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PubMed1984

Regional differences in abdominal pressure swings in dogs.

The pressure swings under the costal (Pcos) and crural diaphragms (Pcru) and between the intestinal loops (Pint) were compared with the swings in gastric pressure (Pga) in 13 supine anesthetized dogs. Pcos, Pcru, and Pint were measured with air-filled latex balloons in eight dogs and saline-filled catheters in five. Pga was measured with an air-filled balloon in all dogs. During quiet breathing differences were often present, the directions of which were variable from animal to animal. During mechanical ventilation, all pressures increased, but both Pcos and Pcru increased more than Pga, whereas only a small change was observed in Pint. During bilateral stimulation of the costal diaphragm, Pcos invariably increased more than Pga and Pint, whereas almost no change was observed in Pcru. During bilateral stimulation of the crural diaphragm, Pcru invariably increased more than Pga, Pint, and Pcos. During abdominal muscle stimulation as during external abdominal compression, Pint always increased more than Pcos and Pcru. During lower rib cage compression, Pga, Pcos, and Pcru increased more than Pint. During sternocleidomastoid stimulation, all pressure swings were negative, but the change in Pint was always smaller than in Pcos, Pcru, or Pga. Inhomogeneities observed with balloons and saline-filled catheters were similar. After the abdomen was filled with 2 liters of saline all pressure swings became much more homogeneous.

Abdomen↗

PubMed2004

Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects.

Valproic acid (VPA) is an anti-epileptic drug that has been associated with polycystic ovary syndrome (PCOS)-like symptoms, including increased ovarian androgen production. The hyperandrogenemia likely reflects the stimulatory action of VPA on theca cell androgen synthesis and has been correlated to its activity as a histone deacteylase inhibitor in these cells. To determine whether VPA induces a PCOS-like genomic phenotype, we compared the gene expression profiles of untreated (UNT) normal, VPA-treated normal, and UNT PCOS theca cells. Hierarchal cluster analysis demonstrated similarities in the gene expression profiles of VPA-treated normal and PCOS theca cells. Statistical analysis identified 1,050 transcripts that have significantly altered mRNA abundance in both VPA-treated normal and UNT PCOS theca cells compared with normal UNT theca cells. Among these 1,050 transcripts were cAMP-GEFII and TRB3, which have increased and decreased mRNA abundance, respectively. The altered abundance of these two mRNAs was correlated to increased basal and insulin-induced phosphorylation of protein kinase B (Akt/PKB). Thus these studies indicate that VPA- and PCOS-induced changes in gene expression enhance Akt/PKB signal transduction in human theca cells. Furthermore, common changes in gene expression in PCOS and VPA-treated normal theca cells suggest a possible mechanism for the development of PCOS-like symptoms, including increased steroid synthesis and arrested follicle development in women receiving chronic VPA therapy.

Anticonvulsants↗

PubMed2001

Insulin resistance in nonobese patients with polycystic ovary syndrome.

OBJECTIVES: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. METHOD: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. RESULTS: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 +/- 1.32 vs. 1.18 +/- 0.53 pg/ml, p < 0.001, and 11.63 +/- 5.37 vs. 4.98 +/- 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 +/- 14.94 vs. 73.98 +/- 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 +/- 4.98 vs. 19.56 +/- 2.21 microU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 +/- 27.8 vs. 427.8 +/- 88.9 micromol x kg(-1) x min(-1), p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = -0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = -0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. CONCLUSIONS: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.

Adolescent↗

PubMed2002

Impact of insulin resistance on pregnancy complications and outcome in women with polycystic ovary syndrome.

The aim of the study was to determine the risk of developing gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH)/pre-eclampsia in a cohort of pregnant women with the polycystic ovary syndrome (PCOS) and known insulin sensitivity status. Pregnancies and neonatal outcome were recorded in a prospective cohort study comprising 29 non-insulin-resistant PCOS women, 23 insulin-resistant PCOS women and a control group of 355 women who had conceived after assisted reproduction. Hypertension, pre-eclampsia and GDM were recorded as well as pregnancy duration, method of delivery and birth weight. The frequency of hypertension was significantly elevated in PCOS women (11.5%) compared to controls (0.3%), p < 0.01. However, the frequency of pre-eclampsia was significantly elevated only in the insulin resistant PCOS women (13.5%) compared to controls (7.0%), p < 0.02. GDM was significantly more frequent in PCOS women (7.7%) than controls (0.6%), p < 0.01. Insulin resistance prior to pregnancy, determined by continuous infusion of glucose with model assessment (CIGMA) test, did not further increase the frequency of GDM. Newborns from PCOS pregnancies were significantly more often delivered by Caesarean section than controls (40.3 vs. 27.3%, p < 0.05) and transferred to neonatal intensive care unit more often than controls (19.2 vs. 9.0%, p < 0.01). Thus we show that the frequencies of pre-eclampsia and GDM are increased in PCOS pregnancies.

Adult↗

PubMed1995

Transvaginal ultrasonographic morphology in polycystic ovarian syndrome.

To assess the morphological findings based on transvaginal ultrasound, the ovarian volume and the number and size of small follicles were studied in 47 patients with polycystic ovarian syndrome (PCOS) diagnosed clinically. Thirty normal volunteers served as controls. The mean ovarian volume (10.3 ml) and number of follicles (10.6) in patients with PCOS were significantly higher than those of controls. An ovarian volume > 6.2 ml and follicles > 10 with a diameter of 2-8 mm were the most prominent features in the ovaries of patients with PCOS and 94% of 47 patients with PCOS had at least one of these ultrasonic findings. However, marked asymmetry of the two ovaries was seen in about 50% of patients with PCOS and a considerable overlap existed between controls and patients with PCOS in the ovarian volume and in the number of follicles. Three (6%) patients with normal ovarian volume and normal number of follicles were observed. Therefore, it is difficult to clearly distinguish a patient with PCOS from a normal woman only by transvaginal ultrasonic criteria using the ovarian volume and/or the number of follicles, although these criteria could be clinically useful for the screening of PCOS.

Adult↗

PubMed2003

Polycystic ovary syndrome in adolescence.

Polycystic ovary syndrome (PCOS) is a common disorder among reproductive-age women, yet the diagnosis may be overlooked during adolescence. Although the clinical and metabolic features are similar to those found in adult women, it can be difficult to distinguish the young woman with PCOS from a normal adolescent. Irregular menses, anovulatory cycles, and acne are not uncommon in adolescent women. Adolescents with a history of premature pubarche, a family history of PCOS, Caribbean-Hispanic and African-American ancestry, and/or obesity are at risk for PCOS and deserve close surveillance. The laboratory evaluation of the adolescent with suspected PCOS or hyperandrogenism should be individualized based on the history, symptoms, and examination findings. The cornerstone of management of PCOS in adolescence includes either a combination oral contraceptive or progestin. Consideration of insulin-sensitizing agents, antiandrogens, topical treatments for acne, and various treatments for hair removal are dependent on the patient's symptoms and concerns. Healthy eating, regular exercise, and for the overweight adolescent, weight reduction, are encouraged to reduce the risk of cardiovascular disease and type II diabetes mellitus. Numerous studies have shown that weight loss and exercise decrease androgen levels, improve insulin sensitivity, and lead to the resumption of ovulation. Although initial studies suggest that Metformin may be particularly useful for treating the PCOS adolescent with insulin resistance and obesity, additional studies are needed to determine the efficacy and long-term outcome. Management of the adolescent with PCOS is challenging and requires a supportive, multidisciplinary team approach for optimal results.

Adolescent↗

PubMed2003

Polycystic ovary syndrome and cardiovascular disease: a premature association?

Women with polycystic ovary syndrome (PCOS) are often assumed, a priori, to be at increased risk for cardiovascular disease (CVD), given the high prevalence of the metabolic syndrome X among them. There is, however, no single definition of PCOS, and for that reason a comparison of studies that have analyzed its association with CVD is compromised from the start. Long-term studies of well characterized women with PCOS are lacking, and the link to primary cardiovascular events such as stroke or myocardial infarction remains more speculative than substantive. Epidemiological studies that have focused on isolated signs and stigmata of PCOS, such as polycystic ovaries, hyperandrogenism, or chronic anovulation, have found mixed results. There are studies that suggest a slight increase in cardiovascular events in women with polycystic ovaries, with perhaps stronger evidence between an increased risk of cardiovascular events in women with menstrual irregularity. However, there is little evidence for an association between hyperandrogenism per se and cardiovascular events. Furthermore, there are less data to substantiate an increased risk of events in women with PCOS identified on the basis of a combination of signs and symptoms, such as hyperandrogenic chronic anovulation. The existing data suggest that PCOS may adversely affect or accelerate the development of an adverse cardiovascular risk profile, and even of subclinical signs of atherosclerosis, but it does not appear to lower the age of clinical presentation to a premenopausal age group. Future studies to identify the risk of cardiovascular events in women with PCOS will benefit from clear and extensive phenotyping of PCOS abnormalities at baseline, from a prospective design, from larger sample sizes, and from longer follow-up.

Anovulation↗

PubMed2002

Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome.

Obesity is associated with considerably reduced plasma GH concentrations, which may contribute to anovulation in (obese) women with polycystic ovary disease (PCOS). This clinical investigation was undertaken to establish whether the GH release process is deranged in obese women with PCOS and, if so, whether the observed anomalies are features of the syndrome or a sequel of body fat accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age, 34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%]. Compared with lean controls, obese PCOS patients exhibited a greater than 60% reduction in basal and a greater than 75% reduction in pulsatile and total daily GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold) slowing of GH pulse frequency. The mean +/- SEM number of statistically significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1 +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these parameters differed from those in the body mass index-matched controls. The approximate entropy ratio was significantly increased in obese women (both PCOS and controls), indicating greater irregularity of the GH release process. Total GH secretion in patients and the two control groups correlated strongly and negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding protein-3 ratio was equivalent in all three study groups. In conclusion, the profoundly reduced and irregular GH release in obese women with PCOS appears to be a corollary of body fat accretion and not of the syndrome per se.

Adult↗

PubMed2002

Estrogen receptor alpha and beta expression in theca and granulosa cells from women with polycystic ovary syndrome.

A defining characteristic of dominant follicles is high estradiol concentrations. Abnormal expression of estrogen receptors (ERs) could contribute to poor follicular development and ovulatory failure in polycystic ovary syndrome (PCOS). The aim of this study was to determine whether there are differences in ERalpha and ERbeta expression in granulosa cells (GC) and theca cells (TC) from women with PCOS, compared with regularly cycling women. GC and TC were obtained by microdissection from 12 polycystic and 23 normal ovaries. ERalpha and ERbeta mRNA and protein expression were measured by semiquantitative RT-PCR and Western blot, respectively. In control ovaries, both GC and TC ERalpha mRNAs were higher in small antral (SA) than in dominant follicles. ERalpha mRNA was similar in PCOS and size-matched control follicles. In control follicles, ERalpha protein concentrations were higher in GC than in TC. In GC, the ERalpha concentrations were comparable among SA, dominant, and PCOS follicles. In TC, ERalpha concentrations were lower in dominant follicles but were markedly increased in PCOS. In control ovaries, GC and TC expression of ERbeta mRNA was higher in SA, compared with dominant follicles. In PCOS, ERbeta mRNA was intermediate between SA and dominant follicles in both GC and TC. In GC, the ERbeta protein concentrations followed the same pattern as mRNA expression; but in TC ERbeta, protein in PCOS was equivalent to that in dominant follicles. The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development.

Adult↗

PubMed2003

Circulating ghrelin concentrations in the polycystic ovary syndrome.

UNLABELLED: Ghrelin is a novel gastric peptide which has orexigenic and adipogenic properties. Circulating ghrelin concentrations are influenced by nutritional status and, probably, regulate food intake and body weight. Obesity is a common feature in women with polycystic ovary syndrome (PCOS). To investigate the relationship of circulating ghrelin concentrations to the hormonal and metabolic features of PCOS women, plasma ghrelin and several hormone concentrations were evaluated in thirty-three women with PCOS and in thirty-two healthy women matched for age and body mass index (BMI). Plasma ghrelin concentrations were similar between the PCOS (179 +/- 27, pmol/l +/- SEM) and the control (181 +/- 24, pmol/l +/- SEM) groups. In both groups, there was a significant (P < 0.001) inverse correlation between fasting ghrelin concentrations and BMI (PCOS: r = -0.45; CONTROLS: r = -0.59). Multivariate regression analysis did not demonstrate any correlation (P = NS) between fasting ghrelin concentrations and the other hormone levels in the PCOS patients. In conclusion, our data demonstrate that in women with PCOS plasma ghrelin concentrations are not different from those of weight matched controls and are inversely correlated with BMI. There is no relationship between circulating ghrelin and the abnormal hormonal pattern of the PCOS syndrome.

Adult↗

PubMed2004

Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy.

The polycystic ovary syndrome (PCOS) is associated with an increased rate of early pregnancy loss (EPL). Hyperinsulinemia is an independent risk factor for EPL and has been found to decrease levels of glycodelin and IGF binding protein-1 (IGFBP-1), two major endometrial proteins. We hypothesized that serum glycodelin IGFBP-1 concentrations would be reduced in women with PCOS during the first trimester of pregnancy. Fasting serum insulin, glycodelin, and IGFBP-1 were measured, and oral glucose tolerance tests were performed in 72 women with PCOS and 62 normal women. Each woman was seen once and assigned to one of three gestational groups: wk 3-5, 6-8, and 9-11. The insulin sensitivity index during oral glucose tolerance test was lower in women with PCOS compared with normal women throughout the first trimester (P < 0.0001). Both serum glycodelin and IGFBP-1 were markedly lower in women with PCOS (for glycodelin: wk 3-5, P < 0.0001; wk 6-8, P = 0.03; wk 9-11, P = 0.19; and for IGFBP-1: wk 3-5 and 6-8, P < 0.0001; wk 9-11, P = 0.0003). Comparing women with PCOS who experienced EPL with those who did not, serum glycodelin was significantly lower during wk 3-8 (P < 0.02) and serum IGFBP-1 during wk 9-11 (P = 0.003). During the first trimester, serum glycodelin and IGFBP-1 concentrations are markedly decreased in PCOS, implicating endometrial epithelial and stromal dysfunction during periimplantation and early pregnancy as a possible mechanism for EPL in PCOS. These decreases are likely to be secondary to hyperinsulinemia and reduced insulin sensitivity.

Abortion, Spontaneous↗

PubMed2004

Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity.

Hyperinsulinemic hyperandrogenism with anovulation, the so-called polycystic ovary syndrome (PCOS), is the most frequent endocrine disorder of young women. One of the stigmata of PCOS is a deficit of lean mass and an excess of fat, in particular, abdominal fat, even in the absence of obesity. Adiponectin and IL-6 are among the adipocytokines that have recently been related to abdominal fat excess, insulin resistance states, and cardiovascular disease risk. We studied the effects of two new treatment options, ethinylestradiol-drospirenone and flutamide-metformin, and of their combination on adipocytokinemia and body adiposity in adolescents and women with PCOS. Adolescents with PCOS (n = 32; age, approximately 15 yr; body mass index, approximately 22 kg/m(2)) were randomly assigned to receive the oral contraceptive (OC) ethinylestradiol-drospirenone, or the low-dose generic duo of flutamide (62.5 mg/d) plus metformin (850 mg/d). Young women with PCOS (n = 22; age, approximately 19 yr; body mass index, approximately 22 kg/m(2)) were randomized to receive the same OC, either alone or with flutamide-metformin. Fasting blood glucose, serum insulin, lipids, androgens, IL-6, adiponectin, and body composition (by absorptiometry) were assessed at the start, and after 3 and/or 9 months. At the start, serum concentrations of the proinflammatory IL-6 were high, and those of the antiinflammatory adiponectin were low; body composition was adipose in each subpopulation. Abnormal adipocytokine levels, hypertriglyceridemia, and body adiposity diverged further from the norm in adolescents on OC; in contrast, girls on flutamide-metformin reverted all study indices toward normal, lost part of their fat excess, and reduced their lean mass deficit. In comparison to the girls on OC, those on flutamide-metformin lost a mean of approximately 4 kg of fat and gained approximately 4 kg of lean mass. Similarly, abnormal adipocytokine levels and adiposity were aggravated in women on OC alone and improved in women on OC plus flutamide-metformin; within 9 months, the latter subgroup lost a mean of approximately 3 kg of fat and gained approximately 3 kg of lean mass, in comparison to women on OC alone. In conclusion, young and nonobese PCOS patients were found to be in a low-grade, chronic inflammation state, and to have a body adiposity that evolves according to the balance of circulating adipocytokines and lipids, rather than to androgen excess or fasting hyperinsulinemia. Monotherapy with ethinylestradiol-drospirenone may not be a prime choice for PCOS, given its inefficacy to attenuate abnormal adipocytokine levels and body adiposity; ethinylestradiol-drospirenone plus flutamide-metformin, however, is a first OC combination that was found capable of reverting both the adipocytokine balance and the body composition toward normal, and that may therefore improve the long-term cardiovascular perspectives of women with PCOS.

Adiponectin↗

PubMed2004

Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome.

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.

Adult↗

PubMed2004

The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome.

White blood cell (WBC) count is a known risk factor for atherosclerotic vascular disease in adult women. Polycystic ovary syndrome (PCOS) is potentially a risk factor for atherosclerosis and cardiovascular disease. The aim of the present study was to investigate leukocyte count in PCOS. One hundred and fifty PCOS women matched for age and body mass index with 150 healthy women were enrolled. WBC count, C-reactive protein, and a complete anthropometrical, metabolic, and hormonal evaluation were performed in both groups. Serum insulin, glucose level, and lipid profile were also measured in each subject. WBC count was significantly higher (P < 0.0001) in PCOS with (interquartile range in parentheses) 7260 (393) cells/mm(3), compared with controls with 5220 (210) cells/mm(3). C-reactive protein levels were significantly increased (P < 0.0001) in PCOS with 2 (1) mg/liter compared with healthy women with 0.7 (0.8) mg/liter. In both groups, there was a significant (P < 0.0001) linear correlation between WBC count and homeostasis model assessment score (PCOS, r = 0.94; controls, r = 0.91). Multiple linear regression analysis showed that other hormone levels are not predictors of leukocyte count both in PCOS and control women. In conclusion, our data demonstrate that PCOS women have an increased WBC count that correlates with homeostasis model assessment values.

Adult↗

PubMed2005

A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11beta-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome.

CONTEXT: The R453Q variant in the hexose-6-phosphate dehydrogenase gene (H6PD) and 83557insA mutations in 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 gene (HSD11B1) interact, resulting in cortisone reductase deficiency (CRD), a rare disorder characterized by a polycystic ovary syndrome (PCOS)-like phenotype. OBJECTIVE: The objective was to study these mutations in PCOS. DESIGN: The design was a case-control study. SETTING: The study was conducted in an academic hospital. PARTICIPANTS: A total of 116 PCOS patients and 76 nonhyperandrogenic controls participated. MAIN OUTCOME MEASURES: Genotype distributions and influence of genotypes on clinical and biochemical variables and, in 28 patients and 12 controls, estimates of 11betaHSD oxoreductase activity were the main outcome measures. RESULTS: Four controls and five patients presented three of four mutant alleles in H6PD R453Q and HSD11B1 83557insA, which is the genotype observed in some subjects with CRD. Estimates of 11betaHSD oxoreductase activity were measured in six of these nine women, ruling out CRD. Moreover, H6PD R453Q and HSD11B1 83557insA genotypes, either separately or in combination, did not influence 11betaHSD oxoreductase activity. The distribution of H6PD R453Q genotypes (R/R, R/Q, and Q/Q) was different in patients and controls (42% of controls and 63% of PCOS patients were R/R; 53% of controls and 31% of PCOS patients were R/Q; and 5% of controls and 6% of PCOS patients were Q/Q; chi(2) = 9.1; P = 0.011). Patients homozygous for R453 alleles presented with increased cortisol and 17-hydroxyprogesterone levels, compared with carriers of Q453 alleles, but these differences were not observed in controls. On the contrary, HSD11B1 83557insA genotypes were not associated with PCOS and did not influence any phenotypic variable. CONCLUSIONS: Digenic triallelic genotypes of the H6PD R453Q variant and HSD11B1 83557insA mutation do not always cause CRD. On the contrary, the H6PD R453Q variant is associated with PCOS and might influence its phenotype by influencing adrenal activity.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2005

Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P < 0.001) and abdominal adiposity; higher levels of androgens, insulin, homeostasis model assessment score of insulin sensitivity, and total and low-density lipoprotein-cholesterol; and significantly lower levels of SHBG and high-density lipoprotein-cholesterol. In the studied population (n = 130), PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.

Adolescent↗

PubMed2005

Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is believed to have a genetic basis. However, no specific susceptibility gene or region has been conclusively identified. OBJECTIVE: The objective of this study was to duplicate a previous study that localized a PCOS susceptibility region to chromosome 19p13.2 and to narrow the susceptibility region. DESIGN: This study was designed to test for genetic linkage and association between PCOS and short tandem repeat polymorphisms in 367 families, by analysis of linkage and family-based association. SETTING: The study was conducted at academic medical centers. PATIENTS OR OTHER PARTICIPANTS: We studied 367 families of predominantly European origin with at least one PCOS patient. Families included 107 affected sibling (sister) pairs (ASPs) in 83 families, and 390 trios with both parents and an affected daughter. The data set comprises two independent groups. Set 1 consists of 44 ASPs and 163 trios. Set 2 consists of 63 ASPs and 227 trios. INTERVENTION(S): The intervention was the drawing of blood for DNA extraction. MAIN OUTCOME MEASURE: We employed measures of evidence for linkage and association between PCOS and 19 STRs. RESULTS: Linkage with PCOS was observed over a broad region of chromosome 19p13.2. The strongest evidence for association was observed with D19S884 (chi2 = 11.85; nominal P < 0.0006; permutation P = 0.034) and duplicated our earlier findings. CONCLUSIONS: The present analysis suggests that a PCOS susceptibility locus maps very close to D19S884. Additional studies that systematically characterize DNA sequence variation in the immediate area of D19S884 are required to identify the PCOS susceptibility variant.

Adult↗

PubMed2005

Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance.

BACKGROUND: It is controversial whether the polycystic ovary syndrome (PCOS) per se increases low-grade chronic inflammation and whether this relates to central fat excess. In addition, the association between circulating sex hormones and body fat distribution in premenopausal women is debated. METHODS: Blood was drawn from 20 patients with PCOS and compared with 15 controls, matched for body mass index and age. Regional fat distribution was assessed using dual x-ray absorptiometry. RESULTS: Compared with controls, patients with PCOS had a higher trunk to extremity fat ratio (T/E fat), were more insulin resistant (higher homeostasis model assessment of insulin resistance and lower SHBG concentrations), and had higher levels of highly sensitive C-reactive protein, TNF-alpha, procalcitonin, and white blood cell count (all P < or = 0.04), even after adjusting for total body fat. However, additional adjusting for T/E fat eliminated or attenuated the effect of PCOS status on estimates of insulin resistance, on inflammatory mediators, and on white blood cell count but not on circulating sex hormones. Independently of each other, total body fat as well as T/E fat correlated with estimates of insulin resistance and most inflammatory mediators (P < or = 0.04). However, the correlations between T/E fat and circulating sex hormones (P < or = 0.02) were greatly reduced after adjustment for the presence of PCOS. CONCLUSION: The increase in low-grade chronic inflammation and in insulin resistance in women with PCOS is primarily associated with increased central fat excess rather than PCOS status per se. Procalcitonin represents a novel marker of the inflammatory activity of body fat and of PCOS.

Adipose Tissue↗