The prevalence of metabolic syndrome in pre- and post-menopausal women attending a tertiary clinic...

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The prevalence of metabolic syndrome in pre- and post-menopausal women attending a tertiary clinic in Turkey Tevfik Yoldemir *, Mithat Erenus Marmara University, School of Medicine, Department of Obstetrics and Gynecology, Istanbul, Turkey 1. Introduction The Framingham Heart Study revealed that there is a gradual increase in the incidence of cardiovascular morbidity and mortality between the ages of 40 and 55 years [1]. Furthermore, at any age, the incidence of cardiovascular disease (CVD) was significantly higher in postmenopausal compared to premenopausal women, suggesting a role for the cessation of ovarian function as a part of the etiology [2]. Menopause has an adverse effect on blood lipid levels. When compared with premenopausal women, postmenopausal women have significant increases in levels of total cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides, and decreasing levels of high density lipoprotein (HDL) and HDL2 cholesterol [3]. Metabolic syndrome (MS) increases in prevalence after the menopause and consists of insulin resistance, abdominal obesity, dyslipidaemia, elevated blood pressure and proinflammatory and prothrombotic states [4]. This syndrome usually precedes the development of diabetes mellitus and carries a twofold increased risk for cardiovascular events [5]. For those women who develop diabetes, the risk of cardiovascular morbidity and mortality is increased two- to six-fold after adjustment for associated risk factors [6]. Estrogen deficiency appears to be associated with an increased risk for the development of most of the clinical features of MS. Whether the menopause affects the prevalence of MS is unclear. Most population-based studies show age as the predominant variable associated with the increased prevalence of MS. The aim of the present study was to investigate the prevalence of MS in post- menopausal women attending a tertiary menopause out-patient clinic in Turkey. 2. Materials and methods One hundred and eighty postmenopausal women between the ages 50 and 60 years, and fifty-three premenopausal women between the ages 40 and 50 years seen at the Marmara University Gynecology or Menopause Outpatient Clinics were enrolled for this cross sectional study between July 2009 and July 2010. The premenopausal women who were eligible and decided to take part in the study after an informed interview were gathered from the Gynecology Outpatient Clinics between these dates. Exclusion criteria for both groups were: (1) the presence of acute infection or chronic inflammatory disease; (2) the use of drugs that can affect metabolism, such as b-blockers, glucocorticoids, diuretics, lipid- lowering agents, antidiabetic agents, antiresorptive agents, and anticoagulants; (3) the use of alcohol; and (4) drug abuse. European Journal of Obstetrics & Gynecology and Reproductive Biology 164 (2012) 172–175 A R T I C L E I N F O Article history: Received 20 December 2011 Received in revised form 9 April 2012 Accepted 12 June 2012 Keywords: Postmenopause Pre-menopause Prevalence Metabolic syndrome A B S T R A C T Objective: To determine the prevalence of metabolic syndrome among pre- and post-menopausal women attending a tertiary clinic in Turkey. Study design: This is a cross-sectional study consisting of one hundred and eighty healthy postmenopausal women and fifty-three healthy premenopausal women evaluated for presence or absence of metabolic syndrome. The t test and Fischer exact test were used for continuous variables and chi-square test was used for categorical variables. Results: The prevalence of metabolic syndrome among pre-menopausal women was 15.09% according to NCEP criteria. The prevalence of metabolic syndrome among postmenopausal women was 19.44% according to NCEP criteria. There was no significant difference in the prevalence of metabolic syndrome between premenopausal and postmenopausal women in our study population. Conclusion: There was no significant difference in the prevalence of metabolic syndrome between premenopausal and postmenopausal women attending a tertiary clinic in Turkey. ß 2012 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Marmara University Hospital, Department of Obstetrics and Gynecology, Fevzi Cakmak District, Mimar Sinan Street No. 41, Ust Kaynarca, Pendik, Istanbul, Turkey. Tel.: +90 216 6254714; fax: +90 216 6570695. E-mail address: tevfi[email protected] (T. Yoldemir). Contents lists available at SciVerse ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/ejo g rb 0301-2115/$ see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejogrb.2012.06.021

Transcript of The prevalence of metabolic syndrome in pre- and post-menopausal women attending a tertiary clinic...

Page 1: The prevalence of metabolic syndrome in pre- and post-menopausal women attending a tertiary clinic in Turkey

European Journal of Obstetrics & Gynecology and Reproductive Biology 164 (2012) 172–175

The prevalence of metabolic syndrome in pre- and post-menopausal womenattending a tertiary clinic in Turkey

Tevfik Yoldemir *, Mithat Erenus

Marmara University, School of Medicine, Department of Obstetrics and Gynecology, Istanbul, Turkey

A R T I C L E I N F O

Article history:

Received 20 December 2011

Received in revised form 9 April 2012

Accepted 12 June 2012

Keywords:

Postmenopause

Pre-menopause

Prevalence

Metabolic syndrome

A B S T R A C T

Objective: To determine the prevalence of metabolic syndrome among pre- and post-menopausal women

attending a tertiary clinic in Turkey.

Study design: This is a cross-sectional study consisting of one hundred and eighty healthy

postmenopausal women and fifty-three healthy premenopausal women evaluated for presence or

absence of metabolic syndrome. The t test and Fischer exact test were used for continuous variables and

chi-square test was used for categorical variables.

Results: The prevalence of metabolic syndrome among pre-menopausal women was 15.09% according to

NCEP criteria. The prevalence of metabolic syndrome among postmenopausal women was 19.44%

according to NCEP criteria. There was no significant difference in the prevalence of metabolic syndrome

between premenopausal and postmenopausal women in our study population.

Conclusion: There was no significant difference in the prevalence of metabolic syndrome between

premenopausal and postmenopausal women attending a tertiary clinic in Turkey.

� 2012 Elsevier Ireland Ltd. All rights reserved.

Contents lists available at SciVerse ScienceDirect

European Journal of Obstetrics & Gynecology andReproductive Biology

jou r nal h o mep ag e: w ww .e lsev ier . co m / loc ate /e jo g rb

1. Introduction

The Framingham Heart Study revealed that there is a gradualincrease in the incidence of cardiovascular morbidity and mortalitybetween the ages of 40 and 55 years [1]. Furthermore, at any age, theincidence of cardiovascular disease (CVD) was significantly higher inpostmenopausal compared to premenopausal women, suggesting arole for the cessation of ovarian function as a part of the etiology [2].Menopause has an adverse effect on blood lipid levels. Whencompared with premenopausal women, postmenopausal womenhave significant increases in levels of total cholesterol, low densitylipoprotein (LDL) cholesterol and triglycerides, and decreasing levelsof high density lipoprotein (HDL) and HDL2 cholesterol [3].

Metabolic syndrome (MS) increases in prevalence after themenopause and consists of insulin resistance, abdominal obesity,dyslipidaemia, elevated blood pressure and proinflammatory andprothrombotic states [4]. This syndrome usually precedes thedevelopment of diabetes mellitus and carries a twofold increasedrisk for cardiovascular events [5]. For those women who developdiabetes, the risk of cardiovascular morbidity and mortality is

* Corresponding author at: Marmara University Hospital, Department of

Obstetrics and Gynecology, Fevzi Cakmak District, Mimar Sinan Street No. 41,

Ust Kaynarca, Pendik, Istanbul, Turkey. Tel.: +90 216 6254714;

fax: +90 216 6570695.

E-mail address: [email protected] (T. Yoldemir).

0301-2115/$ – see front matter � 2012 Elsevier Ireland Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.ejogrb.2012.06.021

increased two- to six-fold after adjustment for associated riskfactors [6].

Estrogen deficiency appears to be associated with an increasedrisk for the development of most of the clinical features of MS.Whether the menopause affects the prevalence of MS is unclear.Most population-based studies show age as the predominantvariable associated with the increased prevalence of MS. The aim ofthe present study was to investigate the prevalence of MS in post-menopausal women attending a tertiary menopause out-patientclinic in Turkey.

2. Materials and methods

One hundred and eighty postmenopausal women between theages 50 and 60 years, and fifty-three premenopausal womenbetween the ages 40 and 50 years seen at the Marmara UniversityGynecology or Menopause Outpatient Clinics were enrolled for thiscross sectional study between July 2009 and July 2010. Thepremenopausal women who were eligible and decided to take partin the study after an informed interview were gathered from theGynecology Outpatient Clinics between these dates. Exclusioncriteria for both groups were: (1) the presence of acute infection orchronic inflammatory disease; (2) the use of drugs that can affectmetabolism, such as b-blockers, glucocorticoids, diuretics, lipid-lowering agents, antidiabetic agents, antiresorptive agents, andanticoagulants; (3) the use of alcohol; and (4) drug abuse.

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T. Yoldemir, M. Erenus / European Journal of Obstetrics & Gynecology and Reproductive Biology 164 (2012) 172–175 173

Post-menopause was defined as the absence of menstruation forthe preceding 12 months or more.

The study was approved by the Institutional Review Board ofMarmara University and the Local Ethics Committee. All patientsgave written informed consent and their complete clinical,obstetric, and gynecologic history was taken before enrollment.All patients received a cervical Pap smear, transvaginal ultrasound,mammography and a physical examination that included abimanual pelvic examination. Laboratory evaluation includedcomplete blood count, coagulation testing, fasting blood glucosetest, lipid profile, hepatic and renal function tests.

The height and weight of each patient were obtained with themwearing indoor clothing and without shoes. BMI was calculated asweight (kg) divided by the square of the height (meter). Systolicblood pressure (BP) and diastolic BP were measured twice on botharms using a calibrated aneroid sphygmomanometer after thesubject had been resting in the supine position for at least 5 min;the average of two measurements was used in the analysis.

Venous blood was collected into vacutainer tubes (Becton &Dickinson) after overnight fasting and centrifuged within 4 h.Serum glucose, total cholesterol, HDL-cholesterol and triglyceridelevels were measured by standard laboratory techniques.

MS was assessed by the National Cholesterol EducationProgram Adult Treatment Panel III (NCEP ATP III) criteria [7]. MSwas diagnosed if three of the following five factors were presentaccording to NCEP criteria; hypertension (diastolic � 85 mmHg,systolic � 130 mmHg), central obesity (waist � 88 cm),HDL � 50 mg/dl, triglycerides � 150 mg/dl, fasting gluco-se � 110 mg/dl. Women were grouped in two groups accordingto whether they had MS or not, based on the inclusion criteria ofthe NCEP ATP III.

All analyses used StataSE 10.0 (Statacorp, TX). Demographiccharacteristics were expressed by using descriptive statistics. The t

test and Fischer exact test were used for continuous variables andthe chi-square test was used for categorical variables. Results wereexpressed as mean and standard deviation (SD) and p < 0.05 wasconsidered statistically significant. Correlations between variableswere calculated by Spearman test.

3. Results

The demographic parameters of the study groups are shown inTable 1. Premenopausal women had a higher mean waist–hip ratio(WHR) even though their mean BMI was similar to that ofpostmenopausal women. Furthermore the mean HDL cholesteroland LDL cholesterol levels were lower in premenopausal womenthan in postmenopausal women. The demographic parameters of

Table 1Demographic parameters of the study groups.a

Postmenopausal (n = 180)

Mean age (years) 57.11 � 6.07

Duration of menopause (years) 10.56 � 7.78

Weight (kg) 70.93 � 11.00

Body mass index (kg/m2) 28.02 � 4.62

Systolic blood pressure (mmHg) 121.26 � 21.51

Diastolic blood pressure (mmHg) 83.75 � 18.35

Waist hip ratio 0.85 � 0.09

Fasting glucose (mg/dl) 98.99 � 22.91

Low density lipoprotein (mg/dl) 138.48 � 36.26

Triglyceride (mg/dl) 131.59 � 64.40

High density lipoprotein (mg/dl) 61.42 � 16.60

Total cholesterol (mg/dl) 225.21 � 42.99

Triglyceride/HDL cholesterol 2.46 � 1.77

Abbreviations: Body mass index calculated as weight in kilograms divided by height ina Values are given as mean � standard deviation (SD).

the pre- and post-menopausal women grouped according to NCEPcriteria are shown in Table 2.

The relative frequency of each marker of MS among pre- andpostmenopausal women is shown in Table 3. Central obesity (waistcircumference � 88 cm) was the most frequent finding in thepostmenopausal group followed by increased triglyceride anddecreased HDL cholesterol levels. Central obesity (waist circum-ference � 88 cm) was the most frequent abnormality in thepremenopausal group followed by decreased HDL cholesteroland increased triglyceride levels. Ninety-two out of 145 postmen-opausal women who did not have MS had never used hormonaltherapy (HT); whereas 23 out of 35 women with MS had neverused HT. The numbers of women with a history of past HT use were53 and 12, respectively. The percentage of past history of HT usewas similar between postmenopausal women without MS andwith MS (p = 0.24). Only the HDL value was statistically significantbetween pre- and post-menopausal women (Table 3). Thepercentage of high HDL values fulfilling one of the NCEP criteriaamong postmenopausal women did not differ between womenwho never used HT or had a past history of HT use (p = 0.25).

According to the NCEP criteria the percentage of women with MSduring the postmenopausal years was comparable to that forwomen in their pre-menopausal years (19.44% vs. 15.09%, p = 0.47).

Among postmenopausal women, the best positive correlationswere found between the MS and triglyceride/HDL cholesterol.Triglyceride and fasting glucose showed a moderate correlation.The only negative correlation was with HDL cholesterol. Age, BMI,WHR and BP showed weak correlations. Among premenopausalwomen, BMI, triglyceride/HDL cholesterol and triglyceride showedmoderate positive correlations and HDL cholesterol showed amoderate negative correlation with MS, whereas all otherparameters had weak correlations (Table 4).

4. Comments

During the menopausal transition there is a dramatic reductionin estradiol levels and a progressive shift toward androgendominance [8,9]. Studies suggest a link between androgenicityand CVD risk factors [10–12]. Several studies have shown a shifttoward a more atherogenic lipid profile in postmenopausalwomen, who tend to have higher total and LDL cholesterol,triglyceride and lipoprotein(a) levels, and lower HDL cholesterollevels compared with premenopausal women. [13,14].

MS is a combination of important CVD risk factors thatfrequently coexist [15]. The syndrome is evident in 20–30% ofmiddle-aged women and has been linked to the development ofCVD and diabetes [16–18]. The incidence varies substantially by

Premenopausal (n = 53) p value

45.34 � 3.06 0.001

� �74.26 � 13.34 0.07

29.08 � 4.75 0.15

121.36 � 21.15 0.98

79.57 � 12.08 0.12

0.89 � 0.08 0.002

95.69 � 16.97 0.34

110.84 � 32.90 0.0001

133.86 � 92.97 0.84

56.00 � 18.32 0.05

191.1 � 36.01 0.0001

2.80 � 2.70 0.30

meters squared.

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Table 4Correlation between metabolic syndrome and various parameters.

Premenopausal Postmenopausal

r valuea p value r valuea p value

Table 2The demographic data of the pre- and postmenopausal womena according to NCEP criteria.

Premenopausal women

Women without MS (n = 45) Women with MS (n = 8) p value

Mean age (years) 45.27 � 2.93 45.75 � 3.88 0.68

Weight (kg) 71.38 � 12.08 90.5 � 7.01 0.0001

Body mass index (kg/m2) 28.08 � 4.30 34.71 � 2.93 0.0001

Systolic blood pressure (mmHg) 118.84 � 20.68 135.5 � 19.08 0.04

Diastolic blood pressure (mmHg) 78.71 � 11.06 84.37 � 16.83 0.23

Waist hip ratio 0.89 � 0.08 0.93 � 0.03 0.14

Fasting glucose (mg/dl) 91.91 � 9.75 116 � 30.43 0.0001

Low density lipoprotein (mg/dl) 113.28 � 31.86 98 � 37.50 0.23

Triglyceride (mg/dl) 112.17 � 52.06 247.75 � 164.20 0.0001

High density lipoprotein (mg/dl) 58.21 � 18.18 44.37 � 15.10 0.049

Total cholesterol (mg/dl) 188.64 � 36.38 204 � 33.12 0.27

Triglyceride/HDL cholesterol 2.09 � 1.09 6.49 � 5.05 0.0001

Postmenopausal women

Women without MS (n = 145) Women with MS (n = 35) p value

Mean age (years) 57.02 � 6.15 57.49 � 5.78 0.69

Duration of menopause (years) 10.56 � 7.78 10.57 � 7.37 0.99

Weight (kg) 69.50 � 10.46 76.83 � 11.45 0.0004

Body mass index (kg/m2) 27.58 � 4.66 29.83 � 4.06 0.01

Systolic blood pressure (mmHg) 119.54 � 19.91 128.29 � 26.25 0.03

Diastolic blood pressure (mmHg) 81.97 � 15.84 91.06 � 25.22 0.01

Waist hip ratio 0.84 � 0.09 0.88 � 0.09 0.06

Fasting glucose (mg/dl) 93.92 � 11.08 119.74 � 40.83 0.0001

Low density lipoprotein (mg/dl) 138.19 � 35.85 139.66 � 38.40 0.83

Triglyceride (mg/dl) 114.75 � 47.34 199.91 � 78.66 0.0001

High density lipoprotein (mg/dl) 64.929 � 13.42 47.17 � 20.47 0.0001

Total cholesterol (mg/dl) 225.53 � 42.15 223.91 � 46.85 0.84

Triglyceride/HDL cholesterol 1.89 � 0.97 4.78 � 2.33 0.0001

Abreviations: MS, metabolic syndrome; body mass index, calculated as weight in kilograms divided by height in meters squared.a Values are given as mean � standard deviation (SD).

T. Yoldemir, M. Erenus / European Journal of Obstetrics & Gynecology and Reproductive Biology 164 (2012) 172–175174

age and ethnicity in both men and women. Anand et al. inmultiethnic communities in Canada found the incidence to be 42%among Native Americans, 26% among South Asians, 22% amongEuropeans, and 11% among Chinese [19]. Ford et al. had found theunadjusted and age-adjusted prevalences of MS were 21.8% and23.7% respectively, according to NCEP/ATP III diagnostic criteria[20]. Its prevalence was seen to increase markedly with age,occurring in <10% of individuals aged 20–29 years, 20% ofindividuals aged 40–49 years, and 45% in individuals aged 60–69 years [20]. In our study premenopausal women with a mean ageof 45.34 years (95% confidence interval (CI) 44.50–46.18) showed asimilar frequency of MS as did the postmenopausal women, whohad a mean age of 57.11 years (95% CI 56.22–58.00). Even thoughthere was, on average, 12 years of age difference between the studygroups, the prevalence of MS was comparable. Mesch et al. [21]reported that MS affected 20–22% of women who were in themenopausal transition and the postmenopausal period; similarresults were reported by Meigs et al. [22]. In our study it seemedthat the menopausal transition per se did not affect the prevalenceof metabolic syndrome. Future studies in older menopausalwomen may show an impact of age on the prevalence of MS inTurkish women older than 60 years, similar to reported data inother ethnic groups described previously [20,23,24].

Table 3Relative frequency of various markers of metabolic syndrome in pre- and

postmenopausal women according to NCEP criteria.

Premenopausal Postmenopausal p value

Hypertension (�130/85 mm Hg) 5 (9) 37 (20.56) 0.12

Central obesity (waist � 88 cm) 34 (64) 126 (70) 0.85

HDL cholesterol (�50 mg/dl) 22 (41.5) 43 (23.89) 0.01

Triglyceride (�150 mg/dl) 11 (20.7) 51 (28.33) 0.47

Fasting glucose (�110 mg/dl) 7 (13.2) 26 (14.44) 0.96

Values are shown as numbers and as percentages in parentheses.

The predictive value of MS has not been superior to theFramingham Risk Score in defining CVD risk [25,26], but itsdiagnosis remains a strong predictor of CVD risk and identifiespotentially high-risk patients. Dekker et al. showed that both menand women with MS had a 2-fold increased risk of CVD [27]. Inwomen, they found that an increase in the number of componentsfor MS translated into an increased risk of CVD. Studies that wereaimed at demonstrating the correlation between menopause andcardiovascular risk factors, including MS, produced conflictingresults. Different study designs, population studied, age, time sincemenopause, spontaneous or surgical menopause, and diagnosticcriteria of MS could have caused serious methodological errors. Ahigher prevalence of each factor and of the MS among menopausalwomen than among women of childbearing age has been the mostcommon result.

Figueiredo Neto et al. [28] showed that there was a higherprevalence of MS among menopausal women, but the differencewas not statistically significant after adjustment for age. They

Triglyceride/HDL cholesterol 0.391 0.005 0.517 <0.0001

HDL cholesterol �0.373 0.008 �0.510 <0.0001

Triglyceride 0.403 0.004 0.462 <0.0001

Fasting blood glucose 0.389 0.005 0.400 <0.0001

BMI 0.493 0.0002 0.229 0.002

WHR 0.339 0.013 0.184 0.014

Systolic BP 0.335 0.014 0.152 0.043

Diastolic BP 0.209 0.133 0.137 0.068

Age 0.054 0.701 0.031 0.682

HDL, high density lipoprotein; BP, blood pressure; BMI, body mass index; WHR,

waist hip ratio.a Spearman correlation.

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concluded that the increase in the prevalence of MS amongpostmenopausal women was caused mainly by the age increase.Likewise, our results did not show a significant difference in theprevalence of MS in post-menopausal women. Casiglia et al. founda higher prevalence of MS components among post-menopausalwomen, but the difference disappeared after an adjustment for age[29]. The authors suggested that the cardiovascular effects usuallyattributed to menopause seemed to be merely a consequence ofthe older age of menopausal women.

Loss of estrogen is associated with an increase in abdominalobesity, which may increase a woman’s risk for developing insulinresistance [30]. An accelerated increase of visceral obesity [31,32]results in an increased waist to hip ratio. In our study the WHR didnot differ between the groups according to NCEP criteria. Weightgain is also common in postmenopausal women not receivinghormone replacement therapy [33]. Abdominal obesity appears tobe a significant cardiac risk factor, independent of weight [34].After adjusting for BMI, lower insulin sensitivity is associated witha higher waist-to-hip ratio. The adjusted odds ratio for thepresence of significant coronary artery disease increased inpatients with MS or diabetes regardless of their weight. Kipet al. reported that MS, and not BMI, predicted future cardiovas-cular risk in women [35]. In both groups BMI values were higher inMS women than non-MS ones.

One limitation of our study is the sample size. The study wasplanned to recruit women in a period of one year. In this period,eligible premenopausal women seen at the Gynecology Out-patient Clinic were interviewed and questioned about theirwillingness to participate in the present study. The number ofwomen between the age of 40 and 50 who agreed to take part wasunintentionally limited.

The present study showed that the menopausal transition doesnot have an impact on the prevalence of MS in our population.Future studies in older women may show the role of age as anindependent risk factor for the occurrence of MS.

References

[1] Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk ofcardiovascular disease: the Framingham Study. Annals of Internal Medicine1976;85:447–52.

[2] Grodstein F, Stampfer M. The epidemiology of coronary heart disease andestrogen replacement in postmenopausal women. Progress in CardiovascularDiseases 1995;38:199–210.

[3] Stevenson JC, Crook D, Godsland IF. Influence of age and menopause on serumlipids and lipoproteins in healthy women. Atherosclerosis 1993;98:83–90.

[4] Grundy SM, Brewer Jr HB, Cleeman JI, Smith Jr SC, Lenfant C. Definition ofmetabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Defini-tion. Arteriosclerosis Thrombosis and Vascular Biology 2004;24:e13–8.

[5] Reilly MP, Wolfe ML, Rhodes T, Girman C, Mehta N, Radar DJ. Measures ofinsulin resistance add incremental value to the clinical diagnosis of metabolicsyndrome in association with coronary atherosclerosis. Circulation2004;110:803–9.

[6] Haffner SM, Lehto S, Ronnemass T, Pyorala K, Laakso M. Mortality fromcoronary heart disease in subjects with type 2 diabetes and in nondiabeticsubjects with and without prior myocardial infarction. New England Journal ofMedicine 1998;339:229–34.

[7] Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Educa-tion Program – Adult Treatment Panel III. International Diabetes Federation,and World Health Organization definitions of the metabolic syndrome aspredictors of incident cardiovascular disease and diabetes. Diabetes Care2007;30:8–13.

[8] Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL. A prospective longitu-dinal study of serum testosterone, dehydroepiandrosterone sulfate, and sexhormone-binding globulin levels through the menopause transition. Journal ofClinical Endocrinology and Metabolism 2000;85:2832–8.

[9] Lasley BL, Santoro N, Randolf JF, et al. The relationship of circulating dehy-droepiandrosterone, testosterone, and estradiol to stages of the menopausaltransition and ethnicity. Journal of Clinical Endocrinology and Metabolism2002;87:3760–7.

[10] Do KA, Green A, Guthrie JR, Dudley EC, Burger HG, Dennerstein L. Longitudinalstudy of risk factors for coronary heart disease across the menopausal transi-tion. American Journal of Epidemiology 2000;151:584–93.

[11] Guthrie JR, Taffe JR, Lehert P, Burger HG, Dennerstein L. Association betweenhormonal changes at menopause and the risk of a coronary event: a longitu-dinal study. Menopause 2004;11:315–22.

[12] Sowers MR, Jannausch M, Randolph JF, et al. Androgens are associated withhemostatic and inflammatory factors among women at the mid-life. Journal ofClinical Endocrinology and Metabolism 2005;90:6064–71.

[13] Jensen J, Nilas L, Christiansen C. Influence of menopause on serum lipids andlipoproteins. Maturitas 1990;12:321–31.

[14] Campos H, McNamara JR, Wilson PW, Ordovas JM, Schaefer EJ. Differences inlow density lipoprotein subfractions and apolipoproteins in premenopausaland postmenopausal women. Journal of Clinical Endocrinology and Metabo-lism 1988;67:30–5.

[15] Anderson RN, Smith BL. Deaths Leading Causes for 2002 National VitalStatistics Reports, vol. 53, no. 17. Hyattsville, MD: National Center for HealthStatistics; 2005.

[16] Bonora E, Kiechl S, Willeit J, et al. Carotid atherosclerosis and coronary heartdisease in the metabolic syndrome: prospective data from the Bruneck Study.Diabetes Care 2003;26:1251–7.

[17] Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortalityassociated with the metabolic syndrome. Diabetes Care 2001;24:683–9.

[18] Malik S, Wong ND, Franklin SS, et al. Impact of the metabolic syndrome onmortality from coronary heart disease, cardiovascular disease, and all causesin United States adults. Circulation 2004;110:1245–50.

[19] Anand SS, Yi Q, Gerstein H, et al. Relationship of metabolic syndrome andfibrinolytic dysfunction in cardiovascular disease. Circulation 2003;108:420–5.

[20] Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among USadults: findings from the third National Health and Nutrition ExaminationSurvey. JAMA 2002;287:356–9.

[21] Mesch VR, Boero LE, Siseles NO, et al. Metabolic syndrome throughout themenopausal transition: influence of age and menopausal status. Climacteric2006;9:40–8.

[22] Meigs J, Wilson P, Nathan D, D’Agostino Sr RB, Williams K, Haffner SM.Prevalence and characteristics of the metabolic syndrome in the San AntonioHeart and Framingham Offspring studies. Diabetes 2003;52:2160–7.

[23] Schneider JG, Tompkins C, Blumenthal RS, Mora S. The metabolic syndrome inwomen. Cardiology in Review 2006;14:286–91.

[24] Kim HM, Park J, Ryu SY, Kim J. The effect of menopause on the metabolicsyndrome among Korean women. Diabetes Care 2007;30:701–6.

[25] Stern MP, Williams K, Gonzalez-Villalpando C, Hunt KJ, Haffner SM. Does themetabolic syndrome improve identification of individuals at risk of type 2diabetes and/or cardiovascular disease. Diabetes Care 2004;27:2676–81.

[26] Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome vsFramingham Risk Score for prediction of coronary heart disease, stroke, andtype 2 diabetes mellitus. Archives of Internal Medicine 2005;165:2644–50.

[27] Dekker JM, Girman C, Rhodes T, et al. Metabolic syndrome and 10-yearcardiovascular disease risk in the Hoorn study. Circulation 2005;112:666–73.

[28] Figueiredo Neto JA, Figueredo ED, Barbosa JB, et al. Metabolic syndrome andmenopause: cross-sectional study in gynecology clinic. Arquivos Brasileiros deCardiologia 2010;95:339–45.

[29] Casiglia E, Tikhonoff V, Caffi S, et al. Menopause does not affect blood pressureand risk profile, and menopausal women do not become similar to men.Journal of Hypertension 2008;26:1983–92.

[30] Poehlman ET, Toth MJ, Gardner AW. Changes in energy balance and bodycomposition at menopause: a controlled longitudinal study. Annals of InternalMedicine 1995;123:673–5.

[31] Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Tokunaga K. Pathophysiol-ogy and pathogenesis of visceral fat obesity. Annals of the New York Academyof Sciences 1995;748:399–406.

[32] Pascot A, Lemieux S, Lemieux I, et al. Age-related increase in visceral adiposetissue and body fat and the metabolic risk profile of premenopausal women.Diabetes Care 1999;22:1471–8.

[33] Gambacciani M, Ciaponi M, Cappagli B, De Simone L, Orlandi R, Genazzani AR.Prospective evaluation of body weight and body fat distribution in earlypostmenopausal women with and without hormonal replacement therapy.Maturitas 2001;39:125–32.

[34] Kanaya AM, Vittinghoff E, Shlipak MG, et al. Association of total and centralobesity with mortality in postmenopausal women with coronary heart dis-ease. American Journal of Epidemiology 2003;158:1161–70.

[35] Kip KE, Marroquin OC, Kelley DE, et al. Clinical importance of obesity versusthe metabolic syndrome in cardiovascular risk in women. Circulation2004;109:706–13.