| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health (E.O.T., J.V.Z., J.R.R., M.Y.B.), Pittsburgh, Pennsylvania 15261; Preventive Heart Care Center, University of Pittsburgh Medical Center (D.A.E.), Pittsburgh, Pennsylvania 15213; and University of Rochester School of Medicine (D.S.G.), Rochester, New York 14642
Address all correspondence and requests for reprints to: Dr. Evelyn O. Talbott, Department of Epidemiology, University of Pittsburgh, 130 DeSoto Street, A526 Crabtree Hall/GSPH, Pittsburgh, Pennsylvania 15261. E-mail: eot1{at}pitt.edu.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Over the past 20 yr, the literature describing cardiovascular disease risk factors among women with PCOS has evolved from case reports and clinical research involving women seen for infertility or androgen excess (8, 9, 10, 11) to larger epidemiological studies (12, 13, 14, 15, 16, 17, 18). These studies demonstrated that PCOS women exhibit significantly adverse lipid and coronary heart disease (CHD) risk profiles at a relatively young age (18), suggesting that these increases may result in premature coronary atherosclerosis. Given the high prevalence of PCOS in the female population, this condition may potentially account for a significant proportion of the atherosclerotic heart disease observed among younger women.
Because CHD is characterized by a long incubation period, metabolic abnormalities observed in the teens and twenties among PCOS women might translate into measurable vascular abnormalities by middle age. Measures of subclinical atherosclerosis, such as the ankle arm index (19) and carotid intima-media thickness (20), allow for the identification, in a noninvasive manner, of subjects at risk for cardiovascular disease early in its course so that risk factor modification can be instituted to delay or prevent cardiovascular events. Using B-mode ultrasonography, Guzick (21) and Talbott et al. (22) recently demonstrated increased carotid intima-media wall thickness among relatively young women with PCOS (45+ yr) compared with control subjects. Moreover, PCOS and age appear to interact to adversely impact carotid wall thickness to a significantly greater degree than that observed with aging alone (P = 0.031) (23).
This unfavorable influence of PCOS on the carotid vasculature in middle age is notable, inasmuch as the difference in lipid levels between PCOS cases and controls appears to narrow as women approach the menopausal transition (24). From these data, one might speculate that long-standing exposure at an early age to an adverse cardiovascular profile, as observed among women with PCOS, leads to premature atherosclerotic changes. Other investigators have also shown significant endothelial dysfunction among PCOS women (25), providing yet another indication of vascular abnormalities. However, cardiovascular disease end-point studies in PCOS have been inconclusive, with some investigations identifying increased cardiac events among women with PCOS (16, 26, 27), and other studies suggesting no increase compared with normal cycling women (28, 29).
Coronary artery calcification (30, 31, 32) assessed by noninvasive electron beam tomography (EBT) correlates with the degree of atherosclerosis found on pathological exam (33) and predicts incident cardiovascular events. Christian et al. (34) determined that the prevalence of coronary artery calcification in a cohort of 36 women with PCOS, aged 30–45 yr, was higher than that observed in a control group of 71 women matched for body mass index (BMI) and age [39% vs. 21%; odds ratio (OR) = 2.4; P = 0.05]. Mean coronary artery calcification (CAC) scores were also greater in PCOS women than in control women (P = 0.04). After adjustment for BMI, however, PCOS was no longer a significant predictor of CAC (OR = 1.99; P = 0.21). In the study by Christian et al. (34), although PCOS as an exposure was diagnosed years earlier, CHD risk factors were measured concurrently with EBT assessment of calcification.
In an extension of our previous research, the present study was designed to 1) evaluate the prevalence of both CAC and aortic calcification (AC) among middle-aged women with PCOS (aged 40–61 yr) compared with controls of similar age and BMI, and 2) explore the relationship between current CAC and AC and factors associated with PCOS and components of the metabolic cardiovascular syndrome measured approximately 9 yr earlier, during the baseline clinic appraisal.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The University of Pittsburgh institutional review board approved the protocol for this study. All participants gave written, informed consent before study enrollment. Details on the identification and recruitment of the original Pittsburgh PCOS cohort have been reported previously (35). Briefly, women with PCOS, diagnosed between 1970 and 1990, were identified from the practice records of physicians at the Division of Reproductive Endocrinology at Magee-Womens Hospital. A clinical diagnosis of PCOS was established at baseline if there was 1) a history of chronic anovulation in association with either 2) evidence of clinical and/or biochemical hyperandrogenism (hirsutism or total testosterone level greater than 2.0 nmol/liter, respectively) or 3) an LH/FSH ratio greater than 2.0. A total of 244 women with PCOS participated in the clinical phase of the investigation and were evaluated in 1993–1994 at baseline. Age (±5 yr)- and race-matched neighborhood control subjects (n = 244) were selected using a combination of voter registration tapes for 1992 from the greater Pittsburgh area and Cole’s Cross Reference Directory of Households (Cole Publications, Lincoln, NE).
In the present study a subset of women with PCOS and controls 40 yr of age or older in 2001–2002, previously evaluated in 1993–1994, were invited to undergo noninvasive EBT of the coronary arteries and aorta. To minimize the disparity in BMI between PCOS cases and controls, women with a BMI of 35 kg/m2 or greater were excluded from the present analysis. Also, any subject reporting a history of type 1 (insulin-dependent) diabetes was excluded. Two subjects reported a diagnosis of type 2 diabetes at baseline. Analyses were conducted with and without the inclusion of these subjects.
A total of 61 white women with PCOS and 85 white controls were included in the present assessment. The overall mean BMI was comparable in PCOS cases and controls (25.8 vs. 24.6 kg/m2, respectively) and was also similar across the range of BMIs assessed in the study: normal weight (<25 kg/m2), 21.9 vs. 22.2 kg/m2; overweight (25–29.9 kg/m2), 27.1 vs. 26.9 kg/m2; and obese (30.0–34.9 kg/m2), 32.1 vs. 32.1 kg/m2, respectively.
Baseline risk factor assessment (1993–1994)
Detailed data collection and laboratory methodologies have been described previously (35). Briefly, height was measured to the nearest half inch on a wall-mounted stadiometer; weight was measured to the nearest half pound. BMI, a measure of relative obesity, was calculated as a mathematical function of weight and height (kilograms per meter squared). Waist and hip circumferences (in centimeters) were measured at the level of the umbilicus and greater trochanter. The waist/hip ratio was calculated as the waist circumference divided by the hip circumference. Blood pressure was assessed in duplicate after a 30-min caffeine restriction and 5-min rest, using a random-zero sphygmomanometer. A questionnaire was administered that included the evaluation of medical, surgical, menstrual, and reproductive histories; current medication use; lifestyle factors; and family history of PCOS.
A 12-h fasting blood sample was obtained at baseline for lipid and hormone assays. All blood samples for both cases and controls were collected and analyzed in 1993–1994 by the same laboratory and methodology. Serum concentrations of total cholesterol, HDLc, HDL2, and triglycerides were measured in the Heinz Lipid Laboratory at the University of Pittsburgh. Total cholesterol was determined by the enzymatic method of Allain et al. (36). HDLc was determined by the method described above after selective precipitation by heparin/manganese and the removal by centrifugation of very low density lipoprotein and low density lipoprotein cholesterol (LDLc). HDL2 and HDL3 were separated from HDLc by mixing with dextran sulfate. HDL2 content was determined by subtracting HDL3 from total HDLc. LDLc was calculated using the Friedewald formula (37). Triglycerides were determined using the enzymatic procedure of Bucolo and David (38). Plasma glucose was analyzed using an enzymatic assay (Yellow Springs Glucose Analyzer; YSI, Inc., Yellow Springs, OH), and plasma insulin was determined by RIA. The homeostasis assessment model for insulin resistance (HOMA-IR; fasting glucose x fasting insulin/22.5) was calculated. Total testosterone levels were measured directly using a radioimmunometric assay (Coat-A-Count; Diagnostic Products, Los Angeles, CA).
For this study the metabolic cardiovascular syndrome was defined at baseline as suggested by the National Cholesterol Education Program Adult Treatment Panel III guidelines (39). MCS was characterized as the clustering within an individual of three or more of the following risk factors: waist circumference greater than 88 cm, hypertriglyceridemia (
150 mg/dl), decreased HDLc (<50 mg/dl), increased blood pressure (130/85 mm Hg) or currently treated for hypertension, or increased fasting glucose (110 mg/dl) or diagnosed or treated for type 2 diabetes. All laboratory values are presented in metric units. Systeme Internationale unit conversion factors are listed in table footnotes.
Coronary and aortic calcium assessment
Coronary and aortic calcium levels were assessed by EBT at the University of Pittsburgh Medical Center Preventive Heart Care Center using the Imatron C-150 Ultrafast CT Scanner (Imatron, South San Francisco, CA). For the coronary arteries, 30–40 contiguous, 3-mm thick transverse images were obtained from the level of the aortic root to the apex of the heart during a maximal breath hold using electrocardiogram triggering, so that each 100-msec exposure was acquired during the same phase of the cardiac cycle (60% of R-R interval). After completion of the coronary scan, an aortic evaluation was obtained. Cross-sectional 6-mm images were acquired from the aortic arch to the iliac bifurcation with a 300-msec exposure time. EBT technicians were blinded to the case/control status of the subjects. Only one scanning sequence was performed to minimize radiation exposure to the study participants. One of the authors (D.A.E.) is director of the University of Pittsburgh Medical Center Preventive Heart Care Center and adjudicated all questionable scans and artifacts.
Coronary and abdominal aorta calcium scores were generated using a base value region of interest computer software program (AccuImage, Diagnostics Corp., San Francisco, CA). All pixels greater than 130 Hounsfield units and 1 mm2 within an operator-defined region of interest in each 3-mm thick image within the coronary arteries or aorta were considered calcified. The Agatston method was used to calculate a calcium score for each region of interest by multiplying the area of all significant pixels by a grade number (1, 2, 3, or 4) indicative of the peak computerized tomography number (i.e. Hounsfield units) (40). The individual regions of interests were summed for a total coronary artery or aortic calcium score.
Statistical analyses
Demographic, anthropometric, lipid, and hormonal data were available from the baseline visit for analysis. Descriptive statistics, including measures of central tendency and dispersion, were computed for all variables of interest for PCOS cases and controls and were compared using the nonparametric Mann-Whitney U test for continuous data or a 
2 or Fisher’s exact test for categorical data. The presence of MCS at baseline was determined by totaling the number of individual components of the syndrome present in a given subject.
The distributions of coronary and aortic calcium were markedly skewed and could not be normalized using traditional mathematical transformations. The prevalence of coronary or aortic calcium was therefore modeled as a binary dichotomous variable (any vs. none).
Baseline risk factors measured 9 yr previously (rather than in a cross-sectional manner) were used to predict current CAC and AC. In univariate logistic regression, we evaluated the MCS components (waist circumference, systolic and diastolic blood pressures, triglycerides, HDLc, HDL2, and glucose) that were individually associated with coronary calcification and/or aortic calcification as possible independent predictors. Other potential CHD risk factors (total testosterone, total cholesterol, LDLc, insulin, HOMA, hormone use, and smoking) were also considered.
In the multivariable logistic regression modeling, the effect of PCOS on CAC or AC, respectively, was assessed after adjustment for age and obesity. BMI and waist circumference were highly correlated in all subjects (r = 0.85). Waist circumference was also moderately correlated with metabolic variables such as HDLc and triglycerides. Therefore, BMI was used to adjust for relative obesity in multiple regression models. Subsequently, components of the metabolic syndrome that were significant in the univariate models were evaluated as possible mediators of the association between PCOS and coronary artery or aortic calcification. The potential contributions of other traditional cardiovascular risk factors were also assessed. Variables that were not associated with both PCOS and calcification were not included in the multivariable logistic models. In the case of similar measures that were highly correlated (such as insulin and HOMA), the variable that was most significantly associated with CAC or AC was included in the models. All statistical analyses were performed using SPSS (version 11.5, SPSS, Inc., Chicago, IL).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Baseline cardiovascular risk factors (mean ± SD) are presented separately for PCOS cases (n = 61) and controls (n = 85; Table 1
). The mean ± SD age at baseline was 38.7 ± 4.8 yr among cases and 40.4 ± 5.3 yr among controls. At follow-up, the subjects were 47.9 ± 5.0 and 49.2 ± 5.4 yr, respectively. At baseline, hormone use, defined as either oral contraceptives or hormone replacement therapy, was similar between PCOS cases and controls (21.3% vs. 17.6%; not significant) as was the percentage of current smokers (18.0% of cases vs. 16.5% of controls; not significant).
|
PCOS and MCS
Table 2 presents the distribution of components of MCS among PCOS cases (n = 59) and controls (n = 85). At baseline, a total of nine PCOS cases (15.3%) vs. three control women (3.5%) had MCS as defined by the presence of three or more of the five critical components. In addition, a total of 33.9% of cases (n = 20) had two or more components of MCS compared with 8.2% of controls (n = 7).
|
Measures of central tendency, overall prevalence (any vs. none), and the distribution of CAC and AC scores (0, 1–9, and 10+) are shown in Table 3. CAC scores were significantly higher among cases than controls (P = 0.033). The minimum and maximum scores for cases and controls were 0–845.5 and 0–139.9, respectively. A total of 28 of 61 cases (45.9%) compared with 26 of 85 controls (30.6%) had evidence of any coronary artery calcium (P = 0.059). The distribution of CAC scores (0, 1–9, and 10+) among PCOS women was shifted toward higher scores compared with control women. Approximately 20% of PCOS women had a CAC score of 10+ or greater compared with 7% of controls.
|
CAC, MCS, and CHD risk factors
Smoking, oral contraceptive/hormone use, total cholesterol, LDLc, and total testosterone did not significantly influence the prevalence of CAC in the total sample of PCOS cases and controls in univariate models (data not shown). Table 4 presents a comparison of MCS components among women with and without CAC, stratified by PCOS status. Mediating factors for CAC for both PCOS cases and controls were age, BMI, waist, systolic blood pressure, triglycerides, and insulin (P < 0.05 for all). HOMA was significant for controls and was of borderline significance for cases. HDLc and HDL2 were significantly lower among PCOS women with coronary calcification compared with cases without coronary calcification, but there was no relationship among controls. Increased diastolic blood pressure was associated with CAC in controls, but not in cases. Fasting glucose was not related to CAC in cases or controls.
|
Total cholesterol and LDLc were higher among both cases and controls with calcification than in those with no calcification, but significantly so only among controls (not shown). The relationship between AC and MCS components, stratified by PCOS status, was explored in Table 5. As observed with CAC, AC in cases and controls was associated with increased age, BMI, and waist circumference. AC was also related to increased diastolic blood pressure as well as clinical markers of insulin resistance (increased fasting insulin and HOMA). Fasting glucose, systolic blood pressure, HDLc, and triglycerides (all components of MCS) were significantly associated with AC in PCOS cases. Interestingly, total testosterone was also significantly elevated among both PCOS cases and controls with AC compared with those without calcification.
|
)After adjustment for age and BMI, PCOS was a significant predictor of CAC in the total sample (n = 146; P = 0.049). Women with PCOS were more than twice as likely as controls to exhibit CAC [OR = 2.31; 95% confidence interval (CI) = 1.00, 5.33]. Factors associated with both CAC and PCOS in univariate models and thus subsequently included in multivariable models were HDLc, triglycerides, and insulin. All models were adjusted for age and BMI. HDLc was of borderline significance (P = 0.054) in predicting CAC and also reduced the effect of PCOS on CAC (OR = 1.99; 95% CI = 0.80,4.95). Triglycerides and insulin were not associated with CAC independently of the effect of age, BMI, or PCOS. However, triglycerides as well as insulin reduced the effect of PCOS (OR = 1.93; 95% CI = 0.77,4.87 and OR = 1.99; 95% CI = 0.80,4.99 respectively). In models that included both triglycerides and insulin or both HDLc and insulin, the independent effect of PCOS was eliminated.
|
)After adjustment for age and BMI, PCOS was of borderline significance as a predictor of AC (OR = 2.13; P = 0.085). Factors associated with both AC and PCOS in univariate models and thus included in subsequent multivariable models were HDLc, triglycerides, insulin, and testosterone. All models were again adjusted for age and BMI. Total testosterone predicted AC in all women (P = 0.034) after adjusting for PCOS status, age, and BMI and also reduced the effect of PCOS on AC. Insulin and HDLc were of borderline significance in predicting AC in all women (P = 0.057 and P = 0.059 respectively). In the final model, which included total testosterone, HDLc, and insulin, no single variable remained a significant independent predictor of AC.
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The prevalence of CAC and AC as well as the magnitude of calcium scores were greater among PCOS cases than controls. Although obesity was clearly a determinant of this association, PCOS appeared to influence coronary and, to a lesser extent, aortic vascular disease in a dimension not completely explained by age and BMI, but related to MCS and insulin resistance. This finding is consistent with our previous study that demonstrated increased carotid artery intima-media wall thickness in PCOS cases 45 yr and older compared with controls (22). These findings in concert suggest a predisposition to premature atherosclerosis in multiple vascular beds in PCOS-affected women.
As previously noted, women with PCOS have features of insulin resistance and MCS, both of which have been associated with increased atherosclerosis and cardiovascular events. MCS was evaluated at baseline among these relatively young PCOS women and controls (mean age, 38.7 and 40.4 yr, respectively) with similar BMI (<35 kg/m2) and was approximately 4.4 times more likely to be demonstrated in the PCOS group. The prevalence of MCS would have most likely been substantially higher, particularly among the women with PCOS, had we not elected to truncate the distribution of BMI at less than 35 kg/m2 to ensure comparability between groups. Eight of nine women with PCOS who met criteria for overt MCS at baseline had measurable coronary calcium at the 9-yr follow-up (data not shown); only one PCOS case with MCS remained free of calcification. Of the five criteria defining MCS in this study, only HDLc and triglycerides appeared to appreciably mediate the effect of PCOS on coronary calcium after adjustment for age and BMI. Although insulin resistance was not a formal component of the criteria for MCS in the present study, hyperinsulinemia appeared to play a role in mediating the PCOS influence on CAC. These results suggest that the presence of MCS and insulin resistance at an early age among women with PCOS may be significantly associated with later life coronary atherosclerosis and other cardiovascular complications.
The relationship among PCOS, MCS, and CAC observed in this study is similar to that demonstrated in two previous investigations in which EBT coronary artery calcium scores, metabolic and anthropometric parameters, and fasting and stimulated concentrations of glucose and insulin were assessed in largely asymptomatic populations. Arad et al. (31) reported on 1160 men and women who were recruited into strata dependent on their CAC scores in the greater than 80th percentile or below the 80th percentile. In multivariate analysis, age, gender, family history of premature heart disease, intraabdominal adiposity as a measure of abdominal height, LDL, and smoking independently predicted calcium scores. The researchers concluded that dimensions of abdominal obesity were significant contributors to insulin resistance and asymptomatic atherosclerosis. In the Framingham Offspring Study, Meigs et al. (44) assessed the risk for subclinical atherosclerosis in subjects with or without insulin resistance and with normal or impaired glucose tolerance. A total of 325 subjects, aged 31–73 yr, were initially evaluated in l991–1995 and assessed for coronary calcium approximately 4–6 yr later. The average age at EBT scan was 58 yr. In adjusted models, those with diabetes and insulin resistance were more likely to have subclinical disease than those without diabetes or insulin resistance.
Type 2 diabetics are dysglycemic and might be considered the extreme extension of MCS, although these entities represent distinctly different pathologic states. There were only two diagnosed type 2 diabetics at baseline in our PCOS population. Results were similar with and without the inclusion of these subjects. Our findings suggest that components of MCS, present at an early age, predict CAC and AC in women with PCOS, and that the relationship significantly predates the development of overt type 2 diabetes in this population.
Similar to our observations related to CAC, PCOS also contributed to increased AC among affected women, although, after adjustment for age and BMI, the relationship was not statistically significant (P = 0.085). Total testosterone was found somewhat unexpectedly to be a significant risk factor for AC among all women in this study, after adjustment for age, BMI, and PCOS case status. Because elevated testosterone is one of the criteria for PCOS diagnosis, it was not unexpected that testosterone might reduce the PCOS-calcification association; however, the finding of the total testosterone-AC association among both cases and controls is intriguing. In a recent analysis in the Study of Women across the Nation, testosterone was also positively associated with aortic calcium among women 55 yr and older, an association that persisted after adjustment for obesity and the Framingham risk score (Tyrrell, K. S., unpublished observations).
In animal models, treatment with testosterone has been shown to induce exacerbation of atherosclerosis in female monkeys, whereas it inhibits the development of atherosclerosis in male rabbits, suggesting gender-specific effects of testosterone on the vascular system (45). In addition, Tep-areenan et al. (46) demonstrated a difference in the relative activity of various steroid hormones in selected vascular beds (coronary vs. pulmonary arteries) in male and female adult Wistar rats. As observed in our study, such differences may also exist in the coronary vs. aortic vascular beds in humans. In the Rotterdam Study, Hak et al. (47) investigated the association of total testosterone with aortic atherosclerosis in 1032 nonsmoking men and women, aged 55 yr of age and older. Relative to men with levels of total testosterone in the lowest tertile, men with testosterone in the highest tertile had age-adjusted relative risks (RRs) that were protective for AC (RR = 0.4; 95% CI, 0.2–0.9). Conversely in women, increased total testosterone was associated with the development of aortic calcification (RR = 3.7; 95% CI, 1.2–11.6). After adjustment for atherosclerotic risk factors, including BMI, the protective effect of testosterone in men remained significant, but the association with calcification in women was somewhat reduced (RR = 2.8; 95% CI, 0.7, 11.5).
Given the results of previous studies, signifying no association between total testosterone and CHD, Hak et al. (47) suggested that "the aorta may be more vulnerable to the effects of endogenous sex steroid hormones," such as testosterone, than other arteries. Our results and those reported by Hak et al. (47) are provocative and underscore the need for further investigation of testosterone as a possible risk factor for atherosclerosis in specific vascular beds in other populations of women with androgen excess as well as in the general population.
In summary, the present finding of increased coronary and aortic calcium as a surrogate for subclinical atherosclerosis in women with PCOS underscores the importance of early identification of both MCS and insulin resistance in this high risk group and has implications for clinical management. Given the large number of women with PCOS and the long incubation period for subclinical atherosclerosis, early and aggressive intervention through lifestyle modification and/or pharmacological therapies (i.e. metformin and insulin sensitizers) may significantly reduce the morbidity and mortality from CHD in the female population.
|
Footnotes |
|---|
Abbreviations: AC, Aortic calcification; BMI, body mass index; CAC, coronary artery calcification; CHD, coronary heart disease; CI, confidence interval; EBT, electron beam tomography; HDLc, high-density lipotropin cholesterol; HOMA-IR, homeostasis assessment model for insulin resistance; LDLc, low-density lipoprotein cholesterol; MCS, metabolic cardiovascular syndrome; OR, odds ratio; PCOS, polycystic ovary syndrome; RR, relative risk.
Received December 30, 2003.
Accepted August 15, 2004.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  E. Diamanti-Kandarakis, S. Livadas, S. A Kandarakis, A. Margeli, and I. Papassotiriou Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism? Eur. J. Endocrinol., April 1, 2008; 158(4): 525 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Guzick Do Cardiovascular Risk Factors in Polycystic Ovarian Syndrome Result in More Cardiovascular Events? J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1170 - 1171. [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Nestler Metformin for the Treatment of the Polycystic Ovary Syndrome N. Engl. J. Med., January 3, 2008; 358(1): 47 - 54. [Full Text] [PDF]
|
|
|
|
|
|
R. Shroff, A. Kerchner, M. Maifeld, E. J. R. Van Beek, D. Jagasia, and A. Dokras Young Obese Women with Polycystic Ovary Syndrome Have Evidence of Early Coronary Atherosclerosis J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4609 - 4614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Luque-Ramirez, C. Mendieta-Azcona, F. Alvarez-Blasco, and H. F. Escobar-Morreale Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome Hum. Reprod., December 1, 2007; 22(12): 3197 - 3203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Moran, M. Noakes, P. M. Clifton, G. A. Wittert, D. P. Belobrajdic, and R. J. Norman C-Reactive Protein before and after Weight Loss in Overweight Women with and without Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2944 - 2951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sir-Petermann, B. Echiburu, M M. Maliqueo, N. Crisosto, F. Sanchez, C. Hitschfeld, M. Carcamo, P. Amigo, and F. Perez-Bravo Serum adiponectin and lipid concentrations in pregnant women with polycystic ovary syndrome Hum. Reprod., July 1, 2007; 22(7): 1830 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. T. Bloomgarden Third Annual World Congress on the Insulin Resistance Syndrome: Associated conditions. Diabetes Care, September 1, 2006; 29(9): 2165 - 2174. [Full Text] [PDF]
|
|
|
|
|
|
T. L. Setji, N. D. Holland, L. L. Sanders, K. C. Pereira, A. M. Diehl, and A. J. Brown Nonalcoholic Steatohepatitis and Nonalcoholic Fatty Liver Disease in Young Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1741 - 1747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Lo, S. L. Feigenbaum, J. Yang, A. R. Pressman, J. V. Selby, and A. S. Go Epidemiology and Adverse Cardiovascular Risk Profile of Diagnosed Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1357 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Carmina, N Napoli, R A Longo, G B Rini, and R A Lobo Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS Eur. J. Endocrinol., January 1, 2006; 154(1): 141 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. F. Escobar-Morreale, J. I. Botella-Carretero, F. Alvarez-Blasco, J. Sancho, and J. L. San Millan The Polycystic Ovary Syndrome Associated with Morbid Obesity May Resolve after Weight Loss Induced by Bariatric Surgery J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6364 - 6369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Azziz, C. Marin, L. Hoq, E. Badamgarav, and P. Song Health Care-Related Economic Burden of the Polycystic Ovary Syndrome during the Reproductive Life Span J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4650 - 4658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Kilicdag, T. Bagis, E. Tarim, E. Aslan, S. Erkanli, E. Simsek, B. Haydardedeoglu, and E. Kuscu Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial Hum. Reprod., June 1, 2005; 20(6): 1521 - 1528. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||
