endothelin-1 and Polycystic-Ovary-Syndrome

Polycystic ovary syndrome (PCOS) is a good example of obesity-related cardiovascular complication affecting young women. PCOS is not only considered a reproductive problem but rather represents a complex endocrine, multifaceted syndrome with important health implications. Several evidences suggest an increased cardiovascular risk of cardiovascular disease associated with this syndrome, characterized by an impairment of heart structure and function, endothelial dysfunction and lipid abnormalities. All these features, probably linked to insulin-resistance, are often present in obese PCOS patients. Cardiovascular abnormalities represent important long-term sequelae of PCOS that need further investigations.

Topics: Biomarkers; Cardiovascular Diseases; Endothelin-1; Female; Humans; Hypertrophy, Left Ventricular; Insulin Resistance; Obesity; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Risk Assessment; Risk Factors

The aim of the present paper is to analyze recent literature concerning the incidence of cardiovascular complications in women suffering from polycystic ovary syndrome (PCOS). The study takes into consideration all the studies that have been published to date in the international literature in order to clarify whether or not PCOS is able to determine an early onset or whether it is responsible for a higher global incidence of cardiovascular complications in adult age. The main difficulty lies in the absence of prospective studies owing to the long period of time existing between the diagnosis of PCOS and cardiovascular disease which notoriously has a long latency period. Much attention has been paid in the literature, on the other hand, to the analysis of the incidence of cardiovascular risk factors in women suffering from PCOS. Although epidemiological studies have not evidenced an increased incidence of death from cardiovascular events in women suffering from PCOS, the above conclusions might well be invalidated by a patient selection bias, by obsolete diagnostic criteria or by medical or surgical therapies that could influence the outcome of the disease and which are not considered as a confusion factor. Undoubtedly, all the data available up to the present suggest that PCOS possesses the intrinsic conditions that lead to an increased incidence of factors predisposing to cardiovascular diseases. Future longitudinal studies of a prospective nature might be useful for understanding whether the higher incidence of predisposing factors might also lead to greater expectation of cardiovascular events or whether medical therapies or other factors (improvement in endocrine symptomatology with the menopause?) may prevent the increase in the expected incidence of these events.

Topics: Biomarkers; Blood Coagulation Disorders; Cardiovascular Diseases; Carotid Stenosis; Endothelin-1; Endothelium, Vascular; Female; Humans; Hyperlipidemias; Hypertension; Incidence; Menstrual Cycle; Myocardial Ischemia; Polycystic Ovary Syndrome; Risk Factors

Polycystic ovary syndrome (PCOS) is a complex syndrome with cardiovascular risk factors, including obesity and insulin resistance. PCOS is also associated with high androgens, increases the risk of cardiovascular dysfunction in women. Due to the complexity of PCOS, had it has been challenging to isolate specific causes of the cardiovascular dysfunction. Our measure of cardiovascular dysfunction (endothelial dysfunction) was most profound in lean women with PCOS. The endothelin-1-induced vasodilation in these PCOS subject, was dependent on the ET. Endothelin-1 (ET-1) is an indicator of endothelial injury and dysfunction and is elevated in women with androgen excess polycystic ovary syndrome (AE-PCOS). The endothelin B receptor (ET

Topics: Adult; Androgens; Cardiovascular Diseases; Dihydrotestosterone; Endothelin-1; Endothelium, Vascular; Estrogens; Ethinyl Estradiol; Female; Glucose Tolerance Test; Humans; Microvessels; Nitric Oxide; Obesity; Polycystic Ovary Syndrome; Receptor, Endothelin B; Skin; Vascular Endothelial Growth Factor A; Vasodilation; Young Adult

The present study was designed in order to: (a) compare ET-1 and ADMA levels, between women with PCOS (n=106) and healthy controls (n=30); (b) determine the effects of treatment with estrogens and anti-androgens on the hormonal features of PCOS, insulin resistance, ET-1 and ADMA levels. Women with PCOS were randomized in five therapeutic protocols: (I) 17beta-estradiol+cyproterone acetate 50mg; (II) conjugated estrogen+CA 50 mg; (III) ethinyl estradiole+CA 2mg; (IV) EE+CA 52 mg; (V) EE+desogestrel. In all women, gonadotropin, PRL, androgen, SHBG, insulin, glucose, ET-1 and ADMA levels were determined; in women with PCOS, testosterone, SHBG, ET-1 and ADMA levels were measured again after 3, 6, 12 months of treatment and insulin and glucose levels after 12 months. ET-1 and ADMA concentrations were higher in women with PCOS, and they were positively correlated with each other. ADMA levels were decreased and IR was increased with treatment. Treatment with synthetic estrogens (EE) resulted in a more pronounced increase in SHBG and a more pronounced decrease in FAI, compared to natural estrogens. Conclusively, PCOS is associated with endothelial dysfunction, which is ameliorated by the administration of estrogens and anti-androgens, independent of IR.

Topics: Adult; Androgen Antagonists; Arginine; Cyproterone Acetate; Desogestrel; Drug Therapy, Combination; Endothelin-1; Estradiol; Estrogens; Estrogens, Conjugated (USP); Ethinyl Estradiol; Female; Hormones; Humans; Insulin Resistance; Polycystic Ovary Syndrome

The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters.. Descriptive clinical trial.. Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels.. FMD was impaired in the PCOS group when compared with controls (3.24+/-0.71% vs 8.81+/-1.07% respectively, P<0.0001), but this difference normalized after metformin treatment (PCOS(post-metformin) vs controls: 8.17+/-1.26 vs 8.81+/-1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 3.24+/-0.71 vs 8.17+/-1.26%, P=0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23+/-0.50 vs 4.99+/-0.69 fmol/l, P=0.01), they improved significantly after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 7.23+/-0.50 vs 3.57+/-0.60 fmol/l, P<0.0001) and their difference compared with the control group was reversed (PCOS(post-metformin) vs controls: 3.57+/-0.60 vs 4.99+/-0.69 fmol/l, P=0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin.. PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Topics: Adult; Brachial Artery; Endothelin-1; Endothelium, Vascular; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Polycystic Ovary Syndrome; Testosterone; Vasodilation

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance (IR). MicroRNAs (miRNAs) are small noncoding RNA associated with ovarian follicle development and female fertility. The objective of this study was to investigate the role of miRNA- 320 and its target gene endothelin-1 (ET-1) as a noninvasive biomarker of PCOS and to evaluate its possible relationship with IR as well as clinic-morphological features of PCOS.. Case-control study enrolled 60 patients with PCOS and 40 control group. We subdivided our PCOS women according to homeostasis model assessments of insulin resistance (HOMA-IR) to PCOS women with and without IR.ET-1 levels were measured by ELISA. We estimated the serum expression level of miRNA- 320 by real-time polymerase chain reaction.. Our results revealed that serum miR-320 expression level was lower in PCOS patients compared to controls, in particular, PCOS women with IR. Moreover, it was negatively correlated to its target gene; ET-I as well as fasting serum insulin (FSI), HOMA-IR, PCOS phenotype; hirsutism score, ovarian volume and antral follicle count (AFC). In the PCOS group, linear regression analysis revealed that only hirsutism and HOMA-IR was the main predictor of expression levels of miRNA - 320 among other clinical and laboratory biomarkers of PCOS. The sensitivity and specificity of serum miR-320 expression levels in diagnosis PCOS was 80, and 97.5% respectively.. The Expression serum levels of miR-320 were lower in PCOS compared to control and it could be a noninvasive diagnostic biomarker of PCOS.

Topics: Adult; Case-Control Studies; Endothelin-1; Female; Humans; MicroRNAs; Polycystic Ovary Syndrome

Although inflammation is clearly associated with obesity, diabetes, and insulin resistance, the role of chronic inflammation in the etiology of polycystic ovary syndrome (PCOS) is unclear.. To determine whether chronic inflammation plays a causal role in the etiology of PCOS, we tested for an association between PCOS and genetic markers mapping to 80 members of the inflammatory pathway.. This was a case-control association study.. The setting was an academic medical center.. A total of 905 index case patients with PCOS and 955 control women (108 intensively phenotyped subjects with normal androgen levels and regular menses and 847 minimally phenotyped subjects with regular menses and no history of PCOS).. Subjects were genotyped at single nucleotide polymorphisms mapping to 80 inflammatory genes. Logistic regression was used to test for an association between 822 single nucleotide polymorphisms and PCOS after adjustment for population stratification, body mass index, and/or age. In the index patients, we also tested for association with 11 quantitative traits (body mass index and testosterone, fasting insulin, fasting glucose, 2-hour postchallenge glucose, LH, FSH, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels).. The evidence for an association with PCOS and with 11 quantitative traits was investigated.. Nominally significant evidence for an association was observed with MAP3K7, IKBKG, TNFRS11A, AKT2, IL6R, and IRF1, but no results remained statistically significant after adjustment for multiple testing.. Genetic variation in the inflammatory pathway is not a major contributor to the etiology of PCOS or related quantitative traits in women with PCOS.

Topics: Case-Control Studies; Cholesterol, HDL; Endothelin-1; Female; Gene Frequency; Glucose Tolerance Test; Humans; Inflammation; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Signal Transduction

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, which is considered not only a reproductive disease but also a metabolic disorder associated with long-term health risks. The aim of this study was to assess the effects of metformin on insulin resistance, oxidant-antioxidant status, endothelial dysfunction, lipid metabolism and their contribution to the risks of cardiovascular disease in women with PCOS. Fifteen women with PCOS and 17 healthy women were included in this case-control study. Nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), Apo A1, Apo B, small, dense LDL cholesterol (sdLDL-C), lipid levels and paraoxonase 1 (PON1) activity were measured in serum/plasma obtained from study groups. Insulin resistance (HOMA index - Homeostasis Model Assessment) and serum sex hormone profiles were also evaluated. Significantly decreased NO levels and PON1 activities, but increased MDA, ET-1 and sdLDL-C were found in PCOS patients compared to those of controls. Serum MDA, ET-1, HOMA and sdLDL-C levels decreased and PON1 activity and NO levels increased significantly after the metformin treatment. There was a positive correlation between MDA and free testosterone (fT), ET-1 and fT; and a negative correlation between PON1 activity and fT. Insulin resistance, dyslipidemia, endothelial dysfunction and oxidative stress might contribute to the excess risk of cardiovascular disease reported in PCOS. Metformin seemed to decrease oxidative stress and improve insulin resistance, dyslipidemia and endothelial dysfunction in PCOS patients.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Aryldialkylphosphatase; Case-Control Studies; Cholesterol, LDL; Endothelin-1; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hypoglycemic Agents; Insulin Resistance; Lipid Metabolism; Luteinizing Hormone; Malondialdehyde; Metformin; Nitric Oxide; Oxidative Stress; Polycystic Ovary Syndrome; Progesterone; Young Adult

The aim of this study was to assess relationship of insulin resistance, oxidant-antioxidant status, endothelial dysfunction, lipid metabolism, and their contribution to the risks of cardiovascular disease in women with polycystic ovary syndrome (PCOS). Forty-five women with PCOS and 17 healthy women were included in this study. Nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), Apo A1, Apo B, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride, small, dense LDL cholesterol (sdLDL-C), large buoyant LDL cholesterol (LbLDL-C) levels, and paraoxonase 1 (PON1) activity were measured in serum/plasma obtained from study groups. Insulin resistance [homeostasis model assessment (HOMA) index] and serum sex hormone binding globulin (SHBG), total testosterone (tT), free testosterone (fT), androstenedione, and dehydroepiandrosteronsulfate (DHEAS) levels were also evaluated. Significantly decreased SHBG, NO, HDL-C levels, and PON1 activities, but increased tT, fT, androstenedione, DHEAS, HOMA index, MDA, ET-1, LDL-C, sdLDL-C, and LbLDL-C values were found in PCOS patients compared with those of controls. There was a positive correlation between MDA and fT levels; and a negative correlation between PON1 activity and fT. Our data show that insulin resistance, dyslipidemia, endothelial dysfunction, and oxidative stress might contribute to the excess risk of cardiovascular disease reported in PCOS patients.

Topics: Adolescent; Apolipoprotein A-I; Apolipoproteins B; Aryldialkylphosphatase; Cardiovascular Diseases; Dyslipidemias; Endothelin-1; Endothelium, Vascular; Female; Humans; Insulin Resistance; Lipoproteins, LDL; Malondialdehyde; Nitric Oxide; Oxidative Stress; Polycystic Ovary Syndrome; Risk Factors; Testosterone; Turkey; Young Adult

To examine the levels of endothelin system components in granulosa lutein cells (GLCs) of women with PCOS and compare them to normally ovulating women undergoing In Vitro Fertilization (IVF). Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. Endothelins are locally produced by endothelial and granulosa cells of the preovulatory follicle. Abnormal expression or production of endothelins may be a contributing factor in PCOS pathogenesis.. Follicular aspirates containing GLCs were obtained from PCOS and normally ovulating patients undergoing oocyte retrieval during the IVF cycle. RNA was extracted and endothelin system components were quantified using real-time PCR. GLCs were cultured in basal media for 7 days, and then challenged with various luteinizing agents (luteinizing hormone, hCG, or forskolin) for 24 h.. In GLCs from women with PCOS, Endothelin-1 mRNA expression was elevated (2.2-fold) as compared with normally ovulating women, whereas endothelin-2 mRNA was reduced (1.8-fold). ET receptors and endothelin-converting enzyme showed the same expression levels in the two groups. In vitro modeling showed that although the steroidogenic response was preserved in GLC, endothelin expression levels were not exhibited in vitro in their original pattern.. Dysregulation of ovarian endothelin expression may induce a pathologic ovulation pattern characteristic of PCOS.

Topics: Adult; Aspartic Acid Endopeptidases; Case-Control Studies; Chorionic Gonadotropin; Colforsin; Endothelin-1; Endothelin-2; Endothelin-Converting Enzymes; Female; Fertilization in Vitro; Gene Expression Regulation; Humans; Luteal Cells; Luteinizing Hormone; Metalloendopeptidases; Oocyte Retrieval; Polycystic Ovary Syndrome; Polymerase Chain Reaction; Receptors, Endothelin; RNA, Messenger; Time Factors; Young Adult

The increased incidence of cardiovascular disease in women with polycystic ovary syndrome (PCOS) has prompted researchers to look for indicators of early atherosclerotic changes in these patients. One of the earliest stages of atherogenesis is endothelial cell dysfunction. The aim of this study was to assess the levels of selected plasma markers of endothelial injury [E-selectin, endothelin-1 (ET-1) and von Willebrand Factor antigen (vWF:Ag)] in PCOS women before and after six months of treatment.. 32 patients with PCOS aged 18-36 years (mean age 25.16 ± 5.80) were included in the study. The control group consisted of 20 healthy women matched for age and body mass. The levels of ET-1, vWF:Ag, E-selectin, fasting glucose, insulin, total cholesterol, HDL and LDL-cholesterol and triglycerides were assessed. In the PCOS group, all these tests were repeated after six months of treatment.. The study showed higher levels of vWF:Ag (p = 0.043), E selectin (p = 0.028), insulin (p = 0.044), glucose (p = 0.036) and LDL (p = 0.006) in PCOS patients versus healthy women. A positive correlation was demonstrated between E selectin and glucose (p = 0.0001), triglycerides (p = 0.014) and uric acid (p = 0.008). vWF:Ag levels showed a positive correlation with glucose (p = 0.04) and triglycerides (p = 0.036). A positive correlation was also found between ET-1 and total cholesterol levels (p = 0.012) in PCOS women. After treatment, there was a significant reduction in E-selectin levels from baseline (p = 0.002) and an increase in the levels of HDL (p = 0.0002) and triglycerides (p = 0.033).. Elevated levels of vWF:Ag and E selectin in PCOS women suggest endothelial dysfunction in this group of patients. Glucose and triglyceride are significant factors affecting endothelial function in PCOS.

Topics: Adolescent; Adult; Atherosclerosis; Biomarkers; Case-Control Studies; E-Selectin; Endothelin-1; Endothelium, Vascular; Female; Humans; Polycystic Ovary Syndrome; von Willebrand Factor

Endothelin-1 is elevated in women with polycystic ovary syndrome (PCOS), and may play a role in the endothelial dysfunction associated with PCOS. Endothelin-1 binds two receptor subtypes, endothelin A (ET-A) and endothelin B (ET-B). We hypothesized that ET-A mediates vasoconstriction in the cutaneous microvasculature in women with and without PCOS. We further hypothesized that while the ET-B receptors mediate vasodilatation in both groups of women, this response would be blunted in women with PCOS. During local skin warming, we used laser Doppler flowmetry combined with intradermal microdialysis to measure skin blood flow (SkBF) during graded ET-A (BQ-123) and ET-B (BQ-788) antagonist infusions in women with (n = 6) and without (n = 8) PCOS. In both groups, SkBF increased during local heating. The percentage of maximal SkBF-[BQ123] sigmoidal dose-response curve indicated a vasodilatory response as the concentration of the antagonist increased (Hill slope 4.96 ± 4.77, 4.74 ± 5.01; logED(50) 2.53 ± 0.09, 2.49 ± 0.09 nm, for PCOS and Control, respectively). In contrast, the % max SkBF-[BQ788] curve indicated a vasoconstrictive response (Hill slope -4.69 ± 3.85, -4.03 ± 3.85; logED(50), 2.56 ± 0.09, 2.41 ± 0.12 nm, in PCOS and Control). Moreover, the SkBF-[BQ788] curve shifted to the right in women with PCOS, suggesting attenuated ET-B receptor mediated vasodilatation during local skin warming compared to Controls. Thus, the endothelium located ET-B receptors function similarly in women with and without PCOS, although with blunted responsiveness in women with PCOS. Our studies suggest that the lower ET-B receptor responsiveness associated with PCOS may reflect lower endothelial-mediated vasodilatation independent of generally lower vascular reactivity.

Topics: Adult; Cardiovascular Diseases; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Endothelin-2; Endothelium, Vascular; Female; Humans; Microcirculation; Microvessels; Oligopeptides; Peptides, Cyclic; Piperidines; Polycystic Ovary Syndrome; Receptor, Endothelin A; Receptor, Endothelin B; Regional Blood Flow; Skin; Vasoconstriction; Vasodilation; Young Adult

We sought to verify if an oral contraceptive (OC) containing drospirenone affects the cardiovascular risk of patients with polycystic ovary syndrome (PCOS).. A total of 28 women with PCOS (16 lean [group A] and 12 overweight [group B]) were assessed at baseline and after 6 months therapy with an OC. Leptin, homocysteine, endothelin-1, and flow-mediated dilatation of brachial artery were measured.. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, did not change in group A; it improved significantly in group B after 6 months of treatment. At baseline and after therapy the plasma levels of homocysteine and endothelin-1 did not differ among the groups. Leptin was significantly lower at baseline in group A compared to group B.. The OC containing drospirenone does not seem to affect the surrogate markers of cardiovascular risk in lean patients with PCOS.

Topics: Adolescent; Adult; Androstenes; Brachial Artery; Cardiovascular Diseases; Contraceptives, Oral; Endothelin-1; Female; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Mineralocorticoid Receptor Antagonists; Obesity; Pilot Projects; Polycystic Ovary Syndrome

To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.. A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 microg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated.. After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects.. Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

Topics: Adult; Body Mass Index; Brachial Artery; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Exercise; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Leisure Activities; Metformin; Placebos; Polycystic Ovary Syndrome; Tunica Intima; Tunica Media; Vasodilation; Vitamin B 12; Waist-Hip Ratio

We examined estradiol and testosterone effects on thermoregulation in women with and without Polycystic Ovary syndrome (PCOS). We hypothesized that core temperature (Tc) threshold for sweating during exercise is delayed in women with PCOS and that testosterone delays the Tc set point for sweating during exercise.. For 16 d, we suppressed estrogens, progesterone, and testosterone with a gonadotropin-releasing hormone antagonist (GnRHant) in seven women with and seven women without PCOS (control); we added 17[beta]-estradiol (0.2 mg.d-1, two patches) on days 4-16 (E2) and testosterone (2.5 mg.d-1, orally) on days 13-16 (E2 + T). Under each hormone condition, subjects cycled in a temperature of 35 degrees C at 60% of age-predicted HRmax for 40 min.. Tc sweating threshold was lower in women in the PCOS group compared with those in the control during GnRHant (37.21 degrees C +/- 0.51 degrees C vs 37.70 degrees C +/- 0.12 degrees C, P < 0.05); neither E2 nor E2 + T influenced the thermoregulatory responses in PCOS. E2 decreased Tc sweating threshold in control (37.06 degrees C +/- 0.69 degrees C, P < 0.05), but E2 + T attenuated this response (37.53 degrees C +/- 0.19 degrees C). Peak sweating rate was greater in women in the PCOS group compared with those in the control group during GnRHant (1.06 +/- 0.47 vs 0.47 +/- 0.11 mg.cm-2.min-1) and E2 + T (0.85 +/- 0.41 vs 0.44 +/- 0.10 mg.cm-2.min-1, P < 0.05). Compared with the control group, total sweat losses were greater in the PCOS group during GnRHant (0.614 +/- 0.189 vs 0.419 +/- 0.098 L) and during E2 + T (0.696 +/- 0.281 vs 0.434 +/- 0.164 L, P < 0.05) but not during E2 (0.639 +/- 0.231 and 0.505 +/- 0.214 L for PCOS and control groups, respectively, P = 0.09).. Thermoregulation was adequate in women with PCOS; however, the women with PCOS achieved thermoregulation at the expense of producing higher sweat volumes.

Topics: Adult; Body Temperature Regulation; Endothelin-1; Estradiol; Exercise; Female; Gonadotropin-Releasing Hormone; Humans; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Progesterone; Sweating; Testosterone; Young Adult

To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls.. Prospective case-control study.. University-based practice.. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]).. Cardiovascular risk markers and hormonal parameters were assessed.. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS.. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D.. Weight and PCOS are two independent variables affecting the endothelial function.

Topics: Adult; Androgens; Blood Flow Velocity; Brachial Artery; Case-Control Studies; Endothelin-1; Endothelium, Vascular; Female; Fibrinogen; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Menstruation; Overweight; Polycystic Ovary Syndrome; Progesterone; Vasodilation; Young Adult

The presence of several cardiovascular risk factors is observed in women with polycystic ovary syndrome (PCOS). On the other hand, the QTc interval duration, which is related to cardiac arrhythmia and sudden death, has not been investigated thoroughly in PCOS population.. To investigate QTc interval duration and its relation to testosterone in women with PCOS.. Cross sectional case-control study.. Outpatient setting, tertiary university medical centre.. We enrolled 119 consecutive patients in whom PCOS was diagnosed based on oligomenorrhea, infertility (>2 yr), ineffective ovarian stimulation, and ultrasonographic criteria. The control group (controls) included 64 age-matched healthy women without clinical or laboratory evidence of PCOS.. In all participants we measured QTc interval duration on a standard electrocardiogram and determined plasma levels of high sensitivity C-reactive protein (hsCRP), endothelin-1 (ET-1), insulin, and testosterone.. Shorter QTc interval duration in PCOS patients.. When compared to controls, PCOS patients displayed higher values of hsCRP (2.35+/-2.14 mg/l vs 1.18+/-1.24 mg/l; p=0.01), ET-1 (23.6+/-10.3 ng/l vs 12.9+/-20.7 ng/l; p=0.03), insulin (18.5+/-7.8 mIU/l vs 10.7+/-9.1 mIU/l; p=0.02), and testosterone (2.7+/-2.1 nmol/l vs 1.4+/-1.7 nmol/l; p=0.01). QTc interval in PCOS patients was significantly shorter than in controls (401+/-61 msec vs 467+/-61 msec; p=0.007), and inversely related to the plasma levels of testosterone (Spearman -0.45, p=0.005).. QTc interval in PCOS patients is short, and inversely associated with increased levels of testosterone. QTc interval duration is not part of an adverse cardiac risk profile in PCOS.

Topics: Adult; C-Reactive Protein; Cardiovascular Diseases; Electrocardiography; Endothelin-1; Female; Heart Conduction System; Humans; Insulin; Polycystic Ovary Syndrome; Risk Factors; Testosterone

Reproductive age women (5-10%) are affected by the polycystic ovarian syndrome (PCOS), a diagnosis which confers lifelong cardiovascular and reproductive health implications. Plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of plasminogen activation, is consistently elevated in women with PCOS, regardless of metabolic status. Interestingly, the plasminogen system has long been implicated in proteolytic processes within the dynamic ovary. A non-physiologic elevation in PAI-1 may thus contribute systemically to endothelial dysfunction and locally to abnormal ovarian phenotype and function. We herein characterize the phenotypic alterations in ovaries from transgenic mice, which constitutively express a stable form of human PAI-1 and determine the plasma testosterone level in these mice as opposed to their unaffected counterparts. Over half of the ovaries from transgenic mice were found to contain large cystic structures, in contrast to wild-type controls of the same genetic background (53% (N = 17) vs 5% (N = 22); P = 0.001). Plasma testosterone was nearly twofold elevated in transgenic female mice versus wild-type females (0.312 ng/ml +/- 0.154 (N = 10) vs 0.181 ng/ml +/- 0.083 (N = 8); P = 0.014). An elevation in PAI-1 therefore appears to predispose mice to the development of this abnormal architecture, which in turn is associated with an increase in plasma testosterone. Therefore, we propose that an inappropriate elevation in PAI-1 contributes to the development of polycystic structures; these findings may thus reorient the efforts aimed at the development of therapeutic agents for the treatment of this increasingly common syndrome.

Topics: Animals; Endothelin-1; Female; Humans; Mice; Mice, Transgenic; Ovary; Plasminogen Activator Inhibitor 1; Polycystic Ovary Syndrome; Promoter Regions, Genetic; Reference Values; Testosterone

To analyze the relationship between QTc interval and cardiovascular risk factors in women with polycystic ovary syndrome (PCOS).. Study group included 119 PCOS women (age: 32.2+/-5.2 years) and the control group 64 age-matched healthy women; they all underwent QT interval measurement, and plasma levels of high-sensitivity CRP (hsCRP), endothelin-1 (ET1), insulin, and testosterone determinations.. In PCOS women hsCRP (2.35+/-2.14 mg/L vs. 1.01+/-1.28 mg/L; P=0.04), ET1 (23.6+/-10.3 ng/L vs. 7.7+/-15.9 ng/L; P=0.01), and insulin (16.5+/-7.8 mIU/L vs. 11.8+/-10.7 mIU/L; P=0.03) levels were significantly higher, and QTc interval significantly shorter than in controls (401+/-61 ms vs. 467+/-61 ms; P=0.007). In 67 (56%) PCOS patients with a short QTc interval (<400 ms), plasma testosterone levels were significantly higher than in PCOS women with normal QTc interval (2.3+/-2.1 nmol/L vs. 1.4+/-1.7 nmol/L; P=0.02).. In patients with polycystic ovary syndrome increased testosterone levels may attenuate the effects of coronary risk factors.

Topics: Adult; C-Reactive Protein; Cardiovascular Diseases; Endothelin-1; Female; Heart Conduction System; Humans; Polycystic Ovary Syndrome; Risk Factors; Testosterone

Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients.. The objective of this study was to evaluate the effects of 6 months of metformin administration on endothelial structure and function in women with PCOS.. This was a prospective, baseline-controlled, clinical study.. The study was performed at University Federico II (Naples, Italy).. Thirty young normal-weight women with PCOS without additional metabolic or cardiovascular diseases were studied.. Metformin (850 mg daily) was administered for 6 months.. The main outcome measures were complete hormonal profile, including total testosterone, SHBG, dehydroepiandrosterone sulfate, prolactin, and gonadotropin levels; serum insulin and glucose levels during a 75-g 2-h oral glucose tolerance test; plasma endothelin-1 concentrations (picomoles per liter +/- sd); serum lipid profile; brachial artery baseline diameter (millimeters +/- sd), diameter after reactive hyperemia (millimeters +/- sd), and flow-mediated dilation (percentage +/- sd); and the intima media thickness (millimeters +/- sd) on both common carotid arteries.. After treatment, SHBG levels and the free androgen index changed significantly (P < 0.001). High-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly (P < 0.001) increased, whereas low-density lipoproteins and plasma endothelin-1 levels were significantly (P < 0.001) reduced. No other change was found in any of the biochemical parameters evaluated. A significant difference was observed in brachial artery baseline diameter (3.24 +/- 0.30 vs. 3.0 +/- 0.30), flow-mediated dilation (14.30 +/- 1.90 vs. 15.70 +/- 1.50) (P < 0.01, each), diameter after reactive hyperemia (3.70 +/- 0.30 vs. 3.55 +/- 0.10) (P < 0.05), and intima media thickness (0.53 +/- 0.09 vs. 0.40 +/- 0.07) (P < 0.001) after metformin treatment in comparison with baseline values.. A 6-month course of metformin improves endothelial structure and function in young, normal-weight women with PCOS.

Topics: Area Under Curve; Cardiovascular Diseases; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Polycystic Ovary Syndrome; Prospective Studies

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS). Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function.

Topics: Adult; Blood Pressure; Endothelin-1; Endothelium, Vascular; Female; Glucose Tolerance Test; Humans; Lipids; Polycystic Ovary Syndrome; Tunica Intima; Vasodilation

Previous studies on the effect of repeated electro-acupuncture (EA) treatments in rats with steriod-induced polycystic ovaries (PCO), EA has been shown to modulate nerve growth factor (NGF) concentration in the ovaries as well as corticotropin releasing factor (CRF) in the median eminence (ME). In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1), a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p < 0.05). In the hypothalamus, however, ET-1 concentrations were found to be significantly higher in the PCO group receiving EA than in the healthy control group (p < 0.05). Concentrations of ovarian NGF protein were significantly higher in the PCO control group compared with the healthy control group (p < 0.001), and these concentrations decreased significantly after repeated EA treatments compared with those in the PCO control group (p < 0.05) and were found to be the same as those in the healthy control group. In conclusion, these results indicate that EA modulates the neuroendocrinological state of the ovaries, most likely by modulating the sympathetic nerve activity in the ovaries, which may be a factor in the maintenance of steroid-induced PCO.

Topics: Adrenal Glands; Animals; Corticotropin-Releasing Hormone; Disease Models, Animal; Electroacupuncture; Endothelin-1; Estradiol; Female; Injections, Intramuscular; Median Eminence; Nerve Growth Factor; Ovary; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; RNA, Messenger; Spinal Cord; Sympathetic Nervous System

Women with polycystic ovary syndrome who present with hyperandrogenemia, hyperinsulinemia, and insulin resistance appear to be at high risk of cardiovascular disease. Elevated levels of endothelin-1, a marker of vasculopathy, have been reported in insulin-resistant subjects with endothelial dysfunction. Male gender also seems to be an aggravating factor for cardiovascular disease. In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels. Plasma endothelin-1 levels were measured in 23 obese (mean age, 24.3 +/- 4.6 yr; body mass index, 35 +/- 5.6 kg/m(2)) and 20 nonobese women with polycystic ovary syndrome (24.1 +/- 3.6 yr; body mass index, 21.8 +/- 2.5 kg/m(2)) as well as in 7 obese and 10 nonobese healthy, normal cycling, age-matched women. Additionally, endothelin-1 levels were evaluated in a subgroup of women with polycystic ovary syndrome (10 obese and 10 nonobese) 6 months postmetformin administration (1700 mg daily). Our results showed that obese and nonobese women with polycystic ovary syndrome had higher levels of endothelin-1 compared with the controls [obese, 2.52 +/- 1.87 vs. 0.44 +/- 0.23 pmol/liter (by analysis of covariance, P < 0.02); nonobese, 1.95 +/- 1.6 vs. 0.43 +/- 0.65 pmol/liter (P < 0.009)]. All of the participating women with polycystic ovary syndrome (n = 43) when compared with the total group of controls (n = 17) demonstrated hyperinsulinemia (polycystic ovary syndrome, 24.5 +/- 19.6; controls, 11.2 +/- 3.4 U/liter; P < 0.03), lower glucose utilization (M40) during the hyperinsulinemic euglycemic clamps (3.4 +/- 2.4 vs. 5.6 +/- 1.75 mg/kg.min; P < 0.045, by one-tailed test), and higher levels of endothelin-1 (polycystic ovary syndrome, 2.52 +/- 1.87; controls, 0.44 +/- 0.23 pmol/liter; P < 0.02, analysis of covariance covariate for body mass index). A positive correlation of endothelin-1 with free T levels was also shown (r = 0.4, P = 0.002) as well as a negative correlation of endothelin-1 with glucose utilization (r = -0.3; P = 0.033) in the total studied population. Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P < 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P < 0.01) women with polycystic ovary syndrome, with no change in body mass

Topics: Adolescent; Adult; Androgens; Blood Glucose; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Polycystic Ovary Syndrome; Regression Analysis