Original Study

What is the Risk of Metabolic Syndrome in Adolescents with

Normal BMI who have Polycystic Ovary Syndrome?
Yunus Aydin MD 1,*, Hikmet Hassa MD 1, Derya Burkankulu MD 2, Didem Arslantas MD 3,
Deniz Sayiner PhD 4, Nebahat Ozerdogan PhD 4
1
Department of Obstetrics and Gynecology, Reproductive Medicine Unit, Eskisehir Osmangazi University, Eskisehir, Turkey
2
Department of Obstetrics and Gynecology, Eskisehir Osmangazi University, Eskisehir, Turkey
3
Department of Public Health, Eskisehir Osmangazi University, Eskisehir, Turkey
4
Midwifery Department of Nursing College, Eskisehir Osmangazi University, Eskisehir, Turkey

a b s t r a c t
Objective: The purpose of this study is to evaluate the effect of polycystic ovarian syndrome (PCOS) on the prevalence of metabolic
syndrome (MBS) in adolescent girls with normal BMI.
Materials and Methods: Our study group consisted of 63 pubertal girls with a BMI less than 25 kg/m2 who were referred to our center with
signs of hirsutism or oligomenorrhea. The diagnosis of PCOS was based on the recent ESHRE/ASRM proposal and required that all 3 of the
Rotterdam criteria for diagnosing PCOS in adolescents be met. The control group consisted of 159 pubertal girls matched for age and BMI.
Glucose, insulin, testosterone, and sex hormone-binding globulin, free testosterone and all lipid parameters measured. For to diagnose the
cases with MBS, modied Cook criteria were used and cases who had at least 3 of 5 criteria's were diagnosed as MBS.
Results: Girls with PCOS had higher blood pressure parameters (systolic/diastolic) (P ! .01), fasting insulin (P 5 .007), low-density lipo-
protein (P 5 .017), triglyceride (P 5 .045), total (P ! .001) and free testosterone (P 5 .001) levels compared to control group. There were
more cases who had at least 1 Cook criterion in girls with PCOS compared to the control group but the difference was not signicant.
However, there were more cases who had MBS in girls with PCOS compared to the control group (P 5 .02).
Conclusion: MBS prevalence is higher in normal BMI adolescent girls with PCOS compared to age and BMI matched control group. So as
clinicians, we must search for the MBS criteria's in girls with PCOS even if they have a normal BMI.
Key Words: Adolescent, Body mass index, Metabolic syndrome, Polycystic ovary syndrome

Introduction false positive rates are high due to increased overlapping of

Polycystic ovarian syndrome (PCOS) affects 5%-10%
of reproductive-aged women. Oligomenorrhea/amenorrhea
with hirsutism is often included in the diagnosis, but the
incidence varies with the application of different diagnostic
criteria.1 In nearly all cases of PCOS, clinical characteristics of
the syndrome start to develop from puberty, but some of the
normal pubertal clinical symptoms (acne or menstrual
irregularity) overlap with the ndings of PCOS. Therefore, if
we assume the abnormal pubertal signs (hirsutism, poly-
cystic ovarian appearance on ultrasonography (US), non-
physiological menstrual delays) as normal variations in
puberty, the diagnosis of PCOS is often delayed. Moreover, as
clinicians, we must not overestimate normal pubertal nd-
ings (physiological menstrual irregularity, multifollicular
appearance on US, increased tendency for acne development)
as the components of PCOS.2 According to the Rotterdam
criteria,3 the incidence of PCOS during puberty is approxi-
mately 18%-21%.4 However, with the application of standard
criteria for the diagnosis of PCOS during the pubertal period,
This study was funded by the Scientic Investigations Department of our Uni-
versity with the number of 201211008. The authors indicate no conicts of interest.
* Address correspondence to: Yunus Aydin, MD, Assistant Professor, Eskisehir
Osmangazi University School of Medicine, Department of Obstetrics and Gynecol-
ogy, Eskisehir, 26480, Turkey; Phone: 905335168740
E-mail address: aydin.yunus@yahoo.com (Y. Aydin).
1083-3188/$ - see front matter 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.jpag.2014.08.011
normal pubertal ndings with the ndings of PCOS.5 There-
fore, as stated in Amsterdam ESHRE/ASRM-Sponsored 3rd
PCOS Consensus Workshop Group, we must determine the
presence of all 3 Rotterdam criteria to diagnose PCOS in
adolescents.1,5
Today, it is abundantly obvious that PCOS is primarily a
metabolic dysfunctional state, in addition to increased hair
growth and irregular menstruation.6 Therefore, cardiovascu-
lar problems, obesity, and insulin resistance are among the
factors determining long-term life expectancy and quality of
life.1 Metabolic dysfunction can start as early as puberty; thus,
correctly diagnosing adolescent girls with PCOS is very
important. In a retrospectively designed study, Roe et al re-
ported that, in adolescent PCOS girls using by the Androgen
Excess-PCOS Society (AE-PCOS) criteria,7 the rate of metabolic
syndrome (10.8%) was higher than that in a matched control
group (1.7%) (P ! .04).6 In contrast, Rossi et al reported that, in
obese adolescent PCOS girls diagnosed using the 1990
National Institutes of Health (NIH) criteria,8 the presence of
PCOS did not add any additional risk for the development of
metabolic syndrome (MBS). Therefore, studies in girls with a
normal body mass index (BMI) and with more certain criteria
for PCOS might be more informative for describing the rela-
tionship between PCOS and MBS.9
In this study, our aim was to investigate the association of
metabolic risk factors and metabolic syndrome with PCOS
272 Y. Aydin et al. / J Pediatr Adolesc Gynecol 28 (2015) 271e274
in adolescent girls with normal BMI and PCOS (diagnosed
by the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS
Consensus Workshop Group criteria), compared with a
matched control group. To our knowledge, this is the rst
study investigating the metabolic risk factors in this kind of
specialized group.
Materials and Methods
This cross-sectional case-control study was conducted in
the Reproductive Medicine Unit of Eskisehir Osmangazi
University between October 2012 and November 2013. The
reported investigations were performed in accordance with
the principles of the Declaration of Helsinki (as revised in
Tokyo, 2004). The study protocol was approved by the
Ethics Committee of our university, and informed consent
was obtained from all of the participants.
We enrolled 63 pubertal girls with a BMI less than 25 kg/m2
who were referred to our center with signs of hirsutism or
oligomenorrhea. The diagnosis of PCOS was based on the
recent ESHRE/ASRM proposal, requiring that all 3 of the Rot-
terdam criteria for diagnosing PCOS in adolescents be met.1 As
recommended by ESHRE/ASRM, the diagnostic criteria
included the presence of: (1) hyperandrogenemia, dened as
elevated blood androgens plus clinical evidence of hyper-
androgenemia; (2) oligomenorrhea present for 2 years (!10
menses per year or at O35-day intervals) or primary amen-
orrhea at the age of 16 years old; and (3) an abdominal US
demonstrating an ovarian volume greater than 10 cm3. The
control group consisted of 159 pubertal girls matched for age
and BMI, all of whom had no history or evidence of oligo-
menorrhea, hirsutism or acne. The exclusion criteria for both
groups were: (1) previously diagnosed cardiovascular dis-
ease; (2) the presence of an endocrine disorder, such as thy-
roid dysfunction or hyperprolactinemia; (3) the presence of
congenital adrenal hyperplasia, androgen-secreting neo-
plasms or severe insulin resistance; (4) a history of any type of
drug use, including contraceptive, anti-diabetic, antihyper-
tensive, anti-androgenic or weight-reduction agents; (5) a
history of smoking or alcohol use; (6) and BMI greater than
25 kg/m2.
Clinical variables, such as weight, height and blood pres-
sure (BP) were assessed in all of the subjects using standard
protocols during outpatient hospital visits. BMI was calcu-
lated as weight divided by the square of height (kg/m2).
All of the biochemical and hormonal measurements
were obtained during the basal portion of the follicular
phase (day 2-5 of menstruation) and were processed in the
biochemistry laboratory of the university hospital. Plasma
was processed from blood samples by adding 1 mg/ml Na2-
EDTA. The blood samples were centrifuged at 3000 g for
15 minutes at 4 C. Immediately after centrifugation, the
plasma samples were frozen and stored at 80 C for a
period of no more than 4 weeks.
Assays for glucose, insulin, testosterone, and sex
hormone-binding globulin (SHBG) were performed using an
automated analyzer (Abbott Architect, Abbott Laboratories,
Abbott Park, IL). Free testosterone levels were measured
with a commercially available ELISA kit (Diasource,
Belgium). All of the lipid parameters (total cholesterol,
triglycerides, high-density lipoprotein cholesterol [HDL
cholesterol], and low-density lipoprotein cholesterol [LDL
cholesterol]) were measured using an enzymatic colori-
metric test. The estimate of insulin resistance, as used for the
homeostasis model assessment score, was calculated as
fasting insulin  fasting glucose/22.5. For all of the hormonal
assays, the intra- and inter-assay coefcients of variation
(CVs) were !5%.
To diagnose cases of MBS, the modied Cook criteria10
were used, and patients were diagnosed with MBS who had
at least 3 of the 5 criteria: (1) waist circumference O 90th
percentile; (2) fasting glucose level $ 100 mg/dl; (3) trigly-
ceride level $ 110 mg/dl; (4) HDL level # 40 mg/dl; and (5)
blood pressure measurement $ 90th percentile.
All of the statistical analyses were performed with SPSS
software, version 20.0 (Statistical Package for Social Science,
SPSS, IBM). Descriptive analysis was used to calculate the
means and standard deviations of the variables. Signicant
differences between mean values were estimated by Pear-
son correlation analysis, the Mann-Whitney U test, and the
Kruskal-Wallis test. The chi-square test was used to eval-
uate the groups according to the MBS criteria. The point of
statistical signicance was noted when probability was
P ! .05.
Results
Table 1 demonstrates the anthropometric, biochemical,
and hormonal data for pubertal girls with PCOS and for the
control group. As stated previously, the control group con-
sisted of 159 pubertal girls matched for age and BMI. Blood
pressure parameters (systolic/diastolic) were signicantly
higher in girls with PCOS (112.44 mm Hg vs 104.49 mm Hg;
P ! .001 for systolic BP/74.12 mm Hg s 69.01 mm Hg;
P ! .007 for diastolic BP). No signicant differences in the
plasma levels of fasting glucose, total cholesterol, HDL, or
SHBG were found in girls with PCOS, compared to the
control group (Table 2).
Conversely, girls with PCOS had higher fasting insulin
(P 5 .007), LDL (P 5 .017), triglyceride (P 5 .045), and total
(P ! .001) and free testosterone (P 5 .001) levels,
compared to the control group (Table 2). More cases with at
least 1 (P 5 .05) and 2 (P 5 .81) of Cook criteria were found
among girls with PCOS compared to the control group
(Table 3). Additionally the prevalence of MBS was 7.9% in
girls with PCOS compared with 0.6% in those without PCOS
(P 5 .02).
Table 1
Baseline Demographic and Clinical Parameters of the Cases with and without PCOS
Cases with Cases without P value
PCOS (n 5 63) PCOS (n 5 159)
Age (y) 15.72  1.20 16.37  1.84 NS
Weight (kg) 57.28  9.31 60.37  11.97 NS
Height (cm) 160.72  6.52 162.49  4.87 NS
BMI (kg/m2) 20.23 (14.04e24.72) 21.03 (15.24e24.09) NS
Waist circumference 77.49  21.36 78.73  10.22 NS
Systolic blood 112.14  12.64 104.49  13.93 !.01
pressure (mmHg)
Diastolic blood 74.12  9.09 69.01  11.29 !.01
pressure (mmHg)
BMI, Body mass index; NS, Non-signicant
 Y. Aydin et al. / J Pediatr Adolesc Gynecol 28 (2015) 271e274 273

Table 2 metabolic syndrome have been varied over the years, and to
Comparison of Androgens, Biochemical Glycemic and Lipid Prole in Cases with and
without PCOS
diagnose MBS in an adolescent population, we must use
different diagnostic criteria from those used in adults.10,16
Cases with Cases without P value
PCOS (n 5 63) PCOS (n 5 159)
In one of the studies of MBS in an adolescent population, in
which the AE-PCOS criteria were applied to diagnose PCOS,
Fasting insulin (mIU/ml) 14.35 10.93 0.007
Fasting glucose (mg/dl) 84.44 85.91 NS Roe et al found an increased rate of MBS in girls with PCOS,
HOMA IR 2.85 2.35 NS compared to the control group.6 In contrast, the mean BMI of
Total cholesterol (mg/dl) 156.48 153.98 NS
girls with PCOS (28.5 kg/m2) was signicantly higher than that
HDL (mg/dl) 61.09 57.98 NS
LDL (mg/dl) 92.88 86.14 0.017 of the control group (24.7 kg/m2) (P ! .01). Consequently, the
Triglyceride (mg/dl) 91.22 78.91 0.045 higher prevalence of MBS in adolescents with PCOS compared
Total testosterone (ng/dl) 45.36 28.23 0.000
to the control group might have depended on the higher BMI
Free testosterone (pg/ml) 3.26 1.99 0.001
SHBG (nmol/liter) 56.93 45.45 NS of the girls with PCOS. Accordingly, the study by Rossi et al is
apoA1, ApolipoproteinA-I; apoB, Apolipoprotein B; FAI, free androgen index; HDL,
very important because they examined the prevalence of MBS
High-density lipoprotein cholesterol; HOMA IR, Homeostasis model assessment in obese adolescents with PCOS and they found that obesity
insulin resistance; LDL, Low-density lipoprotein cholesterol; SHBG, Sex hormo- was a greater determining factor for MBS than the presence of
neebinding globulin; NS, Non-signicant
PCOS.9 However, they used the NIH criteria to diagnose PCOS8
and Cook criteria16 to diagnose MBS.
Discussion The most important factors that distinguish our study were
as follows. (1) To diagnose PCOS cases in adolescents, we used
According to our results, it seems that the presence of the latest criteria described by ESHRE/ASRM. Therefore, we
PCOS increases the risk of MBS in pubertal girls, even if they believe that we distinguished real PCOS cases from normal
have a normal BMI. girls who had 1 or 2 normal pubertal characteristics, such as
In general, MBS consists of metabolic and cardiovascular acne, menstrual irregularity, or multifollicular appearance of
risk factors.11 It is a syndrome mostly predisposing to the ovaries on US; (2) The effects of obesity on PCOS are
atherosclerotic cardiovascular diseases and type II diabetes. obvious; thus, our study and control groups consisted of girls
The primary pathophysiological mechanism is unclear for with normal BMI. We believe that with this approach, we
this syndrome, but it mostly accompanies chronic low-stage eliminated the probable effects of increased BMI on MBS; (3)
inammatory conditions and it mostly affects the length To diagnose MBS in adolescents, we used the latest criteria
and quality of life.12,13 Increases in visceral adiposity and dened by NHANES.10 According to our study, using these
central obesity are believed to be the triggering points.14,15 rened selection criteria, it seems that the presence of PCOS
Furthermore, chronic low-stage inammatory condi- increased the prevalence of MBS in an adolescent population
tions resulting in endothelial dysfunction and metabolic with normal BMI. However, although the criteria for MBS in
dysfunction are also common components of PCOS and adolescents are abundantly clear, clinicians are not screening
today it is clear that PCOS is a systemic disorder that occurs adolescents, regardless of whether the criteria for MBS are
beyond the ovaries.1 Although the prevalence of MBS differs present.17
with the nationality and geographic location of populations, In conclusion, the prevalence of MBS was higher in
the presence of PCOS increases the risk of MBS in adolescent girls with normal BMI and PCOS, compared to an
reproductive-aged women. age- and BMI-matched control group. Thus, as clinicians, we
The effects of PCOS on the prevalence of MBS in the must determine the criteria for MBS in girls with PCOS, even
adolescent population seem contradictory.2 The subject is if they have a normal BMI. In addition to the most important
ambiguous for 2 reasons: First, until now, most of the complaints of adolescent girls with PCOS, such as hirsutism,
studies have used the same criteria in adolescents and acne, and oligomenorrhea, we must consider the criteria for
reproductive-aged women to diagnose PCOS, such as the MBS, which can determine long-term quality of life.
NIH,8 Rotterdam,3 or AE-PCOS7 criteria. However, as stated
in ESHRE/ASRM1 we must use different criteria to diagnose References
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