Black women with polycystic ovary syndrome (PCOS) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with PCOS

Black women with polycystic ovary syndrome (PCOS) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with PCOS Jennifer K. Hillman, M.D.,a Lauren N. C. Johnson, M.D.,b Meghana Limaye, B.S.,b Rebecca A. Feldman, M.D.,b Mary Sammel, D.S.,c and Anuja Dokras, M.D., Ph.D.b a Langone Medical Center, New York, New York; and b Department of Obstetrics and Gynecology and c Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania

Objective: To determine the prevalence of metabolic syndrome (MetSyn) and Framingham cardiovascular disease (CVD) risk in white and black adolescents and adult women with polycystic ovary syndrome (PCOS) compared with controls. Design: Retrospective cohort study. Setting: Center for PCOS. Patient(s): Subjects with PCOS with data on race and cardiometabolic risk (n ¼ 519). Controls were age and race matched from the National Health and Nutrition Examination Survey (NHANES) population (1999–2006). Intervention(s): None. Main Outcome Measure(s): MetSyn, coronary heart disease risk, and general CVD risk. Result(s): Black adolescents and young adults with PCOS had an increased prevalence of MetSyn compared with their white counterparts (adolescents relative risk 2.65 [95% confidence interval 1.29–5.4], adults relative risk 1.44 [95% confidence interval 1.21–2.6]). In contrast, there was no difference in risk of MetSyn between black and white adolescents and adult women in the NHANES dataset. After controlling for age and body mass index, black women with PCOS had a significantly increased prevalence of low high-density lipoprotein and high glucose. The general CVD risk was significantly increased in black adults with PCOS. Conclusion(s): This is the first study to comprehensively demonstrate increased risk of MetSyn in both black adolescents and adult women with PCOS compared with white subjects with PCOS. This racial disparity was not present in the NHANES controls. Longitudinal studies are needed to assess the independent impact Use your smartphone of PCOS and race on CVD risk in women. (Fertil SterilÒ 2014;101:530–5. Ó2014 by American to scan this QR code Society for Reproductive Medicine.) and connect to the Key Words: PCOS, metabolic syndrome, racial disparities, CVD risk Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/hillmanjk-metabolic-syndrome-racial-disparities-pcos-cvd/

P

olycystic ovary syndrome (PCOS) is an endocrine disorder affecting millions of reproductive-aged

women (1). The most common presentation is a triad of symptoms including oligomenorrhea, clinical or biochemical

Received August 12, 2013; revised and accepted October 31, 2013; published online December 30, 2013. J.K.H. has nothing to disclose. L.N.C.J. has nothing to disclose. M.L. has nothing to disclose. R.A.F. has nothing to disclose. M.S. has nothing to disclose. A.D. has nothing to disclose. J.K.H. was recipient of the FOCUS Medical Student Fellowship in Women's Health supported by the Edna G. Kynett Memorial Foundation. L.N.C.J. is recipient of award T32 HD007440 (National Institutes of Health). Reprint requests: Anuja Dokras, M.D., Ph.D., University of Pennsylvania, Department of Obstetrics and Gynecology, 3701 Market St., Suite 800, Philadelphia, Pennsylvania 19104 (E-mail: adokras@ obgyn.upenn.edu). Fertility and Sterility® Vol. 101, No. 2, February 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2013.10.055 530

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hyperandrogenism, and polycysticappearing ovaries on ultrasound (2). The association between PCOS and cardiovascular comorbidities, including insulin resistance, type 2 diabetes, obesity, and dyslipidemia, is well recognized (3). In addition, women with PCOS have an increased prevalence of subclinical atherosclerosis, as demonstrated by endothelial dysfunction, increased carotid intima media thickness, and increased coronary artery calcium scores (4). Given that cardiovascular disease VOL. 101 NO. 2 / FEBRUARY 2014

Fertility and Sterility® (CVD) is one of the leading causes of female morbidity and mortality in the United States (5) and that the diagnosis of PCOS is associated with cardiovascular risk, the timely identification of cardiometabolic risk factors will have a significant impact on the overall health of this population. One of the strongest and earliest predictors of CVD is the presence of metabolic syndrome (MetSyn) (6), a constellation of cardiovascular-related components including abdominal obesity, dyslipidemia, elevated blood pressure, and insulin resistance. More importantly, the diagnosis of MetSyn carries a greater risk of CVD than any of the above individual factors alone. Longitudinal studies of community-based adolescent girls (Bogalusa Heart study) have shown a persistence of multiple cardiovascular risk markers from childhood to adulthood (7). In another longitudinal cohort (Princeton follow-up study) childhood MetSyn and abnormal metabolic risk factors were shown to predict adult type 2 diabetes (8, 9). Additionally, children with MetSyn are nine times more likely to have MetSyn as adults, thereby identifying a high-risk group that may benefit from early intervention (8). A number of crosssectional studies have determined the risk of MetSyn in PCOS. Adolescents with PCOS have increased numbers of cardiometabolic risk factors compared with age-matched controls (10), and these findings are even more prevalent in adults with PCOS. In a meta-analysis including 2,256 adult women with PCOS and 4,130 controls, the odds ratio (OR) for MetSyn was increased (2.88 [95% confidence interval (CI) 2.4–2.45]), and in a body mass index (BMI)-matched population the OR was 2.2 (95% CI 1.36–3.56) (11). The prevalence of MetSyn in the community-based population has been evaluated by the National Health and Nutrition Examination Survey (NHANES), a program designed to assess the health and nutritional status of adults and children in the United States. The NHANES report shows no significant difference in the prevalence of MetSyn by gender but an increase with age (12). Non-Hispanic black men have a lower prevalence of MetSyn compared with non-Hispanic white men, as reflected by the most recent NHANES analysis (13). In females, however, there is no difference in the prevalence of MetSyn by race in adolescents and in adult women aged <35 years. Over age 35, Mexican American women exhibited a significantly higher prevalence of MetSyn compared with non-Hispanic whites and blacks (13). Only a few studies have investigated the racial differences in cardiometabolic factors in women with PCOS (14–16). In two studies conducted at tertiary care centers, black women with PCOS had higher mean highdensity lipoprotein cholesterol (HDL-C) levels and lower mean triglyceride (TG) levels when compared with white women with PCOS (14, 15). It is, however, not clear whether this favorable lipid profile translates into a decreased risk for MetSyn and CVD. There are very limited data on the racial differences in the risk of MetSyn and CVD risk in adolescents and young adults with PCOS (16). The objective of our study was to comprehensively determine the racial differences in prevalence of MetSyn and CVD risk in adolescents and adult women with PCOS compared with age-matched NHANES subjects (controls). VOL. 101 NO. 2 / FEBRUARY 2014

We hypothesize that racial differences in MetSyn would be seen to similar degrees in both adolescents and adults, suggesting early onset and potentially life-long implications.

MATERIALS AND METHODS This study was a retrospective chart review of adolescents (aged <20 years) and adult women evaluated at the PENN PCOS Center from January 1, 2010 through January 31, 2013. Women are referred from a variety of sources, including obstetrics and gynecology, primary care, subspecialty clinics, and self-referral. The institutional review board at the University of Pennsylvania approved this study. Polycystic ovary syndrome was diagnosed in adults as the presence of at least two of three Rotterdam criteria (2). Diagnosis of PCOS in adolescents was confirmed using previously published modified criteria, namely biochemical hyperandrogenism (total T R55 ng/mL) or clinical hyperandrogenism (Ferriman-Gallwey score R8), irregular menses of nine or fewer menses per year at least 2 years after menarche, and polycystic-appearing ovaries, defined as either ovary having a volume R10 cm3 via abdominal or transvaginal ultrasound (17). Laboratory tests and measurements from the physical examination were recorded from the subject's initial evaluation for PCOS. Recorded outcomes included age, blood pressure, height, weight, calculated BMI, total cholesterol, TG, HDL-C, low-density lipoprotein cholesterol (LDL-C), glucose, and insulin. Additional laboratory tests required to establish the diagnosis of PCOS included TSH, prolactin, DHEAS, and 17-hydroxyprogesterone. Fasting glucose and insulin measurements were performed before the initiation of metformin. The racial and ethnic groups were self-reported or reported by a family member (in adolescents) and categorized as non-Hispanic whites and non-Hispanic blacks. Because of the small sample sizes of the other racial groups, only these two races were compared in the study. A diagnosis of MetSyn in the adolescent cohort required three or more of the following criteria based on modified Cook criteria (18): [1] BMI R90th percentile for age, [2] serum TG R150 mg/dL, [3] serum HDL-C %40 mg/dL, [4] systolic and diastolic blood pressure (BP) R90th percentile for age or the use of an antihypertensive medication, and [5] fasting blood glucose R100 mg/dL or the diagnosis of type 2 diabetes mellitus. The diagnosis of MetSyn in adults required three or more of the following: [1] BMI R30 kg/m2, [2] serum TG R150 mg/ dL, [3] serum HDL-C %50 mg/dL, [4] systolic BP R130 mm Hg or diastolic BP R85 mm Hg or the use of an antihypertensive medication, and [5] fasting blood glucose R100 mg/dL or the diagnosis of type 2 diabetes mellitus. Comparisons were made with a cohort of age- and race-matched adolescents and adult women surveyed from 1999 to 2006 by NHANES (13). The Framingham 10-year risk of coronary heart disease (CHD) and the 2008 general CVD risk were calculated for all individuals according to a previously published formula (19). Framingham risk score provides a 10-year CHD (myocardial infarction, coronary death, and angina) risk based on age, HDL-C, total cholesterol, smoking status, and hypertension. The general CVD risk predicts risk of coronary disease, 531

ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY cerebrovascular disease, peripheral vascular arterial disease, and heart failure and is based on the Cox regressional model of proportional hazards (20). Demographic variables were assessed using Student's t test for parametric data and the Mann-Whitney U test for nonparametric data. The c2 test was used for categoric variables, as appropriate. Logistic regression models were used to evaluate associations among MetSyn, Framingham risk scores, and race while adjusting for potential confounders, including age and BMI.

RESULTS During the period of the study a total of 621 subjects with well-defined PCOS had information regarding their cardiometabolic risk. For the purpose of this study we included non-Hispanic white (n ¼ 413) and non-Hispanic black (n ¼ 106) subjects. We did not include the other racial groups, owing to small numbers. Table 1 shows the demographic information for these two groups. Black women with PCOS had significantly higher total T and free T levels (P< .01), with no difference in menstrual cyclicity. Racial differences were noted in the traditional risk factors for CVD (Table 2). Black women with PCOS had significantly higher systolic and diastolic BP compared with white women with PCOS (P< .01). Black women were significantly more obese, with higher fasting insulin and glucose levels than white women with PCOS (P< .01). In contrast, black women with PCOS had significantly lower total cholesterol (P< .05) and lower TG levels (P< .01) compared with white women. We examined the prevalence and relative risk of MetSyn and its individual components in black and white adolescents with PCOS (Tables 3 and 4). Black adolescents had a significantly higher prevalence of MetSyn than white adolescents with PCOS (relative risk [RR] 2.65 [95% CI 1.29– 5.4], P< .01). The most common abnormality in blacks was elevated BMI and hypertension. Overall, black adolescents with PCOS had more positive criteria for MetSyn (2.1  0.9) compared with white adolescents (1.4  1.2, P< .01). When adjusted for age and BMI, there was no difference in risk of abnormal BP or low HDL-C between the two

TABLE 1 Demographics and clinical features of non-Hispanic white and black subjects with PCOS. Variable n Age (y) Age range (y) No. menses/y Total T (ng/mL) Free T (pg/mL) TSH (mIU/mL) PRL (ng/mL) 17OH P (ng/dL) DHEA-S (ng/mL)

Non-Hispanic white

Non-Hispanic black

413 25.0  6.7 11–47 4  3.38 58.83  30.77 6.65  6.41 2.40  3.9 11.00  6.96 80.55  77.73 250.16  148.46

106 26.3  7.3 13–50 4.06  3.1 74.19  37.72** 9.92  8.77** 3.15  1.14** 11.08  7.63 97.18  101.05 200.71  108.01**

Note: Values are mean  SD unless otherwise noted. ** P< .01. Hillman. Racial differences in metabolic risk in PCOS. Fertil Steril 2014.

532

TABLE 2 Traditional CVD risk factors in non-Hispanic white and black subjects with PCOS subjects. Factor Systolic BP (mm Hg) Diastolic BP (mm Hg) Total cholesterol (mg/dL) HDL-C (mg/dL) LDL–C (mg/dL) Triglycerides (mg/dL) Total insulin (mU/mL) Fasting glucose (mg/dL) BMI (kg/m2) BMI <25 (%) BMI 25–30 (%) BMI >30 (%) Smoking history current (%) Past smokers (%) Family history (%) CAD father/brother age <55 y CAD mother/sister Age <65 y FHx_DM2

Non-Hispanic white

Non-Hispanic black

121.49  13.3 72.04  9.75 184.49  34.26 55.05  15.91 106.34  31.17 115.47  67.15 12.45  14.11 83.3  11.6 30.66  8 30 23 47 7.12 17.5

127.33  14.1** 74.88  8.76** 179.07  38.51* 49.24  17.19** 111.41  38.39 100.38  83.92** 23.25  22.31** 88.6  14.8** 35.64  8.56* 10.4 17.1 72.3** 9.9 14.9

8.7

4.2

5.3

2.9

36.2

43.8

Note: Values are mean  SD. FHx_DM2 ¼ family history of diabetes mellitus type 2. * P< .05. ** P< .01. Hillman. Racial differences in metabolic risk in PCOS. Fertil Steril 2014.

groups. We compared these findings with age- and racematched NHANES groups (Table 3) (13). There was no significant difference in the prevalence of MetSyn between black and white adolescents in the NHANES report (RR 0.95 [95% CI 0.4–2.25]; Table 4). In the NHANES dataset increased BMI and low HDL-C were the most common abnormalities. The RR for MetSyn in white adolescents with PCOS compared white age-matched controls from NHANES was 3.72 (95% CI 1.9–7.25, P< .01). The same comparison for black adolescents with PCOS compared with black adolescents from NHANES also showed a RR of 10.13 (95% CI 5.1–20.13, P< .01). We next examined the prevalence of MetSyn and its components in adult women categorized by race (Table 3). Adult black women also had a significantly higher prevalence of MetSyn compared with white women with PCOS (RR 1.44 [95% CI 1.21–2.6], P< .01; Table 3). After adjusting for age and BMI, black women with PCOS had a significantly higher prevalence of low HDL-C (P< .001) and high fasting glucose (P< .001). In contrast, after adjusting for age and BMI, white women had higher TG levels compared with black women (P< .001). Overall, black women had more abnormal criteria for MetSyn (2.32  1.3) compared with white women (1.5  1.3, P< .001). Additionally, more white women had no abnormal criteria for MetSyn compared with black women (28.7% vs. 8.3%, P< .01). Similar to the adolescent NHANES data, there was no difference in the prevalence of MetSyn between adult black and white women in the NHANES report (RR 1.13 [95% CI 0.58–2.21]; Table 3). The most common abnormalities were abnormal BMI and low HDL-C in both races. The RR for MetSyn in white adults with PCOS compared with VOL. 101 NO. 2 / FEBRUARY 2014

Fertility and Sterility®

TABLE 3 Prevalence of metabolic syndrome and its components by age and race in adolescents and women with PCOS. Variable Age <20 y PCOS white PCOS black NHANES white NHANES black Age 20–34 y PCOS white PCOS black NHANES white NHANES black

n

Metabolic syndrome

112 25 397 457

15.9 42.1** 4.4 4.2

244 67 250 157

22.6 40** 14.9 16.6

BMI (criterion)

TG (criterion)

HDL (criterion)

BP (criterion)

Glucose (criterion), R100 mg/dL

(R90th percentile) (R150 mg/dL) (%40 mg/dL) (mm Hg R90th percentile) 49.0 20.2 28.3 24.3 80.0** 22.7 45.5 50.0** 38.9 8.1 25.3 1.0 44.2 3.5* 21.6 3.5* (R30 kg/m2) (R150 mg/dL) (%50 mg/dL) (R130/85 mm Hg) 51.7 24.6 35.6 31.9 72.7** 10.9* 76.6** 45.5* 66.1 15.5 39.9 3.3 75.4* 9.9 42.9 10.6*

7.9 15.0 6.7 4.7 4.9 18.8** 9.0 8.3

Note: Values are percentages except where noted. *P< .05, **P< .01, significantly different between blacks with PCOS vs. age-matched whites with PCOS or blacks from NHANES vs. age-matched whites from NHANES. Hillman. Racial differences in metabolic risk in PCOS. Fertil Steril 2014.

age-matched white adults from NHANES was 1.52 (95% CI 1.02–2.23, P< .01). This difference was also seen in black women with PCOS vs. age-matched black women from NHANES (RR 2.42 [95% CI 1.52–3.82], P< .001). Next we calculated the CVD risk for each race according to the two Framingham risk scores (19). The 10-year CHD risk score and the 10-year general CVD risk score were not significantly different in adolescents, according to race. The 10-year CHD risk score was also not significantly different between adult black and white women with PCOS. In contrast, black women with PCOS had a higher 10-year general CVD risk score (2.23% [95% CI 0.24–19.98]) than their white counterparts (1.42% [95% CI 0.2–8.64], P< .01).

DISCUSSION This study is the first to comprehensively examine racial differences in both prevalence of MetSyn and Framingham CVD risk across the age spectrum namely, in adolescents and young adult women with PCOS seeking health care. Our findings indicate that black adolescents with PCOS have significantly more cardiometabolic risk factors and a higher risk of MetSyn compared with white adolescents. In contrast, our control population including adolescent females from

TABLE 4 Relative risk (95% CI) of metabolic syndrome by age group and race in women with PCOS compared with women from NHANES. <20 y

20–34 y

2.65 (1.29–5.4)**

1.44 (1.21–2.6)**

0.95 (0.4–2.25)

1.13 (0.58–2.21)

3.72 (1.90–7.25)**

1.52 (1.04–2.24)*

10.13 (5.10–20.13)**

2.42 (1.52–3.83)**

Comparison PCOS white vs. PCOS black NHANES white vs. NHANES black PCOS white vs. NHANES white PCOS black vs. NHANES black Note: See reference 13. * P< .01. ** P< .001.

Hillman. Racial differences in metabolic risk in PCOS. Fertil Steril 2014.

VOL. 101 NO. 2 / FEBRUARY 2014

the large NHANES study did not demonstrate differences in the prevalence of MetSyn according to race. Our analysis of young adults also showed that black women with PCOS have significantly more cardiometabolic risk factors and a higher risk of MetSyn compared with white women with PCOS. These findings are also different compared with the NHANES age-matched adult population. In black adults compared with adolescents, the increased cardiometabolic risk persisted even after controlling for obesity, which was the most common abnormal finding in all age groups. A few studies have examined the effect of race on individual components of MetSyn in women with PCOS. In one study, African American women with PCOS (n ¼ 32) had higher mean HDL-C levels, lower non-HDL cholesterol, and lower TG levels than Caucasian women (n ¼ 94) (14). Similar findings were reported in a case–control study including 120 women with PCOS (15). The authors concluded that African American women with PCOS had a more favorable lipid profile. With 519 subjects in our study, we found that black women with PCOS had lower mean HDL-C levels and more importantly a higher prevalence of abnormal HDL-C (<50 mg/dL) compared with white women. In another study including community-based women receiving health care in northern California, African American women with PCOS had a higher prevalence of obesity and hypertension compared with Caucasians (21). After adjusting for age, BMI category, and diabetes status, the odds of hypertension remained highest in blacks (OR 1.32 [95% CI 1.19–1.48]). These findings suggest differences based on race in metabolic risk in PCOS subjects seen in the community and at tertiary referral centers. The co-occurrence of metabolic risk factors (dyslipidemia, obesity, hyperglycemia, and hypertension) suggests the existence of a ‘‘MetSyn’’. Our study demonstrates that despite the possibly favorable lipid profile as reflected by low TGs, black women with PCOS have an increased risk of both MetSyn and higher 10-year general CVD risk. The most common metabolic abnormalities noted in black women with PCOS were obesity, hypertension, and high glucose levels. We also found low TG levels in black women with PCOS, which is consistent with data reported previously (14, 15). Our findings caution that limited evaluation of metabolic risk in black women may result in a 533

ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY missed diagnosis of MetSyn and an underestimation of cardiovascular risk. Very few studies have examined the prevalence of MetSyn in different races in women with PCOS. Welt et al. (16) compared 172 Caucasians and 44 African Americans from Boston and found no racial differences in mean HDL-C levels and prevalence of HDL-C <50 mg/dL. Further, the authors reported no differences in the prevalence of MetSyn between Caucasians and African Americans. Our larger study from Pennsylvania shows a significantly higher risk of MetSyn in both adolescent and adult black women with PCOS. We included adolescents to better understand the early onset of racial differences in cardiometabolic risk. Our findings demonstrate that in both adolescents and adults with PCOS, blacks have a higher prevalence of MetSyn compared with whites. The abnormal components of MetSyn were primarily due to obesity in adolescents. In the young adult population, however, even after controlling for obesity black women have a higher risk of low HDL-C and high glucose levels. Although we did not have data on socioeconomic status in our study, in the NHANES dataset after adjusting for socioeconomic status (i.e., education, income, health eating index, and activity level category) the odds for MetSyn were not significantly different comparing black vs. white adolescents and young adults (13). We used two tools for cardiovascular risk stratification: the commonly used Framingham risk score, which provides a 10-year CHD risk, and the general CVD risk score (22). The sex-specific Framingham CHD prediction performs well among whites and blacks and can also be applied to other ethnic groups (23). In reproductive-aged women with PCOS, however, the risk is usually low because there are negative or zero points for age <40 years. Additionally, assessments that stratify patients according to the number of defined risk factors can identify high-risk women, but they may falsely reassure those with a low risk score who have multiple borderline abnormalities. In 2008 another sex-specific multivariable risk factor algorithm derived from 4,522 women age 30–74 years was published and is used to assess general CVD risk and risk of individual CVD events, including coronary, cerebrovascular, peripheral arterial disease, and heart failure (20). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care. Using this approach we found a higher risk in black women compared with white women with PCOS. Interestingly, in the NHANES study non-Hispanic black adolescents and adults males had a lower prevalence of MetSyn compared with their non-Hispanic white counterparts (13). These differences persisted even after adjusting for multiple environmental confounders (i.e., education, income, health eating index, and activity level category). In contrast, non-Hispanic black females did not have a lower rate of MetSyn at any age, indicating significant gender differences between races. It has been suggested that specific racial/ethnic groups may have a genetic predisposition toward the presence or absence of particular MetSyn components. In particular, non-Hispanic black males and females have lower TG levels compared with their white counterparts. Our findings indicate that despite lower TG levels, black women with PCOS have an increased risk of MetSyn. One study has examined racial dif534

ferences in the prevalence of subclinical atherosclerosis in asymptomatic women with PCOS, using coronary artery calcium scores (24). They reported a higher prevalence of coronary artery calcium in African American women with PCOS (93.8%) compared with Caucasian women with PCOS (60.6%). These findings collectively highlight the need for future studies to examine racial differences in the risk of CVD in women with PCOS. Our study has some limitations. We used BMI as a surrogate for waist circumference in the definition of MetSyn in adolescents. A high correlation between waist circumference and BMI (r ¼ 0.94) has been previously reported in adolescents using 95th percentile for BMI as the threshold criterion for obesity (25). We used the same BMI cutoff for adolescents in our study. To use similar criteria in adolescents and adults, we also used BMI instead of waist circumference as the adult criteria. We did not include a geographically matched control group but chose the larger NHANES dataset because it adequately represented the racial groups that were included in our study. These subjects are community based, whereas our PCOS population was referred to our center and seeking health care. However, this should not have affected racial differences in prevalence of MetSyn within the NHANES dataset. Our data are cross-sectional, and although we have included adolescents and young adults, the persistence of racial differences in risk of MetSyn is not based on longitudinal data. In summary, this study is the first report of racial differences in MetSyn and Framingham CVD risk in both adolescents and adults with PCOS seeking health care. Obesity was the most common abnormality in both age groups. Larger studies in adolescents are needed to confirm the influence of race on cardiometabolic risk. In the meantime early intervention strategies targeted at therapeutic lifestyle changes are essential in this high-risk population. Longitudinal studies should examine the independent influence of PCOS and race on cardiovascular outcomes.

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