormalities that can significantly increase risk for coronary artery disease, type 2 diabetes mellitus, and endometrial carcinoma. PCOS patients should be screened for obstructive sleep apnea. Early recognition may reverse physical signs of the disease, while correcting the metabolic abnormalities that can pose significant health risk if untreated. Although lifestyle modification and pharmacotherapy are used to treat PCOS, there are few long-term outcome data regarding benefits of metabolic interventional strategies. Insulin sensitizers can improve ovulatory function, lower insulin resistance, lower androgen levels, and increase the likelihood of becoming pregnant. Further studies should yield other treatment options.
Davies, Michael J.; Marino, Jennifer L.; Willson, Kristyn J.; March, Wendy A.; Moore, Vivienne M.
Background Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. Objective To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. Design, Setting and Participants Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. Results and Conclusions Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations. PMID:21991389
Gaberšček, Simona; Zaletel, Katja; Schwetz, Verena; Pieber, Thomas; Obermayer-Pietsch, Barbara; Lerchbaum, Elisabeth
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.
Herlihy, A C; Kelly, R E; Hogan, J L; O'Connor, N; Farah, N; Turner, M J
This retrospective cross-sectional study examined if the white cell count (WCC) is increased in women with polycystic ovary syndrome (PCOS) and if so, is it due to PCOS or to the associated obesity? Body mass index (BMI) was calculated and body composition was measured using bioelectrical impedance analysis. Of the 113 women studied, 36 had PCOS and 77 did not. The mean WCC was higher in the PCOS group compared with the non-PCOS group (8.9 × 10(9)/l vs 7.4 × 10(9)/l p = 0.002). This increase was due to a higher neutrophil count (5.6 × 10(9)/l vs 4.3 × 10(9)/l; p = 0.003). There was a leucocytosis (WCC >11 × 10(9)/l) present in 19% of the PCOS group compared with 1% in the non-PCOS group (p < 0.001). The neutrophil count was abnormally high (>7.7 × 10(9)/l) in 14% of the PCOS group compared with 4% in the non-PCOS group (p < 0.001). On regression analysis, however, the only independent variable which explained both the increased WCC and the increased neutrophil count was PCOS. We found that PCOS is associated with an increased WCC due to increased neutrophils, which supports the evidence that PCOS is associated with low-grade inflammation. The increase appears to be due to the underlying PCOS, and not to the increased adiposity associated with PCOS.
Attlee, Amita; Nusralla, Asma; Eqbal, Rashida; Said, Hanaa; Hashim, Mona; Obaid, Reyad Shaker
Background The aim of this study was to assess the occurrence of polycystic ovary syndrome (PCOS) and its association with body composition among students in University of Sharjah (UOS). Materials and Methods This cross-sectional study included a total sample size of 50 female students registering in undergraduate programs at the University of Sharjah using convenience sampling technique. A pretested interview schedule was administered to elicit information pertaining to personal background and medical history related to PCOS. A diag- nostic ultrasound scan was performed for determining PCOS along with a body composition analysis using bioelectrical impedance analysis (BIA) technology. Results Twenty percent (10 out of 50 participants) were diagnosed with PCOS, of whom only 4 individuals were previously diagnosed with PCOS and aware of their conditions, while the reports showed 16% with oligomenorrhea, 4% with polymenorrhea, and none with amen- orrhea. A positive family history was indicated as reported by 22% of the total participants. Significant difference between the body weights of participants having PCOS (66.7 kg) and those without it (58.8 kg) were noted (p=0.043, t=2.084). On the other hand, the body compo- sition related variables including waist-hip ratio (WHR), fat-free mass (FFM), percent body fat (PBF) and visceral fat area (VFA) were relatively higher in participants having PCOS than those without it. However, there was no statistical significance of differences. Comparatively, the participants with PCOS had lower bone mineral density (BMD) than those without it, whereas the difference was statistically non-significant. Conclusion The occurrence of PCOS in the present study is consistent with the global preva- lence. Comparatively, the body composition of PCOS females is different from the normal fe- males. Further studies are required in the Middle East region on larger sample sizes and broader aspects of health including lifestyle and dietary
Jalilian, Nasrin; Haghnazari, Lida; Rasolinia, Samira
Objective: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with obesity. Human and animal studies showed a direct relationship between leptin level and obesity, however, results from different studies were mixed. This study investigated the status of leptin level in PCOS and its relationship with body mass index (BMI) in a group of Iranian women with PCOS. Methods: In this cross-sectional study, 40 women with PCOS and 36 healthy women were assigned to experimental and control groups, respectively. Those in the PCOS group were not prescribed any medications for 3 months prior to the study. Fasting blood samples were then collected during the 2nd or 3rd day of menstruation for laboratory measurement of serum total leptin, blood glucose (fasting blood sugar), serum insulin, follicle-stimulating hormone, and luteinizing hormone (LH). Results: Mean BMI of the PCOS and control groups were 26.62 ± 4.03 kg/m2 and 23.52 ± 2.52 kg/m2, respectively (P = 0.006). The mean total leptin in the PCO group was also 10.69 ± 5.37 ng/mL and 5.73 ± 2.36 ng/mL in the control group (P = 0.0001). A significant relationship was found between leptin level and BMI as well as LH level among women with PCOS (P < 0.05). However, there was no significant correlation between leptin and insulin (P > 0.05). Conclusion: The results of this study indicated an increased leptin level among women with PCOS that positively associated with BMI and LH. PMID:27186548
Rosenfield, Robert L
Consensus has recently been reached by international pediatric subspecialty societies that otherwise unexplained persistent hyperandrogenic anovulation using age- and stage-appropriate standards are appropriate diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescents. The purpose of this review is to summarize these recommendations and discuss their basis and implications. Anovulation is indicated by abnormal uterine bleeding, which exists when menstrual cycle length is outside the normal range or bleeding is excessive: cycles outside 19 to 90 days are always abnormal, and most are 21 to 45 days even during the first postmenarcheal year. Continued menstrual abnormality in a hyperandrogenic adolescent for 1 year prognosticates at least 50% risk of persistence. Hyperandrogenism is best indicated by persistent elevation of serum testosterone above adult norms as determined in a reliable reference laboratory. Because hyperandrogenemia documentation can be problematic, moderate-severe hirsutism constitutes clinical evidence of hyperandrogenism. Moderate-severe inflammatory acne vulgaris unresponsive to topical treatment is an indication to test for hyperandrogenemia. Treatment of PCOS is symptom-directed. Cyclic estrogen-progestin oral contraceptives are ordinarily the preferred first-line medical treatment because they reliably improve both the menstrual abnormality and hyperandrogenism. First-line treatment of the comorbidities of obesity and insulin resistance is lifestyle modification with calorie restriction and increased exercise. Metformin in conjunction with behavior modification is indicated for glucose intolerance. Although persistence of hyperandrogenic anovulation for ≥2 years ensures the distinction of PCOS from physiologic anovulation, early workup is advisable to make a provisional diagnosis so that combined oral contraceptive treatment, which will mask diagnosis by suppressing hyperandrogenemia, is not unnecessarily delayed.
Lakryc, E M; Motta, E L A; Soares, J M; Haidar, M A; de Lima, G Rodrigues; Baracat, E C
Finasteride has been used frequently in the treatment of prostate hyperplasia, but this drug inhibits 5alpha-reductase and for this reason could be useful for the treatment of hirsutism. The aim of this study was to evaluate the clinical and hormonal effects of finasteride on hirsute women with idiopathic hirsutism or polycystic ovary syndrome. Twenty-four women were randomly divided into two groups: those given placebo and those given finasteride 5 mg/day. The treatment period was 6 months. All patients were evaluated before the beginning of treatment (baseline) and after 3 and 6 months of treatment using clinical examination through Ferriman-Gallwey score, blood pressure, cardiac frequency and body mass index. Also, we collected blood for hormonal determination of levels of prolactin, 17alpha-hydroxyprogesterone, follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrosterone sulfate, androstenedione and dihydrotestosterone. Furthermore, all patients were asked about their concerns and satisfaction with the treatment. The results showed that the Ferriman-Gallwey score in the 6th month of finasteride treatment was significantly lower than at baseline and the 3rd month of this drug treatment. The dihydrotestosterone level in the finasteride group was also significantly reduced compared to that in the placebo group. The other hormones did not show any statistical difference during the study. All the patients treated with finasteride perceived a reduction in hirsutism after 6 months. In conclusion, our data suggest that finasteride may be effective for the treatment of the hirsute woman with idiopathic hirsutism or polycystic ovary syndrome.
Pavičić Baldani, Dinka; Škrgatić, Lana; Bukvić Mokos, Zrinka; Trgovčić, Iva
Clinical traits associated with androgen, acne and hirsutism, are important diagnostic features of polycystic ovary syndrome (PCOS). As androgens are necessary for the development of cutaneous signs of PCOS, patients with severe forms of clinical hyperandrogenism are expected to present with higher levels of plasma androgens. This relationship has not been well established and studies examining the relationship have produced inconsistent results. The aim of this study was to analyze the correlation between the severity of clinical traits caused by androgen, acne and hirsutism, with plasma levels of androgens in Croatian women diagnosed with PCOS. One hundred and forty-five women of reproductive age with isolated acne (n=61) or isolated hirsutism (n=84), oligo/amenorrhea and polycystic morphology of the ovaries were enrolled in the study. Acne grade, hirsutism grade, body mass index (BMI) and waist to hip ratio (WHR) were recorded. Hormonal profiles were measured and assessment of insulin resistance was performed. There were no significant associations between acne severity and BMI, WHR and examined hormonal and insulin resistance parameters. There was a significant correlation between sex-hormone binding globulin (SHBG) and free testosterone levels and the severity of hirsutism (ρ=-0.611, P<0.001 and ρ=0.337, P=0.002, respectively). No significant association was found between the hirsutism grade and other hormonal and metabolic parameters examined. In conclusion, acne severity in PCOS patients is not linearly associated with serum androgen levels; therefore, their levels should not be used to determine the dose of anti-androgen therapy. The observed negative correlation between serum SHBG levels and the degree of hirsutism suggests that hormonal contraception, which elevates SHBG, should be used as primary therapy in hirsute PCOS patients.
A number of novel surgical modalities that destroy or remove some ovarian tissue to restore ovarian function in patients with polycystic ovary syndrome have been described in the most recent literature. Although these modalities were reported to have easy applicability and low cost with shorter hospital stay, the efficacy and safety concerns need to be discussed extensively.
Flyckt, Rebecca L; Goldberg, Jeffrey M
Laparoscopic ovarian drilling (LOD) is an alternative to ovulation induction with gonadotropins for polycystic ovarian syndrome (PCOS) patients unresponsive to clomiphene. It is quick and easy to perform, although the number of punctures and energy doses has not been standardized. The mechanism of LOD is unclear, but it is likely mediated by a reduction in intraovarian androgen production. Serum luteinizing hormone and testosterone levels are rapidly normalized, and these changes are sustained over long-term follow-up. Studies have shown that ovulation and pregnancy rates are comparable between ovulation induction with gonadotropins and LOD, but LOD avoids the risks of multiple pregnancy and ovarian hyperstimulation syndrome. LOD is also more cost effective and better tolerated than gonadotropin therapy. Concerns regarding clinically significant adhesion formation and premature ovarian failure are not supported by the available data. Transvaginal hydrolaparoscopy and ultrasound guidance are less invasive techniques for performing ovarian drilling and may encourage LOD earlier in the course of treatment for PCOS.
Mansour, Asieh; Hosseini, Saeed; Larijani, Bagher; Mohajeri-Tehrani, Mohammad Reza
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women. This disease is characterized by infertility, menstrual dysfunction, and hyperandrogenism. Also, PCOS is often associated with hyperlipidemia and impaired glucose tolerance, conditions that are associated with cardiovascular disorder, type 2 diabetes, cancer and hypertension. Evidence supports that some nutrients may affect the hormonal and metabolic disturbances of PCOS. Here in this study, we aimed to review the available literature that assessed the nutrients such as inostol, isoflavonids, resveratrol, vitamin D, and PUFA (polyunsaturated fatty acids), known to influence the hormonal and metabolic disturbances of PCOS, along with the strategies and future directions of nutrient supplementations in such patients. PMID:28096785
Abruzzese, Giselle Adriana; Motta, Alicia Beatriz
Nonalcoholic fatty liver disease (NAFLD) is defined as the accumulation of triglycerides (TGs) within hepatocytes exceeding 5 % of liver weight. NAFLD is a spectrum of pathological processes from nonalcoholic fatty liver or simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. As NAFLD induces metabolic syndrome (MS), then, NAFLD is associated with insulin resistance (IR), type 2 diabetes mellitus (T2DM), hypertension and even Polycystic Ovary Syndrome (PCOS). Because it is well established that patients carrying gene mutations also develop NAFLD in the absence of IR, the genetic predisposition to NAFLD is also discussed. Little is known about the diagnosis and treatment of NAFLD in children and adolescents and the lack of non-invasive diagnostic tools in these populations is a major problem faced by physicians. The present review aims to discuss recent findings of NAFLD in children and adolescents and, considering the features in common with PCOS, we also discuss their relationship.
Karaköse, Melia; Çakal, Erman; Ertan, Kubilay; Delibaşı, Tuncay
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is characterized by menstrual disorders, hyperandrogenism (clinical and/or biochemical) and ultrasonographic features. It is well known that PCOS has unfavourable effects on carbohydrate metabolism, the parameters of cardiovascular disease and lipid profile. Mode of treatment is mainly guided by the main complaint of the patient. A lot of medicines have been used for many years to treat these women. For that reason the recognition the effects of these drugs on the metabolic risk profile is important. The aim of this review was to evaluate the effects of these drugs on metabolic parameters in women with PCOS. PMID:24592098
Complex diseases, such as polycystic ovary syndrome (PCOS), are not limited to specific genes, pathogens, toxicoses, or identifiable environmental influences. PCOS still remains a diagnosis of exclusion despite being the most common female endocrinopathy and the leading cause of metabolic syndrome, ...
Hansen, Keith A
This month, we focus on current research in polycystic ovary syndrome. Dr. Hansen discusses six recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.
Polycystic ovary syndrome (PCOS) is a prevalent hyperandrogenic infertility and cardiometabolic disorder that increases a woman's lifetime risk of type 2 diabetes mellitus. It is heritable and intensely familial. Progress toward a cure has been delayed by absence of an etiology. Evidence is mounting...
Zivanovic, Dubravka; Masirevic, Iva; Ruzicka, Thomas; Braun-Falco, Markus; Nikolic, Milos
The clinical triad of pyoderma gangrenosum, acne conglobata and hidradenitis suppurativa has been named PASH syndrome. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and inflammation. Hidradenitis suppurativa, like acne vulgaris, may be a feature of hyperandrogenism. Obesity may be associated with both hidradenitis suppurativa and PCOS. We describe a possible association between PASH syndrome and PCOS.
Bungum, Leif; Franssohn, Florencia; Bungum, Mona; Humaidan, Peter; Giwercman, Aleksander
Obective To improve the biologic understanding of the Polycystic Ovarian Syndrome (PCOS) condition by examining the circadian variation and relationship between Anti Müllerian Hormone (AMH), gonadotropins and ovarian steroids in PCOS patients compared to normally ovulating and menstruating women. By comparing the pattern of co-variation between AMH and Luteinizing Hormone, two compounds closely linked to hyperandrogenism and anovulation in PCOS, the involvement of the Hypothalamic-Pituitary-Ovarian axis in PCOS pathology could be elucidated. Patients Eight normal-weighted young, anovulatory PCOS-women as study group and ten normal menstruating and ovulating women as controls. Interventions Observational prospective study of the circadian variation in AMH, gonadotropins, sex steroids and androgens in a study and a control group. A circadian profile was performed in each study and control subject during a 24-h period by blood sampling every second hour, starting at 8:00 a.m. and continuing until 8:00 a.m. the following day. Result(s) Significant differences in hormonal levels were found between the groups, with higher concentrations of AMH, LH and androgens in the PCOS group and lower amounts of FSH and progesterone. A distinct difference in the circadian variation pattern of AMH and LH between PCOS patients and normal controls was seen, with PCOS patients presenting a uniform pattern in serum levels of AMH and LH throughout the study period, without significant nadir late-night values as was seen in the control group. In PCOS women, a significant positive association between LH/ FSH and testosterone was found opposite to controls. Main outcome measures Circadian variation in Anti-Müllerian Hormone, gonadotropins and ovarian steroids and the covariation between them. Conclusion A significant difference in the circadian secretion of LH and AMH in PCOS women compared to normally ovulating women indicate an increased GnRH pulse, creating high and constant LH serum
Sørensen, Anja E; Udesen, Pernille B; Wissing, Marie Louise; Englund, Anne Lis M; Dalgaard, Louise T
Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women. PCOS is associated with altered features of androgen metabolism, increased insulin resistance and impaired fertility. Furthermore, PCOS, being a syndrome diagnosis, is heterogeneous and characterized by polycystic ovaries, chronic anovulation and evidence of hyperandrogenism, as well as being associated with chronic low-grade inflammation and an increased life time risk of type 2 diabetes. A number of androgen species contribute to the symptoms of increased androgen exposure seen in many, though not all, cases of PCOS: Testosterone, androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), where the quantitatively highest amount of androgen is found as DHEAS. The sulfation of DHEA to DHEAS depends on a number of enzymes, and altered sulfate metabolism may be associated with and contribute to the pathogenesis of PCOS. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post-transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that these might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. Our understanding of miRNAs, particularly in relation to PCOS, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome.
Sam, Susan; Scoccia, Bert; Yalamanchi, Sudha; Mazzone, Theodore
STUDY QUESTION Are certain ethnic groups with polycystic ovary syndrome (PCOS) at increased risk of metabolic disorders? SUMMARY ANSWER Obese Hispanic women with PCOS are at increased risk of metabolic disorders compared with age- and BMI-matched obese non-Hispanic white women with PCOS in the USA. WHAT IS KNOWN ALREADY Ethnic differences in body composition and metabolic risk are well established. PCOS is a common disorder in women of reproductive age and is associated with high rates of insulin resistance, glucose intolerance and dyslipidemia. STUDY DESIGN, SIZE, DURATION A cross-sectional observational study was performed at an Academic Medical Center on 60 women of reproductive age with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS Blood was obtained after fasting from 17 Hispanic, 22 non-Hispanic black and 21 non-Hispanic white women with PCOS who were similar in age and BMI. Anthropometric parameters, insulin, lipid and lipoprotein levels (measured by nuclear magnetic resonance) were compared between the three groups. MAIN RESULTS AND THE ROLE OF CHANCE Age and BMI did not differ between the groups. Hispanic women with PCOS had higher waist-to-hip ratio (WHR) (P = 0.02), homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.03) and a more atherogenic lipid and lipoprotein profile consisting of lower high-density lipoprotein (HDL) (P = 0.02), higher low-density lipoprotein (LDL) particle number (P = 0.02), higher very low-density lipoprotein particle (VLDL) size (P = 0.03) and lower LDL (P = 0.03) and HDL particle size (P = 0.005) compared with non-Hispanic white women. The differences in HDL, HOMA-IR, VLDL and LDL size did not persist after adjustment for WHR while differences in LDL particle number (P = 0.04) and HDL size (P = 0.01) persisted. LIMITATIONS, REASON FOR CAUTION The sample size for the three groups was small but the findings were still significant. The women were mostly obese so the ethnic differences in metabolic disorders may
Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu
Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS.
Diamanti-Kandarakis, Evanthia; Argyrakopoulou, Georgia; Economou, Frangiskos; Kandaraki, Eleni; Koutsilieris, Michael
The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age today. Women with PCOS often demonstrate defective ovarian steroid biosynthesis and present with hyperandrogenemia. Moreover, 50-70% of PCOS women are insulin resistant and hyperinsulinemic. Insulin acts on the ovary via its own receptor and interacts with gonadotrophins, modulating steroidogenesis. The precise role of insulin and the molecular mechanisms that take place are not yet completely explicated. This review will be focused on insulin's action on the ovary and other target tissues, describing the intracellular signaling pathways implicated in steroidogenesis and their defects in women with PCOS.
Zou, Shien; Sang, Qing; Wang, Huan; Feng, Ruizhi; Li, Qiaoli; Zhao, Xinzhi; Xing, Qinghe; Jin, Li; He, Lin; Wang, Lei
CYP1B1 encodes an estrogen enzyme that oxidizes 17β-estradiol to 4-hydroxyestradiol. The evidence demonstrates there may be a relationship between CYP1B1 and thyroid function. To date, no study has evaluated if genetic polymorphisms that regulate concentrations of serum FT3 and FT4 contribute to Polycyctic Ovary Syndrome (PCOS). To identify polymorphisms in the CYP1B1 locus associated with PCOS, we genotyped three common polymorphisms across the CYP1B1 locus in 226 patients. A test for association of common variants with susceptibility to PCOS was conducted in a large cohort of 609 subjects. The functional polymorphism CYP1B1 L432V (rs1056836) is associated with serum T4 (P = 0.003), serum FT3 (P < 0.001) and serum FT4 concentrations (P < 0.001). Our study provides the first evidence that genetic variants in CYP1B1 can be associated with serum T4, FT4 and FT3 levels in PCOS. These findings imply novel pathophysiological links between the CYP1B1 locus and thyroid function in PCOS.
Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome. PMID:25763405
Matsuzaki, Toshiya; Munkhzaya, Munkhsaikhan; Iwasa, Takeshi; Tungalagsuvd, Altankhuu; Yano, Kiyohito; Mayila, Yiliyasi; Yanagihara, Rie; Tokui, Takako; Kato, Takeshi; Kuwahara, Akira; Matsui, Sumika; Irahara, Minoru
Polycystic ovary syndrome (PCOS) is an ovulatory disorder that affects 6-10% of women of reproductive age. Serum AMH level may be an additional factor, or surrogate of PCOM, in the diagnostic criteria of PCOS. We evaluated the correlations between the serum AMH level and various endocrine and metabolic features in PCOS using the latest fully automated assay. Serum AMH level was compared between 114 PCOS patient (PCOS group) and 95 normal menstrual cycle women (Control group). Correlations between serum AMH level and various endocrine and metabolic factors were analysed in PCOS group. The serum AMH level was significantly higher in the PCOS group (8.35±8.19 ng/mL) than in the Control group (4.99±3.23 ng/mL). The serum AMH level was independently affected by age and the presence of PCOS on multiple regression analysis. Ovarian volume per ovary (OPVO) showed the strongest positive correlation (r=0.62) with the serum AMH level among related factors. On receiver operating characteristic (ROC) curve analysis, the cut-off value of AMH for the diagnosis of PCOS was 7.33 ng/mL, but this value did not have high efficacy (sensitivity 44.7%, specificity 76.8%). A cut-off value of 10 ng/mL had a high specificity of 92.6%, although the sensitivity was low (24.6%). The serum AMH level was elevated and reflected ovarian size in PCOS patients. The serum AMH level could be a surrogate for ultrasound findings of the ovaries in PCOS and might be useful for estimating ovarian findings without transvaginal ultrasound in the diagnosis of PCOS.
Enzevaei, Anahita; Salehpour, Saghar; Tohidi, Maryam; Saharkhiz, Nasrin
Background: Polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is often defined as hyperandrogenic syndrome. These patients are at risk for oligo/amenorrhea, chronic anovulation, infertility, obesity, spontaneous abortion, insulin resistance, hyperinsulinemia and metabolic syndrome. Thyroid disorders especially hypothyroidism is more common in these people. In PCOS patients, subclinical hypothyroidism may aggravate insulin resistance. Objective: The goal was to find any relationship between subclinical hypothyroidism and insulin resistance in PCOS patients. Materials and Methods: In this prospective cross sectional study we included all PCOS patients coming to infertility clinic of Taleghani Hospital in 2010-2012 who had the criteria of Rotterdam for PCOS. Then the clinical examination was done for them and height, weight, body mass index and lab data were measured including thyroid hormone and biochemical profile. The data were analyzed by SPSS software version 20. Results: Among 75 PCOS patients, 19 (25.5%) had subclinical hypothyroidism and 56 patients (74.4%) were euthyroid. The prevalence of insulin resistance was 22.7% and 77.3% of patients had no insulin resistance were normal. Conclusion: We could find no relationship between insulin resistance and subclinical hypothyroidism in PCOS patients. PMID:25114670
Álvarez-Blasco, Francisco; Martínez-García, Ma Ángeles; Luque-Ramírez, Manuel; Parraza, Naiara; San Millán, José L.; Escobar-Morreale, Héctor F.
Background Hp2 alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance. Methodology/Principal Findings Serum haptoglobin and the haptoglobin α–chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp2 alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes. Conclusions/Significance Serum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp2 alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients. PMID:19440331
Lujan, Marla E; Chizen, Donna R; Peppin, Andrew K; Dhir, Anita; Pierson, Roger A
Background There is growing acceptance that polycystic ovaries are an important marker of polycystic ovary syndrome (PCOS) despite significant variability when making the ultrasound diagnosis. To better understand the nature of this variability, we proposed to evaluate the level of inter-observer agreement when identifying and quantifying individual ultrasonographic features of polycystic ovaries. Methods Digital recordings of transvaginal ultrasound scans performed in thirty women with PCOS were assessed by four observers with training in Radiology or Reproductive Endocrinology. Observers evaluated the scans for: 1) number of follicles ≥ 2 mm per ovary, 2) largest follicle diameter, 3) ovarian volume, 4) follicle distribution pattern and 5) presence of a corpus luteum (CL). Lin's concordance correlation coefficients and kappa statistics for multiple raters were used to assess inter-observer agreement. Results Agreement between observers ranged from 0.08 to 0.63 for follicle counts, 0.27 to 0.88 for largest follicle diameter, 0.63 to 0.86 for ovarian volume, 0.51 to 0.76 for follicle distribution pattern and 0.76 to 0.90 for presence of a CL. Overall, reproductive endocrinologists demonstrated better agreement when evaluating ultrasonographic features of polycystic ovaries compared to radiologists (0.71 versus 0.53; p = 0.04). Conclusion Inter-observer agreement for assessing ultrasonographic features of polycystic ovaries was moderate to poor. These findings support the need for standardized training modules to characterize polycystic ovarian morphology on ultrasonography. PMID:19515259
Mohammadbygi, Robabeh; Yousefi, Sayedeh Reyhaneh; Shahghaybi, Sholeh; Zandi, Shokrollah; Sharifi, Karim; Gharibi, Fardin
Objectives: The aim of this study was to determine the effects of Cabergoline administration on uterine blood flow in women suffering from polycystic ovary syndrome (PCOS). Methods: This study is a randomized, controlled, triple-blind trial which is tested on 40 women who were randomly divided into two groups of 20 people and using a randomized block design during which the subjects were assessed and included. They were suffering from polycystic ovarian syndrome. Inclusion criteria were classically defined PCOS criteria including: oligomenorrhea or amenorrhea, clinical or Laboratory findings based on increase in blood level androgen (testosterone) and ultrasound confirmation of PCOS. Exclusion criteria were Pregnancy, lactation, Dopamine Agonist Therapy. After selection of intervention and placebo groups, primary control Doppler ultrasound was done for both groups. Then a weekly dose of Cabergoline 0.5 mg was administered to intervention group for duration of 12 weeks. Placebo group were administered placebo in the same fashion. At the end of 12 weeks, Doppler ultrasound was performed and the results were recorded in the check lists. Results: No significant difference was noticed in both groups with respect to their age, employment, level of education, type of infertility, duration of marriage, and results of RI and PI before intervention. Later PCOS patients under the treatment of Cabergoline showed a significant increase in uterine blood flow Pulsatility Index (PI) before 2.65±0.52 and after 1.98±0.52 and RI before 0.85 and after intervention 0.77), yet no significant difference were found in PCOS patient under the treatment of placebo. Conclusion: PCOS patients were shown to have more resistance in uterine blood flow than healthy people; however, Cabergoline administration proved to increase uterine blood perfusion and regulate menstruation cycle. PMID:24353659
Villa, P; Rossodivita, A; Fulghesu, A M; Cucinelli, F; Barini, A; Apa, R; Belosi, C; Lanzone, A
In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (p<0.01) and LH (p<0.05) plasma levels higher than control group and the highest free androgen index (FAI) values (13 +/- 0.87). All patients with irregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.
Arabzadeh, Somayeh; Hossein, Ghamartaj; Rashidi, Batool Hossein; Hosseini, Marziyeh Agha; Zeraati, Hojjat
BACKGROUND AND OBJECTIVES: The prediction of in vitro fertilization (IVF) outcomes by anti-Müllerian hormone (AMH) measurement is getting increasing attention from clinicians. This study compares the relationship between serum or intrafollicular AMH levels and IVF outcomes in women with and without polycystic ovary syndrome (PCOS). METHODS: This prospective study was carried out in two university-based fertility clinics. Serum samples were collected on cycle day 3 and follicular fluid (FF) was collected on the day of oocyte retrieval from 26 women with PCOS and 42 normo-ovulatory controls. AMH levels were measured in the samples using immunoenzymatic assay. The relationship between serum or FF AMH levels and IVF outcomes, including number of oocytes retrieved, oocyte maturation rate, fertilization rate, implantation rate, high quality grade embryo rate, and biochemical and clinical pregnancy rates were further assessed. RESULTS: Median serum basal AMH and FF AMH levels were significantly higher in the PCOS group as compared to controls, the values being 14.2 ng/mL vs. 3.2 ng/mL (P<.001) and 8.2 ng/g protein vs. 4.7 ng/g protein (P<.01), respectively. In both groups, serum basal AMH levels showed a positive correlation with number of oocytes retrieved (r=0.323; P=.037 in control vs. r=0.529; P=.005 in PCOS). In the control group, there was a positive relationship between serum basal AMH levels and percentage of matured oocytes (r = 0.331; P=.032) and implantation rate (r=0.305; P=.05). CONCLUSION: Serum basal, and not intrafollicular, AMH levels may be a good predictive factor for quantitative and qualitative IVF outcomes in normo-ovulatory, but not in PCOS patients. PMID:20940513
Wang, LianLian; Qi, HongBo; Baker, Philip N; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian
BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. CONCLUSIONS Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.
Garin, Margaret C; Butts, Samantha F; Sarwer, David B; Allison, Kelly C; Senapati, Suneeta; Dokras, Anuja
Ghrelin is an endogenous appetite stimulant that may have a role in ovarian function. Women with polycystic ovary syndrome have anovulation and frequently weight management issues; however the associations between ghrelin and hormonal markers in polycystic ovary syndrome have not been well studied. In order to characterize the association between total ghrelin levels and ovarian function and the possible modification of this relationship by obesity, we examined total ghrelin levels and anti-mullerian hormone, total testosterone, and insulin in obese and non-obese women with and without polycystic ovary syndrome. Total ghrelin levels were lower in obese women with polycystic ovary syndrome (n = 45) compared to obese controls (n = 33) (p = 0.005), but similar in non-obese women with polycystic ovary syndrome (n = 20) compared to non-obese controls (n = 21) (p = NS). In the obese polycystic ovary syndrome group, anti-mullerian hormone was associated with ghrelin levels independent of age, insulin, and total testosterone (p = 0.008). There was no association between total ghrelin and anti-mullerian hormone levels in non-obese women with polycystic ovary syndrome, non-obese controls, or obese controls (p = NS). Our results provide evidence for a potential relationship between ghrelin and ovarian function in obese women with polycystic ovary syndrome that was not observed in non-obese women with polycystic ovary syndrome or controls.
Gozukara, Ilay Ozturk; Gozukara, Kerem Han; Kucur, Suna Kabil; Karakılıc, Eda Ulku; Keskin, Havva; Akdeniz, Derya; Aksoy, Ayse Nur; Carlıoglu, Ayse
Background We aimed to estimate the glomerular filtration rate (GFR) in women with polycystic ovary syndrome (PCOS) and to determine the relationship between GFR with C-reactive protein (CRP) and uric acid. Materials and Methods In this cross-sectional study, one-hundred and forty PCOS women and 60 healthy subjects were evaluated. The study was carried out at Endocrinol- ogy Outpatient Clinic, Erzurum Training and Research Hospital, Erzurum, Turkey, from December 2010 to January 2011. GFRs were estimated by Modification of Diet in Renal Disease (MDRD) formula. CRP, urinary albumin excretion (UAE) and uric acid levels were also measured. Results GFRs were significantly higher in PCOS group than control (135.24 ± 25.62 vs. 114.92 ± 24.07 ml/min per 1.73 m2). CRP levels were significantly higher in PCOS patients (4.4 ± 3.4 vs. 2.12 ± 1.5 mg/l). The PCOS group had significantly higher serum uric acid levels (4.36 ± 1.3 mg/dl vs. 3.2 ± 0.73 mg/dl). There was also significantly higher proteinuria level in PCOS patients. Conclusion Even though PCOS patients had higher GFR, serum uric acid and UAE val- ues than control patients, the renal function was within normal limits. Increased GFR in PCOS women positively correlates with elevated serum CRP and uric acid. PMID:26246875
Johansson, Julia; Stener-Victorin, Elisabet
Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by the coexistence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (PCO). PCOS also represents the largest part of female oligoovulatory infertility, and the management of ovulatory and menstrual dysfunction, comprises a third of the high costs of PCOS treatment. Current pharmacological and surgical treatments for reproductive symptoms are effective, however, associated with negative side effects, such as cardiovascular complications and multiple pregnancies. For menstrual irregularities and ovulation induction in women with PCOS, acupuncture has indicated beneficial effects. This review will focus on the results from randomized controlled acupuncture trials for regulation of menstrual dysfunction and for inducing ovulation in women with PCOS although there are uncontrolled trials with nonetheless interesting results. Animal experimental studies will be further discussed when they can provide a more mechanistic explanatory view. PMID:24073009
Dumesic, Daniel A.; Oberfield, Sharon E.; Stener-Victorin, Elisabet; Marshall, John C.; Laven, Joop S.
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown. PMID:26426951
Reis, Guilherme Victor Oliveira Pimenta Dos; Gontijo, Natália Alves; Rodrigues, Kathryna Fontana; Alves, Michelle Teodoro; Ferreira, Cláudia Natália; Gomes, Karina Braga
Polycystic ovary syndrome (PCOS) is the most frequent endocrinological disorder that affects women of reproductive age, leading to metabolic alterations, such as hyperandrogenism, obesity, menstrual irregularities, insulin resistance, and polycystic ovaries. The etiology remains unclear, but several genetic and environmental factors have been correlated with manifestations of this syndrome. Vitamin D plays important roles in metabolic pathways affected by PCOS, including calcium homeostasis, the insulin pathway, and sex hormone synthesis. Vitamin D concentration has been related with the severity of this disorder, and vitamin D receptor polymorphisms have been shown in some studies to have an association with some of the patterns presented by PCOS. The objective of this study is to provide an up-to-date review about vitamin D receptor polymorphisms and their association with PCOS.
Bergh, Catherine M; Moore, Monica; Gundell, Carolyn
Polycystic ovary syndrome (PCOS) is a polygenic disorder with a variable phenotype that commonly affects women of reproductive age. It can significantly affect a woman's ability to conceive and her quality of life. Effective treatment includes a multidisciplinary team approach that addresses the physiological and psychosocial manifestations of the disorder. Nurses have an important role in promoting early detection, education, and identification of services and resources to improve a woman's fertility and lifelong health.
Zulian, Elisa; Sartorato, Paola; Schiavi, Francesca; Moghetti, Paolo; Castello, Roberto; Mantero, Franco; Opocher, Giuseppe; Scaroni, Carla
To explore the relationship between variation in AGT M235T gene and the development of the polycystic ovary syndrome (PCOS) and its sequelae, in the present study we evaluated AGT polymorphism M235T in women with PCOS and in a control group. Moreover, to detect any relationship between AGT M235T variation and intermediate and quantitative traits relevant to the pathogenesis of cardiovascular disease and PCOS, we looked for genotype-dependent differences within the subjects with PCOS.
Negoro, Yuwono Sri; Afrita, Yohana; Wiweko, Budi; Sumapradja, Kanadi; Natadisastra, Muharam
Objective This study aimed to determine the threshold of anti-Müllerian hormone (AMH) as predictor of follicular growth failure in polycystic ovary syndrome (PCOS) patients treated with clomiphene citrate (CC). Methods Fifty female subjects with PCOS were recruited and divided into two groups based on successful and unsuccessful follicular growth. Related variables such as age, infertility duration, cigarette smoking, use of Moslem hijab, sunlight exposure, fiber intake, body mass index, waist circumference, AMH level, 25-hydroxy vitamin D level, and growth of dominant follicles were obtained, assessed, and statistically analyzed. Results The AMH levels of patients with successful follicular growth were significantly lower (p=0.001) than those with unsuccessful follicular growth (6.10±3.52 vs. 10.43±4.78 ng/mL). A higher volume of fiber intake was also observed in the successful follicular growth group compared to unsuccessful follicular growth group (p=0.001). Our study found the probability of successful follicle growth was a function of AMH level and the amount of fiber intake, expressed as Y=–2.35+(–0.312×AMH level)+(0.464×fiber intake) (area under the curve, 0.88; 95% confidence interval, 0.79–0.98; p<0.001). Conclusion The optimal threshold of AMH level in predicting the failure of follicle growth in patients with PCOS treated with CC was 8.58 ng/mL. PMID:28090459
Glintborg, Dorte; Andersen, Marianne
Hirsutism is a common endocrine disorder, defined as increased growth of terminal hairs in a male pattern. Hirsutism is most often caused by polycystic ovary syndrome (PCOS), whereas only 5% patients are diagnosed with rare endocrine diseases. PCOS may be considered a multiorgan disease causing not only increased adrenal and ovarian sex hormone secretion but also changed secretion of gonadotrophins, growth hormone, and adrenocorticotrophic hormone (ACTH) from the pituitary. The majority of patients with PCOS are insulin resistant and PCOS is characterized by an increased inflammatory state with abdominal obesity and increased secretion of interleukins, chemokines, and adipokines. PCOS is therefore associated with an increased risk of the metabolic syndrome and type 2 diabetes (T2D). Patients with hirsutism present with increased bone mineral density despite decreased D-vitamin levels. The etiology to hirsutism and PCOS is most likely multifactorial including both genetic and environmental factors such as increased fetal stress and intrauterine growth retardation. In the present review, we give a comprehensive overview of the pathophysiology and multiple endocrine disturbances of hirsutism and PCOS.
Shafti, Vida; Shahbazi, Sara
Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders that is associated with different metabolic, reproductive and psychological consequences. The main aim of this study was to compare the sexual function and quality of life in women with polycystic ovary syndrome and healthy women. Materials and methods: This is a causal-comparative study in which 129 women with polycystic ovary syndrome were qualified as the research group. The control group consisted of 125 healthy women. The sampling method was convenient and was done using Rotterdam criteria. Women of both research and control groups responded to the FSFI and WHOQOL-BREF questionnaires. Data were analyzed with SPSS software using MANOVA. Results: According to findings, all of quality of life subscales except environment domain were significantly lower in research group than healthy group (p < 0.01), but none of sexual function subscales were significantly different between two groups (p > 0.05). Conclusion: Women with PCOS in term of some quality of life parameters have lower performance than healthy women. Therefore, it seems to be essential to increase awareness about symptoms and psychological consequences and referring process in order to take advantage of the advisory services. PMID:27648099
Gleicher, Norbert; Weghofer, Andrea; Lee, Irene H; Barad, David H
The FMR1 gene partially appears to control ovarian reserve, with a specific ovarian sub-genotype statistically associated with a polycystic ovary (PCO)- like phenotype. Some forms of PCO have been associated with autoimmunity. We, therefore, investigated in multiple regression analyses associations of ovary-specific FMR1 genotypes with autoimmunity and pregnancy chances (with in vitro fertilization, IVF) in 339 consecutive infertile women (455 IVF cycles), 75 with PCO-like phenotype, adjusted for age, race/ethnicity, medication dosage and number of oocytes retrieved. Patients included 183 (54.0%) with normal (norm) and 156 (46%) with heterozygous (het) FMR1 genotypes; 133 (39.2%) demonstrated laboratory evidence of autoimmunity: 51.1% of het-norm/low, 38.3% of norm and 24.2% het-norm/high genotype and sub-genotypes demonstrated autoimmunity (p=0.003). Prevalence of autoimmunity increased further in PCO-like phenotype patients with het-norm/low genotype (83.3%), remained unchanged with norm (34.0%) and decreased in het-norm/high women (10.0%; P<0.0001). Pregnancy rates were significantly higher with norm (38.6%) than het-norm/low (22.2%, p=0.001). FMR1 sub-genotype het-norm/low is strongly associated with autoimmunity and decreased pregnancy chances in IVF, reaffirming the importance of the distal long arm of the X chromosome (FMR1 maps at Xq27.3) for autoimmunity, ovarian function and, likely, pregnancy chance with IVF.
Gleicher, Norbert; Weghofer, Andrea; Lee, Irene H.; Barad, David H.
The FMR1 gene partially appears to control ovarian reserve, with a specific ovarian sub-genotype statistically associated with a polycystic ovary (PCO)- like phenotype. Some forms of PCO have been associated with autoimmunity. We, therefore, investigated in multiple regression analyses associations of ovary-specific FMR1 genotypes with autoimmunity and pregnancy chances (with in vitro fertilization, IVF) in 339 consecutive infertile women (455 IVF cycles), 75 with PCO-like phenotype, adjusted for age, race/ethnicity, medication dosage and number of oocytes retrieved. Patients included 183 (54.0%) with normal (norm) and 156 (46%) with heterozygous (het) FMR1 genotypes; 133 (39.2%) demonstrated laboratory evidence of autoimmunity: 51.1% of het-norm/low, 38.3% of norm and 24.2% het-norm/high genotype and sub-genotypes demonstrated autoimmunity (p = 0.003). Prevalence of autoimmunity increased further in PCO-like phenotype patients with het-norm/low genotype (83.3%), remained unchanged with norm (34.0%) and decreased in het-norm/high women (10.0%; P<0.0001). Pregnancy rates were significantly higher with norm (38.6%) than het-norm/low (22.2%, p = 0.001). FMR1 sub-genotype het-norm/low is strongly associated with autoimmunity and decreased pregnancy chances in IVF, reaffirming the importance of the distal long arm of the X chromosome (FMR1 maps at Xq27.3) for autoimmunity, ovarian function and, likely, pregnancy chance with IVF. PMID:21179569
Enli, Yasar; Fenkci, Semin Melahat; Fenkci, Veysel; Oztekin, Ozer
This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS.
Zhang, Yuehui; Hu, Min; Meng, Fanci; Sun, Xiaoyan; Xu, Hongfei; Zhang, Jiao; Cui, Peng; Morina, Njomeza; Li, Xin; Li, Wei; Wu, Xiao-Ke; Brännström, Mats; Shao, Ruijin; Billig, Håkan
Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus. At the molecular and cellular levels, metformin normalized the androgen receptor-mediated transcriptional program and restored epithelial-stromal interactions. In contrast to glucose transport, uterine inflammatory gene expression was suppressed through the PI3K-Akt-NFκB network, but without affecting apoptosis. These effects appeared to be independent of AMPK subunit and autophagy-related protein regulation. We found that when metformin treatment partially restored implantation, several implantation-related genes were normalized in the PCOS-like rat uterus. These results improve our understanding of how metformin rescues the disruption of the implantation process due to the uterine defects that result from hyperandrogenism and insulin resistance. Our data provide insights into the molecular and functional clues that might help explain, at least in part, the potential therapeutic options of metformin in PCOS patients with uterine dysfunction.
Huijgen, Nicole A; Louwers, Yvonne V; Willemsen, Sten P; de Vries, Jeanne H M; Steegers-Theunissen, Régine P M; Laven, Joop S E
Polycystic ovary syndrome (PCOS) is generally considered a complex disorder caused by interactions between genetic and environmental factors. In a sub-cohort of women with PCOS visiting the preconception outpatient clinic of a tertiary hospital with follow-up in a periconception cohort, we identified specific dietary patterns and adherence in patients with PCOS with and without hyperandrogenism and the chance of ongoing pregnancy. Food frequency questionnaires were available from 55 patients diagnosed with PCOS during follow-up in routine clinical practice, including 25 with hyperandrogenism and 30 without hyperandrogenism. Strong adherence to the healthy dietary pattern was inversely associated with the hyperandrogenic PCOS phenotype (Adjusted OR 0.27; 95% CI 0.07 to 0.99). In women with PCOS overall, a strong adherence to the healthy dietary pattern showed a three-fold higher chance of ongoing pregnancy (adjusted OR 3.38; 95% CI 1.01 to 11.36) and an association with anti-Müllerian hormone concentration (β -0.569 µg/L; 95% CI -0.97 to -0.17). The effect of this dietary pattern on the chance of ongoing pregnancy and AMH suggests causality, which needs further investigation in prospective studies in the general population.
Turan, Mahfuz; Ucler, Rıfkı; Garca, Mehmet Fatih; Kurdoglu, Zehra; Cankaya, Hakan; Ayral, Abdurrahman; Bozan, Nazım; Kıroglu, Ahmet Faruk; Kurdoglu, Mertihan
Background The purpose of our study was to investigate the association between polycystic ovary syndrome (PCOS) and hearing thresholds. Material/Methods Forty women diagnosed with PCOS (mean age, 24.33±6.38 years) and 40 healthy women controls (mean age, 26.38±6.75 years) were included in prospective study. Each case was tested with low (250, 500, 1000, and 2000 Hz), high (4000, 6000, and 8000 Hz) and extended high (EH) (9000–20000 Hz) frequency audiometry. The fasting plasma glucose, insulin, FSH, LH, total testosterone, and sex hormone-binding globulin were measured in all patients. Results The mean hearing thresholds at EH frequencies were statistically significantly higher in the PCOS group than in the control group (p=0.001 right ear and p=0.015 left ear). There were significant positive correlations among free testosterone index (FTI) values and hirsutism scores with EH frequency hearing thresholds. Conclusions At pure-tone audiometry (PTA) EH frequencies, we detected significantly higher hearing thresholds in PCOS patients than in controls. We also determined that elevated FTI and hirsutism score were positively correlated with elevated hearing thresholds in EH frequencies. These findings support that hyperandrogenism can play a role in the elevation of hearing thresholds in PCOS. PMID:27846196
He, Chunla; Lin, Zhoumeng; Robb, Sara Wagner; Ezeamama, Amara E.
Vitamin D deficiency (VDD) is common in women with and without polycystic ovary syndrome (PCOS) and may be associated with metabolic and endocrine disorders in PCOS. The aim of this meta-analysis is to assess the associations of serum vitamin D levels with metabolic and endocrine dysregulations in women with PCOS, and to determine effects of vitamin D supplementation on metabolic and hormonal functions in PCOS patients. The literature search was undertaken through five databases until 16 January 2015 for both observational and experimental studies concerning relationships between vitamin D and PCOS. A total of 366 citations were identified, of which 30 were selected (n = 3182). We found that lower serum vitamin D levels were related to metabolic and hormonal disorders in women with PCOS. Specifically, PCOS patients with VDD were more likely to have dysglycemia (e.g., increased levels of fasting glucose and homeostatic model assessment-insulin resistance index (HOMA-IR)) compared to those without VDD. This meta-analysis found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in PCOS. VDD may be a comorbid manifestation of PCOS or a minor pathway in PCOS associated metabolic and hormonal dysregulation. Future prospective observational studies and randomized controlled trials with repeated VDD assessment and better characterization of PCOS disease severity at enrollment are needed to clarify whether VDD is a co-determinant of hormonal and metabolic dysregulations in PCOS, represents a consequence of hormonal and metabolic dysregulations in PCOS or both. PMID:26061015
Hernández-Yero, Arturo; Santana Pérez, Felipe; Ovies Carballo, Gisel; Cabrera-Rode, Eduardo
For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS). A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone. PMID:22778733
Alexander, Carolyn J; Tangchitnob, Edward P; Lepor, Norman E
The prevalence of polycystic ovary syndrome (PCOS) is estimated to be nearly 10% among reproductive-age women. PCOS may represent the largest underappreciated segment of the female population at risk of cardiovascular disease. Clinicians providing care to women of childbearing age must recognize the presenting clues, including irregular menses, hirsutism, alopecia, hyperandrogenemia, and obesity. The pathophysiology of PCOS is complex, involving the hypothalamus-pituitary-ovarian axis, ovarian theca cell hyperplasia, hyperinsulinemia, and a multitude of other cytokine- and adipocyte-driven factors. Cardiac risk factors associated with PCOS have public health implications and should drive early screening and intervention measures. There are no consensus guidelines regarding screening for cardiovascular disease in patients with PCOS. Fasting lipid profiles and glucose examinations should be performed regularly. Carotid intimal medial thickness examinations should begin at age 30 years, and coronary calcium screening should begin at age 45 years. Treatment of the associated cardiovascular risk factors, including insulin resistance, hypertension, and dyslipidemia, should be incorporated into the routine PCOS patient wellness care program. PMID:20111659
He, Chunla; Lin, Zhoumeng; Robb, Sara Wagner; Ezeamama, Amara E
Vitamin D deficiency (VDD) is common in women with and without polycystic ovary syndrome (PCOS) and may be associated with metabolic and endocrine disorders in PCOS. The aim of this meta-analysis is to assess the associations of serum vitamin D levels with metabolic and endocrine dysregulations in women with PCOS, and to determine effects of vitamin D supplementation on metabolic and hormonal functions in PCOS patients. The literature search was undertaken through five databases until 16 January 2015 for both observational and experimental studies concerning relationships between vitamin D and PCOS. A total of 366 citations were identified, of which 30 were selected (n = 3182). We found that lower serum vitamin D levels were related to metabolic and hormonal disorders in women with PCOS. Specifically, PCOS patients with VDD were more likely to have dysglycemia (e.g., increased levels of fasting glucose and homeostatic model assessment-insulin resistance index (HOMA-IR)) compared to those without VDD. This meta-analysis found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in PCOS. VDD may be a comorbid manifestation of PCOS or a minor pathway in PCOS associated metabolic and hormonal dysregulation. Future prospective observational studies and randomized controlled trials with repeated VDD assessment and better characterization of PCOS disease severity at enrollment are needed to clarify whether VDD is a co-determinant of hormonal and metabolic dysregulations in PCOS, represents a consequence of hormonal and metabolic dysregulations in PCOS or both.
Tang, Yun-Liang; Yu, Jiao; Zeng, Zhen-Guo; Liu, Ying; Liu, Jian-Ying; Xu, Ji-Xiong
To investigate the association between circulating omentin-1 levels and polycystic ovary syndrome (PCOS) in women, a meta-analysis was performed. A systematic literature search using PubMed, Embase and Web of Science was carried out. Ten articles with 13 studies were included in this meta-analysis, which included a total of 1264 subjects (733 patients with PCOS and 531 controls). The pooled standard mean difference (SMD) and 95% confidence interval (CI) were used to estimate the association between omentin-1 levels and PCOS. Circulating omentin-1 levels were lower in PCOS with an SMD (95% CI) of -0.67 (-0.91, -0.43) and p = 0.000 (random-effects). However, significant heterogeneity was detected across studies (I(2)=73.6% and p = 0.000). The subgroup analysis suggested that omentin-1 levels in PCOS patients were associated with HOMA-IR ratio. Meta-regression analysis indicated region was the main source of heterogeneity (p = 0.048). The results of this meta-analysis suggested that circulating omentin-1 levels are significantly lower in women with PCOS compared with controls, which indicated that omentin-1 may play a role in the pathologic processes of PCOS.
Attaoua, Redha; Ait El Mkadem, Samira; Radian, Serban; Fica, Simona; Hanzu, Felicia; Albu, Alice; Gheorghiu, Monica; Coculescu, Mihai; Grigorescu, Florin
The FTO (Fat mass and obesity associated) locus has recently been associated with obesity and type 2 diabetes (T2D) in humans. To understand the role of the FTO gene in polycystic ovary syndrome (PCOS) we genotyped single nucleotide polymorphism (SNP) rs1421085 (C/T) in women with PCOS (n=207) and controls (n=100) from a Central European population. The homozygous C/C genotype showed increased prevalence in PCOS patients either obese or with metabolic syndrome (MetS) compared to lean PCOS patients or controls (27.6%, 38.9%, 22.3%, and 16.3%, respectively). In logistic regression, this genotype strongly associated with MetS (P<0.0001, OR 3.2, 95% CI 1.8-5.7) and impaired fasting glucose (IFG) with P<0.0007, OR 7.7, 95% CI 2.1-28.6, independently of BMI or age, and to AUC(gluc) during OGTT (P<0.0001, alpha=0.99), indicating an influential role of the FTO gene in the glucose intolerance component of MetS.
Kelley, Carly E; Brown, Ann J; Diehl, Anna Mae; Setji, Tracy L
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases. PMID:25339805
Ketefian, Aline; Jones, Michelle R.; Krauss, Ronald M.; Chen, Yii-Der I.; Legro, Richard S.; Azziz, Ricardo; Goodarzi, Mark O.
Objective To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS). Design Two groups of PCOS and control women (discovery and replication cohorts) were genotyped for single nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. SNPs were tested for association with PCOS status, and with androgenic and metabolic parameters. Setting Tertiary referral center. Patients Discovery cohort: 354 PCOS and 161 control women. Replication cohort: 397 PCOS and 306 control women. Interventions Phenotypic and genotypic assessment. Main outcome measures SNP genotypes, association with PCOS status, and androgenic and metabolic parameters. Results In the discovery cohort, FKBP4 SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS. This finding was not confirmed in the replication cohort analysis; however, when combining the two cohorts, rs4409904 was associated with lower odds of PCOS. In PCOS subjects in the replication cohort as well as in the combined cohort, rs2968909 was associated with lower BMI. Conclusions SNPs in FKBP4, which codes for the AR co-chaperone FKBP52, may be associated with PCOS and BMI in PCOS patients. The remaining genes studied do not appear to be major contributors to the development of PCOS. These findings warrant confirmation in future studies, and genes encoding other androgen pathway components remain to be studied. PMID:26493122
Kelley, Carly E; Brown, Ann J; Diehl, Anna Mae; Setji, Tracy L
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.
Toscani, Mariana; Migliavacca, Raphaella; Sisson de Castro, José Augusto; Spritzer, Poli Mara
Insulin resistance (IR) is an independent risk factor for cardiovascular disease and is a prevalent metabolic disturbance among women with polycystic ovary syndrome (PCOS). Central adiposity, a marker of IR and an accurate anthropometric method to estimate truncal adiposity, may represent a key clinical tool for IR screening in subpopulations at higher metabolic and cardiovascular risk, such as women with PCOS. The aims of the present study were (1) to investigate the influence of androgens on IR and central obesity in overweight or obese hirsute women with or without PCOS and (2) to test the reliability of the sum of trunk skinfolds (subscapular, suprailiac, and abdominal) to estimate truncal adiposity. This observational, cross-sectional study included 37 hirsute patients with body mass index of 25 kg/m(2) or greater and aged between 14 and 41 years. Twenty-four had PCOS, and 13 had ovulatory cycles, normal androgen levels, and isolated hirsutism, named idiopathic hirsutism (IH). Nutritional, anthropometric, clinical, and laboratory evaluations were performed. Body composition was assessed by measurement of waist circumference and skinfold thickness and by dual-energy x-ray absorptiometry (DXA). Both groups presented similar ages, body mass index, and hirsutism score. The PCOS group had higher androgen levels, homeostasis model assessment (HOMA) index, and fasting insulin levels. Free androgen index was positively associated with HOMA, independent of truncal adiposity (r = 0.441, P = .009). Strong correlations were also observed between truncal adiposity measured by DXA and both the sum of trunk skinfolds (r = 0.863, P = .0001) and waist circumference in hirsute patients (r = 0.947, P = .0001). In our study, IR (HOMA index >/=3.8) was associated with truncal obesity, with a more androgenic profile, and with an unfavorable lipid profile. In conclusion, hirsutism per se appears not to be a risk for IR and related cardiovascular disease unless there is presence of
Azadi-Yazdi, Maryam; Nadjarzadeh, Azadeh; Khosravi-Boroujeni, Hossein; Salehi-Abargouei, Amin
It is suggested that vitamin D status is associated with androgenic profile in women with polycystic ovarian syndrome (PCOS). Although several clinical trials are known in this regard, the results were inconsistent. Therefore, this study was aimed to conduct a systematic review and meta-analysis of published clinical trials to elucidate the possible effect of vitamin D supplementation on the androgen levels in adult females with PCOS. PubMed, SCOPUS, and Google Scholar were searched to identify related articles published up to January 2017. Mean ± standard deviation (SD) of changes in serum total testosterone, sex hormone binding globulin (SHBG), and free testosterone were extracted to calculate Hedges' g to be used as effect size for meta-analysis. DerSimonian and Liard random effects model was incorporated to summarize the effects. Six clinical trials with 183 participants aged 18-41 years with follow-up period between 3-24 weeks were included. Our analysis revealed that vitamin D supplementation significantly reduces total testosterone (Hedges' g=-0.32, 95% CI: -0.55 to -0.10; p=0.005); this effect remained significant in single group trials after subgroup analysis. Vitamin D supplementation did not affect serum free testosterone (Hedges' g=-0.21, 95% CI: -0.44 to 0.079; p=0.08) or SHBG levels (Hedges' g=0, 95% CI, 0.22-0.22; p=0.98). The present systematic review and meta-analysis revealed that vitamin D supplementation might significantly affect serum total testosterone while it is not effective in improving other markers of androgenic profile. Future double-blind, placebo-controlled clinical trials are highly recommended.
Li, Hui; Li, Lin; Gu, Jian; Li, Yu; Chen, Xiaoli; Yang, Dongzi
This hospital-based observational study aims to estimate differences in metabolic abnormalities between different polycystic ovary syndrome (PCOS) phenotypes and their distribution characteristics. The prevalence of metabolic abnormalities among different PCOS phenotypes, including diabetes mellitus (DM), metabolic syndrome (MS), pre-diabetes mellitus (pre-DM), insulin resistance (IR) and dyslipidemia were compared. A total of 2436 women who were ≥18 years old and who were hospitalized in Sun Yat-Sen University affiliated hospital from 1998 to 2015 in GuangZhou, China, were included in this study. PCOS phenotypes were recorded according to the 2003 Rotterdam criteria, including the polycystic ovary morphology (PCO), hyperandrogenism (HA) and ovulation dysfunction (OD) phenotype (PCO+HA+OD); the ovulation phenotype (PCO+HA); the non-PCO phenotype (HA+OD); and the non-HA phenotype (PCO+OD). Notably, 56% of the patients had the classic phenotype (PCO+HA+OD). Importantly, there was no significant difference in the prevalence of metabolic abnormalities or the distribution characteristics of the metabolic abnormalities among these four PCOS phenotypes. Our study supports the notion that metabolic abnormalities and the distribution characteristics of metabolic abnormalities should not be used to distinguish among the various clinical PCOS phenotypes. PMID:27902723
Xue, Hongxi; Zhao, Han; Zhao, Yueran; Liu, Xin; Chen, Zijiang; Ma, Jinlong
Background: Polycystic ovary syndrome (PCOS) is a common and complex multisystemic genetic disease. Previous genome-wide association study (GWAS) of PCOS has found several potentially causative single nucleotide polymorphisms (SNPs) in Han Chinese population. The goal of present investigation was to assess the potential association between rs1121980, rs1421085, rs1558902, rs8050136 SNPs and PCOS. In order to make a better elucidation of this disease, further investigations of association between SNPs susceptibility and PCOS become necessary. Methods: In the present study, we enrolled 212 patients with PCOS and 198 control subjects. Four polymorphisms of FTO gene (rs1121980, rs1421085, rs1558902, rs8050136) were genotyped by Taqman-MGB method, and their relationship with PCOS was speculated. Results: The allele frequency has no significant difference between the PCOS group and the controls. Genotype frequencies of the four SNPs in the additive, dominant and recessive models showed no significant difference between PCOS cases and controls. Conclusions: Our results demonstrate that FTO gene has little association in PCOS development. PMID:26722565
Shim, Unjin; Kim, Han-Na; Lee, Hyejin; Oh, Jee-Young
Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes. Methods We used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed. Results The pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05). Conclusions By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS. PMID:26308735
Aydos, Alp; Gurel, Aykut; Oztemur Islakoglu, Yasemin; Noyan, Senem; Gokce, Bagdagul; Ecemis, Tolga; Kaya, Cemil; Aksu, Arif Tarik; Gur Dedeoglu, Bala
Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder which affects women of reproductive age with prevalence of 8-18%. The oocyte within the follicle is surrounded by cumulus cells (CCs), which connect with mural granulosa cells (MGCs) that are responsible for secreting steroid hormones. The main aim of this study is comparing gene expression profiles of MGCs and CCs in PCOS and control samples to identify PCOS-specific differentially expressed genes (DEGs). In this study, two microarray databases were searched for mRNA expression microarray studies performed with CCs and MGCs obtained from PCOS patients and control samples. Three independent studies were selected to be integrated with naive meta-analysis since raw meta-data from these studies were found to be highly correlated. DEGs in these somatic cells were identified for PCOS and control groups. This study enabled us to reveal dysregulation in MAPK (mitogen activated protein kinase), insulin and Wnt signaling pathways between CCs and MGCs in PCOS. The meta-analysis results together with qRT-PCR validations provide evidence that molecular signaling is dysregulated through MGCs and CCs in PCOS, which is important for follicle and oocyte maturation and may contribute to the pathogenesis of the syndrome.
The use of steroid sex hormones for noncontraceptive benefits has been endorsed by several medical societies. In women with polycystic ovary syndrome (PCOS), hormonal contraceptives are first-line therapy for concurrent treatment of menstrual irregularity, acne, and hirsutism. The association of PCOS with obesity, diabetes, and dyslipidemia frequently brings up the debate regarding risks versus benefits of hormonal contraceptives in this population. In women with PCOS, the lack of large-scale studies evaluating the risks with varying doses of ethinyl estradiol, types of progestins, and presence of confounding factors such as obesity, smoking, and other cardiometabolic comorbidities is a significant limitation in these deliberations. Although it is important to assess the absolute risk for major morbidities including cardiovascular events, currently, there are a paucity of long-term data for these outcomes in PCOS. Most of the current studies do not suggest an increase in risk of prediabetes/diabetes, clinically significant dyslipidemia, inflammatory changes, or depressive/anxiety symptoms with oral contraceptive pill use. Screening of women with PCOS for cardiometabolic and psychiatric comorbidities is routinely recommended. This information should be used by health care providers to individualize the choice of hormonal contraceptive treatment, adequately counsel patients regarding risks and benefits, and formulate an appropriate follow-up plan.
Kellesarian, S V; Malignaggi, V R; Kellesarian, T V; Al-Kheraif, A A; Alwageet, M M; Malmstrom, H; Romanos, G E; Javed, F
The purpose of the present study was to review systematically the association between periodontal diseases (PDs) and polycystic ovary syndrome (PCOS). To address the focused question, 'Is there a relationship between PD and PCOS?' indexed databases were searched up to October 2016 without time or language restrictions using different combinations of the following key words: PCOS, ovarian cysts, PD, periodontitis, gingival diseases and gingivitis. Letters to the Editor, commentaries, historic reviews, case-report, unpublished articles and animal/experimental studies were excluded. Seven case-control studies were included. The number of study participants ranged between 52 and 196 females aged between 15 and 45 years. In three and three studies, proinflammatory cytokines were assessed in gingival crevicular fluid and saliva samples, respectively. In one study, salivary microbes were investigated. All studies reported that a positive association exists between PD and PCOS. In conclusion, there is a positive association between PD and PCOS; however, further well-designed longitudinal controlled clinical trials are needed in this regard. It is recommended that physicians should refer patients with PCOS to oral health-care providers for comprehensive oral evaluation and treatment.International Journal of Impotence Research advance online publication, 9 March 2017; doi:10.1038/ijir.2017.7.
Aydos, Alp; Gurel, Aykut; Oztemur Islakoglu, Yasemin; Noyan, Senem; Gokce, Bagdagul; Ecemis, Tolga; Kaya, Cemil; Aksu, Arif Tarik
Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder which affects women of reproductive age with prevalence of 8–18%. The oocyte within the follicle is surrounded by cumulus cells (CCs), which connect with mural granulosa cells (MGCs) that are responsible for secreting steroid hormones. The main aim of this study is comparing gene expression profiles of MGCs and CCs in PCOS and control samples to identify PCOS-specific differentially expressed genes (DEGs). In this study, two microarray databases were searched for mRNA expression microarray studies performed with CCs and MGCs obtained from PCOS patients and control samples. Three independent studies were selected to be integrated with naive meta-analysis since raw meta-data from these studies were found to be highly correlated. DEGs in these somatic cells were identified for PCOS and control groups. This study enabled us to reveal dysregulation in MAPK (mitogen activated protein kinase), insulin and Wnt signaling pathways between CCs and MGCs in PCOS. The meta-analysis results together with qRT-PCR validations provide evidence that molecular signaling is dysregulated through MGCs and CCs in PCOS, which is important for follicle and oocyte maturation and may contribute to the pathogenesis of the syndrome. PMID:27997581
Pasquali, Renato; Gambineri, Alessandra
Hirsutism is a common medical complaint among women of reproductive age, and it affects the majority of women with the polycystic ovary syndrome (PCOS). Increased rate of androgen production and its availability in tissue represent the main pathophysiological mechanisms responsible for hirsutism. In addition, androgens may be generated de novo in the hair follicle; therefore, circulating androgen levels do not quantify the real exposure of the hair follicle to androgens, as a quota is locally generated. Hirsutism is a clinical sign and not a disease in itself; its presence does not therefore necessarily require treatment, particularly in mild-to-moderate forms, and when an affected woman does not worry about it. Physicians should decide whether hirsutism is to be treated or not by evaluating not only the severity of the phenomenon but also the subjective perception of the patient, which does not necessarily correspond to the true extent of hair growth. In any case, a physician should manage a woman with hirsutism only on the basis of a diagnosis of the underlying cause, and after a clear explanation of the efficacy of each therapeutic choice. Cosmetic procedures and pharmacological intervention are commonly used in the treatment of hirsutism and are discussed in this paper. Importantly, there are different phenotypes of women with hirsutism and PCOS that may require specific attention in the choice of treatment. In particular, when obesity is present, lifestyle intervention should be always considered, and if necessary combined with pharmacotherapy.
Nasiri Amiri, Fatemeh; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Montazeri, Ali; Mohammadpour Thamtan, Reza Ali
Background: Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disorder. It has significant and diverse clinical consequences including reproductive, metabolic, and psychological morbidities as well as predisposition to malignancies. It is unclear how women with PCOS experience symptoms of this syndrome. Objectives: The aim of this study was to clarify the dimensions and components of quality of life in iranian women with PCOS. Patients and Methods: This study was a qualitative study to explore and document perceptions of women with PCOS about their disorder and quality of life. Semi-structured interviews with open ended questions were conducted with 23 women with PCOS. The interviews were continued to reach data saturation. The study was conducted in the Reproductive Endocrinology Research Center of Shahid Beheshti University of Medical Sciences. All the interviews were recorded and transcribed. Constant comparative analysis of the data was conducted manually according to the Strauss and Corbin analysis method. Results: The study revealed that the most important factors affecting quality of life in women with PCOS were the role functioning items as well as physical, mental, emotional, cognitive, and social dimensions. Conclusions: Comprehensive cares concerning various mental, emotional, cognitive, and social dimensions of quality of life should be planned for women with PCOS. PMID:24829583
Keen, Mohammad Abid; Shah, Iffat Hassan; Sheikh, Gousia
Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, affecting 5–10% of reproductive-aged women. The dermatologic manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, androgenic alopecia, and acanthosis nigricans, are among the cardinal manifestations of PCOS. Aim: To study the incidence and prevalence of various cutaneous manifestations in patients with PCOS and to correlate these skin manifestations with hormonal changes. Settings and Design: This study was conducted at a dermatology centre over a period of 1 year from November 2012 to 2013. Materials and Methods: The present study included 100 women diagnosed to have PCOS. Hormonal analysis as well as radiological assessment was done in all the cases. Cutaneous manifestations were ascertained and inferences were drawn. Statistical Analysis: Statistical analysis was carried out by the Chi-square test and independent samples t-test. Statistical significance was determined at a level of P < 0.05. Results: In our study, the prevalence of hirsutism, acne, female pattern hair loss, acanthosis nigricans, seborrhea, striae and acrochordons was 78%, 48%, 31%, 30%, 29%, 13%, and 9%, respectively. Conclusion: Dermatologic manifestations of PCOS play a significant role in making the diagnosis and constitute a substantial portion of the symptoms experienced by women with this syndrome.
De Simone, Clara; Caldarola, Giacomo; Corbeddu, Marialuisa; Moro, Francesca; Tropea, Anna; Moretta, Gaia; Apa, Rosanna
Psoriasis is a common, chronic, relapsing immune-mediated inflammatory disease (IMID) of the skin. IMIDs are multifactorial diseases characterized by common molecular pathways leading to a systemic inflammation. Patients with an IMID are also at higher risk of developing co-morbidities, such as adverse pregnancy outcomes, than the general population. A higher rate of pregnancy complications have been seen in inflammatory bowel disease and rheumatoid arthritis. The data for psoriasis are inconsistent but it appears that women with moderate-to-severe psoriasis may also have an increased risk of poor pregnancy outcomes. The cause of this association is unknown, although it may be related to elevated proinflammatory cytokines such as IL-6 and TNF-α, the high prevalence of comorbidities and other unhealthy behaviours, or the high prevalence of polycystic ovary syndrome (PCOS). In a recent study, PCOS prevalence in a psoriatic cohort (n = 51) was higher than in non-psoriatic women (n = 102) (47% versus 11%), and women with PCOS and psoriasis had a greater probability of insulin resistance, hyperinsulinaemia, and dyslipidaemia as well as a more severe skin condition, than those with psoriasis alone. Further studies are necessary to clarify the impact of psoriasis on pregnancy and in particular if these effects are mediated by concomitant PCOS.
Çelik, Ebru; Türkçüoğlu, Ilgın; Ata, Barış; Karaer, Abdullah; Kırıcı, Pınar; Eraslan, Sevil; Taşkapan, Çağatay; Berker, Bülent
Objective To compare the prevalence of various metabolic and cardiovascular risk factors and insulin resistance between polycystic ovary syndrome (PCOS) patients with or without hyperandrogenism. Material and Methods This is a retrospective cross-sectional study involving women with PCOS as diagnosed according to the Androgen Excess (AE) Society definition (n=504) and women with normoandrogenemic PCOS (n=183). Anthropometrics, lipid profile, glucose, insulin, oral glucose tolerance test (OGTT), and reproductive hormone levels were evaluated. Results Women with PCOS diagnosed according to the AE Society had a significantly higher prevalence of metabolic syndrome compared with the normoandrogenemic PCOS phenotype: odds ratio (OR) 2.95 [95% confidence interval (CI) 1.21–7.21]. There was no significant difference in the prevalence glucose intolerance test between the groups [OR: 2.15, 95% CI 0.71–6.56]. The prevalence of low high density lipoprotein (HDL)-cholesterol in the group under the AE-PCOS Society criteria was higher than that of the normoandrogenemic PCOS group [OR: 2.82, 95%CI 1.29–3.36]. Conclusion The risks of metabolic syndrome and cardiovascular disease may vary among the phenotypes of PCOS based on the Rotterdam criteria. This new data may be of reference in informing women with PCOS, although further prospective studies are needed to validate this proposition. PMID:27990089
Shabir, Iram; Ganie, Mohd Ashraf; Praveen, Edavan P; Khurana, Madan L; John, Jomimol; Gupta, Nandita; Kumar, Guresh; Ammini, Ariachery C
Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in women. It is associated with wide variety of metabolic disorders. The present study assessed morning plasma cortisol in women with PCOS. One hundred and ninety seven cases and 55 controls were enrolled for this study. The mean age of patients and controls were 23 ± 5.6 years and 25 ± 4.3 years. One hundred twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were significantly higher in lean PCOS women compared to controls (13.4 ± 5.1 versus 11.3 ± 4.5, p < 0.01) and over-weight PCOS women group (13.4 ± 5.1 versus 9.3 ± 3.2, p < 0.01). There was a trend for less acne and hirsutism with increase in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning plasma cortisol correlated negatively with BMI in PCOS women with normal glucose tolerance.
Tsai, Shih-Jen; Yang, Albert C.; Huang, Min-Wei; Chen, Pan-Ming; Wang, Shu-Li; Lu, Ti; Shen, Cheng-Che
Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established. Objective We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. Methods We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists. Results The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y). Conclusions PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated. PMID:24816764
Foroozanfard, Fatemeh; Soleimani, Alireza; Arbab, Elham; Samimi, Mansooreh; Tamadon, Mohammad Reza
Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders with an inflammatory basis. It is associated with hyperandrogenism in women and can be also associated with increased activity of the renin-angiotensin system (RAS). Approximately 5% to 10% of women of reproductive age are affected by this disease. This syndrome is the main cause of infertility. Blood pressure may be one of the complications of the syndrome. Objectives In this study, we sought to assess the role of the IL-17 inflammatory cytokine in increasing blood pressure in patients with PCOS. Patients and Methods In this cross-sectional study, after obtaining informed consent, we evaluated 85 patients with PCOS. IL-17 serum level was measured after separating the serum via ELISA method. The results obtained for the two groups of patients with high blood pressure and normal blood pressure were compared with each other. Results The daytime blood pressure was abnormal in eight patients, while it was normal in 72 patients. The blood pressure during the day had a direct correlation with the IL-17serum level; as a result, the mean IL-17 serum level in patients with high blood pressure was 77.10 ± 17.94 ρ g/ml while in those with normal blood pressure it was 55.20 ± 13.71 ρ g/ml (P = 0.001). High blood pressure during the night also showed a direct relation with theIL-17 serum level (P = 0.001). In addition, increasing of ambulatory 24-hourblood pressure was significantly related with IL-17 serum level, in such a way that the IL-17 serum level of people with high blood pressure rose by almost 22 ρg/ml during 24 hours (P = 0.001). Conclusions Our results showed an association between PCO syndrome and inflammatory factors. The IL-17 serum level was directly associated with the increase in blood pressure. PMID:28042549
Demir, B; Pasa, S; Demir, S; Tumer, C; Atay, A E; Gul, T; Atamer, Y
This study investigated the severity of hirsutism and its correlation with serum total testosterone (tT) levels in 87 patients with polycystic ovary syndrome (PCOS) and 85 healthy control subjects from the south-eastern region of Turkey. A wide range of variability exists in both hirsutism and modified Ferriman-Gallwey (mFG) scores. Similar mFG scores and serum tT levels were found compared with previous studies of general populations, but lower scores than those previously reported from Turkey. The incidence of hirsutism was lower in hyperandrogenic PCOS patients compared with non-hyperandrogenic PCOS patients. There was no correlation between serum tT levels and the rate of hirsutism in patients with PCOS. Heritability, testosterone receptor sensitivity, 5α reductase activity or environmental/socioeconomic factors may play a role in the development of clinical hirsutism. Larger scale studies are needed to clarify which other factors may be responsible and to confirm these results.
Karaköse, Melia; Çakal, Erman; Topaloğlu, Oya; Arslan, Müyesser Sayki; Giniş, Zeynep; Şahin, Mustafa; Delibaıı, Tuncay
Objective The aim of this study was to determine the frequency of non-thyroidal illness syndrome (NTIS) in patients with polycystic ovary syndrome (PCOS). Material and Methods During a 6-month period, 52 patients with PCOS were recruited for this cross-sectional study. The control group included 68 age-matched female volunteers. Serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), anti-thyroperoxidase antibody (anti-TPO Ab), and anti-thyroglobulin antibody (anti-Tg Ab) were measured. Results The TSH level in the PCOS patients and controls did not differ significantly (1.9±1.2 μIU/mL vs. 1.8±0.9 μIU/mL, p>0.05). Serum fT3 and fT4 levels in the controls were significantly lower than those in the PCOS patients (fT3: 2.7±0.3 pg/mL vs. 2.9±0.3 pg/mL, p=0.02; fT4: 1.0±0.1 ng/dL vs. 1.1±0.1 ng/dL, p=0.03). The Hs-CRP (high-sensitivity C-reactive protein) level in the PCOS patients was significantly higher than in the controls (3.5±4.9 mg/L vs. 1.7±2.7 mg/L, p=0.03). A statistically significant relationship was observed between Hs-CRP and fT4 (r=0.245, p=0.015). However, NTIS was not observed in either group. Conclusion Thyroid function abnormalities could be observed in PCOS; however, NTIS was not noted in the present study despite the inflammatory state of the PCOS patients. PMID:24592109
Espinós-Gómez, Juan J; Rodriguez-Espinosa, J; Ordóñez-Llanos, J; Calaf-Alsina, J
Polycystic ovary syndrome (PCOS) is associated with the metabolic syndrome (MetS). The metabolic disorders are not universal and may vary with race, age and phenotype. Our purpose was to determine the clinical and biochemical characteristics of Mediterranean PCOS women with MetS, compare them with non-MetS PCOS patients, and assess the ability of clinical data and biochemical tests to predict these abnormalities within our population. A total of 218 subjects, 196 PCOS women and 22 controls, undergo a physical examination and laboratory evaluation for a diagnosis of MetS. MetS was categorized according to NCEP ATP III guidelines. PCOS patients were analyzed separately and compared in three subgroups: three or more MetS criteria, two criteria, one or no criteria. The overall prevalence of MetS was 21.4%. Women with MetS had higher glucose (G) levels than PCOS women with two criteria (5.7 ± 1.5 vs 5 ± 0.4, p < 0.05). Both groups were comparable for all the other parameters. Waist circumference (WC), body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), bioavailable testosterone (uT), triglycerides (TG) and insulin (I) levels were significantly higher and sex hormone-binding globulin (SHBG) levels, high-density lipoprotein (HDL), HOMA and QUICKI indexes significantly lower in both groups, MetS and patients with two criteria, compared with women with one or no criteria and the control group. WC, HDL and TG were the best predictors of PCOS patients at risk for MetS. In conclusion, we recommend considering PCOS patients with two criteria of MetS as having the same risk as patients with the full syndrome. Waist circumference with HDL and triglycerides is an efficient combined test to identify PCOS women at risk for metabolic and cardiovascular diseases.
The Investigators Collected 534 PCOS Patients as the Case Group,and 580 Infertile Women With Normal Ovulatory Cycle of the Control Group;; At the Same Time, the Investigators Continuedly Collect Cases to October 2012, and Totally Collected 579 Patients With PCOS Altogether;; 534 Patients in the Cases Group and 580 Women in the Control Group Received no Measures, While 579 Patients Received Drugs;; The Investigators Monitored Basic Indexes in Blood of All the Subjects in This Suvey,and Also Monitored Indexes of 579 Patients After Treatment.
Paradisi, G; Fulghesu, A M; Ferrazzani, S; Moretti, S; Proto, C; Soranna, L; Caruso, A; Lanzone, A
To elucidate the mechanism of metabolic adaptation of women with polycystic ovary syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of PCOS patients with or without gestational diabetes were studied longitudinally during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100 g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study. Plasma concentrations of insulin and glucose were determined by radioimmunoassay and glucose oxidase technique, respectively. Five of 13 PCOS patients developed gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both fasting glucose and insulin plasma concentrations did not change significantly during pregnancy and no difference was seen between the two groups. On the contrary PCOS-GD group early exhibited higher values of area under the curve (AUC) for glucose and insulin response to OGTT with respect to those found in PCOS-nGD group. This difference was already significant in the first gestational trimester. Moreover insulin sensitivity value (M) was significantly lower in the first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD group. However, as gestation proceeded, M value decreased in PCOS-nDG group and the difference from PCOS patients developing gestational diabetes was not sustained into the second and third trimesters. Both groups had similar body mass index values and AUC insulin increase from first to third trimester of gestation. It is concluded that early alteration of insulin sensitivity and secretion constitute specific risk factors in PCOS patients for the development of abnormalities of glucose tolerance.
Tan, Jing; Wang, Qiu-Yi; Feng, Gui-Mei; Li, Xue-Ying; Huang, Wei
Background: Polycystic ovary syndrome (PCOS) and its characteristic symptoms have been associated with physical and psychological issues in women of reproductive age. The current study was conducted in response to the dearth of systematic research related to psychological functioning and quality of life in patients with PCOS in Southwest China, and to determine whether patients with PCOS exhibit poorer mental health (MH) compared to healthy women of the same age and living in the same region, without a PCOS diagnosis. Methods: We enrolled 120 outpatients with PCOS and 100 healthy controls in this study. Standardized questionnaires were administered to assess general MH conditions (General Health Questionnaire-12-item version), anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory), as well as health-related quality of life (HRQoL) measured using the 36-item short-form health survey. The independent samples t-test was conducted for continuous study variables. For categorical variables, the Pearson Chi-square test, Fisher's exact test, and logistic regression were performed. Results: The prevalence of anxiety (13.3% vs. 2.0%) and depression (27.5% vs. 3.0%) was higher in patients with PCOS compared to the controls (both P < 0.05). Patients with PCOS had decreased HRQoL. Patients with PCOS who had fertility requirements were more likely to be anxious and depressed than those without fertility requirements (anxiety: 22.6% [12/53] vs. 5.9% [4/67], χ2 = 7.117, P = 0.008; depression: 37.7% (20/53) vs.19.4% (13/67), χ2 = 4.988, P = 0.026). Conclusions: PCOS and related symptoms may be risk factors for depression and anxiety. Professionals should be concerned with the MH of women with PCOS, and psychological therapy should be considered. PMID:28139507
Williams, Sophie; Sheffield, David; Knibb, Rebecca C
Polycystic ovary syndrome is an endocrine disorder affecting 1 in 10 women. Women with polycystic ovary syndrome can experience co-morbidities, including depressive symptoms. This research explores the experience of living with polycystic ovary syndrome and co-morbidities. Totally, 10 participants with polycystic ovary syndrome took part in Skype™ interviews and analysed using thematic analysis. Four themes emerged from the data: change (to life plans and changing nature of condition); support (healthcare professionals, education and relationships); co-morbidities (living with other conditions and depression, self-harm and suicidal ideation) and identity (feminine identity and us and them). The findings highlight the need for screening of women with polycystic ovary syndrome for depressive disorders.
Sheffield, David; Knibb, Rebecca C
Polycystic ovary syndrome is an endocrine disorder affecting 1 in 10 women. Women with polycystic ovary syndrome can experience co-morbidities, including depressive symptoms. This research explores the experience of living with polycystic ovary syndrome and co-morbidities. Totally, 10 participants with polycystic ovary syndrome took part in Skype™ interviews and analysed using thematic analysis. Four themes emerged from the data: change (to life plans and changing nature of condition); support (healthcare professionals, education and relationships); co-morbidities (living with other conditions and depression, self-harm and suicidal ideation) and identity (feminine identity and us and them). The findings highlight the need for screening of women with polycystic ovary syndrome for depressive disorders. PMID:28070371
Guo, Zhizhun; Qiu, Huiling; Wang, Lingling; Wang, Lijun; Wang, Chonggang; Chen, Meng; Zuo, Zhenghong
To investigate the serum concentrations of organochlorine pesticides (OCPs) in patients with polycystic ovary syndrome (PCOS), a total of 178 women were studied. The concentrations of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) in serum were determined using Gas Chromatography Mass-Mass Spectrometer. No differences with statistical significance in the mean HCH, p,p'-DDD, p,p'-DDE concentrations were observed between the patients with PCOS and the control group. Serum p,p'-DDT (P = 0.016) and o,p'-DDT (P = 0.000) levels were significantly higher in patients with PCOS compared with the control group. The results of the association between OCPs levels and hormone levels indicated that o,p'-DDT may play a role in the pathogenesis of PCOS by affecting hormones levels. Further trials should be investigated with the findings in this study to obtain new pathogenesis of PCOS.
Ito, Y; Fisher, C R; Conte, F A; Grumbach, M M; Simpson, E R
We identified two mutations in the CYP19 gene responsible for aromatase deficiency in an 18-year-old 46,XX female with ambiguous external genitalia at birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from genomic DNA and sequenced directly. Direct sequencing of the amplified DNA from the patient revealed two single-base changes, at bp 1303 (C-->T) and bp 1310 (G-->A) in exon X, which were newly found missense mutations and resulted in codon changes of R435C and C437Y, respectively. Subcloning followed by sequencing confirmed that the patient is a compound heterozygote. The results of restriction fragment length polymorphism analysis and direct sequencing of the amplified exon X DNA from the patient's mother indicate maternal inheritance of the R435C mutation. Transient expression experiments showed that the R435C mutant protein had approximately 1.1% of the activity of the wild type, whereas C437Y was totally inactive. Cysteine-437 is the conserved cysteine in the heme-binding region believed to serve as the fifth coordinating ligand of the heme iron. To our knowledge, this patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency. Recognition that such defects exist will lead to a better understanding of the role of this enzyme in human development and disease. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8265607
Caldwell, Aimee S L; Edwards, Melissa C; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B; Handelsman, David J; Walters, Kirsty A
Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS.
Blay, Sergio Luís; Aguiar, João Vicente Augusto; Passos, Ives Cavalcante
Background The association between depression, anxiety, and polycystic ovary syndrome (PCOS) is still unclear. Therefore, a systematic review and meta-analysis was conducted to assess the rates of comorbid psychiatric disorders among women with PCOS compared to women without it. Methods PubMed/MEDLINE, Embase, PsycINFO, and Web of Science databases were searched from inception to November 27, 2015. Studies were eligible for inclusion if they were original reports in which the rates of mood (bipolar disorder, dysthymia, or major depressive disorder), obsessive–compulsive spectrum disorders, trauma- and stressor-related disorders, anxiety disorders or psychotic disorders, somatic symptom and related disorders, or eating disorders had been investigated among women with an established diagnosis of PCOS and compared with women without PCOS. Psychiatric diagnosis should have been established by means of a structured diagnostic interview or through a validated screening tool. Data were extracted and pooled using random effects models. Results Six studies were included in the meta-analysis; of these, five reported the rates of anxiety and six provided data on the rates of depression. The rate of subjects with anxiety symptoms was higher in patients with PCOS compared to women without PCOS (odds ratio (OR) =2.76; 95% confidence interval (CI) 1.26 to 6.02; Log OR =1.013; P=0.011). The rate of subjects with depressive symptoms was higher in patients with PCOS compared to women without PCOS (OR =3.51; 95% CI 1.97 to 6.24; Log OR =1.255; P<0.001). Conclusion Anxiety and depression symptoms are more prevalent in patients with PCOS. PMID:27877043
Soydan, Sidika Sinem; Deniz, Kagan; Uckan, Sina; Unal, Aslı Dogruk; Tutuncu, Neslihan Bascıl
The prevalence of temporomandibular disorders is higher among women than men (ratio 3:1 -9:1). Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in women, which is characterised by chronic low-grade inflammation and excess of androgenic hormones that lead to metabolic aberrations and ovarian dysfunction. Increased activities of various matrix metalloproteinases (particularly MMP-2 and 9) in the serum of these patients has been reported, and it has been hypothesised that high activities of MMP may contribute to loss of matrix and chronic inflammation of the fibrocartilage in temporomandibular disorders. Our aim was to evaluate the incidence of temopormandibular dysfunction in women with PCOS compared with an age-matched, disease-free, control group. We studied 50 patients with previously diagnosed PCOS and 50 volunteers who had normal menstrual cycles. We made a comprehensive clinical examination of the temporomandibular joint (TMJ) and muscles of mastication in both groups and recorded the Visual Analogue Scores (VAS) for pain. There were significant differences (p<0.001) in the incidence of temporomandibular disorders (n=43 (86%) in the PCOS group compared with n=12 24% in the control group), muscle tenderness(n=32 (64%) in the PCOS group compared with n=14 (28%) in the control group) and pain in the TMJ (mean (SD) VAS 2.9 (2.61) compared with 0.3 (1.56). We confirm the higher incidence and severity of disorders of the TMJ in patients with PCOS and suspect that chronic low-grade inflammation may play a part in the aetiology of the disease.
Morotti, Elena; Battaglia, Bruno; Fabbri, Raffaella; Paradisi, Roberto; Venturoli, Stefano; Battaglia, Cesare
Background: To verify if in lean polycystic ovary syndrome (PCOS) patients, the smok- ing habitude might increase the risk of cardiovascular (CV) disease. Materials and Methods: In this prospective observational study, eighty-one women were divided into the following three groups: group I with 27 non-smokers, group II with 26 light-smokers (1-10 cigarettes/day), and group III with 28 heavy smokers (>10 cigarettes/ day). They were submitted to fasting blood sampling; blood measurement of nitrites/ni- trates (NO2-/ NO3), biochemical and hormonal parameters; ovarian ultrasonographic (US) analysis; doppler evaluation of uterine and ophthalmic arteries; brachial artery flow-medi- ated vasodilatation; 24-hour ambulatory blood pressure monitoring; and oral glucose toler- ance test (OGTT). Results: Doppler analysis revealed higher uterine and ophthalmic arteries pulsatility in- dex (PI) and ophthalmic artery back pressure in group III compared with group I. The brachial artery diameter and PI, at baseline, was similar among all groups. After the re- active hyperemia, a more intense vasodilatation was observed in group I in comparison with group III. The 24-hour blood pressure demonstrated that, in group III patients, the 24-hour, day- and night-time diastolic blood pressure (DBP), was higher in comparison with non-smokers. The atherogenic index of plasma (AIP) was higher in heavy smokers than in non-smokers. The leukocytes and homocysteine (HCY) values were increased in group III. The NO2-/ NO3- plasma levels were reduced in heavy smokers in compari- son with non-smokers. The insulin, glucose and C-peptide plasma values were higher in group III than in other groups. In heavy smokers, the estimates of insulin sensitivity (ISI) and pancreatic β-cell function (HOMA-B) were higher compared to the other groups. Conclusion: Smoking habitude in lean PCOS patients may increase the soft markers of CV risk. PMID:24520500
Bagheri, Morteza; Abdi Rad, Isa; Hosseini Jazani, Nima; Nanbakhsh, Fariba
Background: Polycystic ovary syndrome (PCOS) is known as a metabolic disorder. The results of recent studies implied that vitamin D receptor (VDR) genetic variants may impact PCOS and insulin resistance in women with PCOS. The aim of the present study was to determine the VDR TaqI gene variant in exon 9 (T/C) (rs731236) in normal controls and patients with PCOS for the first time in Iranian Azeri women. Materials and Methods: In this case control study between April 2011 and June 2012, a total of 76 women aged 18-40 years (38 patients with PCOS and 38 healthy women as normal controls) participated. Genotypes of VDR TaqI in exon 9 (T/C) (rs731236) were determined using the PCR-RFLP method. Results: The frequencies of VDR TaqI T anc C alleles were 0.605 and 0.395 in cases and 0.697 and 0.303 in controls. Also, the genotypic frequencies of VDR TaqI were 16) (42.11), 14(36.84), and 8(21.05) in cases, and 17(44.74), 19(50), and 2(5.26) in controls for TT, TC and CC genotypes respectively. There was no difference in genotype and allele frequencies between PCOS and controls (p value>0.05) with the exception of the CC genotype (p value=0.04). Conclusion: This report, a first of its own kind in Iranian Azeri patients, suggests that the CC genotype of VDR TaqI in exon 9 (rs731236) is associated with PCOS. PMID:24520473
Ghaneei, Azam; Jowkar, Akram; Hasani Ghavam, Mohammad Reza; Ghaneei, Mohammad Ebrahim
Background: 30% of patients with polycystic ovary syndrome (PCOS) show mild, transient hyperprolactinemia. It is suggested that a reduction of the dopamine inhibitory effect might raise both prolactin and luteinizing hormone. Objective: To investigate the adjuvant cabergoline therapy effects on menstrual irregularity and androgen system in PCOS women with hyperprolactinemia. Materials and Methods: This randomized clinical trial was done on 110 polycystic ovary syndrome women with increased serum prolactin concentration [1.5 fold more than normal level (>37.5 ng/ml)]. Participants were divided into two groups: Case group (n=55) treated with metformin 1gr/day and cabergoline 0.5 mg/week for 4 months and control group (n=55) treated with metformin 1g/day and placebo weekly. Testosterone, prolactin, and dehydroepiandrosterone sulfate level were measured before and four months after intervention in two groups. Also, situation of menstrual cycles asked and recorded before and after intervention. Results: We found decrease in the mean of dehydroepiandrosterone sulfate, weight and total testosterone level in the two groups after intervention but their changes were not significant. Patients in case group showed a significant decrease in serum prolactin level before and after intervention (p<0.001), but no difference was found in control group. All patients in both studied groups had irregular menstrual cycles, which regulate after intervention and the difference was significant (p=0.02). Conclusion: The results showed that cabergoline can be used as a safe administration in PCOS patients with hyperprolactinemia to improve the menstrual cycles. Considering that the administration of cabergoline plus metformin may reduce the required duration and dose of metformin, patient acceptability of this approach is higher. PMID:25999998
The National Institutes of Health, Office of Disease Prevention, has described polycystic ovary syndrome (PCOS) as a major public health problem for women in the USA. This study examines the suitability of the National Health Care Surveys, collected by the Centers for Disease Control and Prevention, to understand patient demographics and behavioral health services associated with PCOS-related medical visits. Data were from the 2005-2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. PCOS-related medical visits were identified using the International Classification of Diseases, 9th Revision, Clinical Modification code 256.4. Items on mental health and health education ordered or provided did not meet the National Center for Health Statistics criteria necessary to produce reliable national estimates (i.e., at least 30 unweighted records and a relative standard error <30%). Findings underscore the need to strengthen national surveillance to further understand behavioral health care for patients with PCOS.
Christakou, Charikleia D; Diamanti-Kandarakis, Evanthia
Polycystic ovary syndrome (PCOS) is associated with a clustering of metabolic and cardiovascular risk factors. Insulin resistance is implicated as the major player in the metabolic abnormalities and contributes to the increased cardiovascular risk associated with the syndrome. However, androgen excess appears to participate as an independent parameter, which further aggravates the cardiovascular and metabolic aberrations in affected women with PCOS. The resultant impact of hyperandrogenemia possibly acquires clinical significance for women's health in the context of PCOS, particularly since recent data support an increased incidence of coronary artery disease and of cardiovascular events directly related to androgen levels in women with the syndrome.
Pfister, Gertrud; Rømer, Kristine
This article explores women's lived experiences with polycystic ovary syndrome (PCOS) on the basis of semistructured interviews with 21 Danish women. It provides insights about the problems that they experienced and how they coped with PCOS. The interviews revealed that they were highly influenced by society's femininity norms. Many of them perceived their bodies as "different" because of the symptoms of PCOS, namely, hirsutism. They used different strategies to live up to body ideals and cope with the symptoms. However, hirsutism had a decisive negative influence on the women's everyday lives, particularly with regard to male partners and sexual relations.
Housman, Elizabeth; Reynolds, Rachel V
Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women who are of reproductive age. The pathogenesis involves several associated hormonal pathways that culminate in metabolic, reproductive, and cardiovascular effects. The hallmark features of hyperandrogenism and hyperinsulinemia have systemic long-term implications. Dermatologists frequently evaluate and manage the cutaneous manifestations of PCOS (ie, acanthosis nigricans, hirsutism, acne, and alopecia), and therefore play a key role in its diagnosis and management. In part I of this continuing medical education article, we review the definition, etiology, pathogenesis, and clinical features of PCOS.
Pembe, A B; Abeid, M S
The aim of this study was to determine prevalence of polycystic ovaries (PCO) and associated clinical and biochemical features among women with infertility attending gynaecological outpatient department (GOPD) at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. All women with infertility attending the GOPD from 11th September 2006 to 15th February 2007 were recruited to the study. Information on socio-demographic, obstetric and menstrual characteristics was collected. Anthropometric measurement, clinical examination of acne and hirsutism, vaginal ultrasonography for PCO and biochemical analysis of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were performed. All 102 women who attended the GOPD during the study period due to infertility were recruited. Two women were excluded after diagnosis of pregnancy made by hormonal assay and ultrasonography thus remaining with 100 women for analysis. Oligomenorrhoea and acne were significantly higher in a group of women with PCO than among women with normal ovaries. The mean hirsutism score though was not significant, was higher in women with PCO than in women with normal ovaries (5.1 +/- 2.7 vs. 4 +/- 2.4, P < 0.057). Using the Rotterdam criteria 32 (32%) women were diagnosed to have polycystic ovary syndrome (PCOS). Among these women 25 (78.1%) had PCO, 24 (75%) had signs of oligoanovulation, and 18 (56.3%) had hirsutism. Among 68 women with no PCOS, 7 (10.3%) had polycystic ovaries, 15 (22.1%) had signs of oligoanovulation and 6 (8.8%) had hirsutism. In conclusion, polycystic ovaries are common among women with infertility, however are not necessarily associated with polycystic ovary syndrome. Doctors should investigate their clients for PCOS and offer appropriate treatment.
Kumar, Amar Nagesh; Naidu, Jupalle Nagaiah; Satyanarayana, Uppala; Ramalingam, Krishnan; Anitha, Medabalmi
Background Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders among women of reproductive age and the leading cause of female infertility. This study intends to evaluate the lipid profile, hormonal levels [free T3 (fT3), free T4 (fT4), thyroid stimulating hormone (TSH), insulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin] in PCOS women from Nellore and its surrounding districts of Andhra Pradesh, India. Materials and Methods This cross-sectional study included 80 newly diagnosed PCOS women and an equal number of age and body mass index (BMI) matched healthy controls. We used the photometry methods to determine serum glucose levels and the lipid profile. An immunoturbidometry method was employed to measure high sensitive C-reactive protein (hsCRP). All hormonal parameters were measured using chemiluminescence immunoassays. Insulin resistance was evaluated using the homeostatic model assessment-insulin resistance (HOMA-IR) method. Statistical analysis was done using SPSS software version 20.0. Results The PCOS patients presented statistically higher levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-c, P<0.0001) when compared to those of controls. PCOS patients had elevated fasting glucose, hsCRP, fasting insulin, TSH, LH and prolactin levels (P<0.001). An increased LH/FSH ratio (>1.5) was seen in women with PCOS compared with control women. In addition, we observed a direct correlation between fasting insulin with fasting glucose and HOMA-IR. LH was inversely proportional to BMI. Conclusion The present study showed a higher prevalence of insulin resistance, dyslipidemia, and hypothyroidism in PCOS women. Furthermore this study showed increased LH concentrations, a higher LH/FSH ratio, and higher prolactin levels in PCOS women. PMID:27123196
Muscogiuri, Giovanna; Palomba, Stefano; Caggiano, Mario; Tafuri, Domenico; Colao, Annamaria; Orio, Francesco
Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroid disease (AITD). The aim of the study was to investigate the association of AITD with 25(OH) vitamin D levels in women with polycystic ovary syndrome (PCOS). Fifty women with PCOS were consecutively enrolled and underwent routine health checkups, which included measurements of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyreoglobulin (TG-Ab) antibodies, FT3, FT4, and TSH. Selecting 50 nmol/L as cut-off point, low 25(OH) vitamin D levels were detected in 23 of 50 patients (46 %). AITD was diagnosed when TPO-Ab levels exceeding 80 U/ml and/or TG-Ab levels exceeding 70 U/ml. AITD was detected in 12 of 50 patients (24 %). The levels of 25(OH) vitamin D were significantly lower in women with PCOS and AITD when compared with women with PCOS and without AITD (p = 0.02). In women with AITD no correlation was found between 25(OH) vitamin D and TG-Ab (r = 0.48; p = 0.16), TPO-Ab (r = 0.43; p = 0.21), TSH (r = 0.38; p = 0.27), FT3 (r = -0.40; p = 0.25) and FT4 levels (r = -0.54; p = 0.10). These findings suggest that low levels of 25(OH) vitamin D were significantly associated with AITD in women with PCOS.
Scaruffi, Elisabetta; Gambineri, Alessandra; Cattaneo, Stefania; Turra, Jenni; Vettor, Roberto; Mioni, Roberto
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. PMID:25429283
Labruijere, Sieneke; van Houten, E Leonie A F; de Vries, René; Musterd-Bagghoe, Usha M; Garrelds, Ingrid M; Kramer, Piet; Danser, A H Jan; Villalón, Carlos M; Visser, Jenny A; Van Den Brink, Antoinette Maassen
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of there productive age, but the exact pathophysiological mechanisms involved remain unclear. Cardiovascular disease risk is increased in PCOS patients and endothelial damage has been observed. We recently developed a mouse model of PCOS with reproductive and metabolic characteristics resembling those observed in women with PCOS. In this model we studied vascular function with particular emphasis on markers of vascular endothelial function. Animals were treated for 90 days with dihydrotestosterone (DHT; 27.5 mg/day) or placebo using subcutaneous continuous-release pellets. Aortas were isolated for isometric force recordings in organ baths to investigate endothelial and vascular smooth muscle characteristics. Lungs were used to analyze endothelial nitric oxide synthase (eNOS) expression and phosphorylation. Asymmetric dimethylarginine (ADMA) levels were investigated in serum to assess endothelial damage. Expression of androgen receptor (Ar) mRNA was studied in aortas. DHT treatment (compared with placebo) induced i) a significant decrease in acetylcholine-induced aortic relaxations, with no change in calcitonin gene related peptide- or sodium nitroprusside-induced relaxations, as well as 5-hydroxytryptamine-induced contractions; ii) no change in eNOS expression/phosphorylation in lungs or in plasma ADMA levels; and iii) a twofold increase in aortic AR expression. Our results suggest that, in DHT-exposed mice, hyperandrogenemia specifically decreases endothelium dependent vasorelaxation without deterioration of smooth muscle function. This study may initiate further investigations to elucidate underlying mechanism for the phenotype that is present in these animals, as well as in PCOS patients.
Background Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women. Methods The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured. Results T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol. Conclusion PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype. PMID:23216997
Liu, Rui; Zhang, Chenhong; Shi, Yu; Zhang, Feng; Li, Linxia; Wang, Xuejiao; Ling, Yunxia; Fu, Huaqing; Dong, Weiping; Shen, Jian; Reeves, Andrew; Greenberg, Andrew S.; Zhao, Liping; Peng, Yongde; Ding, Xiaoying
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. Gut microbiota has been implicated to play a critical role in metabolic diseases and may modulate the secretion of mediators of the brain–gut axis. Interaction between gut microbiota and the endocrine and biochemical disturbances in PCOS still remains elusive. Here, we showed an altered gut microbiota significantly correlated with PCOS phenotype. There were 33 patients with PCOS (non-obese PCOS individuals, PN, n = 12; obese PCOS individuals, PO, n = 21) as well as 15 control subjects (non-obese control individuals, CN, n = 9; obese control individuals, CO, n = 6) enrolled in our study. The plasma levels of serotonin, ghrelin, and peptide YY (PYY) were significantly decreased in patients with PCOS compared with controls, and have a significantly negative correlation with waist circumference and testosterone. Sequencing of the V3–V4 region of the 16S rRNA gene in fecal samples revealed the substantial differences of gut microbial species between the PCOS and non-obese controls. Bacterial species were clustered into 23 co-abundance groups (CAGs) based on the SparCC correlation coefficients of their relative abundance. The CAGs increased in PCOS, including the bacteria belonging to Bacteroides, Escherichia/Shigella and Streptococcus, were negatively correlated with ghrelin, and positively correlated with testosterone and BMI. Furthermore, the CAGs that were decreased in PCOS, including the bacteria from Akkermansia and Ruminococcaceae, showed opposite relationship with body-weight, sex-hormone, and brain–gut peptides. In conclusion, gut microbial dysbiosis in women with PCOS is associated with the disease phenotypes. PMID:28293234
ANNAGÜR, Bilge Burçak; TAZEGÜL, Aybike; AKBABA, Nursel
Introduction In the current study we aimed to determine body image, self-esteem and depressive symptomatology in women with Polycystic ovary syndrome (PCOS) and compare with healthy controls. Method This study was conducted among the patients with untreated PCOS who admitted to the Outpatient Clinic of Gynecology and Obstetrics of Faculty of Medicine of Selçuk University. A total 83 consecutive women with PCOS met the criteria of present study were included in the study. Age matched healthy controls (n=64) were recruited from employees at Selçuk University Hospital. PCOS was defined according to Rotterdam criteria. After socio-demographic characteristics of the participants were recorded, Body Image Scale, Rosenberg Self-Esteem Scale and Beck Depression Inventory were completed by the participants. Results Patients with PCOS and healthy controls did not differ in some sociodemographic variables, including age, education and economic status (p>.05). Previous psychiatric history was more prevalent among the PCOS group (p<. 05). Body mass index (BMI) was ≤25 kg/m2 in both groups. BMI values in the PCOS group were significantly higher than in the controls (p<.05). BDI scores were significantly higher in the PCOS group compared to that in the healthy controls (p<.05). There was no significant difference between the PCOS group and healthy controls in BIS and RSES scores (p>.05). Conclusion The present study suggests that PCOS seems to be associated with depressive symptomatology. Furthermore, rising BMI values of these women may be an indicator for the onset of PCOS. However, these results should be confirmed by prospective studies.
Liu, Rui; Zhang, Chenhong; Shi, Yu; Zhang, Feng; Li, Linxia; Wang, Xuejiao; Ling, Yunxia; Fu, Huaqing; Dong, Weiping; Shen, Jian; Reeves, Andrew; Greenberg, Andrew S; Zhao, Liping; Peng, Yongde; Ding, Xiaoying
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. Gut microbiota has been implicated to play a critical role in metabolic diseases and may modulate the secretion of mediators of the brain-gut axis. Interaction between gut microbiota and the endocrine and biochemical disturbances in PCOS still remains elusive. Here, we showed an altered gut microbiota significantly correlated with PCOS phenotype. There were 33 patients with PCOS (non-obese PCOS individuals, PN, n = 12; obese PCOS individuals, PO, n = 21) as well as 15 control subjects (non-obese control individuals, CN, n = 9; obese control individuals, CO, n = 6) enrolled in our study. The plasma levels of serotonin, ghrelin, and peptide YY (PYY) were significantly decreased in patients with PCOS compared with controls, and have a significantly negative correlation with waist circumference and testosterone. Sequencing of the V3-V4 region of the 16S rRNA gene in fecal samples revealed the substantial differences of gut microbial species between the PCOS and non-obese controls. Bacterial species were clustered into 23 co-abundance groups (CAGs) based on the SparCC correlation coefficients of their relative abundance. The CAGs increased in PCOS, including the bacteria belonging to Bacteroides, Escherichia/Shigella and Streptococcus, were negatively correlated with ghrelin, and positively correlated with testosterone and BMI. Furthermore, the CAGs that were decreased in PCOS, including the bacteria from Akkermansia and Ruminococcaceae, showed opposite relationship with body-weight, sex-hormone, and brain-gut peptides. In conclusion, gut microbial dysbiosis in women with PCOS is associated with the disease phenotypes.
Wang, LianLian; Qi, HongBo; Baker, Philip N.; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian
Background Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15–40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. Material/Methods We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50–100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. Results CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93–1.95) vs. 1.08 (0.85–1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. Conclusions Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation. PMID:28246376
Orio, F; Ferrarini, E; Cascella, T; Dimida, A; Palomba, S; Gianetti, E; Colao, A; Agretti, P; Vitti, P; Lombardi, G; Pinchera, A; Tonacchera, M
This study was designed to assess the relationship between mutations in the FSH receptor (FSHr) gene and polycystic ovary syndrome (PCOS) in Italian women. The study population included 50 patients with PCOS and 50 age- and body mass index (BMI)-matched controls. A complete anthropometrical, hormonal and pelvic ultrasonographic evaluation was performed in all subjects. Genomic DNA was extracted from peripheral lymphocytes and then each exon of the FSHr gene was amplified by PCR. The mutation identified was cloned and the functional properties were studied after transient expression in COS-7 cells. Direct sequencing of exons 1-10 of the FSHr gene revealed the presence of a heterozygous AAT/ATT mutation affecting the isoleucine residue at position 411, which was replaced by an asparagine, in the second transmembrane segment (I411N). This mutation was only found in one woman with PCOS and not in her parents. This mutation was not present in 50 age and BMI controls and in another 150 women not affected by PCOS. The functional study after transient expression in COS-7 cells revealed that this I411N had similar functional characteristics with respect to the wild type FSHr (wtFSHr). Genetic analyses of polymorphisms in the human FSHr gene were also performed. All 50 women with PCOS harbored the A307T polymorphic variant, 56% harbored N680S, 30% S680S and 14% N680N polymorphisms. In conclusion, the present study demonstrates that mutations of the FSHr gene are rare in Italian women. The only mutation that we found does not appear to have any pathophysiological significance in PCOS.
Mahmoudi, Touraj; Majidzadeh-A, Keivan; Farahani, Hamid; Mirakhorli, Mojgan; Dabiri, Reza; Nobakht, Hossein; Asadi, Asadollah
Background: Vitamin D and insulin play an important role in susceptibility to polycystic ovary syndrome (PCOS), and therefore vitamin D receptor (VDR), parathyroid hormone (PTH), and insulin receptor (INSR) gene variants might be involved in the pathogenesis of PCOS. Objective: The present study was designed to investigate the possible associations between polymorphisms in VDR, PTH, and INSR genes and the risk of PCOS. Materials and Methods: VDR, PTH, and INSR gene variants were genotyped in 35 women with PCOS and 35 controls using Polymerase chain reaction – Restriction fragment length polymorphism method. Furthermore, serum levels of glucose and insulin were measured in all participants. Results: No significant differences were observed for the VDR FokI, VDR Tru9I, VDR TaqI, PTH DraII, INSR NsiI, and INSR PmlI gene polymorphisms between the women with PCOS and controls. However, after adjustment for confounding factors, the VDR BsmI “Bb” genotype and the VDR ApaI "Aa" genotype were significantly under transmitted to the patients (p= 0.016; OR= 0.250; 95% CI= 0.081-0.769, and p= 0.017; OR= 0.260; 95% CI= 0.086-0.788, respectively). Furthermore, in the women with PCOS, insulin levels were lower in the participants with the INSR NsiI "NN" genotype compared with those with the "Nn + nn" genotypes (P= 0.045). Conclusion: The results showed an association between the VDR gene BsmI and ApaI polymorphisms and PCOS risk. These data also indicated that the INSR "NN" genotype was a marker of decreased insulin in women with PCOS. Our findings, however, do not lend support to the hypothesis that PTH gene DraII variant plays a role in susceptibility to PCOS. PMID:27141540
Rossi, Brooke; Sukalich, Sara; Droz, Jennifer; Griffin, Adam; Cook, Stephen; Blumkin, Aaron; Guzick, David S.; Hoeger, Kathleen M.
Context: Adults with polycystic ovary syndrome (PCOS) may be at increased risk for metabolic syndrome (MBS) and related cardiovascular disease. It is not clear whether PCOS diagnosed in adolescence increases the risk of MBS in this age group. Objective: The aim was to compare the prevalence and related characteristics of MBS in obese adolescents with and without PCOS. Design: We conducted a cross-sectional study of overweight and obese PCOS adolescents and BMI matched controls. Patients and Participants: A total of 74 subjects, 43 with PCOS and 31 controls, participated in the study. Interventions: Each subject underwent a physical examination and laboratory evaluation for a diagnosis of MBS. Regional fat distribution was determined by computerized tomography scan in the PCOS adolescents. Main Outcome Measures: We measured the prevalence of MBS and its components in adolescent subjects and controls. Results: The PCOS group had larger ovarian volume and higher measures of total testosterone and free androgen index than controls, but there were no differences in waist circumference, fasting glucose, blood pressure, or lipids. PCOS adolescents demonstrated more glucose abnormalities and higher plasminogen activator inhibitor-1. By pediatric criteria, 53% of the PCOS and 55% of the control adolescents had MBS. By adult criteria, 26% of PCOS and 29% of controls met diagnostic criteria for MBS. Conclusions: Obese adolescent women have a high prevalence of MBS, and PCOS does not add additional risk for MBS. There appears to be an association between MBS and visceral adiposity. PCOS is associated with increased incidence of glucose intolerance and increased plasminogen activator inhibitor-1. Our results reinforce the importance of obesity counseling in adolescents to recognize the possible risk of future cardiovascular disease in these young women. PMID:18812482
Sahin, I; Celik, O; Celik, N; Keskin, L; Dogru, A; Dogru, I; Yürekli, M; Yologlu, S
The aim of the study was to investigate adrenomedullin (ADM) levels and its relation with insulin resistance in women with polycystic ovary syndrome (PCOS). Twenty-nine women with PCOS and 29 age- and body mass index (BMI)- matched control subjects were included in the study. PCOS was defined according to criteria by the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM)-sponsored PCOS consensus workshop group. A full clinical and biochemical examination including basal hormones and metabolic profile was performed. Insulin resistance was calculated by using the homeostasis model assessment of insulin resistance index (HOMA-IR). Plasma ADM levels were measured by high performance liquid chromatographic (HPLC) method. Plasma ADM, fasting insulin levels and HOMA-IR were significantly higher in patients with PCOS than the control group. ADM levels were positively correlated with insulin levels and HOMA-IR index. The best cut-off value of ADM levels to identify the presence of insulin resistance (HOMA-IR≥2.7) was 30.44 ng/ml. Calculated odds ratio of insulin resistance by using logistic regression analysis, as predicted by ADM, was 0.15 (95% confidence interval, 0.037-0.628; p=0.009). In multiple regression analysis, ADM level was an independent predictor of HOMA-IR index. Our finding indicated that ADM levels increased in women with PCOS in accordance with HOMA-IR. ADM could be a significant independent determinant of insulin resistance in women with PCOS.
Conway, Gerard; Dewailly, Didier; Diamanti-Kandarakis, Evanthia; Escobar-Morreale, Héctor F; Franks, Stephen; Gambineri, Alessandra; Kelestimur, Fahrettin; Macut, Djuro; Micic, Dragan; Pasquali, Renato; Pfeifer, Marija; Pignatelli, Duarte; Pugeat, Michel; Yildiz, Bulent O
Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
Nasiri Amiri, Fatemeh; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Mohammadpour Thamtan, Reza Ali; Shiva, Niloofar
Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting up to one in every five women of reproductive age. The majority of researches on PCOS focus on its biomedical aspects, often overlooking and neglecting women’s own perceptions and experiences. Objectives: This study aimed to explore women’s perception and experiences that influence their personal gender role. Patients and Methods: This research is a qualitative study by conventional content analysis. Semi-structured interviews were conducted with 23 reproductive aged women with PCOS, recruited from the reproductive endocrinology research center. , in-depth interviews were continued to reach data saturation. The study was carried out at the reproductive endocrinology research center of Shahid Beheshti University in Tehran All the interviews were recorded and transcribed, and qualitative content analysis of the data was conducted manually. Results: Four themes were identified. Content analysis of the interviews revealed these women mainly perceived themselves with lack of physical attractiveness, loss of womanhood, interruption of sexual role and disruption of fertility potential, feelings were related to symptoms e.g. ‘excess’ hair; absent or disrupted menstrual cycle, obesity and infertility commonly experienced by women with PCOS. Conclusions: Women with PCOS are challenged in their perceptions of themselves as “feminine” because of their hairy appearance, irregular menses and lack of fertility and this influences their gender roles. Medical practitioners must understand how PCOS precisely affects women’s roles and initiate management aimed at reconstructing their “womanhood”, along with their medical treatment. PMID:24719724
Rees, D. Aled; Udiawar, Maneesh; Berlot, Rok; Jones, Derek K.
Context: Polycystic ovary syndrome (PCOS) is a disorder characterized by insulin resistance and hyperandrogenism, which leads to an increased risk of type 2 diabetes in later life. Androgens and insulin signaling affect brain function but little is known about brain structure and function in younger adults with PCOS. Objective: To establish whether young women with PCOS display altered white matter microstructure and cognitive function. Patients, interventions, and main outcome measures: Eighteen individuals with PCOS (age, 31 ± 6 y; body mass index [BMI] 30 ± 6 kg/m2) and 18 control subjects (age, 31 ± 7 y; BMI, 29 ± 6 kg/m2), matched for age, IQ, and BMI, underwent anthropometric and metabolic evaluation, diffusion tensor MRI, a technique especially sensitive to brain white matter structure, and cognitive assessment. Cognitive scores and white matter diffusion metrics were compared between groups. White matter microstructure was evaluated across the whole white matter skeleton using tract-based spatial statistics. Associations with metabolic indices were also evaluated. Results: PCOS was associated with a widespread reduction in axial diffusivity (diffusion along the main axis of white matter fibers) and increased tissue volume fraction (the proportion of volume filled by white or grey matter rather than cerebrospinal fluid) in the corpus callosum. Cognitive performance was reduced compared with controls (first principal component, t = 2.9, P = .007), reflecting subtle decrements across a broad range of cognitive tests, despite similar education and premorbid intelligence. In PCOS, there was a reversal of the relationship seen in controls between brain microstructure and both androgens and insulin resistance. Conclusions: White matter microstructure is altered, and cognitive performance is compromised, in young adults with PCOS. These alterations in brain structure and function are independent of age, education and BMI. If reversible, these changes represent
Ciampelli, M; Muzj, G; Leoni, F; Romualdi, D; Belosi, C; Cento, R M; Lanzone, A
To evaluate the effects of acute lowering of FFAs on glucose-induced insulin secretion and GH response to GHRH in polycystic ovary syndrome (PCOS), 27 PCOS subjects (11 lean and 16 obese) and 17 body mass index-matched controls (8 lean and 9 obese) were investigated. Patients underwent an oral glucose tolerance test and a GHRH test before and after administration of the antilipolytic drug acipimox (250 mg orally 3 h and 1 h before the starting of the tests). Blood samples were collected for 2 h after GHRH bolus and for 4 h after the oral glucose tolerance test. Serum concentrations of GH, insulin, glucose, and c-peptide were assayed in each sample, and the results were expressed as area under the curve (AUC). No significant differences were found as to glucose, insulin, and c-peptide AUC before and after acute FFA plasma reduction in any of the investigated groups. Basally, lower GH-AUC was found in lean PCOS compared with body mass index-matched controls and in obese vs. lean controls; no significant differences were found as to the same variable between the two obese groups. The acipimox induced FFA suppression elicited in the four groups a sustained increase in the GH response to its trophic hormone; indeed, the GH-AUC nearly doubled with respect to basal evaluation in all the studied groups. However, the antilipolytic drug was not able to abolish the differences found between lean groups in basal conditions. In conclusion, the presented data confirm that FFAs have a main role in regulating GH secretion at the pituitary level; however, it does not seem that they could explain the GH as well as insulin dysfunction of PCOS.
Shahebrahimi, Karoon; Jalilian, Nasrin; Bazgir, Nasrin; Rezaei, Mansour
Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years) were treated orally with either metformin (500 mg 3 times daily) or pioglitazone (30 mg daily) for 3 months. Clinical (body weight, blood pressure [BP], and body mass index) and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA]) were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008), wrist circle (P = 0.011), weight (P = 0.047), diastolic BP (P = 0.023), and DHEA (P = 0.035). A significant decrease in TG was seen with pioglitazone treatment (P = 0.047). In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin. PMID:27867884
Forneris, M L; Aguado, L I; Oliveros, L B
It is known that noradrenergic sympathetic nerve fibers connect the ovary and the spleen from the celiac ganglion. The modulation of the ovarian steroidogenesis in rats with polycystic ovary (PCO) by secretions of culture splenocytes from control (non PCO), PCO and PCO rats with superior ovarian nerve transection (PCO+SON-t) is investigated. Splenocytes from PCO rats increased progesterone (P) and decreasing estradiol (E) and androstenedione (A) release, a steroidogenic response different from that obtained with splenocytes of control rats. PCO also decreased the number of splenocyte beta-adrenergic receptors (betaR). SON transection reverted the effect of PCO on splenocytes betaR numbers and secretions of these splenocytes also reverted the stimulatory effect of PCO on P release, while norepinephrine (NE) treatment to PCO+SON-t splenocytes decreased their betaR number and their secretions restored the stimulation on progesterone release. Inversely, PCO+SON-t splenocyte secretions intensified the inhibition in estradiol with no effect on A. Treatment of PCO+SON-t splenocytes with NE or neuropeptide Y partially reverted the effects of PCO and SON-t The P and E-A response of PCO ovary might be differentially regulated by the splenocyte secretions through the neural connection involving ovary, SON, celiac ganglion and spleen and the neurotransmitter NE.
Melo, Anderson Sanches; Ferriani, Rui Alberto; Navarro, Paula Andrea
Polycystic ovary syndrome represents 80% of anovulatory infertility cases. Treatment initially includes preconception guidelines, such as lifestyle changes (weight loss), folic acid therapy to prevent the risk of fetal neural tube defects and halting the consumption of tobacco and alcohol. The first-line pharmacological treatment for inducing ovulation consists of a clomiphene citrate treatment for timed intercourse. The second-line pharmacological treatment includes the administration of exogenous gonadotropins or laparoscopic ovarian surgery (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective with cumulative live birth rates of approximately 70%. Ovarian drilling should be performed when laparoscopy is indicated; this procedure is typically effective in approximately 50% of cases. Finally, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is the third-line treatment and is recommended when the previous interventions fail. This option is also the first choice in cases of bilateral tubal occlusion or semen alterations that impair the occurrence of natural pregnancy. Evidence for the routine use of metformin in infertility treatment of anovulatory women with polycystic ovary syndrome is not available. Aromatase inhibitors are promising and longer term studies are necessary to prove their safety. PMID:26602525
Platt, Adrienne M
School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure.
Cao, Si-Fan; Hu, Wen-Long; Wu, Min-Min; Jiang, Li-Yan
Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high-intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development.
Villarroel, Claudio; López, Patricia; Merino, Paulina M; Iñiguez, Germán; Sir-Petermann, Teresa; Codner, Ethel
We evaluated the association of hirsutism and oligomenorrhea (persistent menstrual cycles > 45 days) as screening criteria for the detection of biochemical hyperandrogenism (BH) and polycystic ovaries (PCOM) during adolescence and determined which androgens, granulosa cell hormone, ultrasonographic parameters have the best association with polycystic ovary syndrome (PCOS). Hirsute girls with oligomenorrhea (N = 26 Hirs/Oligo group) and non-hirsute girls with regular cycles (N = 63, C group) were studied. Prevalence of BH and PCOM, diagnostic performance of androgens and ultrasound parameters for PCOS diagnosis were analyzed. BH and PCOM prevalence were higher in the Hirs/Oligo girls than in the C girls (76.9% versus 25.5%; 92.3% versus 33.3%, respectively; p < 0.0001). A complete PCOS phenotype (Hirs/Oligo with BH and PCOM) was observed in 73.1% of the Hirs/Oligo group. The presence of both BH and PCOM was observed in 7.9% of the C group. The parameters with the best diagnostic performance were free androgen index ≥6.1, testosterone ≥2.4 nmol/L, follicle number ≥12 and ovarian volume ≥10 ml anti-Müllerian hormone (AMH) exhibited a low diagnostic accuracy. Hirsutism and persistent menstrual cycle over 45 days are highly associated with BH and PCOM suggesting that the presences of both criteria are necessary for the diagnosis of PCOS during adolescence.
Xu, Yingqiao; Zhang, Hua; Li, Qingchun; Lao, Kaixue; Wang, Yanlin
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder, generally exhibiting the characteristic features of hyperandrogenemia, insulin resistance (IR) and obesity. Nesfatin-1 is derived from the precursor nucleobindin2 (NUCB2), and plays an active role in energy balance, glucose metabolism and most likely gonadal function. In order to explore the role of nesfatin-1, we employed a rat model that uses letrozole to induce PCOS. The PCOS rats exhibited increased body weight, irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. The expression of both nesfatin-1 mRNA and protein in the ovarian tissues of PCOS group decreased significantly compared to the control group (p < 0.05). Nesfatin-1 expression in peripheral blood also decreased in the PCOS group, in contrast with the control group. Furthermore, we found that nesfatin-1 had a positive correlation with FSH, E2 and P, whereas it had a negative correlation with LH, and total T (p < 0.05). When taken together, these data indicated that the decrease in nesfatin-1 may contribute to the mechanism governing PCOS, and might provide a new potential target for therapies aimed at treating PCOS.
Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi
The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914
Mohammadi, Elahe; Rafraf, Maryam
Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with increased risk of cardiovascular disease. The purpose of this study was to investigate the ef¬fects of omega-3 fatty acids on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Methods: This double-blind randomized controlled clinical trial was conducted on 64 PCOS pa¬tients with 20-35 years old. Thirty two of the subjects had taken 4 g/day omega -3 fatty acids and 32 patients were given placebo for 8 weeks. Fasting blood samples, anthropometric measure¬ments and dietary intakes were collected at the beginning and the end of the study. Serum total cholesterol, triglyceride, and HDL-C were measured using the enzymatic methods. LDL-C con¬centration was calculated by the Friedewald formula and arylesterase activity of serum PON1 was measured. Data were analyzed using SPSS software. Results: Omega-3 fatty acids significantly decreased TC/HDL-C and LDL-C/HDL-C ratios (P = 0.009 for both) and significantly increased serum PON1 activity (P = 0.048) compared with placebo. Changes in TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at the end of the study in comparison to placebo group. Reduction in TC/HDL-C, LDL-C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also significant in omega-3 fatty acids group at the end of the study compared with baseline values (P <0.001, P < 0.001, P = 0.004, and P = 0.001, respectively). Conclusion: Omega-3 fatty acids may decrease the risk for cardiovascular disease through the improvement in paraxonase-1 activity and reduction in some lipids ratio in PCOS women. PMID:24688934
Sørensen, Anja E.; Wissing, Marie Louise; Englund, Anne Lis M.
Context: Polycystic ovary syndrome (PCOS) has a largely unknown etiology and presents with a clinical heterogeneous patient group. Small noncoding microRNA (miRNA) might prove promising as biomarker candidates for PCOS patient stratification. Altered miRNA expression profiles have been observed in few studies. Objective: The aim was to assess the miRNA expression profile in follicular fluid from PCOS patients and healthy, regularly cycling, matched controls. Design and Setting: Experimental case-control study including 49 PCOS women (19 of which were hyperandrogenic and 30 normo-androgenic) and 21 healthy matched women all undergoing in vitro fertilization treatment. Interventions and Main Outcome: Anthropometric and relevant clinical baseline measurements were obtained. Relative expression of miRNA levels were estimated using miRNA quantitative PCR arrays and validated by quantitative RT-PCR. Correlation between miRNAs and clinical relevant measurements was estimated. Results: PCOS women, both normo-androgenic and hyperandrogenic, had decreased levels of miR-24-3p, -29a, -151-3p, and -574-3p compared with controls. Furthermore, miR-518f-3p was differentially expressed within the PCOS group with high levels observed in the hyperandrogenic group compared with the normo-androgenic PCOS patients. Serum levels of total and free T were positively correlated with miR-518f-3p in PCOS subjects (P = .001). Distinction between PCOS and controls could be made using miR-151-3p alone with an area under the curve of 0.91 or a combination of four selected miRNAs (area under the curve, 0.93). Bioinformatic target analysis points to an involvement of these miRNAs in biological pathways involving regulation of cell proliferation, extracellular matrix, and processes in intermediary metabolism. Conclusion: Our study provides evidence that the miRNA expression profile in follicular fluid is altered in PCOS and indicates that specific follicular fluid miRNAs are associated with
Adiwijaya; Purnama, B.; Hasyim, A.; Septiani, M. D.; Wisesty, U. N.; Astuti, W.
Polycystic Ovary Syndrome(PCOS) is the most common endocrine disorders affected to female in their reproductive cycle. This has gained the attention from married couple which affected by infertility. One of the diagnostic criteria considereded by the doctor is analysing manually the ovary USG image to detect the number and size of ovary's follicle. This analysis may affect low varibilites, reproducibility, and efficiency. To overcome this problems. automatic scheme is suggested to detect the follicle on USG image in supporting PCOS diagnosis. The first scheme is determining the initial homogeneous region which will be segmented into real follicle form The next scheme is selecting the appropriate regions to follicle criteria. then measuring the segmented region attribute as the follicle. The measurement remains the number and size that aimed at categorizing the image into the PCOS or non-PCOS. The method used is region growing which includes region-based and seed-based. To measure the follicle diameter. there will be the different method including stereology and euclidean distance. The most optimum system plan to detect PCO is by using region growing and by using euclidean distance on quantification of follicle.
Lindheim, Lisa; Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Pieber, Thomas R.; Gorkiewicz, Gregor; Obermayer-Pietsch, Barbara
Background: Polycystic ovary syndrome (PCOS) is a common female endocrine condition of unclear etiology characterized by hyperandrogenism, oligo/amenorrhoea, and polycystic ovarian morphology. PCOS is often complicated by infertility, overweight/obesity, insulin resistance, and low-grade inflammation. The gut microbiome is known to contribute to several of these conditions. Recently, an association between stool and saliva microbiome community profiles was shown, making saliva a possible convenient, non-invasive sample type for detecting gut microbiome changes in systemic disease. In this study, we describe the saliva microbiome of PCOS patients and the association of microbiome features with PCOS-related parameters. Methods: 16S rRNA gene amplicon sequencing was performed on saliva samples from 24 PCOS patients and 20 healthy controls. Data processing and microbiome analyses were conducted in mothur and QIIME. All study subjects were characterized regarding reproductive, metabolic, and inflammatory parameters. Results: PCOS patients showed a decrease in bacteria from the phylum Actinobacteria and a borderline significant shift in bacterial community composition in unweighted UniFrac analysis. No differences between patients and controls were found in alpha diversity, weighted UniFrac analysis, or on other taxonomic levels. We found no association of saliva alpha diversity, beta diversity, or taxonomic composition with serum testosterone, oligo/amenorrhoea, overweight, insulin resistance, inflammatory markers, age, or diet. Conclusions: In this pilot study, patients with PCOS showed a reduced salivary relative abundance of Actinobacteria. Reproductive and metabolic components of the syndrome were not associated with saliva microbiome parameters, indicating that the majority of between-subject variation in saliva microbiome profiles remains to be explained. PMID:27610099
Verma, Swati; Jindal, Umesh N.
We report a case of polycystic ovary syndrome and prolonged infertility in which endometrial intraepithelial neoplasia was reversed with high dose progesterone therapy. Spontaneous conception after failure of assisted reproductive techniques highlights the role of endometrial receptivity. PMID:28216918
Bulut, Gulay; Kurdoglu, Zehra; Dönmez, Yeliz Bozdemir; Kurdoglu, Mertihan; Erten, Remzi
Objective: In our study, we aimed to investigate the effects of Jun N-terminal kinase inhibitor (SP600125) on fibrosis and inflammation in rats with polycystic ovary syndrome (PCOS). Method: 50 Wistar-albino rats were divided into five groups (n=10 each): control group, sham group, PCOS group, SP600125+ PCOS group and SP600125 group. In the estradiol valerate (EV)-treated group in which PCOS was injected with a single 4 mg/kg i.p. of EV in 0.2 ml sesame oil and the rats were sacrificed on day 60. The estradiol valerate (EV)-treated + SP600125-treated group was injected with a single 4 mg/kg i.p. of EV in 0.2 ml sesame oil. As of day 60, the treatment group was additionally given 15 mg/kg i.p. of SP600125 once daily for 4 consecutive days and the rats were sacrificed on day 65. Histopathological findings (ovarian morphology, edema, inflammatory cell infiltration, vascular congestion and hyperemia) and collagen type IV immunoexpression were assessed. Results: The SP600125+ PCOS group showed a significant level of improvement in ovarian follicle morphology, edema, inflammatory infiltrate, vascular congestion and hyperemia as compared with the PCOS group. Furthermore, collagen type IV immunoexpression showed a significant reduction in staining intensity on the theca cell layer and ovary stroma as compared to the PCOS group. Conclusion: This study demonstrates the therapeutic effect of SP600125 in the prevention of PCOS in an experimental model. PMID:26464620
Ehrmann, David A.; Littlejohn, Elizabeth E.
Background: Menstrual irregularity and above-average testosterone levels in adolescence may presage polycystic ovary syndrome (PCOS) in adulthood but persist in only a minority. Prolonged anovulatory cycles in normal adolescents are associated with increased testosterone levels. Thus, questions have been raised about the accuracy of PCOS diagnosed in adolescents. Objective: The purpose of this study was to follow-up hyperandrogenic adolescents with features of PCOS to test the hypothesis that adolescent functional ovarian hyperandrogenism (FOH) persists into adulthood. Study Subjects: A series of adults previously reported to have adolescent PCOS, with most documented to have FOH by GnRH agonist or dexamethasone androgen-suppression test criteria, were recalled. Methods: Recall occurred >3 years after the initial diagnosis and at the age of >18.0 years. Respondents underwent examination, baseline androgen evaluation, and an oral glucose tolerance test after discontinuing oral contraceptive therapy. Results: Of the adolescent hyperandrogenic patients, 68% (15 of 22) were traceable, and 60% of those traced returned for follow-up, including half (n = 8) of the original FOH group. The baseline characteristics of respondents and nonrespondents were not significantly different. Patients with FOH were reevaluated when their mean age was 23.0 years (range, 18.4–29.4 years), gynecologic age was 10.7 years (range, 5.5–18.4 years), and body mass index was 42.3 kg/m2 (range, 28.3–52.1 kg/m2; P = .02 vs adolescence). Serum free testosterone was 24 pg/mL (range, 10–38 pg/mL, normal, 3–9 pg/mL; not significant vs adolescence); all were oligomenorrheic. Whereas 3 of 8 had impaired glucose tolerance as adolescents, at follow-up 6 of 8 had developed abnormal glucose tolerance (2 with type 2 diabetes mellitus). Conclusions: Adolescents with FOH, which underlies most PCOS, uniformly have persistent hyperandrogenism, and glucose tolerance tends to deteriorate. Testing ovarian
Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo
Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832
Panidis, Dimitrios; Tziomalos, Konstantinos; Papadakis, Efstathios; Vosnakis, Christos; Chatzis, Panagiotis; Katsikis, Ilias
Obesity is frequently present in patients with polycystic ovary syndrome (PCOS) and plays an important role in the pathogenesis of the metabolic, endocrine, and reproductive abnormalities associated with this syndrome. We aimed to summarize the effects of lifestyle changes and anti-obesity pharmacotherapy in patients with PCOS. We reviewed the literature regarding the effects of lifestyle changes and anti-obesity agents on the metabolic and endocrine abnormalities of PCOS. Lifestyle changes, including diet, exercise, and behavioral modification, appear to improve the metabolic and reproductive abnormalities of overweight and obese patients with PCOS. Therefore, lifestyle changes appear to represent the first-line management for all overweight and obese patients with PCOS. However, the optimal composition of diet and the optimal type of exercise in these patients are unknown. Anti-obesity agents that have been studied in PCOS include orlistat, sibutramine, and rimonabant. However, the latter two agents have been withdrawn from the market because of side effects. Long-term studies with orlistat in overweight and obese diabetic patients showed greater weight loss and metabolic and cardiovascular benefits than those achieved with lifestyle changes alone. However, there are limited data on the efficacy of orlistat in women with PCOS. In conclusion, lifestyle changes (diet, exercise and behavioral modification), particularly when combined with anti-obesity agents, exert beneficial effects on the endocrine abnormalities of obese patients with PCOS and improve metabolic parameters.
Yildiz, Bulent O.; Azziz, Ricardo
Significant advances have been made in our understanding of ovarian dysfunction in polycystic ovary syndrome (PCOS), and alterations in adipose tissue function are likely to play an important role in its pathophysiology. This review highlights the principal novel concepts presented at the 4th special scientific meeting of the Androgen Excess and PCOS Society, “Ovarian and Adipose Tissue Dysfunction: Potential Roles in Polycystic Ovary Syndrome,” which occurred on June 6, 2008 in San Francisco, California. PMID:19394000
Roland, Alison V.; Moenter, Suzanne M.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy with elusive origins. A clinically heterogeneous disorder, PCOS is likely to have multiple etiologies comprised of both genetic and environmental factors. Reproductive neuroendocrine dysfunction involving increased frequency and amplitude of gonadotropin-releasing hormone (GnRH) release, as reflected by pulsatile luteinizing hormone (LH) secretion, is an important pathophysiologic component in PCOS. Whether this defect is primary or secondary to other changes in PCOS is unclear, but it contributes significantly to ongoing reproductive dysfunction. This review highlights recent work in animal models, with a particular emphasis on the mouse, demonstrating the ability of pre- and postnatal steroidal and metabolic factors to drive changes in GnRH/LH pulsatility and GnRH neuron function consistent with the observed abnormalities in PCOS. This work has begun to elucidate how a complex interplay of ovarian, metabolic, and neuroendocrine factors culminates in this syndrome. PMID:24747343
Scarpitta, A M; Sinagra, D
Polycystic ovary syndrome (PCOS) is a heterogeneous pathological condition characterized by a number of clinical, endocrine and pathological anatomic aspects. The heterogeneity of these factors and the variability of their presence makes it difficult to classify the syndrome and define it precisely as a separate nosographic entity. It is also difficult to position it with precision among the insulin-resistant syndromes in view of the multiple pathogenetic hypotheses that have been proposed over the years which are still the subject of numerous studies and deserve further confirmation. Data regarding beta-cell secretion in PCOS are also discordant; numerous experimental findings are therefore required to define this aspect correctly. On the basis of the most recent data reported in the international literature, the authors affirm the importance of considering this syndrome both from a purely endocrine point of view and in metabolic terms, for the therapeutic purpose of restoring hormone status and preventing, where possible, the onset of metabolic changes.
Rutkowska, Aleksandra; Rachoń, Dominik
Polycystic ovary syndrome (PCOS) is the most common and the most heterogeneous endocrine disorder in premenopausal women. Apart from signs of hyperandrogenism such as acne, hirsutism and hair loss, women with PCOS usually present with menstrual irregularities and fertility problems.Additionally, they are often characterized by impaired glucose tolerance, which usually leads to the development of type 2 diabetes mellitus (T2DM). This review article describes current and novel approach to the pathomechanisms of PCOS and the potential role of an endocrine disrupting chemical ("endocrine disruptor" - ED) - bisphenol A (BPA), which is commonly used as a plasticizer and due to its molecular structure can interact with estrogen receptors (ERs). Recent observations point to the higher levels of BPA in biological fluids of women with PCOS and its role in the pathogenesis of hyperandrogenism and hyperinsulinemia. It seems that mother's exposure to BPA during pregnancy may also lead to the development of PCOS in the female offspring.
Giallauria, Francesco; Palomba, Stefano; Vigorito, Carlo; Tafuri, Maria Giovanna; Colao, Annamaria; Lombardi, Gaetano; Orio, Francesco
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women and is characterized by chronic ovulatory dysfunction and hyperandrogenism. Clinical studies have shown that hyperandrogenism is linked with insulin resistance/metabolic syndrome in PCOS women. This review article summarizes the several potential mechanisms for the association of androgen excess with insulin resistance, including both direct and indirect actions of androgens on insulin target tissues. This review article also focuses on the beneficial effects of exercise training and diet on glucose metabolism and hyperandrogenism in PCOS women, pointing out that whether in conjunction with pharmacotherapy or as a stand-alone treatment, diet and exercise training represent a fundamental strategy in the treatment of PCOS women.
Mantelli, Flavio; Moretti, Costanzo; Macchi, Ilaria; Massaro-Giordano, Giacomina; Cozzupoli, Grazia Maria; Lambiase, Alessandro; Bonini, Stefano
Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in women of reproductive age. Although its clinical consequences have been known for a long time to extend beyond the reproductive system, with type-2 diabetes and obesity being the most common, the involvement of the ocular surface in PCOS has been described only more recently. The ocular surface is a morphofunctional unit comprising eyelid margin, tear film, cornea, and conjunctiva. Increasing evidence indicates that these structures are under a sex hormone control and relevant diseases such as ocular allergy and dry eye are often caused by alterations in circulating or local steroid hormones levels. Novel treatments targeting sex hormone receptors on ocular surface epithelial cells are also being developed. In this review we aim to describe the current knowledge on the effects of sex hormones at the ocular surface, with a special focus on the effects of androgen imbalance in PCOS.
Baskind, N Ellissa; Balen, Adam H
Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous disorder linked with disturbances of reproductive, endocrine and metabolic function. The definition and aetiological hypotheses of PCOS are continually developing to incorporate evolving evidence of the syndrome, which appears to be both multifactorial and polygenic. The pathophysiology of PCOS encompasses inherent ovarian dysfunction that is strongly influenced by external factors including the hypothalamic-pituitary axis and hyperinsulinaemia. Neuroendocrine abnormalities including increased gonadotrophin-releasing hormone (GnRH) pulse frequency with consequent hypersecretion of luteinising hormone (LH) affects ovarian androgen synthesis, folliculogenesis and oocyte development. Disturbed ovarian-pituitary and hypothalamic feedback accentuates the gonadotrophin abnormalities, and there is emerging evidence putatively implicating dysfunction of the Kiss 1 system. Within the follicle subunit itself, there are intra-ovarian paracrine modulators, cytokines and growth factors, which appear to play a role. Adrenally derived androgens may also contribute to the pathogenesis of PCOS, but their role is less defined.
Insenser, María; Montes-Nieto, Rafael; Murri, Mora; Escobar-Morreale, Héctor F
Polycystic ovary syndrome (PCOS) is considered a complex multifactorial disorder resulting from the interaction of genetic, environmental, and lifestyle influences. Nontargeted proteomics and metabolomics have been used in the past years with the aim of identifying molecules potentially involved in the pathophysiology of this frequent disorder. The biomolecules identified so far participate in many metabolic pathways, including energy metabolism (glucose and lipid metabolism), protein metabolic processes and protein folding, cytoskeleton structure, immune response, inflammation and iron metabolism, fibrinolysis and thrombosis, oxidative stress and intracellular calcium metabolism. These molecules provide key information about molecular functions altered in PCOS and raise questions concerning their precise role in the pathogenesis of this syndrome. The biomolecules identified by nontargeted proteomic and metabolomic approaches should be considered as candidates in future studies aiming to define specific molecular phenotypes of PCOS.
Shorakae, S; Boyle, J; Teede, H
Polycystic ovary syndrome (PCOS) is a prevalent, chronic and heterogeneous endocrine condition, with reproductive, metabolic and psychological features. Insulin resistance and hyperandrogenaemia are the key pathophysiological hormonal abnormalities. Insulin resistance is a significant contributor to the reproductive and metabolic complications of PCOS, both independently and in the setting of excess bodyweight. While the diagnostic criteria are now internationally uniformly accepted, individual components of the criteria are ill-defined, making diagnosis challenging. This, along with low awareness of PCOS, has resulted in a significant proportion of women remaining undiagnosed. While reproductive features are best recognised in PCOS and form the basis of the diagnostic criteria, awareness of psychological and metabolic features, recommended screening protocols, and management strategies to prevent metabolic complications are important. In this review, we focus on diagnostic criteria, and reproductive, metabolic and psychological features of PCOS, as well as recommended screening and management strategies suggested by national and international evidence-based guidelines.
Brzozowska, Maria; Karowicz-Bilińska, Agata
Vitamin D deficiency connected with insufficient production in the skin and limited alimentation delivery disrupts the function of all systems of the body and increases the risk of chronic diseases. Many studies have reported associations between low serum 25-hydroxyvitamin D [25(OH)D] level and symptoms of the polycystic ovary syndrome (PCOS) - insulin resistance, hirsutism, and infertility associated with both, ovulatory disorders and abnormal endometrial receptivity. The beneficial effects of vitamin D supplementation on insulin resistance, ovarian follicles maturation, ovulation and menstrual regularity were confirmed. Due to limited evidence, the additional randomized trials are required to establish the correct dose of vitamin D and confirm the effectiveness of vitamin D treatment in PCOS disorders. However; it seems evident that correct supplementation of vitamin D is beneficial in the management of women with PCOS and low 25(OH)D serum levels, and that it could be helpful in improving the effects of PCOS treatment.
Thomson, Rebecca L; Spedding, Simon; Buckley, Jonathan D
Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS), with the 67-85% of women with PCOS having serum concentrations of 25-hydroxy vitamin D (25OHD) <20 ng/ml. Vitamin D deficiency may exacerbate symptoms of PCOS, with observational studies showing lower 25OHD levels were associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity and elevated cardiovascular disease risk factors. There is some, but limited, evidence for beneficial effects of vitamin D supplementation on menstrual dysfunction and insulin resistance in women with PCOS. Vitamin D deficiency may play a role in exacerbating PCOS, and there may be a place for vitamin D supplementation in the management of this syndrome, but current evidence is limited and additional randomized controlled trials are required to confirm the potential benefits of vitamin D supplementation in this population.
Schattmann, Linda; Sherwin, Barbara B
We investigated the possible influence of testosterone (T) on cognitive functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder associated with elevated levels of free testosterone (free T). Performance on a battery of neuropsychological tests in 29 women with elevated free T levels due to PCOS was compared to the performance of 22 age- and education-matched, healthy control women with free T levels in the normal female range. Women with PCOS had significantly higher levels of free T (estimated by the free androgen index) and demonstrated significantly worse performance on tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory than the healthy control women. No differences between the groups were found on tests of mental rotation, spatial visualization, spatial perception, or perceptual speed. These results suggest that, in women, elevations in free T may be associated with poorer performance on cognitive tasks that tend to show a female advantage.
Kelley, Scott T.; Skarra, Danalea V.; Rivera, Alissa J.; Thackray, Varykina G.
Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet. PMID:26731268
Wang, Yu; Fu, Xin; Xu, Jing; Wang, Qiuhong; Kuang, Haixue
Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology was utilized to predict the potential targets of berberine related to PCOS and the potential drug-drug interaction base on the disease network. In conclusion, berberine is a promising polypharmacological drug for treating PCOS, and for enhancing the efficacy of clinical drugs. PMID:27306862
Kao, Yu-Hsun; Chiu, Wan-Chun; Hsu, Ming-I; Chen, Yi-Jen
Polycystic ovary syndrome (PCOS), the most common endocrine disorder affecting women of reproductive age, is characterized by hyperandrogenism and insulin resistance. Women with PCOS have a higher risk for cardiovascular diseases (CVDs) and endothelial dysfunction. The mechanisms underlying these risks are unclear. Human peripheral blood contains circulating endothelial progenitor cells (EPCs) derived from bone marrow that have the ability to proliferate and differentiate into mature endothelial cells, which may contribute to vessel homeostasis and repair. PCOS is associated with insulin resistance, hyperinsulinemia, and dyslipidemia, which may result in EPC dysfunction. In this review, we summarize the potential mechanisms of EPC dysfunction in PCOS, which possibly result in a higher genesis of CVDs in PCOS-affected subjects. PMID:24520442
Costello, Michael F; Ledger, William L
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age and by far the most common cause of anovulatory infertility. Lifestyle change alone, and not in combination with pharmacological ovulation induction such as clomifene citrate or metformin, is generally considered the first-line treatment for the management of infertile anovulatory women with PCOS who are overweight or obese. Clomifene citrate should be considered as a first-line pharmacological therapy to improve fertility outcomes. Second-line medical treatments may include ovulation induction with gonadotropins (in clomifene citrate-resistant or clomifene citrate failure women) or laparoscopic ovarian drilling (in clomifene citrate-resistant women) or possibly with metformin combined with clomifene citrate (in clomifene citrate-resistant women). There is currently insufficient evidence to recommend aromatase inhibitors over that of clomifene citrate in infertile anovulatory women with PCOS in general or specifically in therapy-naive or clomifene citrate-resistant women with PCOS.
Costello, Michael F; Misso, Marie L; Wong, Jennifer; Hart, Roger; Rombauts, Luk; Melder, Angela; Norman, Robert J; Teede, Helena J
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. First-line medical ovulation induction therapy to improve fertility outcomes is clomiphene citrate, whilst gonadotrophins, laparoscopic ovarian surgery or possibly metformin are second line in clomiphene citrate-resistant PCOS women. There is currently insufficient evidence to recommend aromatase inhibitors over that of clomiphene citrate in infertile anovulatory PCOS women in general or specifically in therapy naive or clomiphene citrate-resistant PCOS women. IVF/ICSI treatment is recommended either as a third-line treatment or in the presence of other infertility factors.
Farrell-Turner, Kristen A
Comments on an article by Poleshuck and Woods (see record 2014-16756-003). The recent article by Poleshuck and Woods covered several areas of women's health that are defined, preceded, and/or followed by adverse psychosocial functioning. In a well-written and otherwise thorough summary of several women's health issues that are pertinent to mental health professionals, they neglected to mention polycystic ovary syndrome (PCOS), which is a very common disorder (8% to 17% prevalence; March et al., 2010) that is associated with several interrelated physiological and psychological disorders. The current author is submitting this comment because it is important that mental health professionals are familiar with the diagnostic criteria for PCOS, its impact on mental health functioning and on the development of several increasingly common chronic diseases, and how mental health professionals can play a role in reducing psychosocial disturbances and development of chronic disease among women with PCOS.
Background Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. Methods Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90–92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. Results In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. Conclusions This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries. PMID:23866168
Abazar, Elaheh; Taghian, Farzaneh; Mardanian, Farahnaz; Forozandeh, Dashti
Background: Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders. The PCOS manifest by hyperandrogenism, hypertension and cholesterol and lipoprotein improper profiles. Changing the life style, e.g. increasing physical activities is the first approach in controlling PCOS. Materials and Methods: Twenty-four women affected by polycystic ovary syndrome (PCOS) after medical screening were divided in to two groups: Experimental group (n = 12) and control group (n = 12), with the average age, weight, height, BMI and WHR of 26.87 ± 4.43 years, 75.71 ± 10.65 kg. 159.29 ± 6.44 cm, 29.86 ± 3.22 kg/m2 and 91.75 ± 5.86 respectively. First the body composition such as BMI, WHR, percent body fat, weight and body fat mass were measured. In fasting blood samples the level of HDL, LDL, VLDL, triglyceride and cholesterol were measured. Then the experiment group underwent the effect of an aerobic exercise program. After 12 weeks, all the measured variables before intervention the test were re-measured. Correlated t-test was used for comparing the two groups before and after intervention the test and independent t-test was used for comparing the two groups (P < 0.05). Results: The results showed that after 12 weeks of exercise, BMI, WHR, fat rate, weight and fat mass and triglyceride had significant reduction and HDL had significant increase. But no significant changes happened in LDL, VLDL, and cholesterol levels. Conclusion: Reducing the weight by aerobic exercise in obese women and affected by PCOS can correct lipoprotein profile and improving health. PMID:25878993
Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Lebkowska, Agnieszka; Milewski, Robert; Górska, Maria; Otziomek, Elzbieta; Nikolajuk, Agnieszka; Wolczynski, Slawomir; Kowalska, Irina
Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δ irisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δ irisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δ irisin (β=0.70, p=0.0002), FFAs 60' during the clamp study (β=-0.22, p=0.01), SHBG (β=0.54, p<0.0001) and the interaction between Δ irisin and PCOS (β=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.
McBreairty, Laura E; Zello, Gordon A; Gordon, Julianne J; Serrao, Shani B; Pierson, Roger A; Chizen, Donna R; Chilibeck, Philip D
Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting women of reproductive age manifesting with polycystic ovaries, menstrual irregularities, hyperandrogenism, hirsutism, and insulin resistance. The oligomenorrhea and amenorrhea characteristic to PCOS are associated with low bone mineral density (BMD); conversely, the hyperandrogenism and hyperinsulinemia may elicit a protective effect on BMD. As bone geometric properties provide additional information about bone strength, the objective of this study was to compare measures of hip geometry in women with PCOS to a healthy female population. Using dual-energy X-ray absorptiometry, BMD and measures of hip geometry were determined in women with PCOS (n = 60) and healthy controls (n = 60) aged 18-35 years. Clinical biochemical measures were also determined in women with PCOS. Measures of hip geometry, including cross-sectional area, cross-sectional moment of inertia, subperiosteal width (SPW), and section modulus, were similar between groups following correction for body mass index (BMI) (all p > 0.05) with intertrochanter SPW significantly lower in women with PCOS (p < 0.05). BMI-corrected whole body BMD as well as the lumbar spine and regions of proximal femur were also comparable between groups. In women with PCOS, BMI-corrected correlations were found between insulin and femoral shaft SPW (r = 0.322, p < 0.05), glucose and femoral neck (r = 0.301, p < 0.05), and trochanter BMD (0.348, p < 0.05), as well as between testosterone and femoral neck BMD (0.376, p < 0.05) and narrow neck cross-sectional area (0.306, p < 0.05). This study demonstrates that women with PCOS may have compromised intertrochanter SPW while oligomenorrhea appears to have no detrimental effect on bone density or geometry in women with PCOS.
Shishehgar, Farnaz; Tehrani, Fahimeh Ramezani; Mirmiran, Parvin; Hajian, Sepideh; Baghestani, Ahmad Reza; Moslehi, Nazanin
Polycystic Ovary syndrome (PCOS) is a complicated endocrinopathy affecting women in reproductive age. The crucial role of obesity and insulin resistance in progression of metabolic and cardiovascular features of PCOS has been confirmed. Although it has been suggested that there is a possible association between dietary pattern and risk of PCOS, few studies investigating the diet composition of PCOS women. The aim of this study was to compare the dietary intakes between women with polycystic ovary syndrome (PCOS) and eumenorrheic non hirsute women. This was a case control study of 142 women with PCOS and 140 eumenorrheic non hirsute healthy age and BMI matched controls. We compared the dietary intakes of our study group using a validated food frequency questionnaire (FFQ), using T-test or Mann-Whitney to compare the means of two groups. One way Anova was used to compare the tertiles of GI and GL in each group and a two way ANOVA was used to compare between tertiles of GI-GL and groups. The results demonstrated that energy and macronutrient intakes in PCOS women compared to controls were similar. PCOS group consumed more food items with high glycemic index (p=0.042) and less legumes (P=0.026) and vegetables (p=0.037) than controls. Both groups in the highest tertile of glycemic load (GL) had higher body mass index and waist circumference. Considering the results of this study, it was concluded that PCOS women had a dietary pattern that was characterized by a higher consumption of high GI food items and lower legumes and vegetables. PMID:27157182
Di Pietro, Mariana; Scotti, Leopoldina; Irusta, Griselda; Tesone, Marta; Parborell, Fernanda; Abramovich, Dalhia
Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies.
Erol, Onur; Özel, Mustafa Kemal; Ellidağ, Hamit Yaşar; Toptaş, Tayfun; Derbent, Aysel Uysal; Yılmaz, Necat
The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m(2)) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the
Marti, Nesa; Galván, José A; Pandey, Amit V; Trippel, Mafalda; Tapia, Coya; Müller, Michel; Perren, Aurel; Flück, Christa E
Recently, dihydrotestosterone biosynthesis through the backdoor pathway has been implicated for the human testis in addition to the classic pathway for testosterone (T) synthesis. In the human ovary, androgen precursors are crucial for estrogen synthesis and hyperandrogenism in pathologies such as the polycystic ovary syndrome is partially due to ovarian overproduction. However, a role for the backdoor pathway is only established for the testis and the adrenal, but not for the human ovary. To investigate whether the backdoor pathway exists in normal and PCOS ovaries, we performed specific gene and protein expression studies on ovarian tissues. We found aldo-keto reductases (AKR1C1-1C4), 5α-reductases (SRD5A1/2) and retinol dehydrogenase (RoDH) expressed in the human ovary, indicating that the ovary might produce dihydrotestosterone via the backdoor pathway. Immunohistochemical studies showed specific localization of these proteins to the theca cells. PCOS ovaries show enhanced expression, what may account for the hyperandrogenism.
Krysiak, Robert; Okopien, Bogusław
The effect of metformin treatment on the hypothalamic-pituitary-thyroid axis is relatively weakly understood. This study included 24 prediabetic patients with polycystic ovary syndrome and untreated subclinical hypothyroidism, 12 of whom had already been treated with bromocriptine (5.0-7.5 mg daily). The included patients received metformin (2.55 g daily) for 6 months. Glucose homeostasis markers, serum prolactin, and thyroid function tests were determined before, after 3 months, and at the end of the treatment. Beyond improving glucose homeostasis, metformin administered for 6 months reduced serum levels of thyrotropin but did not affect serum levels of total and free thyroid hormones. Thyrotropin-lowering effect of this agent was stronger in patients not treated with bromocriptine than in patients receiving this drug, and weakly correlated with an improvement in insulin sensitivity. The obtained results indicate that metformin treatment may have an impact on thyrotrope function in hypothyroid patients, probably by enhancing the effect of thyroid hormone action in the pituitary.
Witchel, Selma F; Tena-Sempere, Manuel
Polycystic ovary syndrome (PCOS) is a highly prevalent heterogeneous disease characterized by ovulatory dysfunction, hyperandrogenism, and metabolic alterations. Women with PCOS commonly display dysregulated gonadotropin secretion with higher LH pulsatility and perturbed LH-FSH ratios, which likely contributes to the ovarian phenotype and might be indicative of disrupted GnRH secretory activity. Although the involvement of altered androgen and insulin levels in the pathogenesis of the neuroendocrine alterations of PCOS has been explored in various experimental and clinical settings, the ultimate mechanisms whereby such neurohormonal perturbations take place remain partially unknown. In recent years, kisspeptins, the products of the Kiss1 gene that operate via the surface receptor Gpr54, have emerged as essential elements of the reproductive brain that play an indispensable role in the control of gonadotropin secretion and ovulation. In addition, Kiss1 neurons in the brain are targets and transmitters of the regulatory actions of sex steroids and metabolic cues on the reproductive axis during early organizing periods and adulthood. Furthermore, Kiss1/kisspeptin expression has been documented in the ovary in various species, including humans; yet clear evidence for the involvement of kisspeptin signaling in the control of ovulation, or its alterations, is still pending. Based on these physiologic features, we discuss the putative pathophysiologic implications of alterations of the Kiss1 system in the generation of PCOS and summarize the scarce experimental and clinical evidence that might support such a role.
Abbott, D H; Barnett, D K; Bruns, C M; Dumesic, D A
The aetiology of polycystic ovary syndrome (PCOS) remains unknown. This familial syndrome is prevalent among reproductive-aged women and its inheritance indicates a dominant regulatory gene with incomplete penetrance. However, promising candidate genes have proven unreliable as markers for the PCOS phenotype. This lack of genetic linkage may represent both extreme heterogeneity of PCOS and difficulty in establishing a universally accepted PCOS diagnosis. Nevertheless, hyperandrogenism is one of the most consistently expressed PCOS traits. Animal models that mimic fetal androgen excess may thus provide unique insight into the origins of the PCOS syndrome. Many female mammals exposed to androgen excess in utero or during early post-natal life typically show masculinized and defeminized behaviour, ovulatory dysfunction and virilized genitalia, although behavioural and ovulatory dysfunction can coexist without virilized genitalia based upon the timing of androgen excess. One animal model shows particular relevance to PCOS: the prenatally androgenized female rhesus monkey. Females exposed to androgen excess early in gestation exhibit hyperandrogenism, oligomenorrhoea and enlarged, polyfollicular ovaries, in addition to LH hypersecretion, impaired embryo development, insulin resistance accompanying abdominal obesity, impaired insulin response to glucose and hyperlipidaemia. Female monkeys exposed to androgen excess late in gestation mimic these programmed changes, except for LH and insulin secretion defects. In utero androgen excess may thus variably perturb multiple organ system programming and thereby provide a single, fetal origin for a heterogeneous adult syndrome.
Shabir, Iram; Ganie, Mohd Ashraf; Zargar, Mohd Afzal; Bhat, Dilafroz; Mir, Mohd Muzzafar; Jan, Aleem; Shah, Zaffar Amin; Jan, Vicar; Rasool, Riyaz; Naqati, Andleeb
Background: Polycystic ovary syndrome (PCOS) is the most complex and common endocrine disorder of women in reproductive years. In addition to irregular menstrual cycles, chronic anovulation and hyperandrogenism, it has many metabolic manifestations such as obesity, hyperlipidemia, hyperinsulinemia, insulin resistance, dysglycemia, increased risk of cardiovascular disease or possibly endometrial cancer. Familial clustering of PCOS in consistence with the genetic susceptibility has been described. Materials and Methods: The present study assessed the clinical, biochemical and hormonal parameters including prevalence of metabolic syndrome by two different criteria in the first- degree relatives of patients with PCOS. Results: The average age of 37 index patients was 23 ± 3.6 years, with the mean age of menarche as 13.3 ± 1.2 years. The mean age and age of menarche in mothers (n = 22) was 48.8 ± 5.1 and 13 ± 1.3 years, respectively, whereas as it was 23.5 ± 4.7 and 13.3 ± 1.2 years in sisters (n = 22), respectively. Metabolic syndrome (MS) defined by International Diabetes Federation (IDF) criteria was present in 10 index patients, 1 brother, 4 sisters, 17 mothers and 15 fathers while as by Adult Treatment Panel III (ATP III) it was in 8 index patients, 5 sisters, 16 mothers and 11 fathers. Conclusion: The presence of MS or related metabolic derangements is high in the family members of women with PCOS. PMID:24944933
Connolly, Fiona; Rae, Michael T.; Butler, Mairead; Klibanov, Alexander L.; Sboros, Vassilis; McNeilly, Alan S.; Duncan, W. Colin
In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30–100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles. PMID:25343339
Connolly, Fiona; Rae, Michael T; Butler, Mairead; Klibanov, Alexander L; Sboros, Vassilis; McNeilly, Alan S; Duncan, W Colin
In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30-100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.
Desai, Namrata Ajaykumar; Patel, Snehal S
The incidence of cardiovascular disease (CVD) in patients with polycystic ovary syndrome (PCOS) is very high and conventional risk factors only partially explain excessive risk of developing CVD in patients of PCOS. The pathophysiology of PCOS is very unique, and several hormonal and metabolic changes occur. Several observations suggest that serum IGF-1 levels decrease in insulin resistance, which results in IGF-1 deficiency. In patient of PCOS, close relationships have been demonstrated between insulin resistance and serum IGF-1 levels. Hyperinsulinemic insulin resistance results in a general augmentation of steroidogenesis and LH release in PCOS. The action of IGF-1 varies in different tissues possibly via autocrine or paracrine mechanisms. The increase or decrease in IGF-1 in different tissues results in differential outcomes. Several studies suggest that lowered circulating IGF-1 levels play important role in the initiation of the cardiac hypertrophic response which results in the risk of cardiovascular disease. While recent results suggests that individual with elevated IGF-1 is protected against cardiovascular disease. Thus IGF-1 shows versatile pleiotropic actions. This review provides a current perspective on increased level of IGF-1 in PCOS and also adds to the current controversy regarding the roles of IGF-1 in cardiovascular disease.
Marciniak, Aleksandra; Nawrocka-Rutkowska, Jolanta; Wiśniewska, Berenika; Brodowska, Agnieszka; Starczewski, Andrzej
Polycystic ovary syndrome (PCOS) is a disorder which concern even 5-10% of women in reproductive age. PCOS is a cause of hyperandrogenism and menstrual disorders with chronic anovulation. The most common clinical symptoms observed in PCOS are hirsutism, acne and obesity. Patients with PCOS often suffer from metabolic disorders like insulin resistance, hyperinsulinemia, dyslipidemia, arteriosclerosis and other abnormalities of the metabolic syndrome. 35 to 60% of women with PCOS are obese and about 50% of them have insulin resistance and hyperinsulinemia. The pathogenesis of atherosclerosis emphasizes the role of inflammatory processes. There are a number of markers of the inflammation process. They are also observed in PCOS and may indicate an increased risk of cardiovascular disease in women. More than 46% of women with PCOS can be diagnosed with metabolic syndrome. Because of the fact that patients with PCOS are at higher risk group of the earlier development of complications such as diabetes t 2, atherosclerosis, hypertension and cardiovascular system diseases, it is important to carry out metabolic disorders diagnosis in every patient with PCOS. It will help to estimate the risk of complications and allow for the implementation of prevention or treatment of metabolic diseases belonging to the image of PCOS.
Guido, M; Romualdi, D; Belosi, C; Selvaggi, L; Lanzone, A
Obese hyperinsulinemic women with polycystic ovary syndrome (PCOS) present a markedly increased risk of developing glycaemic alterations during pregnancy, commonly recognized as a "diabetogenic" condition. This risk seems to be safely reduced by the administration of metformin during gestation. We analyzed the metabolic changes in two hyperinsulinemic PCOS women, who became pregnant after 8 weeks of metformin therapy and continued taking the drug till delivery. An oral glucose tolerance test and an euglycemic hyperinsulinemic clamp were performed at baseline and, during metformin therapy, in pre-conceptional state and at each trimester of gestation. A pronounced decrease in peripheral insulin sensitivity occurred as the pregnancies proceeded (at the third trimester 51.7% and 41.1% of pregestational values in patient 1 and 2 respectively), along with an increase in stimulated insulin secretion (at the third trimester 120% and 50.6% of pregestational values in patient 1 and 2 respectively). Despite these findings, none of the studied subjects developed gestational diabetes or impaired glucose tolerance. This confirms that metformin may exert a protective role against such disturbances in hyperinsulinemic PCOS patients, probably by avoiding the gestational physiologic changes leading to a loss of the metabolic balance achieved by these subjects out of pregnancy.
Qiao, Jie; Feng, Huai L.
BACKGROUND Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate. METHODS For this review, we searched the database MEDLINE (1950 to January 2010) and Google for all full texts and/or abstract articles published in English with content related to oocyte maturation and embryo developmental competence. RESULTS The search showed that alteration of many factors may directly or indirectly impair the competence of maturating oocytes through endocrine and local paracrine/autocrine actions, resulting in a lower pregnancy rate in patients with PCOS. The extra-ovarian factors identified included gonadotrophins, hyperandrogenemia and hyperinsulinemia, although intra-ovarian factors included members of the epidermal, fibroblast, insulin-like and neurotrophin families of growth factors, as well as the cytokines. CONCLUSIONS Any abnormality in the extra- and/or intra-ovarian factors may negatively affect the granulosa cell–oocyte interaction, oocyte maturation and potential embryonic developmental competence, contributing to unsuccessful outcomes for patients with PCOS who are undergoing assisted reproduction. PMID:20639519
Background Polycystic Ovary Syndrome is a common, chronic condition which affects women living with the condition both physically and psychologically. Social support may be beneficial to sufferers in coping with chronic conditions and the Internet is becoming a common place for accessing social support and information. The aim of this study was to consider the experiences of women living with Polycystic Ovary Syndrome who access and participate in an online support group discussion forum dedicated to issues surrounding this condition. Methods Fifty participants responded to a series of open-ended questions via an online survey. Results Thematic analysis revealed a number of empowering and disempowering experiences associated with online support group participation. The empowering processes reported by members of the group included: Connecting with others who understand; Access to information and advice; Interaction with healthcare professionals; Treatment-related decision making; Improved adjustment and management. In terms disempowering processes, only two were described by group participants: Reading about the negative experiences of others and Feeling like an outsider. Conclusions For women living with Polycystic Ovary Syndrome, participation within an online support group may help to empower them in a range of important ways however, there may be some disempowering consequences. PMID:24341398
Yakubov, Yakov; Mandel, Louis
Polycystic ovarian syndrome (PCOS) is recognized by the presence of polycystic ovaries, irregular menstruation, and increased androgen levels. Many patients have insulin resistance or impaired glucose tolerance and an associated development of type 2 diabetes mellitus. A patient with PCOS is presented whose cosmetic concerns centered on the prolonged existence of substantial bilateral parotid swelling. The pathophysiology, diagnosis, and therapy of sialosis are discussed.
The present study tested the hypothesis that if polycystic ovary syndrome (PCOS) results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON) will result in ovulation by the denervated ovary, and the restoration of progesterone (P4), testosterone (T) and estradiol (E2) normal serum level. A single 2 mg dose of estradiol valerate (EV) to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh) and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry. PMID:20723258
Vejrazkova, D; Lischkova, O; Vankova, M; Stanicka, S; Vrbikova, J; Lukasova, P; Vcelak, J; Vacinova, G; Bendlova, B
Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are distinct pathologies with impaired insulin sensitivity as a common feature. The aim of this study was to evaluate the response of fat tissue adipokines and gastrointestinal incretins to glucose load in patients diagnosed with one of the two disorders and to compare it with healthy controls. Oral glucose tolerance test (oGTT) was performed in 77 lean young women: 22 had positive history of GDM, 19 were PCOS patients, and 36 were healthy controls. Hormones were evaluated in fasting and in 60 min intervals during the 3 hour oGTT using Bio-Plex ProHuman Diabetes 10-Plex Assay for C-peptide, ghrelin, GIP, GLP1, glucagon, insulin, leptin, total PAI1, resistin, visfatin and Bio-Plex ProHuman Diabetes Adipsin and Adiponectin Assays (Bio-Rad). Despite lean body composition, both PCOS and GDM women were more insulin resistant than controls. Significant postchallenge differences between the GDM and PCOS groups were observed in secretion of adipsin, leptin, glucagon, visfatin, ghrelin, GIP, and also GLP1 with higher levels in GDM. Conversely, PCOS was associated with the highest resistin, C-peptide, and PAI1 levels. Our data suggest that decreased insulin sensitivity observed in lean women with GDM and PCOS is associated with distinct hormonal response of fat and gastrointestinal tissue to glucose load.
Manco, Melania; Castagneto-Gissey, Lidia; Arrighi, Eugenio; Carnicelli, Annamaria; Brufani, Claudia; Luciano, Rosa; Mingrone, Geltrude
Background Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls. Research Design and Methods Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method). Results Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons). Conclusion Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls. PMID:24705280
Ramezanali, Fariba; Ashrafi, Mahnaz; Hemat, Mandana; Arabipoor, Arezoo; Jalali, Samaneh; Moini, Ashraf
This cross-sectional study aimed to evaluate IVF/intracytoplasmic sperm injection (ICSI) outcomes in different polycystic ovary syndrome (PCOS) phenotypes (A, B, C and D) compared with a control group and the predictive values of serum anti-Müllerian hormone (AMH) in PCOS phenotypes for main outcomes. This study evaluated 386 PCOS women and 350 patients with male factor infertility. Women with phenotypes A and C had significantly higher concentrations of AMH than those with phenotype B (P < 0.001). Clinical pregnancy rate (CPR) in the phenotype D group (53.3%) was higher than other groups (32.5%, 26.4% and 36.8%, respectively, in phenotypes A, B and C), but not to a significant level. Multivariable regression analysis, after adjusting for women's age and body mass index, revealed that PCOS phenotypes A and B were associated with a decreased CPR compared with the control group (odds ratio [OR]: 0.46, confidence interval [CI]: 0.26-0.8, P = 0.007 and OR: 0.34, CI: 0.18-0.62, P = 0.001, respectively). It seems a combination of hyperandrogenism and chronic anovulation is associated with a negative impact on the CPR in these patients. These results demonstrated that AMH concentration is related to PCO morphology but not predictive for CPR and live birth rate.
Ou, Huang-tz; Chen, Pei-Chi
Objectives To develop the Chinese version of the Polycystic Ovary Syndrome Health-related Quality of Life Questionnaire (Chi-PCOSQ). Research Design and Method This cross-sectional study was conducted in a medical center in Taiwan. Eighty women who met the criteria were enrolled: female, age range of 18–45 years, competent in the Chinese language, had been diagnosed with polycystic ovary syndrome (PCOS), and were regularly followed at outpatient clinics (defined as at least two outpatient visits before enrollment). The PCOSQ was translated and culturally adapted according to standard procedures. A semi-structured interview was applied to assess face validity. Exploratory factor analysis (EFA) was applied to determine scale constructs. Measurements of internal consistency via Cronbach’s α, test-retest reliability via intraclass correlation coefficient (ICC), construct validity, and discriminative validity were performed. Results Five additional items, representing the issues of acne, hair loss, and fear of getting diabetes, were incorporated into the original scale. A six-factor structure emerged as a result of the EFA, explaining 71.9% of the variance observed. The reliability analyses demonstrated satisfactory results for Cronbach’s α ranging from 0.78–0.96, and for ICC ranging from 0.73–0.86. Construct validity was confirmed by significant correlation between the domains of the Chi-PCOSQ and generic health-related quality of life (HRQoL) measures (WHOQOL-BREF, EQ-5D) and clinical parameters (body mass index, waist-hip ratio, blood pressure). The known-group analysis indicated that the Chi-PCOSQ is a discriminative tool that differentiates patients according to their HRQoL. Conclusion The Chi-PCOSQ seems internally consistent, culturally acceptable, and our preliminary evidence suggests that it may be reliable and valid. The Chi-PCOSQ is a promising assessment tool to address the HRQoL of women affected by PCOS in Chinese-speaking countries and to
Zhang, Jing; Si, Qinqin; Li, Jinqiong
Objective: To evaluate the therapeutic effects of metformin and clomiphene in combination with lifestyle adjustment on infertility in women with obese polycystic ovarian syndrome (PCOS). Methods: A total of 101 infertile women with obese PCOS admitted to our hospital from July 2013 to July 2015 were randomly divided into an observation group (n=51) and a control group (n=50). The control group was treated with metformin plus clomiphene, based on which the observation group was also subjected to lifestyle adjustment. The body weight, body mass index (BMI) and waist-to-hip ratio (WHR) were measured before and after treatment. The changes of reproductive hormones, ovaries and endometrium were detected, and the rates of menstrual recovery, ovulation and pregnancy were observed. Results: The body weight and BMI of the observation group after treatment were significantly lower than those before treatment and of the control group (P<0.05). There was no significant difference in WHR between the two groups. In the observation group, there were significant differences in LH, T, LH/FSH, FINS and TG levels before and after treatment and from those of the control group after treatment (P<0.05). Both the left and right ovarian volumes of the observation group after treatment were significantly lower than those before treatment and of the control group after treatment (P<0.05). The menstrual recovery, ovulation and pregnancy rates of the observation group were significantly higher than those of the control group (P<0.05). Conclusion: Lifestyle adjustment combined with metformin and clomiphene can improve the reproductive endocrine and lipid metabolism of obese PCOS patients, decrease the volumes of left and right ovaries, and increase the menstrual recovery, ovulation and pregnancy rates. PMID:28367163
Swaroop, Anand; Jaipuriar, Amrita Sarkari; Gupta, Sushil Kumar; Bagchi, Manashi; Kumar, Pawan; Preuss, Harry G.; Bagchi, Debasis
Polycystic ovary syndrome (PCOS) is one of the most prevalent hormonal disorders among women of reproductive age causing irregular menstrual cycles, excessive body or facial hair, miscarriage and infertility. The latter being a most common PCOS symptoms. Because the symptoms are seemingly unrelated to one another, PCOS is often overlooked and undiagnosed. The present study is an open label, one-arm, non-randomized, post-marketing surveillance study in 50 premenopausal women (18-45 years, BMI<42) diagnosed with PCOS using a novel Trigonella foenum-graecum seed extract (fenugreek seed extract, Furocyst, 2 capsules of 500 mg each/day) extract, enriched in approximately 40% furostanolic saponins, over a period of 90 consecutive days. The study was conducted to determine its efficacy on the reduction of ovarian volume and the number of ovarian cysts. Ethical committee approval was obtained for this study. Furocyst treatment caused significant reduction in ovary volume. Approximately 46% of study population showed reduction in cyst size, while 36% of subjects showed complete dissolution of cyst. It is important to mention that 71% of subjects reported the return of regular menstrual cycle on completion of the treatment and 12% of subjects subsequently became pregnant. Overall, 94% of patients benefitted from the regimen. Significant increases in luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were observed compared to the baseline values. Extensive blood chemistry, hematological and biochemical assays demonstrated the broad-spectrum safety. Furocyst caused significant decrease in both ovarian volume and the number of ovarian cysts. Serum ALT, BUN and CK were assessed to demonstrate the broad-spectrum safety of Furocyst. No significant adverse effects were observed. In summary, Furocyst was efficacious in ameliorating the symptoms of PCOS. PMID:26516311
Swaroop, Anand; Jaipuriar, Amrita Sarkari; Gupta, Sushil Kumar; Bagchi, Manashi; Kumar, Pawan; Preuss, Harry G; Bagchi, Debasis
Polycystic ovary syndrome (PCOS) is one of the most prevalent hormonal disorders among women of reproductive age causing irregular menstrual cycles, excessive body or facial hair, miscarriage and infertility. The latter being a most common PCOS symptoms. Because the symptoms are seemingly unrelated to one another, PCOS is often overlooked and undiagnosed. The present study is an open label, one-arm, non-randomized, post-marketing surveillance study in 50 premenopausal women (18-45 years, BMI<42) diagnosed with PCOS using a novel Trigonella foenum-graecum seed extract (fenugreek seed extract, Furocyst, 2 capsules of 500 mg each/day) extract, enriched in approximately 40% furostanolic saponins, over a period of 90 consecutive days. The study was conducted to determine its efficacy on the reduction of ovarian volume and the number of ovarian cysts. Ethical committee approval was obtained for this study. Furocyst treatment caused significant reduction in ovary volume. Approximately 46% of study population showed reduction in cyst size, while 36% of subjects showed complete dissolution of cyst. It is important to mention that 71% of subjects reported the return of regular menstrual cycle on completion of the treatment and 12% of subjects subsequently became pregnant. Overall, 94% of patients benefitted from the regimen. Significant increases in luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were observed compared to the baseline values. Extensive blood chemistry, hematological and biochemical assays demonstrated the broad-spectrum safety. Furocyst caused significant decrease in both ovarian volume and the number of ovarian cysts. Serum ALT, BUN and CK were assessed to demonstrate the broad-spectrum safety of Furocyst. No significant adverse effects were observed. In summary, Furocyst was efficacious in ameliorating the symptoms of PCOS.
Objective To evaluate the relationship between serum gonadotropin level and parameters related to insulin resistance in Korean women with polycystic ovary syndrome (PCOS). Methods This retrospective study included 138 women aged 18 to 35 years who were newly diagnosed with PCOS according to the Rotterdam consensus. Participants were divided into three groups based on the serum luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio in the early follicular phase: group 1 (LH/FSH <1), group 2 (1.0≤ LH/FSH >2.0), and group 3 (LH/FSH ≥2.0). The correlations between the LH/FSH ratio and various metabolic parameters were evaluated using Pearson correlation coefficients. Results Patients with higher LH/FSH ratios showed higher total antral follicle counts and higher total ovarian volume. In the comparison of anthropometric and biochemical parameters among the three groups, the waist to hip ratio was the only parameter that differed significantly among the groups (P=0.003). Correlation analysis revealed no significant correlations between serum LH/FSH ratios and biochemical parameters related to insulin resistance. However, after adjustments for age and body mass index, a significant correlation between total cholesterol level and serum LH/FSH ratio was observed (r=0.221, P=0.018). Conclusion Most parameters related to insulin resistance, with the exception of total cholesterol level, are unrelated to the inappropriate pattern of serum gonadotropin secretion in Korean women with PCOS. PMID:27896252
Lin, Annie W; Lujan, Marla E
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age worldwide. In addition to deleterious effects on fertility imparted by PCOS, women with PCOS are at increased risk of obesity, diabetes, cardiovascular disease, depression, and certain cancers. Hormonal and metabolic aberrations in PCOS have the potential to influence dietary intake and physical activity levels. There are emerging global data that women with PCOS have different baseline dietary energy intakes compared with women without PCOS. These alterations in diet may exacerbate clinical symptoms and compound risk of chronic disease in patients. Few studies have compared baseline physical activity levels between women with and without PCOS. Although comparisons between studies are confounded by several factors, the data point to no differences in activity levels among PCOS and non-PCOS groups. This review provides an assessment of the current literature on baseline dietary intake and physical activity levels in women with PCOS. Future recommendations to strengthen research in this area are provided, given the implications to aid in the development of effective nutrition-focused interventions for PCOS.
Jędrzejuk, Diana; Laczmański, Lukasz; Kuliczkowska, Justyna; Lenarcik, Agnieszka; Trzmiel-Bira, Anna; Hirnle, Lidia; Dorobisz, Urszula; Milewicz, Andrzej; Lwow, Felicja; Urbanovych, A; Słoka, Natalia
The endocannabinoid system is postulated to play an important role in the etiology of obesity, insulin resistance, fat distribution and metabolic disorders. Insulin resistance associated with abdominal obesity plays a leading role in the etiology of hyperandrogenism and other clinical features of the polycystic ovary syndrome (PCOS). A total of 174 women 16-38 years old, diagnosed with PCOS according to the Rotterdam criteria are recruited. Control group consisted of 125 healthy women 18-45 years old. Medical history, physical examination, anthropometric parameters and metabolic parameters were carried out. Six CNR1 gene polymorphisms were diagnosed. We observed a significantly three times higher risk of GG genotype in the polymorphism rs12720071 in women with PCOS versus the control group (p = 0.0344, OR = 3.01). A similar, significant 8-fold higher risk (p = 0.0176, OR = 8.81) was demonstrated for genotype CC polymorphism rs806368 associated with PCOS. We observed a 3.6-fold increased risk of hyperandrogenemia (free androgen index - FAI > 7) in patients with GG genotype in the rs12720071 polymorphism and AA genotype in the polymorphism rs1049353 (OR = 2.7). Our study may indicate a role of the endocannabinoid system in the occurrence of a specific hyperandrogenemia phenotype of PCOS.
Trottier, Andréanne; Battista, Marie-Claude; Geller, David H; Moreau, Brigitte; Carpentier, André C; Simoneau-Roy, Judith; Baillargeon, Jean-Patrice
Objective To assess metabolic and endocrine defects in girls genetically predisposed to polycystic ovary syndrome (PCOS). Design Controlled cross-sectional study. Setting University hospital. Patients Nine girls aged 8–14 years having a first-degree relative diagnosed with PCOS (PCOSr) and 10 age-matched girls unrelated to PCOS. Intervention None. Main outcome measure Insulin sensitivity determined by frequently sampled intravenous glucose tolerance testing (ISFSivGTT) and insulin-induced non-esterified fatty acid suppression (NEFAsupp), estimated by the log-linear slope of NEFA levels during the first 20 min of FSivGTT. Results In comparison to controls, PCOSr had higher body mass index Z-score (BMI-z), waist circumference and waist/height ratio. Levels of the androgen 17α-hydroxyprogesterone (17OHPg) were significantly increased in PCOSr, independently of adiposity, and inversely correlated with ISFSivGTT. ISFSivGTT was decreased and NEFAsupp was less steep in PCOSr as compared to controls, independently of BMI-z and 17OHPg. NEFAsupp was more pronounced with increasing ISFSivGTT, independently of adiposity. Conclusions Girls at high risk of developing PCOS display increased adiposity and 17OHPg levels, but are mainly characterized by global insulin resistance and resistance to insulin-induced suppression of lipolysis that were independent of adiposity and 17OHPg levels. Therefore, genetic predisposition to PCOS may be related to early insulin resistance and adipocyte dysfunction. PMID:22985947
Álvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F
The polycystic ovary syndrome (PCOS) is a complex polygenic disorder in which environmental factors play an important modifying role. We aimed to find differences in diet and life-style that might contribute to the development of PCOS among overweight or obese premenopausal women. We compared diet composition and self-reported physical activity among 22 patients with PCOS and 59 women without androgen excess recruited from a total of 113 consecutive premenopausal women reporting for management of weight excess. After correcting for a difference in age between women with PCOS and controls, there were no overall statistical significant differences between them in the total caloric intake, in the intake of macro- and micro-nutrients, caffeine, fiber and alcohol, in the proportion of women exercising regularly, or in the number of hours of exercise per week. The proportion of fat in the diets of the overweight and obese women irrespective of PCOS was well-above current recommendations, yet this excessive fat intake occurred at the expense of monounsaturated fatty acids mostly. In conclusion, diet composition and physical activity were apparently not decisive for the development of PCOS among overweight and obese premenopausal women.
The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression of lipoprotein(a) and oxidized low-density lipoprotein, lipid profiles and biomarkers of oxidative stress in patients with polycystic ovary syndrome.
Rahmani, Elham; Samimi, Mansooreh; Ebrahimi, Faraneh Afshar; Foroozanfard, Fatemeh; Ahmadi, Shahnaz; Rahimi, Maryam; Jamilian, Mehri; Aghadavod, Esmat; Bahmani, Fereshteh; Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Asemi, Zatollah
This study was conducted to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression of lipoprotein(a) (Lp[a]) and oxidized low-density lipoprotein (Ox-LDL), lipid profiles and biomarkers of oxidative stress in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was done on 68 women diagnosed with PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly assigned into two groups to receive either 1000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-Linolenic acid plus 400 IU vitamin E supplements (n = 34) or placebo (n = 34) for 12 weeks. Lp(a) and Ox-LDL mRNA levels were quantified in peripheral blood mononuclear cells of PCOS women with RT-PCR method. Lipid profiles and biomarkers of oxidative stress were quantified at the beginning of the study and after 12-week intervention. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated expressed levels of Lp(a) mRNA (P < 0.001) and Ox-LDL mRNA (P < 0.001) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo group, omega-3 fatty acids and vitamin E co-supplementation resulted in a significant decrease in serum triglycerides (-22.1 ± 22.3 vs. +7.7 ± 23.6 mg/dL, P < 0.001), VLDL- (-4.4 ± 4.5 vs. +1.5 ± 4.7 mg/dL, P < 0.001), total- (-20.3 ± 16.6 vs. +12.2 ± 26.1 mg/dL, P < 0.001), LDL- (-16.7 ± 15.3 vs. +11.9 ± 26.1 mg/dL, P < 0.001) and total-/HDL-cholesterol (-0.5 ± 0.6 vs. +0.4 ± 0.8, P < 0.001). There were a significant increase in plasma total antioxidant capacity (+89.4 ± 108.9 vs. +5.9 ± 116.2 mmol/L, P = 0.003) and a significant decrease in malondialdehyde levels (-0.3 ± 0.4 vs. -0.008 ± 0.6 μmol/L, P = 0.01) by combined omega-3 fatty acids and vitamin E intake compared with
Unni, C. Sumithra N.; Lakshman, Lakshmi R.; Vaidyanathan, Kannan; Subhakumari, K.N.; Menon, N. Leela
Background & objectives: Plasma amino acid levels are known to be altered in conditions like sepsis and burns which are situations of metabolic stress. Polycystic ovary syndrome (PCOS), a condition which affects a woman throughout her life, is said to be associated with metabolic stress. This study was undertaken to assess if there were significant alterations in the levels of plasma amino acids in women with PCOS. Methods: Sixty five women with PCOS along with the similar number of age matched normal controls were included in this study. Levels of 14 amino acids were determined using reverse phase high performance liquid chromatography. Results: The levels of methionine, cystine, isoleucine, phenylalanine, valine, tyrosine, proline, glycine, lysine and histidine were found to be significantly (P<0.001) lower in cases than in controls. Arginine and alanine levels were found to be significantly (P<0.001) higher in cases compared with controls. Interpretation & conclusions: Our findings showed significant derangement in the levels of plasma amino acids in women with PCOS which might be due to the oxidative and metabolic stress associated with it. Further studies need to be done to confirm the findings. PMID:26658589
Raja-Khan, Nazia; Stener-Victorin, Elisabet; Wu, XiaoKe; Legro, Richard S
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses, and infertility. Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance, obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current treatments for PCOS are only moderately effective at controlling symptoms and preventing complications. This article describes how the physiological effects of major complementary and alternative medicine (CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are mediated via activation of somatic afferent nerves innervating the skin and muscle, which, via modulation of the activity in the somatic and autonomic nervous system, may modulate endocrine and metabolic functions in PCOS. Chinese herbal medicines and dietary supplements may also exert beneficial physiological effects in PCOS, but there is minimal evidence that these CAM treatments are safe and effective. Mindfulness has not been investigated in PCOS, but it has been shown to reduce psychological distress and exert positive effects on the central and autonomic nervous systems, hypothalamic-pituitary-adrenal axis, and immune system, leading to reductions in blood pressure, glucose, and inflammation. In conclusion, CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive effects in PCOS. However, most studies of CAM treatments for PCOS are small, nonrandomized, or uncontrolled. Future well-designed studies are needed to further evaluate the safety, effectiveness, and mechanisms of CAM treatments for PCOS.
Huang-Doran, Isabel; Franks, Stephen
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID:27375552
Brüggmann, Dörthe; Berges, Lea; Klingelhöfer, Doris; Bauer, Jan; Bendels, Michael; Louwen, Frank; Jaque, Jenny; Groneberg, David A
Polycystic ovary syndrome (PCOS) is the most common cause of female infertility worldwide. Although the related research output is constantly growing, no detailed global map of the scientific architecture has so far been created encompassing quantitative, qualitative, socioeconomic and gender aspects. We used the NewQIS platform to assess all PCOS-related publications indexed between 1900 and 2014 in the Web of Science, and applied density equalizing mapping projections, scientometric techniques and economic benchmarking procedures. A total of 6261 PCOS-specific publications and 703 international research collaborations were found. The USA was identified as the most active country in total and collaborative research activity. In the socioeconomic analysis, the USA was also ranked first (25.49 PCOS-related publications per gross domestic product [GDP]/capita), followed by the UK, Italy and Greece. When research activity was related to population size, Scandinavian countries and Greece were leading the field. For many highly productive countries, gender analysis revealed a high ratio of female scientists working on PCOS with the exception of Japan. In this study, we have created the first picture of global PCOS research, which largely differs from other gynaecologic conditions and indicates that most related research and collaborations originate from high-income countries.
Ong, Madeleine; Peng, Jie; Jin, Xingliang; Qu, Xianqin
Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder characterized by androgen excess and ovulatory dysfunction; it is now known to be closely linked to metabolic syndrome. Recent research suggests that insulin resistance plays an important role in the pathogenesis of PCOS which may lead to the excessive production of androgens by ovarian theca cells. Currently there is no single drug that can treat both the reproductive and metabolic complications of the disorder. Existing pharmaceutical agents such as hormonal therapies have been associated with side effects and are not appropriate for PCOS women with infertility. Additionally, insulin sensitizing agents useful for treating the metabolic abnormalities in PCOS have limited efficacy for treating reproductive aspects of the disorder. Chinese herbal medicines have a long history of treating gynaecological problems and infertility and therefore may be a novel approach to the treatment of PCOS. Current research demonstrates that the compounds isolated from herbs have shown beneficial effects for PCOS and when combined in an herbal formula can target both reproductive and metabolic defects simultaneously. Therefore, further investigation into Chinese herbal medicine in the treatment of PCOS is warranted.
Yu, Hai-Feng; Chen, Hong-Su; Rao, Da-Pang; Gong, Jian
Abstract Background: Polycystic ovary syndrome (PCOS) is inconsistently associated with increased risk of adverse pregnancy outcomes. The purpose of this meta-analysis was to summarize the evidence regarding the strength of the association between pregnancy in women with PCOS and pregnancy complications. Methods: We systematically searched PubMed, EmBase, and the Cochrane Library to identify observational studies up to January 2016. The primary focus was pregnancy outcomes, including gestational diabetes mellitus (GDM), preeclampsia, pregnancy-induced hypertension (PIH), preterm delivery, cesarean delivery, oligohydramnios, and polyhydramnios. Effect estimates were pooled using the random-effects model. The analysis was further stratified by factors that could affect these associations. Results: We included 40 observational studies that reported data on a total of 17,816 pregnancies with PCOS and 123,756 pregnancies without PCOS. Overall, PCOS in pregnancy was associated with greater risk of GDM, preeclampsia, PIH, preterm delivery, cesarean delivery, miscarriage, hypoglycemia, and perinatal death. However, PCOS in pregnancy had little or no effect on oligohydramnios, polyhydramnios, large-for-gestational age (LGA), small-for-gestational-age (SGA), fetal growth restriction (FGR), preterm premature membrane rupture, fasting blood glucose (FBG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, total cholesterol, congenital malformation, macrosomia, and respiratory distress syndrome. Subgroup analysis suggested that these associations might be influenced by study design and pre-BMI. Conclusion: PCOS in pregnancy is associated with a significantly increased risk of adverse pregnancy, fetal, and neonatal outcomes. PMID:28002314
Pathak, Gauri; Nichter, Mark
Polycystic ovary syndrome (PCOS) is an endocrine disorder linked to type II diabetes and the leading cause of female infertility worldwide. Despite being considered a "lifestyle" disease, PCOS has received scant attention in the social science literature. In India, media accounts citing prominent doctors have expressed concern that the syndrome affects a growing number of urban middle-class Indian women. The general public, doctors, and afflicted women all attribute the condition to stress, lifestyle changes, "Westernization," modernization, and disrupted circadian rhythms. These factors are associated with changes in diets, gender roles, and aspirations since 1991, when the introduction of neoliberal reforms opened up the country to processes of globalization. Women with PCOS have come to be seen as living embodiments of the biosocial stresses associated with modern urban middle-class living, and discourse about PCOS serves as commentary indexing anxieties about social and political-economic shifts in the country. In this paper, based on ethnographic fieldwork in Mumbai, India, with 141 participants from 2012 to 2014, we point to local understanding of PCOS as corresponding to an ecosocial perspective that highlights the structural vulnerabilities of urban middle-class women. Whereas most research on structural vulnerabilities and health has centered on economically and otherwise disadvantaged groups, we use PCOS as a case study to draw attention to the rise of lifestyle disorders linked to the impact of globalization and the pressures of "modern" identities and aspirations among middle-class populations.
Love, John G; McKenzie, John S; Nikokavoura, Efsevia A; Broom, John; Rolland, Catherine; Johnston, Kelly L
Polycystic ovary syndrome (PCOS) is variously reported to affect between 5% and 26% of reproductive age women in the UK and accounts for up to 75% of women attending fertility clinics due to anovulation. The first-line treatment option for overweight/obese women with PCOS is diet and lifestyle interventions. However, optimal dietary guidelines are missing, with very little research having been done in this area. This paper presents the findings from a qualitative study (using semistructured interviews) of ten obese women who had PCOS and who had used LighterLife Total (LLT), a commercial weight loss program which utilizes a very low-calorie diet in conjunction with behavioral change therapy underpinned by group support. We investigated the women’s history of obesity, their experiences of other diets compared with LLT, and the on-going impact that this has had on their lives. Findings show that most women reported greater success using this weight loss program in terms of achieving and maintaining weight loss when compared with other diets. Furthermore, all the women nominated LLT as their model weight loss intervention with only a few modifications. PMID:27499648
Selen, Ebru Selin; Bolandnazar, Zeinab; Tonelli, Marco; Bütz, Daniel E; Haviland, Julia A; Porter, Warren P; Assadi-Porter, Fariba M
Polycystic ovary syndrome (PCOS) is associated with metabolic and endocrine disorders in women of reproductive age. The etiology of PCOS is still unknown. Mice prenatally treated with glucocorticoids exhibit metabolic disturbances that are similar to those seen in women with PCOS. We used an untargeted nuclear magnetic resonance (NMR)-based metabolomics approach to understand the metabolic changes occurring in the plasma and kidney over time in female glucocorticoid-treated (GC-treated) mice. There are significant changes in plasma amino acid levels (valine, tyrosine, and proline) and their intermediates (2-hydroxybutyrate, 4-aminobutyrate, and taurine), whereas in kidneys, the TCA cycle metabolism (citrate, fumarate, and succinate) and the pentose phosphate (PP) pathway products (inosine and uracil) are significantly altered (p < 0.05) from 8 to 16 weeks of age. Levels of NADH, NAD(+), NAD(+)/NADH, and NADH redox in kidneys indicate increased mitochondrial oxidative stress from 8 to 16 weeks in GC-treated mice. These results indicate that altered metabolic substrates in the plasma and kidneys of treated mice are associated with altered amino acid metabolism, increased cytoplasmic PP, and increased mitochondrial activity, leading to a more oxidized state. This study identifies biomarkers associated with metabolic dysfunction in kidney mitochondria of a prenatal gluococorticoid-treated mouse model of PCOS that may be used as early predictive biomarkers of oxidative stress in the PCOS metabolic disorder in women.
Abbott, David H; Levine, Jon E; Dumesic, Daniel A
Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset.
Beydoun, Hind A.; Stadtmauer, Laurel; Beydoun, May A.; Russell, Helena; Zhao, Yueqin; Oehninger, Sergio
The purpose of the study is to examine the effects of polycystic ovary syndrome (PCOS) and body mass index (BMI) on selected indicators of in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment success. A retrospective cohort study was conducted using existing data on 69 IVF/ICSI treatment cycles undergone by PCOS women and an individually matched sample of 69 IVF/ICSI treatment cycles undergone by non-PCOS women at a major fertility treatment center. BMI (kg/m2) was analyzed as a continuous and categorical (< 25, 25−29.9 ≥ 30) variable. Results indicated that PCOS was directly associated with the number of oocytes retrieved. Irrespective of PCOS status, continuous BMI was inversely associated with total and mature oocytes retrieved. Multiple linear regression analyses indicated no significant effects of PCOS or continuous BMI on the number of mature oocytes fertilized per mature oocyte retrieved or inseminated. Similarly, multiple logistic regression analyses suggested no significant effect of PCOS and continuous BMI on the odds of pregnancy, miscarriage or live birth. Furthermore, categorical BMI did not influence process and outcome measures of IVF/ICSI treatment success. PCOS and continuous BMI appear to have significant and distinct effects on early stages but not on later stages of IVF/ICSI treatment. PMID:19490792
Raja-Khan, Nazia; Shuja, Showieb A.; Kunselman, Allen R.; Hogeman, Cynthia S.; Demers, Laurence M.; Gnatuk, Carol L.; Legro, Richard S.
Objective To examine changes in brachial artery conductance (BAC) during reactive hyperemia in women with polycystic ovary syndrome (PCOS) compared to controls. Study Design This is a pilot case-control study performed at a single academic medical center. Changes in BAC during reactive hyperemia were evaluated in 31 women with PCOS and 11 healthy control women. Fasting glucose, insulin, lipids and androgen levels were also determined. A mixed-effects model was used to compare the PCOS curve to the control curve for change in BAC from baseline during reactive hyperemia. Results Body mass index (BMI) and testosterone levels were significantly increased in the PCOS group compared to controls (P < 0.05). In addition, the PCOS group had higher total and LDL cholesterol levels (P = 0.05 and 0.09, respectively). Change in BAC from baseline during reactive hyperemia was significantly increased in the PCOS group compared to controls even after adjusting for age, BMI and LDL cholesterol levels (P < 0.0001). There were no significant differences between the two groups in age, blood pressure, or fasting glucose or insulin levels. Conclusions Brachial artery conductance during reactive hyperemia is significantly increased in women with PCOS compared to controls and may be a novel early indicator of increased cardiovascular risk in women with PCOS. PMID:21112136
Kokosar, Milana; Benrick, Anna; Perfilyev, Alexander; Fornes, Romina; Nilsson, Emma; Maliqueo, Manuel; Behre, Carl Johan; Sazonova, Antonina; Ohlsson, Claes; Ling, Charlotte; Stener-Victorin, Elisabet
Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed “gene-CpG” probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease. PMID:26975253
Ghazeeri, Ghina S; Nassar, Anwar H; Younes, Zeina; Awwad, Johnny T
This article is a review of the literature assessing pregnancy outcomes and the effect of metformin treatment among women with polycystic ovary syndrome (PCOS). A review of research published in English was undertaken using PubMed and MEDLINE databases. The weight of the available evidence suggests that pregnant women with PCOS are at an increased risk of developing gestational diabetes, hypertensive disorders of pregnancy, preterm birth and early pregnancy loss. Obesity is a contributory factor for the increased risk of gestational diabetes in this group of women and is estimated to affect 5-40% of pregnant women with PCOS. The prevalence of other obstetric complications is estimated at 10-30% for gestational hypertension, 8-15% for pre-eclampsia and 6-15% for preterm birth. The association between PCOS and early pregnancy loss may not be direct, wherein the presence of PCOS-associated hyperinsulinemia, leading to hyperandrogenemia, has been implicated in the pathophysiology of early pregnancy loss. Apart from the role of metformin in improving the metabolic consequences accompanying PCOS, it has been shown to improve pregnancy rates in women with PCOS who are resistant to clomiphene citrate. In conclusion, pregnancy in women with PCOS is associated with adverse obstetric outcomes (multiple adverse obstetric risk). Whether metformin should be administered throughout pregnancy still remains controversial. Further prospective studies that foster a larger number of participants and adjust for all potentially confounding factors are needed.
Conte, Francesca; Banting, Lauren; Teede, Helena J; Stepto, Nigel K
This review was designed to consider the available literature concerning mental health and physical activity in women with polycystic ovary syndrome (PCOS). A systematic approach was taken and two electronic databases (PubMed and EBSCO Research articles published between 1970 and 2013) were searched in 2013 to inform a narrative review. Inclusion criteria encompassed requirements for the research to involve a physical activity intervention and assessment of mental health outcomes in women with PCOS. Seven articles considered mental health outcomes and physical activity interventions for women with PCOS. The results demonstrated positive outcomes following physical activity intervention for health-related quality of life, depression, and anxiety. Only one paper reported the independent effects of physical activity on mental health. All other interventions included multi-factor lifestyle interventions or did not establish a control group. Physical activity is likely to be beneficial to the mental health of women with PCOS; however, more research is required to establish the nature of the relationship between physical activity and mental health outcomes.
Lim, S S; Norman, R J; Davies, M J; Moran, L J
While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone-binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total-cholesterol and low-density lipoprotein-cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.
Pertynska-Marczewska, Magdalena; Diamanti-Kandarakis, Evanthia; Zhang, John; Merhi, Zaher
Polycystic ovary syndrome (PCOS), a heterogeneous syndrome of reproductive and metabolic alterations, is associated with increased long-term risk of cardiovascular complications. This phenomenon has been linked to an increase in oxidative stress and inflammatory markers. Advanced glycation end products (AGEs) are pro-inflammatory molecules that trigger a state of intracellular oxidative stress and inflammation after binding to their cell membrane receptors RAGE. The activation of the AGE-RAGE axis has been well known to play a role in atherosclerosis in both men and women. Women with PCOS have systemic chronic inflammatory condition even at the ovarian level as represented by elevated levels of serum/ovarian AGEs and increased expression of the pro-inflammatory RAGE in ovarian tissue. Data also showed the presence of sRAGE in the follicular fluid and its potential protective role against the harmful effect of AGEs on ovarian function. Thus, whether AGE-RAGE axis constitutes a link between metabolic and endothelial dysfunction in women with PCOS is addressed in this review. Additionally, we discuss the role of hormonal changes observed in PCOS and how they are linked with the AGE-RAGE axis in order to better understand the nature of this complex syndrome whose consequences extend well beyond reproduction.
Zhao, Luqian; Zhu, Zhigang; Lou, Huiling; Zhu, Guodong; Huang, Weimin; Zhang, Shaogang; Liu, Feng
Some studies reported a significant association between polycystic ovary syndrome (PCOS) and risk of cardiovascular disease (CVD). However, the results are controversial. A systematic search was conducted in the PubMed, Science Direct, EMBASE, and Cochrane Library databases. Five case-control studies and 5 cohort studies were selected, involving a total of 104392 subjects in this meta-analysis. PCOS was significantly associated with the increased risk of CVD (OR = 1.30; 95% CI 1.09 – 1.56; P = 0.004). In the subgroup analysis of study design, both case-control studies and prospective cohort studies showed significant results (OR = 1.79; 95% CI 1.16 – 2.77; P = 0.009; OR = 1.20; 95% CI 1.06 – 1.37; P = 0.005), while retrospective cohort studies did not show positive result (OR = 0.91; 95% CI 0.60 – 1.40; P = 0.68). In a further stratified analysis by type of CVD, a significant association was found between PCOS and coronary heart disease (CHD) (OR = 1.44; 95% CI 1.13 – 1.84; P = 0.004). However, no significant association was observed between PCOS and myocardial infarction (MI) (OR = 1.01; 95% CI 0.68 – 1.51; P = 0.95). In conclusion, this meta-analysis suggested that PCOS is significantly associated with increased CHD risk. PMID:27220885
Roessler, Kirsten K; Glintborg, Dorte; Ravn, Pernille; Birkebaek, Camilla; Andersen, Marianne
The objective of the present study was to examine the psychological impact of a group-oriented approach to disease management and health behaviour in women with polycystic ovary syndrome (PCOS). Seventeen overweight PCOS women were randomised in a crossover design of eight weeks high-intensity aerobic exercise followed by eight weeks of group counselling (n=8) or vice versa (n=9). Interpersonal communication, emotional and relational aspects were observed and analysed throughout the period focusing on changes in health behaviour. The most salient findings showed supportive relationships expressed as group cohesion, exchange of narratives of illness and of disorder-specific aspects. Individual relationships between the participants were important for changes in behaviour, especially those generating feedback from the other participants and reducing social isolation. The results were most encouraging in the group that had initial counselling sessions before the physical intervention. It can be concluded that group counselling sessions focusing on supportive relationships followed by high-intensity aerobic training have beneficial effects on wellbeing, health and exercise behaviour.
Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng
Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.
Rojas, Joselyn; Chávez-Castillo, Mervin; Bermúdez, Valmore
Maintenance of gestation implicates complex function of multiple endocrine mechanisms, and disruptions of the global metabolic environment prompt profound consequences on fetomaternal well-being during pregnancy and postpartum. Polycystic Ovary Syndrome (PCOS) and gestational diabetes mellitus (GDM) are very frequent conditions which increase risk for pregnancy complications, including early pregnancy loss, pregnancy-induced hypertensive disorders, and preterm labor, among many others. Insulin resistance (IR) plays a pivotal role in the pathogenesis of both PCOS and GDM, representing an important therapeutic target, with metformin being the most widely prescribed insulin-sensitizing antidiabetic drug. Although traditional views neglect use of oral antidiabetic agents during pregnancy, increasing evidence of safety during gestation has led to metformin now being recognized as a valuable tool in prevention of IR-related pregnancy complications and management of GDM. Metformin has been demonstrated to reduce rates of early pregnancy loss and onset of GDM in women with PCOS, and it appears to offer better metabolic control than insulin and other oral antidiabetic drugs during pregnancy. This review aims to summarize key aspects of current evidence concerning molecular and epidemiological knowledge on metformin use during pregnancy in the setting of PCOS and GDM. PMID:25763406
Farrell, Kristen; Antoni, Michael
Objectives The purpose of this review is to summarize physiological and psychological characteristics that are common among women diagnosed with polycystic ovary syndrome (PCOS) and provide evidence suggesting that addressing psychological disturbances can reduce or alleviate physical symptoms of PCOS via behavioral pathways and physiological pathways. Methods Empirical studies and expert consensuses pertaining to physiological, psychological and medical management aspects of PCOS were identified and presented in this review. Papers were identified via searching Pubmed, PsycInfo, Medline ISI, CINAHL, or a web browser (i.e., Google) using numerous combinations of terms pertaining to physiological, psychological, and medical management aspects of PCOS. A paper was chosen to be included in this review if it reported findings and/or provided information that related to and helped support the main purpose(s) of this review paper. Results Available literature on the physiological (i.e., hyperandrogenism, central obesity, inflammation, insulin resistance) and psychological (i.e., depression, anxiety, eating disorders) factors among women with PCOS provides evidence that these various aspects of PCOS are strongly inter-related. Discussion The existence of these relationships among physiological and psychological factors strongly suggests that medical management of PCOS would greatly benefit from inclusion of psychological and behavioral approaches. PMID:20471009
Wang, Rui; Mol, Ben Willem J
The Rotterdam criteria for polycystic ovary syndrome (PCOS) are used by a wide range of medical professionals and researchers. However, the development of these criteria was based on expert meetings and not on evidence-based treatment guidance. Over the last decade, the Rotterdam criteria have been useful in guiding research, and a number of clinical studies on PCOS have been published consequently. We plead to revisit the Rotterdam criteria based on the available evidence in prognostic studies and randomized controlled trials. In this opinion paper, we provide arguments of the strengths and limitations of the Rotterdam criteria in guiding treatment selections and predicting prognoses in women with infertility. While the Rotterdam criteria have shown their advantages in predicting reproductive prognosis, the next step is to evaluate whether they can guide treatment choices in infertility as well as other health aspects of the syndrome. Based on available data in clinical studies, we should be able to determine whether the Rotterdam criteria are evidence-based criteria.
Sun, Ying; Yuan, Yi; Yang, Hua; Li, Jingjie; Feng, Tian; Ouyang, Yongri; Jin, Tianbo; Liu, Ming
Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5-7% of reproductive age women worldwide. The aim of our study was to explore the PCOS-related single nucleotide polymorphism (SNP) associations between common genetic variants and PCOS risk in a Han Chinese women population. Methods: In this case-control study, 285 Chinese Han women aged 28.50±6.858 years with PCOS and 299 controls of a mean age of 32.66±7.018 years were compared. We selected recently published genome-wide association studies (GWAS) which identified several genetic loci in PCOS. All the SNPs were genotyped by Sequenom Mass-ARRAY technology. Associations between the gene and the risk of PCOS were tested using various genetic models by Statistical Package for the Social Sciences and Plink. Results: We found that rs705702 in the RAB5B/SUOX was associated with PCOS (odds ratio=1.42; 95% confidence interval=1.08-1.87, p=0.011) and increased the PCOS risk. The genotypic model analysis also showed that rs705702 was associated with PCOS risk. Conclusion: Our results suggest that SNPs rs705702 in gene RAB5B/SUOX was associated with PCOS in Han Chinese women. PMID:27217259
Liu, Jian-Qiao; Mai, Zi-Xin; Zeng, Yan-Ting
The need for development of new therapeutic agents for polycystic ovary syndrome (PCOS) is urgent due to general lack of efficient and specialized drugs currently available. We aimed to explore the metabolic mechanism of PCOS and inferred drug reposition for PCOS by a subpathway-based method. Using the GSE34526 microarray data from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between PCOS and normal samples. Then, we identified 13 significantly enriched metabolic subpathways that may be involved in the development of PCOS. Finally, by an integrated analysis of PCOS-involved subpathways and drug-affected subpathways, we identified 54 novel small molecular drugs capable to target the PCOS-involved subpathways. We also mapped the DEGs of PCOS and a potential novel drug (alprostadil) into purine metabolism pathway to illustrate the potentially active mechanism of alprostadil on PCOS. Candidate agents identified by our approach may provide insights into a novel therapy approach for PCOS. PMID:25015903
Sedighi, Sedigheh; Akbari, Sedigheh Amir Ali; Afrakhteh, Maryam; Esteki, Taraneh; Majd, Hamid Alavi; Mahmoodi, Zohreh
Given the high prevalence of polycystic ovary syndrome (PCOS), and that a lifestyle is recognized effective in development of many diseases, this study aimed to compare lifestyle of women with PCOS and healthy women. Nor are there sufficient studies on the difference between lifestyle of these people with that of healthy people. Furthermore, studies show that changes in lifestyle improve this disease. This descriptive-comparative study was conducted on 65 women with PCOS and 65 healthy women of 18 to 45 years old who presented to hospitals affiliated to Shahid Beheshti University of Medical Sciences in 2013. The subjects were selected using multi stage random sampling method. The data were collected using questionnaires for diet, International Physical Activity Questionnaire, and unhealthy behaviors and were analyzed in SPSS v. 17, using descriptive statistics, Man-Whitney, independent t, Chi-square and logistic regression tests. The results showed there was a significant relationship between PCOS and inappropriate diet (p=0.009), low physical activity (p=0.009), but no relationship was observed between PCOS and unhealthy behaviors. Given the results obtained, training and awareness raising is necessary for women and girls especially about appropriate diet and regular physical activity. PMID:25560358
Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong
Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS.
Jeanes, Yvonne M; Reeves, Sue
Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.
Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra
Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have. PMID:27570464
Rahiminejad, Mohammad Ehsan; Moaddab, Amirhossein; Zaryoun, Hassan; Rabiee, Soghra; Moaddab, Arta; Khodadoustan, Amin
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, affecting 4-18% of them. Previous studies also showed that periodontal diseases are associated with different components of the metabolic syndrome. The aim of this study is to determine the association between PCOS and periodontal diseases. Materials and Methods: A total of 196 women (98 with PCOS and 98 healthy controls) were enrolled. PCOS diagnosis was confirmed by history, clinical signs, physical examination, laboratory parameters, and ultrasound studies. Both cases and controls were examined by the same periodontist. Periodontal parameters including bleeding on probing (BOP), probing depth, clinical attachment loss (CAL), plaque index, and tooth loss were investigated in all participants. Pregnant women, smokers, individuals with a history of malignancy or osteoporosis, and those taking prophylactic antibiotics for dental procedures or receiving periodontal treatment during the 6-month period before examination were excluded. Data were analyzed using t-test, Chi-square test, and linear regression. Statistical significance was set at P < 0.05. Results: CAL and sites with BOP were significantly higher in women with PCOS (P < 0.05). However, no significant difference was observed in the tooth loss rate between PCOS and non-PCOS participants (P = 0.384). Conclusion: The prevalence of periodontal disease seems to be higher in women with PCOS. This may be related to the role of chronic systemic inflammation in the pathophysiology of both PCOS and periodontal diseases. PMID:26759585
Saha, Lekha; Kaur, Sharonjeet; Saha, Pradip Kumar
Clomiphene citrate (CC) has been the gold-standard drug for ovulation induction in polycystic ovary syndrome (PCOS), but still CC resistance is seen in approximately 15-40% in women with PCOS. N-acetyl cysteine (NAC), a safe and cheap drug available in the market many years ago as mucolytic agent, was found to have a role in infertility management. Recently, some reports discussed the possible beneficial effects of NAC on ovulation. The biological properties of the NAC make this drug a potential candidate for its use in the infertility treatment, especially in the PCOS in inducing or augmenting ovulation. An updated electronic search was performed through PUBMED, MEDLINE, and COCHRANE and focused on peer-reviewed, full text, randomized controlled trials, and observational cohort or case-control studies for role of NAC in CC-resistant PCOS. Thorough search through all the clinical studies showed mixed results. Studies with positive results showed improvement in induction of ovulation as compared to negative studies showing contrary results. More randomized clinical trials are still needed to establish its definitive role in CC-resistant PCOS.
Huang, Ying; Gao, Jiang-Man; Zhang, Chun-Mei; Zhao, Hong-Cui; Qiao, Jie
Polycystic ovary syndrome (PCOS) is a common reproductive disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity, which may have significant implications for pregnancy outcomes and long-term health of women. Daughters born to PCOS mothers constitute a high-risk group for metabolic and reproductive derangements, but no report has described potential growth and metabolic risk factors for such female offspring. Hence, we used a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS to study the mechanisms underlying the pathology of PCOS by investigating the growth, developmental characteristics, metabolic indexes and expression profiles of key genes of offspring born to the models. We found that the average litter size was significantly smaller in the DHEA group, and female offspring had sustained higher body weight, increased body fat and triglyceride content in serum and liver; they also exhibited decreased energy expenditure, oxygen consumption and impaired glucose tolerance. Genes related to glucolipid metabolism such as Pparγ, Acot1/2, Fgf21, Pdk4 and Inhbb were upregulated in the liver of the offspring in DHEA group compared with those in controls, whereas Cyp17a1 expression was significantly decreased. However, the expression of these genes was not detected in male offspring. Our results show that female offspring in DHEA group exhibit perturbed growth and glucolipid metabolism that were not observed in male offspring. PMID:27798284
Lu, Caixia; Zhao, Xinjie; Li, Yan; Li, Yanjie; Yuan, Chengkun; Xu, Fang; Meng, Xiaoyu; Hou, Lihui; Xu, Guowang
Polycystic ovary syndrome (PCOS) is a most common, heterogeneous, complex endocrinopathy disease. Traditional Chinese medicine (TCM) has been used in the treatment of PCOS for many years. However, the mechanism underlying TCM remains obscure and challenging. In this study, 30 PCOS subjects were separated into normoinsulinemic group (NI=13) and hyperinsulinemic group (HI=17), and treated for three menstrual cycles with TCM Formula, Bushen Huatan Formula (BHF). A metabolomics approach based on ultra-high-performance liquid chromatography (UPLC) coupled with linear ion trap Orbi-trap mass spectrometer (LTQ Orbi-trap MS) is used to investigate serum metabolic changes of TCM intervention to PCOS. After BHF intervention for three menstrual cycles, the serum levels of glycerophosphorylethanolamine (GPEA), creatine, creatinine decreased in both NI and HI groups. Furthermore, in NI group, the main manifestation was the changes of phospholipid metabolism. While in HI group, lysine, phenol sulfate, phe-phe etc. decreased, and ornithine, proline, betaine, acetylcholine etc. increased. Combined with clinical biochemical data, BHF was proved effective to PCOS by reducing the inflammatory reaction and oxidative stress. This study also illustrates that the LC-MS based metabolomic approach is a helpful tool to evaluate curative effect and to understand the mechanisms of TCM.
Ohlsson Gotby, Agnes; Nordenström, Anna; Falhammar, Henrik; Nordenskjöld, Agneta; Linden Hirschberg, Angelica; Frisén, Louise; Landén, Mikael; Lichtenstein, Paul
Both prenatal and circulating testosterone and other androgens have been suggested to influence the individual's propensity to commit crime, but empirical evidence is limited and inconsistent. Congenital Adrenal Hyperplasia (CAH) and Polycystic Ovary Syndrome (PCOS) are both hyperandrogenic conditions but with an important difference; whereas subjects with CAH are exposed to high concentrations of androgens in utero, women with PCOS are subjected to high androgens in adulthood. Comparing these groups can therefore yield important insights of androgenic effects on behavior. In the current study, information on medical diagnoses and convicted crimes were gathered from Swedish population-based registers. The associations between diagnoses of CAH or PCOS and any crime, violent crime or sex crime were estimated with conditional logistic regression. Results showed that CAH in women and men did not predict criminality, whereas an increased risk for any crime and violent crime was found in PCOS women. Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior. Further research into hyperandrogenic conditions holds opportunities to deepen our understanding of the etiology of crime and psychopathology.
Sharif, Elham; Rahman, Sumaya; Zia, Yumna; Rizk, Nasser M
This was a prospective cross-sectional study in which 126 female students between the ages of 18 and 30 years were evaluated for the frequency of polycystic ovary syndrome (PCOS) through clinical interview, questionnaire, and anthropometric measurements. The diagnostic criteria of the US National Institutes of Health criteria were used. Menstrual irregularities (MI) were identified, and clinical hyperandrogenism was evaluated by self-assessment of hirsutism using modified Ferriman–Gallwey score. Blood analysis was done for measurement of prolactin, thyroid-stimulating hormone, and the androgen hormones. Of all the students, 37 (30.8%) had MI, 38 (31.7%) had clinical hirsutism, 37 (30.8%) had acne, and 76 (63.3%) had a family history of type 2 diabetes. The estimated frequency of PCOS was 18.33% according to the US National Institutes of Health definition. Hormonal analysis demonstrated a significant increase in androgens (total testosterone, dehydroepiandrosterone sulfate, and free testosterone), and a significant decrease in sex hormone-binding globulin in our PCOS group, with a P-value <0.05. This study revealed a higher level of the androgen hormones among PCOS subjects with a frequency of PCOS (18.33%) similar to the global estimates of 10%–20%. PMID:28031728
Li, Xin; Cui, Peng; Jiang, Hong-Yuan; Guo, Yan-Rong; Pishdari, Bano; Hu, Min; Feng, Yi; Billig, Håkan; Shao, Ruijin
Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network. PMID:26045896
Zhai, Jun; Liu, Chun-xi; Tian, Zuo-rong; Jiang, Qiu-hui; Sun, Ying-pu
The objective was to explore the effects of metformin on the expression of endometrial glucose transporter 4 (GLUT4) and analyze the related factors of GLUT4 in patients with polycystic ovary syndrome (PCOS). This study included 20 obese patients with PCOS (PCOS group) and 20 obese patients who had infertility caused by oviducal or pelvic factors but had no PCOS (control group). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol-2 (E(2)), testosterone (T), fasting serum glucose (FSG), fasting insulin serum (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and endometrial GLUT4 expression were determined in the two groups. In PCOS group, patients were given 500 mg of metformin three times per day for 3 mo, and then the parameters above were determined again and compared with that before metformin treatment. The parameters above also were compared between PCOS and control groups. The correlation of GLUT4 with its related factors was analyzed. The levels of T, FINS, and HOMA-IR were higher in PCOS group than in the control group (P < 0.01). The levels of protein and mRNA of endometrial GLUT4 were lower in the PCOS group than in the control group (P < 0.001). The expression of protein and mRNA of endometrial GLUT4 increased after metformin treatment (P < 0.001). HOMA-IR was negatively correlated with GLUT4 expression (P = 0.027). In patients with PCOS, the levels of protein and mRNA of endometrial GLUT4 were lower compared with that in non-PCOS women, and HOMA-IR was strongly associated with endometrial GLUT4 expression. Metformin may up-regulate endometrial GLUT4 expression to improve endometrial IR.
Li, Xin; Cui, Peng; Jiang, Hong-Yuan; Guo, Yan-Rong; Pishdari, Bano; Hu, Min; Feng, Yi; Billig, Håkan; Shao, Ruijin
Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network.
de Medeiros, Sebastiao Freitas; Yamamoto, Marcia Marly Winck; Bueno, Herica Bernardes; Belizario, Danilla; Barbosa, Jacklyne Silva
Background To determine the prevalence of elevated glycated hemoglobin (HbA1c) and to examine its relationship with other carbohydrate metabolic parameter among Brazilian women with polycystic ovary syndrome (PCOS). Methods A cross-sectional study including 288 PCOS patients was conducted. Anthropometrical, clinical, biochemical and endocrine parameters were evaluated. Results The mean age was 26.92 ± 5.51 years. HbA1c mean concentration was 5.83±1.34%. In 38.54% of patients, HbA1c was ≥ 5.7%. HbA1c was positively correlated with body weight (r = 0.142, P = 0.017), body mass index (P = 0.000), waist:hip ratio (P = 0.000), fat mass (P = 0.000), conicity index (P = 0.000), triglyceride (P = 0.001), C-peptide (P = 0.000), total testosterone (P = 0.003), free testosterone (P = 0.000), free androgen index (P = 0.006) and fasting insulin (P = 0.025). Using the oral glucose tolerance test, HbA1c showed positive correlation with glucose concentrations at any point in time (P < 0.05). Conclusions HbA1c was elevated in nearly 40% of PCOS patients and it showed positive correlation with several anthropometric and metabolic factors and androgen levels. The current study provides further evidence that HbA1C is higher in PCOS patients and may have a potential role in the prediction of dysglycemic disease in these women. PMID:24883154
Guido, M; Belosi, C; Selvaggi, L; Lattanzi, F; Apa, R; Fulghesu, A M; Lanzone, A
Recent studies have proposed that, in women affected by the polycystic ovary syndrome (PCOS), aging is able to regularize the menstrual cyclicity. To evaluate the ovarian response in PCOS patients according to their age, we studied 33 PCOS patients, 20 of whom with an age ranging from 28 to 34 years (younger PCOS) and 13 ranging from 35 to 45 years (older PCOS). All patients underwent an ovulation induction therapeutic protocol with low-dose recombinant follicle stimulating hormone, for a total of 80 cycles (44 cycles for the younger PCOS group and 36 cycles for the older PCOS group). No significant difference was found between the days of therapy (12.3 +/- 5.4 vs. 13.5 +/- 5.6 days), total amount of drugs (980.7 +/- 568.9 IU vs. 1063.9 +/- 469.5 IU) or ovulation rate (93% vs. 89%) in the two groups. The two groups showed a significant difference in the maximum estradiol level (2053.5 +/- 1497.2 vs. 1269.0 +/- 911.5 pmol/l, p < 0.01), the number of the recruited and preovulatory follicles (1.7 +/- 2.5 vs. 0.64 +/- 0.9, p < 0.05 and 1.7 +/- 1.1 vs. 1.2 +/- 0.5, p < 0.01, respectively) and the pregnancy rate (36% vs. 14%, p < 0.05). In conclusion, our data clearly showed that, also in PCOS, advanced age is a negative prognostic factor in the ovarian response to ovulation induction therapies.
Suvarna, Yashasvi; Maity, Nivedita; Kalra, Pramila; Shivamurthy, MC
Objective The 2013 Endocrine Society guidelines state that hormonal contraceptives should be used for treating both menstrual irregularity and hirsutism in patients with polycystic ovary syndrome (PCOS). Metformin should be reserved for the treatment of women presenting with only menstrual irregularity because it has limited benefits in treating hyperandrogenism associated with PCOS. A high prevalence of insulin resistance is noted among the South Asians, and these guidelines may not hold good for this population. Thus, this study was conducted to investigate and compare the effects of metformin and an oral contraceptive containing drospirenone on menstrual pattern, body mass index, serum testosterone levels, and dehydroepiandrosterone sulfate (DHEAS) levels at baseline to 6 months of therapy in the treatment groups. Material and Methods This was a prospective observational study that was conducted over a year in patients visiting the Endocrinology outpatient department at a tertiary care center in a south Indian city. Forty-six subjects diagnosed with PCOS as per the Rotterdam criteria were included. They received either metformin twice daily or an oral contraceptive containing drospirenone once daily as a monthly regimen for 6 months. Results Metformin regularized menstrual cycles in 72% of patients who were followed up at 6 months. No significant difference was observed between the two treatment groups with respect to decreasing the body mass index, serum testosterone levels, and DHEAS levels (p=0.40, p=0.65, and p=0.22, respectively). Conclusion Metformin is effective in regularizing menstrual cycles, decreasing body mass index, and treating hyperandrogenism in Indian women diagnosed with PCOS. PMID:27026772
Zulian, E; Sartorato, P; Benedini, S; Baro, G; Armanini, D; Mantero, F; Scaroni, C
This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women.
Nazli, Yunus; Colak, Necmettin; Aksoy, Omer N; Cakir, Omer
Thyroid vein thrombosis is a rare variety of venous thrombosis. The use of oral contraceptives and heterozygous methylenetetrahydrofolate reductase (MTHFR) gene mutation could have synergistic effects on the onset of venous thromboembolism. We report a 28-year-old woman with thyroid vein thrombosis. The thrombosis was possibly provoked by a combination of heterozygous MTHFR gene mutation and the use of a combined oral contraceptive (COC) containing cyproterone acetate/ethinylestradiol (CPA/EE) for polycystic ovary syndrome (PCOS). The patient was treated successfully with low molecular weight heparin and oral anticoagulation. The thyroid vein thrombosis resolved and the patient was advised to maintain lifelong use of anticoagulation therapy. Our report emphasizes that the combination of heterozygous MTHFR gene mutation, PCOS, and the use of a COC-containing CPA/EE could increase risk of thyroid vein thrombosis in young adults.
Qiu, Shuwei; Jiang, Zhongli
Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232
Selimoglu, H; Duran, C; Kiyici, S; Ersoy, C; Guclu, M; Ozkaya, G; Tuncel, E; Erturk, E; Imamoglu, S
Insulin resistance (IR) is one of the common features of the polycystic ovary syndrome (PCOS), and recent studies indicate the possible role of vitamin D in the pathogenesis of IR and glucose metabolism. Aim of this study was aimed to determine the effect of vitamin D replacement therapy on glucose metabolism, insulin, and androgen levels in obese, insulin-resistant women with PCOS. Eleven women with PCOS were included in the study. Mean age of the patients was 23.6+/-5.7 yr, body mass index 33.9+/-5.1 kg/m(2). Six patients (54.5%) had acantosis nigricans and 10 (90.9%) oligoamenorrhea. The mean Ferriman Gallwey score was 14.1+/-4.6. Only 2 women were within the normal limits of vitamin D levels as >20 ng/ml. Three weeks after the administration of the single dose of 300,000 units of vitamin D3 orally, 25-hydroxyvitamin D3 significantly increased from 16.9+/-16 ng/ml to 37.1+/-14.6 ng/ml (p: 0.027) and only 2 women were detected to have vitamin D3 levels <20 ng/ml. Although glucose and insulin levels were decreased non-significantly, homeostasis model assessment (HOMA)-IR significantly decreased from 4.41+/-1.38 to 3.67+/-1.48 (p: 0.043). No significant alterations were witnessed at the levels of DHEAS, total and free testosterone, androstenedione. No correlation was found between vitamin D with HOMA and other hormonal parameters. In conclusion, women with PCOS have mostly insufficient vitamin D levels, and vitamin D replacement therapy may have a beneficial effect on IR in obese women with PCOS.
Razavi, M; Jamilian, M; Kashan, Z Fakhrieh; Heidar, Z; Mohseni, M; Ghandi, Y; Bagherian, T; Asemi, Z
Selenium supplementation could be effective on reproductive outcomes, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS). The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes, biomarkers of inflammation, and oxidative stress in PCOS patients. The present randomized double-blind, placebo-controlled trial was conducted on 64 women aged 18-40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences, Ardabil, Iran. The participants were randomly assigned to 2 groups receiving either 200 μg selenium daily (n=32) or placebo (n=32) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured and compared both before and after the treatment. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group: 18.8 (6/32) vs. 3.1% (1/32), p=0.04. In addition, alopecia (40.6 vs. 9.4%, p=0.004) and acne (46.9 vs. 12.5 %, p=0.003) decreased following the consumption of selenium supplements compared with placebo. Additionally, patients who received selenium supplements had significantly decreased serum dehydroepiandrosterone (DHEA) levels (p=0.02), hirsutism (modified Ferriman-Gallwey scores) (p<0.001), serum high sensitivity C-reactive protein (hs-CRP) (p=0.02), and plasma malondialdehyde (MDA) levels (p=0.01) compared with placebo. We did not observe any significant effects of taking selenium supplements on other hormonal profiles, nitric oxide (NO), and other biomarkers of oxidative stress. Taken together, selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. Supporting Information for this article is available online at http://www.thieme-connect.de/products.
Charalampakis, Vasileios; Tahrani, Abd A; Helmy, Ahmed; Gupta, Janesh K; Singhal, Rishi
One of the most effective methods to tackle obesity and its related comorbidities is bariatric surgery. Polycystic ovary syndrome (PCOS) and endometrial hyperplasia (EH), which are associated with increased risk of endometrial carcinoma, have been identified as potentially new indications for bariatric surgery. PCOS is the most common endocrine disorder in women in the reproductive age and is associated with several components of the metabolic syndrome such as obesity, insulin resistance and hypertension. EH is a pre-cancerous condition which arises in the presence of chronic exposure to estrogen unopposed by progesterone such as both in PCOS and obesity. The main bariatric procedures are Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding. These procedures are well established and when correctly selected and performed by experienced bariatric surgeons, they can achieve significant weight loss and remission of obesity related co-morbidities. Studies have shown that bariatric surgery can play an important role in the management of patients with PCOS and improve fertility. Similarly, bariatric surgery has a positive effect on endometrial hyperplasia, making surgically induced weight loss a potentially attractive option for endometrial cancer prevention and treatment. Obesity has an adverse impact on spontaneous pregnancy, assisted reproduction methods and feto-maternal outcomes. After bariatric surgery obese women with subfertility can achieve spontaneous pregnancy. However, while bariatric surgery reduces the risk of pre-eclampsia and gestational diabetes, there is an increased risk of small for gestational age and possible increased risk of stillborn or neonatal death. In this article we will review the evidence regarding the use of bariatric surgery as a treatment modality in patients with PCOS and EH. We also provide an overview of the common bariatric procedures.
Mirabolghasemi, Ghadire; Kamyab, Zahra
Background Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that can lead to irregular menstrual cycles and hyperandrogenism. Reduced levels of progesterone and increased estrogen in these women can perpetually stimulate the endometrial tissue of the uterus. In this study, we assess the effect of PCOS induction by estradiol valerate (EV) in a rat model. Materials and Methods In this experimental study, adult female Wistar rats that weighed approximately 200 g were divided into control, sham, and experimental groups (n=6 per group). The experimental group received subcutaneous injections of 2 mg EV for induction of PCOS. We confirmed the presence of PCOS in the experimental group rats. Rats from all groups were subsequently killed, after which their uteri were removed and fixed for histological and cytological analyses. The uterine tissue sections were stained with hematoxylin and eosin (H&E) and iron hematoxylin (iron-H). We examined epithelium height, thickness of the uterus wall, and frequency of the mitotic cells. The data were assessed at α=0.05. Results Uterine tissue findings from the experimental group showed significant increases in the height of the uterus luminal epithelium, the thickness of the uterus wall, and the frequency of eosinophils in the endometrial stroma. We observed an increased frequency of mitotic cells in the experimental group in both luminal and glandular epithelia of the uterus. An increased rate of the glandular epithelium region was noticeable and significant. Conclusion Induction of PCOS by EV could change the proliferation rate in the endo- metrial tissue of the uterus. PMID:28367305
Boomsma, C M; Eijkemans, M J C; Hughes, E G; Visser, G H A; Fauser, B C J M; Macklon, N S
Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.
Connolly, Fiona; Rae, Michael T.; Späth, Katharina; Boswell, Lyndsey; McNeilly, Alan S.; Duncan, W. Colin
Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. PMID:26148093
Motta, Alicia Beatriz
Polycystic Ovary Syndrome (PCOS) is one of the common endocrine diseases that affects women in their reproductive age. PCOS has diverse clinical implications that include reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, cardiovascular diseases) and psychological features (increased anxiety, depression and worsened quality of life). The exact patho-physiology of PCOS is complex and remains largely unclear. The prevalence of PCOS is estimated at 4-18%, depending on diverse factors discussed ahead. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and body weight. During the last decades, obesity and excess weight are major chronic diseases all around the word. Obesity increases some features of PCOS such as hyperandrogenism, hirsutism, infertility and pregnancy complications. Both obesity and insulin resistance increase diabetes mellitus type 2 and cardiovascular diseases. Moreover, obesity impairs insulin resistance and exacerbates reproductive and metabolic features of PCOS. It is well known that obesity is associated with anovulation, pregnancy loss and late pregnancy complications (pre-eclampsia, gestational diabetes). Obesity in PCOS is also linked to failure or delayed response to the various treatments including clomiphene citrate, gonadotropins and laparoscopic ovarian diathermy. It has been reported that, after losing as little as 5 % of initial body weight obese women with PCOS improved spontaneous ovulation rates and spontaneous pregnancy. Therefore, the weight loss prior to conception improves live birth rate in obese women with or without PCOS. The treatment of obesity may include lifestyle therapy (diet and exercise), pharmacological treatment and bariatric surgery. In summary, weight loss is considered the first-line therapy in obese women with PCOS. In the present review, the consequence and
Chen, Mei-Jou; Yang, Wei-Shiung; Yang, Jehn-Hsiahn; Chen, Chi-Ling; Ho, Hong-Nerng; Yang, Yu-Shih
The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: >or=19%) in women with PCOS increased the risk of elevated blood pressure (SBP >or=130 mm Hg and/or DBP >or=85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.
Connolly, Fiona; Rae, Michael T; Späth, Katharina; Boswell, Lyndsey; McNeilly, Alan S; Duncan, W Colin
Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day 102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development.
Vázquez, María Jesús; Romero-Ruiz, Antonio; Tena-Sempere, Manuel
As an essential function for perpetuation of species, reproduction, including puberty onset, is sensitive to the size of body energy stores and the metabolic state of the organism. Accordingly, impaired energy homeostasis, ranging from extreme leanness, such as in anorexia or cachexia, to morbid obesity has an impact on the timing of puberty and is often associated to fertility problems. The neuroendocrine basis for such phenomenon is the close connection between numerous metabolic hormones and nutritional cues with the various elements of the so-called hypothalamic-pituitary-gonadal (HPG) axis. Yet, despite previous fragmentary knowledge, it was only the discovery of the adipose-hormone, leptin, in 1994 what revolutionized our understanding on how metabolic and reproductive systems closely interplay and allowed the definition of the neurohormonal causes of perturbations of puberty and fertility in conditions of impaired body energy homeostasis. In this article, we aim to provide a synoptic view of the mechanisms whereby leptin engages in the regulation of different elements of the HPG axis, with special attention to its effects and mechanisms of action on the different elements of the reproductive brain and its proven direct effects in the gonads. In addition, we will summarize the state-of-the-art regarding the putative roles of leptin during gestation, including its potential function as placental hormone. Finally, comments will be made on the eventual leptin alterations in reproductive disorders, with special attention to the polycystic ovary syndrome (PCOS), a disease in which reproductive, metabolic and neuroendocrine alterations are commonly observed. All in all, we intend to provide an updated account of our knowledge on the physiological roles of leptin in the metabolic regulation of the reproductive axis and its eventual pathophysiological implications in prevalent reproductive disorders, such as PCOS.
Peng, Yingqian; Zhang, Wei; Yang, Ping; Tian, Ye; Su, Shizhen; Zhang, Changming; Chen, Zi-Jiang; Zhao, Han
A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese. We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects. Marker SNPs rs1351592 (2q34, ERBB4), rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50) were genotyped using TaqMan-MGB probe assay. Genotyping analysis showed the allele frequency of rs1351592 in gene ERBB4 was significantly different (P = 1.05E-03) between PCOS cases and control group, and remained significant even after BMI adjustment (Padjusted = 2.09E-04). However, the allele frequencies of the other two risk variants, rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50), were not significantly different in the replication cohort. Our results demonstrate that ERBB4, with the strongest association in European PCOS, also confers risk for PCOS in Han Chinese. PMID:28195137
Benetti-Pinto, Cristina Laguna; Piccolo, Vanessa Berini; Yela, Daniela Angerame; Garmes, Heraldo
Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 - 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.
Diamond, Michael P.; Kruger, Michael; Santoro, Nanette; Zhang, Heping; Casson, Peter; Schlaff, William; Coutifaris, Christos; Brzyski, Robert; Christman, Gregory; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Steinkampf, Michael P.; Gosman, Gabriella G.; Nestler, John E.; Carson, Sandra; Myers, Evan E.; Eisenberg, Esther; Legro, Richard S.
Objective To estimate whether progestin-induced endometrial shedding, prior to ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). Methods A secondary analysis of the data from 626 women with PCOS from the National Institutes of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). Results While ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live birth per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; p<0.001). The difference was more marked when rate was calculated per ovulation (live birth per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; p < .001). Conclusion Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared to anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin prior to ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS. PMID:22525900
Ganie, Mohd Ashraf; Marwaha, Raman Kumar; Dhingra, Atul; Nisar, Sobia; Mani, Kaliavani; Masoodi, Shariq; Chakraborty, Semanti; Rashid, Aafia
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.
Peng, Yingqian; Zhang, Wei; Yang, Ping; Tian, Ye; Su, Shizhen; Zhang, Changming; Chen, Zi-Jiang; Zhao, Han
A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese. We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects. Marker SNPs rs1351592 (2q34, ERBB4), rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50) were genotyped using TaqMan-MGB probe assay. Genotyping analysis showed the allele frequency of rs1351592 in gene ERBB4 was significantly different (P = 1.05E-03) between PCOS cases and control group, and remained significant even after BMI adjustment (Padjusted = 2.09E-04). However, the allele frequencies of the other two risk variants, rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50), were not significantly different in the replication cohort. Our results demonstrate that ERBB4, with the strongest association in European PCOS, also confers risk for PCOS in Han Chinese.
Velija-Asimi, Zelija; Burekovic, Azra; Dujic, Tanja; Dizdarevic-Bostandzic, Amela; Semiz, Sabina
Our aim was to determine the incidence of prediabetes and risk of developing cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS). This prospective, observational study included 148 women with PCOS, without Type 2 diabetes mellitus (T2DM) and CVD present at baseline. In the fasting blood samples, we measured lipids, glucose, and insulin levels during oral glucose tolerance test, levels of C-reactive protein (CRP), steroids, 25-hydroxyvitamin D (25-OHD), prolactin, thyroid-stimulating hormone, and parathyroid hormone. The follow-up period was 3 years. At baseline, prevalent prediabetes was present in 18 (12%) of PCOS cases and it progressed to T2DM in 5 (3%) of the cases. Incident prediabetes during the follow-up was noted in 47 (32%) women or 4.7 per 1000 persons/year. Prediabetes was associated with elevated body mass index (BMI) (odds ratio [OR] = 1.089, confidence interval [CI]: 1.010; 1.174, p = 0.026), high baseline levels of CRP (OR = 3.286, CI: 1.299; 8.312, p = 0.012), homeostatic model assessment - insulin resistance (IR) (OR = 2.628, CI: 1.535; 4.498, p < 0.001), and high lipid accumulation product (LAP) (OR = 1.009, CI: 1.003; 1.016, p = 0.005). Furthermore, prediabetes was associated with low 25-OHD (OR = 0.795, CI: 0.724; 0.880, p ≤ 0.05). In addition, cardiovascular risk in PCOS women with prediabetes was high (hazard ratio = 1.092, CI: 1.036; 1.128, p < 0.001). We showed association of prediabetes with high BMI, IR, markers of inflammation, LAP, and low serum 25-OHD concentration. IR appears to be more relevant than the other predictors of prediabetes risk in this study. PCOS women are considered as a high-risk population for prediabetes.
Spritzer, Poli Mara; Lecke, Sheila Bünecker; Fabris, Vitor Costa; Ziegelmann, Patrícia Klarmann; Amaral, Lívio
Polycystic ovary syndrome (PCOS) is a prevalent condition in women of reproductive age. PCOS is characterized by androgen excess and chronic anovulation and associated with low-grade inflammation and metabolic comorbidities. Some trace elements have been linked to pathophysiological mechanisms of oxidative stress and inflammation in different disorders. Therefore, we conducted a systematic review and meta-analysis of the available evidence regarding trace element concentrations in PCOS. We reviewed MEDLINE and EMBASE in search of case-control, cross-sectional, and cohort studies published until September 2015. Of 183 studies identified, six were selected for systematic review. All used the Rotterdam criteria for the diagnosis of PCOS. Two studies evaluating chromium and one assessing cobalt levels did not observe differences between PCOS and controls. Another study recorded similar nickel and vanadium levels between the groups, but lower selenium concentrations in women with PCOS compared to controls. Four studies were included in the random effects model meta-analysis, for a total of 264 PCOS and 151 control women. Copper levels were found to be higher in women with PCOS than in controls [mean difference 0.12 ppm (95 % CI 0.07; 0.17 ppm); I (2) = 0 %]. Manganese [mean difference 0.04 ppm (95 % CI -0.05; 0.13 ppm); I (2) = 94.4 %] and zinc concentrations [mean difference 0.02 ppm (95 % CI -0.12; 0.16 ppm); I (2) = 92.4 %] were similar between the groups. The present results suggest a relationship between increased copper concentration and PCOS. This systematic review and meta-analysis is registered in PROSPERO under number CRD42016034036.
Salama, Amany Alsayed; Amine, Ezzat Khamis; Salem, Hesham Abd Elfattah; Abd El Fattah, Nesrin Kamal
Background: Polycystic ovary syndrome (PCOS) is of clinical and public health importance, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive, metabolic, and psychological features. Aim: The study was to investigate the effect of anti-inflammatory dietary combo on metabolic, endocrine, inflammatory, and reproductive profiles in overweight and obese women with PCOS. Materials and Methods: A total of 100 nonpregnant, overweight, and obese adult females with PCOS according to the Rotterdam criteria, were screened during the year 2012, and 75 completed the trial. At baseline and study end, fasting blood samples were drawn to measure biological markers, body fat percent (BFP), and visceral fat area (VFA) were assessed by the InBody720 device and anthropometric measurements were done for all participants who were subjected to an anti-inflammatory hypocaloric diet and physical activity for 12 weeks. Results: At study completion, we achieved moderate weight loss of (± 7%) and significant improvements in body composition, hormones and menstrual cyclicity, blood pressure, glucose homeostasis, dyslipidemia, C-reactive protein (CRP), and serum amyloid A (SAA) (surrogate measures of cardiovascular risk (CVR)). This was a clinically relevant weight loss that is associated with a reduced prevalence of type 2 diabetes mellitus (DM2) and metabolic syndrome (MS) in the general population and improved fertility outcomes in PCOS. We achieved 63% regain of menstrual cyclicity and 12% spontaneous pregnancy rate within 12 week. Conclusions: We have explored an additional dietary treatment option with good prognostic metabolic and reproductive responses to weight loss that occur in overweight and obese PCOS. PMID:26258078
Kort, Daniel H; Kostolias, Alessandra; Sullivan, Chantae; Lobo, Roger A
Adipocytokines may alter normal metabolic function and play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). We prospectively evaluated a cohort of obese and non-obese women with PCOS and non-PCOS controls for both novel (chemerin and omentin-1) and established (leptin and adiponectin) adipokines. Compared with age-matched controls, non-obese women with PCOS had decreased serum omentin-1 (191.1 ng/ml versus 269.7 ng/ml, p = 0.0001), while serum chemerin was not significantly altered in women with PCOS (53.95 ng/ml versus 48.61 ng/ml, p = 0.11). The findings were similar in the entire group of women with PCOS. However, in women with PCOS, chemerin correlated with leptin (r = 0.508, p = 0.004), adiponectin (r = -0.36, p = 0.014), and the leptin/adiponectin (L/A) ratio (r = 0.605, p < 0.0001), while there were no such correlations with omentin-1. In women with PCOS, chemerin correlated with BMI (r = 0.317, p = 0.034), abdominal subcutaneous fat (r = 0.451, p = 0.0019), and insulin resistance (HOMA-IR, r = 0.428, p = 0.0034), while omentin-1 did not correlate with any parameter. These data suggest that chemerin although not significantly elevated in women with PCOS correlates with adiposity and insulin resistance, and it is the single best adipokine measured in this regard. Chemerin, through its inflammatory role as a chemo-attractant in adipose tissue, may be an important determinant of insulin resistance in PCOS.
Zeng, Xian-Ling; Zhang, Ya-Fei; Tian, Quan; Xue, Yan; An, Rui-Fang
Abstract Aim: The aim of the study is to evaluate the effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome (PCOS). Methods: We searched electronic databases and bibliographies of relevant papers to identify studies comparing the pregnancy outcomes in the metformin group with those in the placebo or blank control group. Then, we did this meta-analysis based on the PRISMA guidelines. The primary outcomes included early pregnancy loss (EPL), preterm delivery, term delivery, and gestational diabetes mellitus (GDM). Secondary outcomes included pregnancy-induced hypertension (PIH), intrauterine growth restriction (IUGR), fetal malformation, vaginal delivery (VD), cesarean section (CS), and metformin's side effects, such as nausea or gastrointestinal discomfort. Certainly, data about neonatal death and macrosomia were analyzed if data available. Results: Finally, 13 studies including 5 randomized controlled trials (RCT) and 8 cohort studies involving 1606 pregnant women with PCOS were analyzed. The pooled OR of EPL was 0.19 with obvious statistical significance, manifesting that metformin help to lower the rate of EPL (95% CI 0.12–0.28, P < 0.00001). Simultaneously, metformin showed the advantage of reducing the prevalence of preterm delivery (OR 0.37, 95% CI 0.20–0.68, P = 0.002). In addition, metformin could promote term delivery greatly and the pooled OR was 5.23 with sharp statistical difference (95% CI 3.12–8.75, P < 0.00001). Conclusion: Metformin treatment in women with PCOS throughout pregnancy could increase the possibility of term delivery, VD and reduce the risk of EPL, preterm labor, pregnancy complications such as GDM and PIH, with no serious side effects. Moreover, metformin was not teratogenic based on the limited data. So we may recommend metformin treatment for women with PCOS during the whole pregnancy period for it is quite beneficial and safe for both mothers and babies. PMID:27603343
Kiałka, Marta; Milewicz, Tomasz; Sztefko, Krystyna; Rogatko, Iwona; Majewska, Renata
Background Despite the strong preclinical rationale, there are only very few data considering the utility of metformin as a potential pain therapeutic in humans. The aim of this study was to determine the association between metformin therapy and pressure pain threshold (PPT) in lean women with polycystic ovary syndrome (PCOS). We hypothesized that metformin therapy in lean PCOS women increases PPT. Materials and methods Twenty-seven lean PCOS women with free androgen index phenotype >5 and 18 lean healthy controls were enrolled in the study. Fifteen of the PCOS women were randomly assigned to be treated with metformin 1,500 mg daily for 6 months. PPT and plasma β-endorphin levels were measured in all women at the beginning of the study and after 6 months of observation. Results We observed an increase in PPT values measured on deltoid and trapezius muscle in the PCOS with metformin group after 6 months of metformin administration (4.81±0.88 kg/cm2, P<0.001 on deltoid muscle, and 5.71±1.16 kg/cm2 on trapezius muscle). We did not observe any significant changes in PPT values in the PCOS without treatment group and in controls. We did not observe any significant changes in serum β-endorphin levels in any studied groups during the 6-month observation. Conclusion We conclude that metformin therapy increases PPT in lean PCOS women, without affecting plasma β-endorphin concentration. Our results may suggest the potential role of metformin in pain therapy. We propose that larger, randomized studies on metformin impact on pain perception should be performed. PMID:27536069
Jalilian, Anahita; Kiani, Faezeh; Sayehmiri, Fatemeh; Sayehmiri, Kourosh; Khodaee, Zahra; Akbari, Malihe
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the most common cause of infertility due to anovulation. There is no single criterion for the diagnosis of this syndrome. Objective: The purpose of this study was to investigate the prevalence of PCOS and its associated complications in Iranian women using meta-analysis method. Materials and Methods: Prevalence of PCOS was investigated from the SID, Goggle scholar, PubMed, Magiran, Irandoc, and Iranmedex, and weighting of each study was calculated according to sample size and prevalence of the binomial distribution. Data were analyzed using a random-effects model meta-analysis (Random effects model) and the software R and Stata Version 11.2. Results: 30 studies conducted between the years 2006 to 2011 were entered into meta-analysis. The total sample size was 19, 226 women aged between 10-45 years. The prevalence of PCOS based on National institute of child health and human disease of the U.S was, 6.8% (95 % CI: 4.11–8.5), based on Rotterdam was 19.5% (95 % CI: 2.24-8.14), and based on ultrasound was 4.41% (95% CI: 5.68-4.14). Also, the prevalence of hirsutism was estimated to be 13%, acne 26%, androgenic alopecia 9%, menstrual disorders 28%, overweight 21%, obesity 19%, and infertility 8%. Conclusion: The prevalence of PCOS in Iran is not high. However, given the risk of complications such as heart disease - cardiovascular and infertility, prevention of PCOS is important; we suggest that health officials must submit plans for the community in this respect. PMID:26644787
Velija-Asimi, Zelija; Burekovic, Azra; Dujic, Tanja; Dizdarevic-Bostandzic, Amela; Semiz, Sabina
Our aim was to determine the incidence of prediabetes and risk of developing cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS). This prospective, observational study included 148 women with PCOS, without Type 2 diabetes mellitus (T2DM) and CVD present at baseline. In the fasting blood samples, we measured lipids, glucose, and insulin levels during oral glucose tolerance test, levels of C-reactive protein (CRP), steroids, 25-hydroxyvitamin D (25-OHD), prolactin, thyroid-stimulating hormone, and parathyroid hormone. The follow-up period was 3 years. At baseline, prevalent prediabetes was present in 18 (12%) of PCOS cases and it progressed to T2DM in 5 (3%) of the cases. Incident prediabetes during the follow-up was noted in 47 (32%) women or 4.7 per 1000 persons/year. Prediabetes was associated with elevated body mass index (BMI) (odds ratio [OR] = 1.089, confidence interval [CI]: 1.010; 1.174, p = 0.026), high baseline levels of CRP (OR = 3.286, CI: 1.299; 8.312, p = 0.012), homeostatic model assessment - insulin resistance (IR) (OR = 2.628, CI: 1.535; 4.498, p < 0.001), and high lipid accumulation product (LAP) (OR = 1.009, CI: 1.003; 1.016, p = 0.005). Furthermore, prediabetes was associated with low 25-OHD (OR = 0.795, CI: 0.724; 0.880, p ≤ 0.05). In addition, cardiovascular risk in PCOS women with prediabetes was high (hazard ratio = 1.092, CI: 1.036; 1.128, p < 0.001). We showed association of prediabetes with high BMI, IR, markers of inflammation, LAP, and low serum 25-OHD concentration. IR appears to be more relevant than the other predictors of prediabetes risk in this study. PCOS women are considered as a high-risk population for prediabetes. PMID:27648989
Simmonds, Michael J.; Milne, Nikki; Ong, Kee; Brotherton, Emily; McNamee, Antony P.; Horobin, Jarod; Sabapathy, Surendran
Classic features of polycystic ovary syndrome (PCOS) include derangement of metabolic and cardiovascular health, and vascular dysfunction is commonly reported. These comorbidities indicate impaired blood flow; however, other than limited reports of increased plasma viscosity, surprisingly little is known regarding the physical properties of blood in PCOS. We aimed to investigate whether haemorheology was impaired in women with PCOS. We thus measured a comprehensive haemorheological profile, in a case-control design, of lean women with PCOS and age-matched healthy controls. A clinical examination determined similar cardiovascular risk for the two groups. Whole blood and plasma viscosity was measured using a cone-plate viscometer. The magnitude and rate of red blood cell (RBC) aggregation was determined using a light-transmission aggregometer, and the degree of RBC deformability was measured via laser-diffraction ektacytometry. Plasma viscosity was significantly increased in women with PCOS. Blood viscosity was also increased for PCOS at lower-to-moderate shear rates in both native and standardised haematocrit samples. The magnitude of RBC aggregation–a primary determinant of low-shear blood viscosity–was significantly increased in PCOS at native and 0.4 L·L-1 haematocrit. No difference was detected between PCOS and CON groups for RBC deformability measurements. A novel measure indicating the effectiveness of oxygen transport by RBC (i.e., the haematocrit-to-viscosity ratio; HVR) was decreased at all shear rates in women with PCOS. In a group of young and lean women with PCOS with an unremarkable cardiovascular risk profile based on clinical data, significant haemorheological impairment was observed. The degree of haemorheological derangement observed in the present study reflects that of overt chronic disease, and provides an avenue for future therapeutic intervention in PCOS. PMID:27902766
Tasali, Esra; Chapotot, Florian; Leproult, Rachel; Whitmore, Harry
Context: Women with polycystic ovary syndrome (PCOS) are insulin resistant and have a high risk of early-onset diabetes and cardiovascular disease. Obstructive sleep apnea (OSA) has adverse cardiometabolic consequences and is highly prevalent in women with PCOS. We sought to determine whether continuous positive airway pressure (CPAP) treatment of OSA has beneficial effects on cardiometabolic function in PCOS. Methods: Laboratory polysomnography and cardiometabolic measurements including insulin sensitivity and secretion (iv glucose tolerance test); 24-h profiles of plasma catecholamines, cortisol, and leptin; and daytime profiles of blood pressure and cardiac autonomic activity (heart rate variability) were obtained at baseline and again after 8 wk of home CPAP treatment with daily usage monitoring. Results: CPAP treatment modestly improved insulin sensitivity after controlling for body mass index (P = 0.013). The change in insulin sensitivity correlated positively with CPAP use (adjusted P = 0.027) and negatively with body mass index (adjusted P = 0.003). Daytime and nighttime norepinephrine levels were decreased after CPAP (P = 0.002), and the reductions were greater with increased CPAP use (P = 0.03). Epinephrine, cortisol, and leptin levels were not changed significantly. Daytime diastolic blood pressure decreased by an average of 2.3 mm Hg after CPAP (P = 0.035). Cardiac sympathovagal balance was 44% lower (P = 0.007) after CPAP, reflecting a shift toward lower sympathetic activity. Conclusions: In young obese women with PCOS, successful treatment of OSA improves insulin sensitivity, decreases sympathetic output, and reduces diastolic blood pressure. The magnitude of these beneficial effects is modulated by the hours of CPAP use and the degree of obesity. PMID:21123449
Chen, Tsung-Sheng; Chen, Yi-Ting; Liu, Chia-Hsin; Sun, Chi-Ching; Mao, Frank Chiahung
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and one of the most common causes of anovulatory infertility. In addition, insulin resistance is commonly associated with PCOS and contributed to pathophysiology connected to dietary minerals including chromium (Cr), copper (Cu), iron (Fe), and zinc (Zn). The aims of this study were to explore whether PCOS in mice alters levels of these elements and determine if Cr supplementation resolves changes. Twenty-four female BALB/c mice were divided into three groups of eight mice [normal control (NC), PCOS+placebo milk (PP), and PCOS+Cr-containing milk (PCr)]. Each group received a high-fat diet for 4 weeks. Our results show significantly higher levels of dehydroepiandrosterone (DHEA) (p<0.001), fasting glucose (p<0.05), and fasting insulin (p<0.05) in the PP group compared with both NC and PCr group. However, Cr levels were significantly lower in muscle, bone, and serum in the PP group (p<0.05) compared with NC and PCr groups. In liver, bone, and serum, Fe levels were significantly higher in the PP group compared with the NC group (p<0.05). In addition, we found significant correlations between Cu/Zn ratio and fasting insulin in all mice (r=0.61; p=0.002). Given that significant research shows that Cr supplementation improves fasting glucose, fasting insulin, and metal metabolism disorders for PCOS mice, our data suggest that trace element levels can serve as biomarkers to prescribe therapeutic supplementation to maintain a healthy metabolic balance and treat disease conditions.
Ku, Ivy A.; Shah, Sanjiv J.; Daviglus, Martha L.; Schreiner, Pamela J.; Konety, Suma H.; Williams, O. Dale; Siscovick, David; Bibbins-Domingo, Kirsten
Objective: The aim of the study was to determine whether young women with polycystic ovary syndrome (PCOS) have evidence of early structural changes in echocardiographic parameters as a measurement of cardiovascular risk. Methods: We investigated the association of PCOS and echocardiographic parameters in 984 black and white women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort followed prospectively for 20 yr. Women ages 34–46 (Year 16) completed questionnaires recalling symptoms of oligomenorrhea and hirsutism in their 20s and 30s. Serum androgens were obtained at Year 2. Women in their 20s and 30s were classified into four mutually exclusive groups: 1) PCOS; 2) isolated oligomenorrhea (IO); 3) isolated hyperandrogenism (IH); and 4) reference group. Outcome measures were defined as echocardiography data from Year 5. We used multivariable linear regression models to evaluate the association of PCOS and its components with left ventricular (LV) mass index, left atrial (LA) diameter, LV ejection fraction (LVEF), and mitral inflow early wave to late wave ratio. Results: Among 984 participants, 42 women (4.3%) were classified as PCOS, 67 (6.8%) as IO, and 178 (18.0%) as IH. In multivariable linear regression analyses, women with PCOS had a 3.14 g/m2.7 (95% confidence interval, 0.48–5.81) higher LV mass index compared to the reference group (approximately 10% higher). PCOS women also had a 0.11 cm/m (95% confidence interval, 0.02–0.19) larger LA diameter, after adjustment for age and race. Conclusion: PCOS, but not IO or IH, is associated with a higher LV mass index and larger LA diameter in young women, suggestive of early adverse cardiac remodeling. Additional longitudinal studies are needed to evaluate whether this difference persists over time. PMID:23012389
RIBEIRO, VICTOR B.; KOGURE, GISLAINE S.; REIS, ROSANA M.; GASTALDI, ADA C.; DE ARAÚJO, JOÃO E.; MAZON, JOSÉ H.; BORGHI, AUDREY; SOUZA, HUGO C.D.
Polycystic ovary syndrome (PCOS) may present important comorbidities, such as cardiovascular and metabolic diseases, which are often preceded by changes in cardiac autonomic modulation. Different types of physical exercises are frequently indicated for the prevention and treatment of PCOS. However, little is known about the effects of strength training on the metabolic, hormonal, and cardiac autonomic parameters. Therefore, our aim was to investigate the effects of strength training on the autonomic modulation of heart rate variability (HRV) and its relation to endocrine-metabolic parameters in women with PCOS. Fifty-three women were divided into two groups: CONTROL (n=26) and PCOS (n=27). The strength training lasted 4 months, which was divided into mesocycles of 4 weeks each. The training load started with 70% of one repetition maximum (1RM). Blood samples were collected before and after intervention for analysis of fasting insulin and glucose, HOMA-IR, testosterone, androstenedione and testosterone/androstenedione (T/A) ratio. Spectral analysis of HRV was performed to assess cardiac autonomic modulation indexes. The PCOS group presented higher insulin and testosterone levels, T/A ratio, along with increased sympathetic cardiac autonomic modulation before intervention. The training protocol used did not cause any change of endocrine-metabolic parameters in the CONTROL group. Interestingly, in the PCOS group, reduced testosterone levels and T/A ratio. Additionally, strength training did not have an effect on the spectral parameter values of HRV obtained in both groups. Strength training was not able to alter HRV autonomic modulation in women with PCOS, however may reduce testosterone levels and T/A ratio. PMID:27990221
Pasquali, R; Gambineri, A; Pagotto, U
The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.
Moran, Lisa J; Thomson, R L; Buckley, J D; Noakes, M; Clifton, P M; Norman, R J; Brinkworth, G D
Polycystic ovary syndrome (PCOS) is a common condition affecting reproductive-aged women with features including hyperandrogenism and menstrual irregularity frequently treated with hormonal steroidal contraceptives. Women with PCOS appear to have lower bone mineral density (BMD). While steroidal contraceptives may positively affect bone health, their effect on BMD in PCOS is not known. The aim of this study was to assess BMD in women with PCOS according to recent contraceptive use. A cross-sectional analysis of 95 pre-menopausal overweight or obese sedentary women with PCOS [age 29.4 ± 6.4 years, body mass index (BMI) 36.1 ± 5.3 kg/m(2)] who either recently took steroidal contraceptives (ceased 3 months prior) or were not taking steroidal contraceptives was conducted. Clinical outcomes included BMD, anthropometry, insulin, glucose, reproductive hormones, dietary intake and vitamin use. BMD was significantly lower for women who used contraceptives compared to those who did not (mean difference 0.06 g/cm(2) 95 % confidence interval -0.11, -0.02, p = 0.005). In regression models, lower BMD was independently associated with contraceptive use (β = -0.05, 95 % CI -0.094, -0.002, p = 0.042), higher testosterone (β = -0.03, 95 % CI -0.05, -0.0008, p = 0.043) and lower BMI (β = 0.006, 95 % CI 0.002, 0.01, p = 0.007) (r (2) = 0.22, p = 0.001 for entire model). We report for the first time that overweight and obese women with PCOS with recent steroidal contraceptive use had lower BMD in comparison to non-users independent of factors known to contribute to BMD. Whether this observation is directly related to steroidal contraceptive use or other factors requires further investigation.
Brown, Russell E; Wilkinson, Diane A; Imran, Syed A; Caraty, Alain; Wilkinson, Michael
An intact hypothalamic kiss1/kisspeptin/kiss1r complex is a prerequisite for reproductive competence, and kisspeptin treatment could be a practical therapeutic approach to some problems of infertility. One such disorder is polycystic ovarian syndrome (PCOS), a common cause of infertility affecting more than 100 million women. A rodent model of PCOS is the prepubertal female rat treated for a prolonged period with dihydrotestosterone (DHT), which induces many of the metabolic characteristics of the syndrome. We hypothesized that hypothalamic kiss1 mRNA levels, and kisspeptin immunoreactivity (ir), would be abnormal in these rats. Prepubertal female rats were exposed to DHT for 60 days. Rats were killed in two groups: at 26 and 60 days of DHT exposure. Kiss1 mRNA was quantified in hypothalamus, pituitary, ovary and visceral adipose tissue. Separate groups of rats provided brain tissue for immunohistochemical analysis of kisspeptin-ir. At 26 days of DHT exposure, hypothalamic kiss1 mRNA was severely depleted. In contrast DHT had no effect on pituitary kiss1 expression but it significantly increased levels of kiss1 mRNA in fat (+9-fold; p<0.01) and in ovary (+3-fold; p<0.05). At 60days, kiss1 expression had reverted to normal in hypothalamus and ovary but remained elevated in fat (+4-fold; p<0.05). Immunohistochemical analysis revealed that after 26 days of exposure to DHT, kisspeptin-ir was almost completely absent in the arcuate nucleus and a large depletion in kisspeptin +ve fibers was also seen in the paraventricular nucleus, supraoptic nucleus and in the anteroventral periventricular area. At 60 days, despite restored normal levels of kiss1 mRNA, hypothalamic kisspeptin-ir remained depleted in the treated rats. In summary Kiss1 gene expression is differentially affected in various tissues by chronic exposure to dihydrotestosterone in a rat model of polycystic ovary syndrome. In hypothalamus, specifically, kiss1 mRNA, and levels of kisspeptin immunoreactivity, are
Lam, Uyen D P; Lerchbaum, Elisabeth; Schweighofer, Natascha; Trummer, Olivia; Eberhard, Katharina; Genser, Bernd; Pieber, Thomas R; Obermayer-Pietsch, Barbara
Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3'UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5'-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI>25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, p<0.001; 60 min, p=0.009; 120 min, p=0.009) as well as triglyceride (p=0.032) levels. MEP1A is a possible target gene for disease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS.
Mehrabian, Ferdous; Ghasemi-Tehrani, Hatav; Mohamadkhani, Mahboobe; Moeinoddini, Maryam; Karimzadeh, Pooya
Background: Polycystic ovary syndrome (PCOS) is one of the common endocrine disorders in women of reproductive ages. It is associated with a range of disorders, such as dyslipidemia, hypertension, insulin resistance (IR), compensatory hyperinsulinemia, gestational, and type 2 diabetes, and increased risk of cardiovascular morbidity. There are different treatments available for PCOS. The purpose of this study was to determine and compare the effects of metformin, flutamide plus oral contraceptives (OCs), and simvastatin on the metabolic consequences of PCOS. Materials and Methods: This study was a single-blind clinical trial. The subjects were selected from a group of patient with PCOS and metabolic syndrome, who were referred to the midwifery clinic of Al-Zahra Hospital and Beheshti Hospital, Isfahan, Iran. A total of 111 subjects were randomly assigned to three groups: metformin, flutamide plus OCs, and simvastatin groups. The measurements were performed at baseline and after 6 months of therapy. Paired t-test, analysis of variance (ANOVA), and chi-square test were applied in this study. Results: A total of 102 subjects were analyzed in this study, 34 subjects were allotted in each group. The prevalence of IR was statistically different between three groups (P-value = 0.001). After a 6-month course, metformin showed larger reduction in fasting blood sugar (FBS) level (P-value < 0.001). However, except for metformin, two other treatments reduced C-reactive protein (CRP) level significantly (both P-values < 0.001). The level of triglycerides (TGs) decreased considerably in all groups (all P-values < 0.001). Both metformin and simvastatin decreased BMI significantly (both P-values < 0.001). None of the treatments changed high-density lipoprotein (HDL) level (all P-values > 0.05). Conclusion: Metformin performed better in FBS reduction. Simvastatin had better performance in terms of reducing TG level and waist circumference. PMID:27904553
Thomson, R L; Buckley, J D; Brinkworth, G D
Polycystic ovary syndrome (PCOS) is characterized by the presence of polycystic ovaries, menstrual dysfunction, infertility and biochemical and clinical hyperandrogenism and is associated with an increased prevalence of cardiometabolic risk factors and psychological problems. Despite the well-established benefits of exercise training and its recommendation as a cornerstone of PCOS management, few well-controlled randomized studies have been conducted evaluating the benefits of exercise training and specific exercise regimes in women with PCOS. From the limited studies there appears to be a beneficial effect of exercise either alone or in combination with energy restriction has shown to improve fitness, cardiovascular, hormonal, reproductive and psychological outcomes. While the addition of regular exercise to energy restriction appears to only have additional benefits for improving body composition, these greater improvements are likely to have long-term implications. While lifestyle modification including regular exercise appears to be an effective strategy for the management of overweight PCOS women, methodological limitations in the studies limit the generalizability of the findings. Future research with rigorous study designs is needed to determine specific exercise guidelines that will provide the greatest benefit for these women.
Fulghesu, A M; Ciampelli, M; Belosi, C; Apa, R; Guido, M; Caruso, A; Mancuso, S; Lanzone, A
The aim of the present study was to analyze the opioid influence on LH pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the effectiveness of a long-term opioid antagonist (naltrexone) treatment in improving the pulsatile GnRH therapy which is successful in this syndrome. Ten obese women affected by PCOS participated in the study. Patients were hospitalized during the early follicular phase and underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since pregnancies did not occurr in any patient, after spontaneous or progestin-induced menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally for 8 weeks and during treatment repeated the basal protocol study and the ovulation induction cycle with the same modalities. The naltrexone treatment significantly reduced the insulin response to OGTT and the LH response to GnRH bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning the ovulation induction by pulsatile GnRH, naltrexone treatment was able to improve, although not significantly, the ovulation rate (60% pre-treatment vs 90% post-treatment). Furthermore, the maximum diameter of the dominant follicle and the pre-ovulatory estradiol concentration were higher after long-term opioid blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post-treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs 986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile GnRH co-treatment two pregnancies occurred. In conclusion, our data show that naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian responsiveness to ovulation induction in obese PCOS patients when compared to pulsatile GnRH alone. This action seems to be related to
Sun, Xianchang; Wu, Xingguo; Duan, Yunmin; Liu, Guanghai; Yu, Xinyan; Zhang, Wenjuan
Backgriond Polycystic ovary syndrome (PCOS) is a complex disease that has both genetic and environmental components. Adiponectin plays an important role in the regulation of insulin sensitivity and insulin resistance (IR) in PCOS. The aim of this study was to determine 2 single-nucleotide polymorphisms (SNPs) variants (rs12495941 and rs17300539) of the adiponectin gene (ADIPOQ) in polycystic ovary syndrome (PCOS) families. Material/Methods We recruited 197 PCOS probands, their biological parents, and 192 controls. Anthropometric variables, including hip circumference (HC) and waist circumference (WC), were measured in all subjects during their first visit to the outpatient department. Serum T, FBG, FINS, TC, TG, LDL, and HDL levels were measured. PCOS patients were divided into 2 groups based on BMI: group A (BMI <25 kg/m2) and group B (BMI ≥25 kg/m2). Parents of PCOS were accordingly categorized into group C and group D (fathers), and group E and group F (mothers). The associations among ADIPOQ rs12495941, rs17300539, and PCOS were analyzed using the transmission disequilibrium test (TDT). Results A significant association was found between SNP rs17300539 and PCOS in our Chinese population. The levels of TG and FINS and the genotype frequencies of rs17300539 are significantly different between overweight and lean PCOS. No significant association was detected for rs12495941. Conclusions TDT confirms that rs17300539 of ADIPOQ is strongly associated with the risk of PCOS in a Chinese Han population, but rs12495941 of ADIPOQ is not associated with the occurrence of PCOS. PMID:28060790
Pau, Cindy T.; Mosbruger, Tim; Saxena, Richa; Welt, Corrine K.
Genome-wide association studies and replication analyses have identified (n = 5) or replicated (n = 10) DNA variants associated with risk for polycystic ovary syndrome (PCOS) in European women. However, the causal gene and underlying mechanism for PCOS risk at these loci have not been determined. We hypothesized that analysis of phenotype, gene expression and metformin response as a function of genotype would identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci. To test the hypothesis, subjects with PCOS (n = 427) diagnosed according to the NIH criteria (< 9 menses per year and clinical or biochemical hyperandrogenism) and controls (n = 407) with extensive phenotyping were studied. A subset of subjects (n = 38) underwent a subcutaneous adipose tissue biopsy for RNA sequencing and were subsequently treated with metformin for 12 weeks with standardized outcomes measured. Data were analyzed according to genotype at PCOS risk loci and adjusted for the false discovery rate. A gene variant in the THADA locus was associated with response to metformin and metformin was a predicted upstream regulator at the same locus. Genotype at the FSHB locus was associated with LH levels. Genes near the PCOS risk loci demonstrated differences in expression as a function of genotype in adipose including BLK and NEIL2 (GATA4 locus), GLIPR1 and PHLDA1 (KRR1 locus). Based on the phenotypes, expression quantitative trait loci (eQTL), and upstream regulatory and pathway analyses we hypothesize that there are PCOS subtypes. FSHB, FHSR and LHR loci may influence PCOS risk based on their relationship to gonadotropin levels. The THADA, GATA4, ERBB4, SUMO1P1, KRR1 and RAB5B loci appear to confer risk through metabolic mechanisms. The IRF1, SUMO1P1 and KRR1 loci may confer PCOS risk in development. The TOX3 and GATA4 loci appear to be involved in inflammation and its consequences. The data suggest potential PCOS subtypes and point to
Barr, Suzanne; Reeves, Sue; Sharp, Kay; Jeanes, Yvonne M
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5% to 10% of women worldwide. Approximately half of women with PCOS are lean, yet may still present with central obesity and metabolic disturbances. Low-glycemic index (GI) dietary intervention studies have demonstrated improvements in insulin sensitivity in insulin-resistant populations; however, there is little evidence of this effect in women with PCOS. This research aimed to determine the efficacy of an isocaloric low-GI dietary intervention on insulin sensitivity, independent of weight change, in women with PCOS. A nonrandomized 12-week low-GI dietary intervention, preceded by a 12-week habitual diet control phase and proceeded by a 12-week follow-up phase was conducted. Dietary intake, body composition, and metabolic risk markers were determined at baseline, after completion of the habitual diet control phase, and after the low-GI dietary intervention. Twenty-six participants were recruited at baseline, 22 commenced and 21 participants completed the low-GI dietary intervention phase. The primary outcome was change in insulin sensitivity. Secondary outcomes included assessment of changes to lipids, body composition, and estimated macronutrient intake. Repeated measures analysis of variance with Bonferroni correction were used to detect changes to outcomes across study timepoints. Twenty-one women with PCOS with mean (± standard deviation) age of 32.1±6.7 years completed the 12-week low-GI dietary intervention. As expected, no significant changes occurred during the 12-week habitual diet control phase. However, during the dietary intervention phase, dietary GI decreased from 54.5±3.5 to 48.6±5.1 (P<0.001) with a concurrent small reduction in saturated fat intake (12.4%±3% to 11.7%±3% contribution from energy, P=0.03), despite no specific recommendations to modify fat intake. Measures of insulin sensitivity and nonesterified fatty acid improved after intervention (P=0.03 and P=0
Dodson, William C.; Kris-Etherton, Penny M.; Kunselman, Allen R.; Stetter, Christy M.; Williams, Nancy I.; Gnatuk, Carol L.; Estes, Stephanie J.; Fleming, Jennifer; Allison, Kelly C.; Sarwer, David B.; Coutifaris, Christos; Dokras, Anuja
Context: Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit. Objective: This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS. Design, Setting, and Participants: This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18–40 y and body mass index 27–42 kg/m2. Intervention: Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) (“OCP”); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss (“Lifestyle”); or 3) combined treatment with both OCP and lifestyle modification (“Combined”). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery. Main Outcome Measures: Weight, ovulation, and live birth were measured. Results: We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, −6.2%; 95% confidence interval (CI), −7.4–−5.0; and Combined (mean weight loss, −6.4%; 95% CI, −7.6–−5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42–4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95
Nylander, Malin; Frøssing, Signe; Kistorp, Caroline; Faber, Jens; Skouby, Sven O
Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulin-resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0-7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32-31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01-0.25, P < 0.05) and 0.38 min (95% CI 0.09-0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0-23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI -4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.
Jeanes, Y M; Reeves, S; Gibson, E L; Piggott, C; May, V A; Hart, K H
Polycystic Ovary Syndrome (PCOS), the most common endocrine condition in women, is often anecdotally associated with binge eating behaviours and food cravings; however there is a paucity of research. This study aimed to report the prevalence of binge eating and food cravings and their relation to obesity risk in women with PCOS. Participants completed an online survey including the Bulimia Investigatory Test, Edinburgh, Food Cravings-Trait Questionnaire and the Three Factor Eating Questionnaire revised-18. The study included obese (n = 340), overweight (n = 70) and lean (n = 45) women with PCOS and lean healthy women (n = 40). Sixty percent of obese women with PCOS were categorised with binge-eating behaviour, with 39% presenting with clinically significant behaviour. Obese women with PCOS presented with high mean food cravings-trait scores (131.6 ± 28.9) that were significantly greater compared with lean (114.0 ± 34.9) and overweight women with PCOS (120.1 ± 29.5; p < 0.001). Multiple regression exploring relations between eating styles and adiposity explained 57% of the variance in binge eating symptom scores in women with PCOS (F = 130.4; p < 0.001, n = 463): significant predictors were food cravings total score (beta = 0.53; p < 0.001), emotional eating score (beta = 0.18; p < 0.001), body mass index (beta = 0.11; p < 0.001) and uncontrolled eating score (beta = 0.009; p = 0.02). Compared with lean healthy women, lean women with PCOS exhibited significantly higher binge eating symptom scores (10.9 ± 7.8 versus 7.4 ± 6.0; p < 0.05), though similar total food craving scores (114.0 ± 34.9 versus 105.6 ± 26.6: NS). This study is the largest, to date, to robustly report that a high proportion of women with PCOS exhibit binge eating behaviours. We recommend screening women with PCOS for binge eating behaviours to help inform the choice of weight management approach for this clinical population.
Yilmaz, S A; Kebapcilar, A; Koplay, M; Kerimoglu, O S; Pekin, A T; Gencoglu, B; Dogan, N U; Celik, C
This study explores the relationship between clinical cardiovascular risk factors and clinical androgen excess, with direct comparison to radial artery intima media thickness (rIMT). rIMT of 91 patients with polycystic ovary syndrome (PCOS) were compared with 72 healthy women. Patients were divided into three groups with regard to body mass index (BMI). Group1 = 56 women (31 controls and 25 PCOS) with low BMI(18-22.49 kg/m(2)), Group2 = 36 women (15 controls and 21 PCOS) with normal BMI (22.5-24.99 kg/m(2)) and Group3 = 71 women (26 controls and 45 PCOS) with high BMI (25-30 kg/m(2)). rIMT was significantly higher in patients with PCOS (p = 0.007). rIMT was significantly higher group1 and group3 in patients with PCOS compared to controls (p = 0.007 and p = 0.042, respectively). There was a significant positive association between rIMT levels and fT in women with PCOS in group1 (r = 0.24, p = 0.04). rIMT levels correlated to fT levels in women with PCOS in group3 (r = 0.32, p = 0.03). Modified Ferriman-Gallwey (mFG) scores demonstrated a positive association with free testosterone, total testosterone, free androgen index, waist circumference (WC), LH levels, insulin levels, Homeostasis Model Assessment index(HOMA-IR), rIMT and a negative correlation with sex hormone binding globulin in group1 and group2. mFG scores demonstrated a positive association with free testosterone (r = 0.33, p = 0.029) in group3, but no association was found between mFG and WC, HOMA-IR in group3. Our findings indicate that clinical androgen excess may be associated with cardiovascular disease in patients with PCOS.
Kauffman, Alexander S; Thackray, Varykina G; Ryan, Genevieve E; Tolson, Kristen P; Glidewell-Kenney, Christine A; Semaan, Sheila J; Poling, Matthew C; Iwata, Nahoko; Breen, Kellie M; Duleba, Antoni J; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J; Mellon, Pamela L
Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition.
Kauffman, Alexander S.; Thackray, Varykina G.; Ryan, Genevieve E.; Tolson, Kristen P.; Glidewell-Kenney, Christine A.; Semaan, Sheila J.; Poling, Matthew C.; Iwata, Nahoko; Breen, Kellie M.; Duleba, Antoni J.; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J.; Mellon, Pamela L.
Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175
Jiang, Shi-Wen; Xu, Siliang; Chen, Haibin; Liu, Xiaoqiang; Tang, Zuoqing; Cui, Yugui; Liu, Jiayin
SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers. Recent studies indicated that through interaction with PP2A, SET may upregulate androgen biosynthesis and contribute to hyperandrogenism in polycystic ovary syndrome (PCOS) patients. This review article summarizes data concerning the SET expression in ovaries from PCOS and normal women, and analyzes the role/regulatory mechanism of SET for androgen biosynthesis in PCOS, as well as the significance of this action in the development of PCOS. The potential value of SET-triggered pathway as a therapeutic target and the application of anti-SET reagents for treating hyperandrogenism in PCOS patients are also discussed.
Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Iwasa, Takeshi; Munkhzaya, Munkhsaikhan; Yanagihara, Rie; Tokui, Takako; Yano, Kiyohito; Mayila, Yiliyasi; Kato, Takeshi; Kuwahara, Akira; Matsui, Sumika; Irahara, Minoru
Hypersecretion of luteinizing hormone (LH) is a common endocrinological finding of polycystic ovary syndrome (PCOS). This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of gonadotropin-releasing hormone (GnRH). We evaluated the relationship between the hypothalamic-pituitary-gonadal axis (HPG axis) and kisspeptin using a rat model of PCOS induced by letrozole. Letrozole pellets (0.4 mg/day) and control pellets were placed subcutaneously onto the backs of 3-week-old female Wistar rats. Body weight, vaginal opening and vaginal smear were checked daily. Blood and tissues of ovary, uterus and brain were collected at 12-weeks of age. An hypothalamic block was cut into anterior and posterior blocks, which included the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), respectively, in order to estimate hypothalamic kisspeptin expression in each area. The letrozole group showed a similar phenotype to human PCOS such as heavier body weight, heavier ovary, persistent anovulatory state, multiple enlarged follicles with no corpus luteum and higher LH and testosterone (T) levels compared to the control group. Kisspeptin mRNA expression in the posterior hypothalamic block including ARC was higher in the letrozole group than in the control group although its expression in the anterior hypothalamic block was similar between groups. These results suggest that enhanced KNDy neuron activity in ARC contributes to hypersecretion of LH in PCOS and might be a therapeutic target to rescue ovulatory disorder of PCOS in the future.
Lecke, S B; Morsch, D M; Spritzer, P M
We reviewed emerging evidence linking serum levels and adipose tissue expression of leptin and adiponectin in women with polycystic ovary syndrome (PCOS). Previous data obtained by our group from a sample of overweight/obese PCOS women and a control sample of normal weight controls, both stratified by BMI, were reanalyzed. Circulating levels of leptin and adiponectin were determined by commercially available enzyme-linked immunosorbent assays. Adipose tissue total RNA was reserve-transcripted into complementary DNA samples, which were used as templates for quantitative real-time PCR amplification. Positive correlations were found between serum and mRNA levels for both leptin (r = 0.321; P = 0.005) and adiponectin (r = 0.266; P = 0.024). Determination of leptin and adiponectin serum levels could serve as an indirect method to assess adipocyte production, since leptin and adiponectin are predominantly produced by subcutaneous adipocytes in women.
Dumont, Agathe; Robin, Geoffroy; Catteau-Jonard, Sophie; Dewailly, Didier
Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation and hyperandrogenism in young women. Excessive ovarian production of Anti-Müllerian Hormone, secreted by growing follicles in excess, is now considered as an important feature of PCOS. The aim of this review is first to update the current knowledge about the role of AMH in the pathophysiology of PCOS. Then, this review will discuss the improvement that serum AMH assay brings in the diagnosis of PCOS. Last, this review will explain the utility of serum AMH assay in the management of infertility in women with PCOS and its utility as a marker of treatment efficiency on PCOS symptoms. It must be emphasized however that the lack of an international standard for the serum AMH assay, mainly because of technical issues, makes it difficult to define consensual thresholds, and thus impairs the widespread use of this new ovarian marker. Hopefully, this should soon improve.
Hanzu, Felicia A; Radian, Serban; Attaoua, Redha; Ait-El-Mkadem, Samira; Fica, Simona; Gheorghiu, Monica; Coculescu, Mihai; Grigorescu, Florin
To assess the role of the insulin receptor gene in polycystic ovary syndrome (PCOS) we performed a case-control study in a female population (n=226) from Central Europe by examining the genetic associations of single nucleotide polymorphisms (rs8107575, rs2245648, rs2245649, rs2963, rs2245655, and rs2962) and inferred haplotypes around exon 9 of this gene. The ancestral T allele of single nucleotide polymorphism rs2963 or the corresponding haplotype (GGTC-C) showed association with PCOS with odds ratio 2.99, 95% confidence interval 1.4-6.3, independent of obesity but related to the presence of Acanthosis nigricans and insulin resistance, metabolic syndrome, or hyperandrogeny, thus providing a frame for future fine mapping of the susceptibility loci in PCOS.
Joseph, Shaini; Barai, Ram Shankar; Bhujbalrao, Rasika; Idicula-Thomas, Susan
Polycystic ovary syndrome (PCOS) is one of the major causes of female subfertility worldwide and ≈ 7-10% of women in reproductive age are affected by it. The affected individuals exhibit varying types and levels of comorbid conditions, along with the classical PCOS symptoms. Extensive studies on PCOS across diverse ethnic populations have resulted in a plethora of information on dysregulated genes, gene polymorphisms and diseases linked to PCOS. However, efforts have not been taken to collate and link these data. Our group, for the first time, has compiled PCOS-related information available through scientific literature; cross-linked it with molecular, biochemical and clinical databases and presented it as a user-friendly, web-based online knowledgebase for the benefit of the scientific and clinical community. Manually curated information on associated genes, single nucleotide polymorphisms, diseases, gene ontology terms and pathways along with supporting reference literature has been collated and included in PCOSKB (http://pcoskb.bicnirrh.res.in).
Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting women of fertile age. It is associated with several risk factors and long-term health consequences. Chronic anovulation combined with relative estrogen excess and consequent prolonged stimulatory effect on the endometrium can lead to the pathogenesis of hormonal dependant carcinoma. PCOS is thus traditionally reported to be associated with increased risk of endometrial, as well as breast and ovarian cancers. This article provides a critical literature review of the relationship between PCOS and the incidence of estrogen-dependant gynecological tumours, and it then discusses whether the commonly cited risk factor association can be substantiated by high quality studies which comply with the requirements of "evidence-based medicine."
Background There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups. Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS. PMID:22276997
Vargas, M Luisa; Almario, Rogelio U; Buchan, Wendy; Kim, Kyoungmi; Karakas, Sidika E
The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) were considered, fish oil and flaxseed oil lowered serum triglyceride (P = .0154 and P = .0176, respectively). Fish oil increased glucose at 120 minutes of OGTT (P = .0355), decreased the Matsuda index (P = .0378), and tended to decrease acu