Hyperandrogenemia is implicated in

both the metabolic and reproductive

morbidities of polycystic
ovary syndrome
Yeon-Ah Sung, M.D.,
a
Jee-Young Oh, M.D.,
a
Hyewon Chung, M.D.,
b
and Hyejin Lee, M.D.
a
a
Department of Internal Medicine and
b
Department of Obstetrics and Gynecology, Ewha Womans University School of
Medicine, Seoul, South Korea
Objective: To determine the features of polycystic ovary syndrome (PCOS) that are implicated in the associated reproductive and
metabolic morbidities.
Design: Cross-sectional casecontrol study.
Setting: Academic medical setting.
Patient(s): A total of 1,062 women with PCOS and 1,887 women without PCOS.
Intervention(s): None.
Main Outcome Measure(s): Physical examination including hirsutism scoring, biochemical and hormone measurements, ovarian
ultrasound, and a 75-g oral glucose tolerance test to measure glucose and insulin levels.
Result(s): A factor analysis identied four dominant factors in women with PCOS. These factors were interpreted as follows: [1]
metabolic and hyperandrogenemia factor, [2] oligomenorrhea and hyperandrogenemia factor, [3] blood pressure factor, and [4] ovarian
morphology factor. In women with PCOS, hyperandrogenemia was a signicant predictor of metabolic syndrome after adjusting for
age, body mass index, and insulin resistance in the regression analysis.
Conclusion(s): A factor analysis identied multiple factors that are responsible for the abnormalities associated with PCOS. Hyperan-
drogenemia was a common underlying feature of the metabolic and reproductive abnormalities
in women with PCOS but not in women without PCOS. (Fertil Steril

2014;101:8405. 2014
by American Society for Reproductive Medicine.)
Key Words: Hyperandrogenemia, metabolic morbidity, reproductive morbidity, polycystic
ovary syndrome
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P
olycystic ovary syndrome (PCOS)
is a heterogeneous disorder with
a broad spectrum of phenotypes
that includes metabolic and reproductive
features. Until recently, no universally
accepted clinical denition existed for
PCOS. Various diagnostic criteria have
been proposed that generally center on
the features of hyperandrogenism, oligo-
menorrhea, and polycystic ovarian
morphology (13). Essentially, for the
phenotypes to be part of the syndrome,
they should exhibit common
characteristics beyond those associated
with the syndrome denition (3).
Sometimes a feature that is not included
in the denition is chosen as the
commonality. Insulin resistance is a
pathophysiologic contributor in
approximately 50%80% of women
with PCOS, although it is not a
diagnostic criterion (4). Abnormal
glucose metabolism, dyslipidemia, and
an increased risk of cardiovascular
disease are more common in women
with PCOS than in age-matched women.
Therefore, PCOS seems to be a complex
syndrome that includes both reproduc-
tive and metabolic features (5, 6).
We hypothesized that PCOS is a
metabolic and reproductive disease
and used factor analysis to investigate
the clustering of the metabolic features
and components of PCOS. Factor
Received September 25, 2013; revised November 15, 2013; accepted November 18, 2013; published
online January 11, 2014.
Y.-A.S. has nothing to disclose. J.-Y.O. has nothing to disclose. H.C. has nothing to disclose. H.L. has
nothing to disclose.
Financial support was received from the Ewha Global Top5 Grant 2012 of Ewha Womans University.
Reprint requests: Hyejin Lee, M.D., Division of Endocrinology, Department of Internal Medicine, Ewha
Womans University Medical Center, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul 158-710,
South Korea (E-mail: hyejinlee@ewha.ac.kr).
Fertility and Sterility Vol. 101, No. 3, March 2014 0015-0282/$36.00
Copyright 2014 American Society for Reproductive Medicine, Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.fertnstert.2013.11.027
840 VOL. 101 NO. 3 / MARCH 2014
ORIGINAL ARTICLES: REPRODUCTIVE ENDOCRINOLOGY
analysis is a multivariate correlation method that reduces the
number of intercorrelated variables into smaller clusters con-
sisting of variables with little or no correlation. Each cluster
can be interpreted as the expression of a separate underlying
physiological process or the manifestation of a physiologic
phenotype (710). Although it has been used to study the
clustering of metabolic abnormalities, to our knowledge
factor analysis has not been used to investigate the
relationships between the components of PCOS. In this study
we determined which components of PCOS were implicated
in both the reproductive and metabolic morbidities, and
these components differed from those of non-PCOS.
MATERIALS AND METHODS
Subjects
The present cross-sectional study was conducted using the
data from the Biospecimen collection from women with
PCOS and control for the infertility study project. This
project was intended to collect the biospecimen and epidemi-
ologic information in women with PCOS and healthy
controls. Polycystic ovary syndrome is one of the common
causes of infertility, therefore we planned to build the
database of women with PCOS and healthy controls. These
volunteers, including women with menstrual irregularity
and healthy women, were recruited by local advertising.
This study was performed at the Endocrinology and Gynecol-
ogy Clinics at Ewha Womans University Hospital between
December 2008 and October 2010. A trained nurse contacted
the eligible candidates by telephone to determine whether
they were both capable and willing to participate in the study.
After excluding those who did not meet the eligibility criteria,
we invited volunteers to visit our hospital on the morning of
the third day of their menstrual period, after an overnight fast
of at least 8 hours. We explained the purpose and character-
istics of the study and obtained signed informed consent.
During that period, we recruited 1,062 women with PCOS
and 1,887 control women without PCOS. The participants
were recruited from Seoul and the surrounding urban area
and consisted of students (n 1,481), ofce clerks
(n 622), professional workers (n 471), and unemployed
women, including housewives (n 375).
As proposed at the American Society for Reproductive
Medicine and the European Society for Human Reproduction
and Embryology consensus meeting (2), PCOS was diagnosed
as the presence of two or more of the following three criteria:
oligomenorrhea, hyperandrogenism, and polycystic ovaries.
Oligomenorrhea is dened as fewer than eight menstrual cycles
per year. Biochemical hyperandrogenemia is dened as a total
or free T level above the 95th percentile (total T R67 ng/dL or
free T R0.84 ng/dL) on the basis of the T levels in 1,120 healthy,
regular-cycling women (11). Clinical hyperandrogenism is
dened as hirsutism with a modied Ferriman-Gallwey (mFG)
score of R3 (12). The criteria for diagnosing polycystic ovaries
requires the visualizationof R12 follicles per ovary that are 29
mmin diameter or an ovarian volume >10 cm
3
by transvaginal
ultrasonography or transabdominal ultrasonography with a
distended bladder for virgin women. Individuals with specic
disorders, such as adult-onset congenital adrenal hyperplasia,
hyperprolactinemia, and androgen-secreting neoplasia, were
excluded fromour study. Patients taking medications (e.g., ste-
roids, oral contraceptives, metformin, or thiazide diuretics)
before starting the study were excluded. Among the volunteers,
1,880 women were recruited as the non-PCOS group after
excluding the women with PCOS. None of the participants
hadafamilyhistoryof diabetes or PCOS. Subjects wereexcluded
if they had been taking hormonal medication within 3 months
of the evaluation or had used other drugs that could affect basal
parameter status.
The institutional review board of Ewha Womans Univer-
sity Mokdong Hospital approved this study.
Methods
Height and weight were measured in all the subjects, and body
mass index (BMI) was calculated as weight (kg)/height (m)
2
.
Waist circumference was measured on bare skin at the nar-
rowest indentation between the 10th rib and the iliac crest
at mid-respiration. Blood pressure was calculated as the
mean of two manual sphygmomanometer readings with the
patient in the seated position. Hirsutism was assessed using
the mFG scoring method by one trained nurse.
After an overnight fast of at least 8 hours a venous blood
sample was obtained from each subject on the third day of the
follicular phase of the menstrual cycle. In case of amenorrhea,
the sample was obtained on random day, and we assessed the
serum P levels. Those women with P levels <4 ng/mL were
considered anovulatory.
Ultrasound examinations were performed with a 7-MHz
transvaginal transducer (Logic 400, General Electric). The 701
virgin women (210 women with PCOS; 491 women without
PCOS) who refused transvaginal ultrasound received transab-
dominal ultrasonography. Ovarian volume was calculated
according to a simplied formula for an ellipsoid (0.5 length
width thickness) (13). Ovarian volume was dened as the
average volume of bothovaries, andthe ovarianfollicle number
was dened as the average number of follicles in each ovary.
Total T levels were measured via the chemiluminescent
immunoassay method using a commercially available kit
(Siemens), and sex hormonebinding globulin (SHBG) levels
were measured by an immunoradiometric assay using a
commercially available kit (DPC). Free T levels were calculated
using the formula available on the International Society for
Studyof the AgingMale Website (www.issam.ch/freetesto.htm),
which is based on the total T, SHBG, and albumin levels in the
same sample from each subject (11). The free androgen index
(FAI) was calculated as 100 [T concentration (nmol/L)/SHBG
concentration (nmol/L)].
The 75-g oral glucose tolerance test was performed in the
morning after an overnight fast. A polyethylene catheter was
placed into the antecubital vein before the test. After 30 min
of supine rest, venous blood samples were drawn at baseline
and 120 min after administration of the 75-g glucose load.
Plasma glucose levels were measured via the glucose oxidase
method (Beckman Model Glucose Analyzer 2), and insulin
levels were measured by a radioimmunoassay using a
commercially available kit (BioSource). Fasting total serum
cholesterol, triglyceride, and high-density lipoprotein (HDL)
VOL. 101 NO. 3 / MARCH 2014 841
Fertility and Sterility
cholesterol levels were measured using an enzymatic assay
performed with an automated analyzer (Hitachi 7150 Auto-
matic Chemistry Analyzer). Insulin resistance was calculated
according to the Homeostatic Model Assessment of Insulin
Resistance (HOMA-IR) using fasting glucose and insulin
levels [HOMA-IR fasting insulin (mIU/mL) fasting
glucose (mmol/L)/22.5]. Metabolic syndrome was diagnosed
according to the National Cholesterol Education Program's
Adult Treatment Panel III, which requires the presence of
central obesity with a waist circumference R80 cm (14),
dyslipidemia with triglycerides R150 mg/dL, and HDL
cholesterol <50 mg/dL. Hypertension and hyperglycemia
were diagnosed as a blood pressure R130/85 mm Hg and a
fasting plasma glucose R100 mg/dL, respectively. Metabolic
syndrome was diagnosed when at least three of ve metabolic
abnormalities were present (15).
Statistical Analyses
The statistical analyses were performed using the Statistical
Package for the Social Sciences 19.0 software package for
Windows (IBM). Quantitative variables are reported as the
means SDs. The Kolmogorov-Smirnov statistic was used
to analyze the continuous variables for normality, and
logarithmic transformations were applied as necessary to
ensure the normal distribution of skewed variables. Two
groups with different parameters were compared using
Student's unpaired t test. The differences in the prevalence
of metabolic syndrome were compared using the Cochran-
Mantel-Haenszel c
2
test. To investigate the association of
metabolic syndrome with age, BMI, oligomenorrhea,
hyperandrogenemia, and HOMA-IR, multivariate logistic
regression analyses were performed to determine the odds
ratios and the corresponding 95% condence intervals.
Factor analysis was performed to describe the clusters of
reproductive and metabolic variables and to extract the initial
set of uncorrelated factors; to produce interpretable factors,
the selected principal components were rotated using varimax
rotation. Only variables with factor loading on a summary
factor R0.40 were used for interpretation. The analyzed vari-
ables included the following: anthropometric components
(i.e., BMI and waist circumference), blood pressure compo-
nents (i.e., systolic and diastolic blood pressure), dyslipidemia
components (i.e., triglycerides, HDL cholesterol, and total
cholesterol), glucose and insulin resistance components (i.e.,
fasting glucose, postload 2-hour glucose, and HOMA-IR),
hyperandrogenism components (i.e., free T and mFG score),
ovarian components (i.e., ovarian follicle number and ovarian
volume), and the oligomenorrhea component (number of
menses per year).
RESULTS
Of the 1,062 women with PCOS, 87.2% had oligomenorrhea,
60.7% had hyperandrogenemia, 25.1% had hirsutism, and
84.3% had polycystic ovarian morphology. Women with
PCOS were younger and more likely to be obese than women
without PCOS (P<.01). Women with PCOS exhibited higher
blood pressures, total and free T levels, FAIs, postload
2-hour glucose levels, fasting insulin levels, postload
2-hour insulin levels, HOMA-IR values, total cholesterol
levels, and triglyceride levels, and exhibited lower SHBG
levels than women without PCOS (P<.05; Table 1). These
differences persisted after adjustment for BMI, with the
exception of systolic and diastolic blood pressure.
In women with PCOS, the factor analysis reduced 15
highly intercorrelated variables to four separate factors that
accounted for 71.9% of the total variance in the data
(Table 2). These factors were interpreted as the following:
[1] metabolic and hyperandrogenemia factor, with positive
loadings of BMI, waist circumference, triglycerides, HOMA-
IR, fasting glucose, postload 2-hour glucose, and free T and
a negative loading of HDL cholesterol; [2] oligomenorrhea
and hyperandrogenemia factor, with a positive loading of
the number of menses per year and a negative loading of
free T; [3] blood pressure factor, with positive loadings of
systolic and diastolic blood pressure; and [4] ovarian
morphology factor, with positive loadings of ovarian volume
and follicle number (Table 2). In women without PCOS,
different clusterings of the four separate factors were
extracted: [1] obesity and blood pressure factor, with positive
loadings of BMI, waist circumference, and systolic and
diastolic blood pressure; [2] metabolic factor, with positive
loadings of triglycerides, HOMA-IR, fasting glucose, and
postload 2-hour glucose; [3] obesity and reproductive factors,
with positive loadings of BMI, waist circumference, and free T
and a negative loading of the number of menses per year; and
[4] dyslipidemia factor, with positive loadings of HDL and
total cholesterol.
Women with PCOS with hyperandrogenemia were
more likely to be obese than women with PCOS without
hyperandrogenemia. The systolic blood pressure, diastolic
blood pressure, total cholesterol, triglycerides, fasting
glucose, postload 2-hour glucose, fasting insulin, postload
2-hour insulin, and HOMA-IR were signicantly higher in
women with PCOS with hyperandrogenemia than in those
without hyperandrogenemia (all P<.05). After adjusting
for BMI, the systolic blood pressure, triglycerides, fasting
insulin, postload 2-hour insulin, and HOMA-IR remained
signicantly different between women with PCOS with
and without hyperandrogenemia (all P<.05). Metabolic
syndrome was signicantly more prevalent in women
with PCOS with hyperandrogenemia (15.1% vs. 2.7%,
P<.05; Table 3).
Logistic regression analysis demonstrated that hyperan-
drogenemia was signicantly associated with metabolic
syndrome after adjusting for age, BMI, HOMA-IR, and the
number of menses per year in women with PCOS (odds ratio
4.797, P.035; Table 4). This association was not observed
in women without PCOS (data not shown).
DISCUSSION
Polycystic ovary syndrome is a heterogeneous disease with a
complex pathophysiology that remains largely unknown.
Women with PCOS may present with a variety of serious
clinical manifestations, including reproductive indications
(16) and metabolic abnormalities (17, 18). An understanding
of how the reproductive and metabolic variables cluster
842 VOL. 101 NO. 3 / MARCH 2014
ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY
could help to determine the pathophysiology of PCOS and
dene the syndrome.
This is the rst study to evaluate which components of
PCOS are implicated in both the reproductive and metabolic
morbidities, using factor analysis. We found that hyperandro-
genemia represented both the reproductive and metabolic
components. Factor analysis can reveal underlying structures
among variables that are highly interrelated. Factor analysis
reduces a large set of variables to a small domain of underly-
ing factors, and these domains can be interpreted to represent
distinct physiologic phenotypes (10). If an analysis reveals
more than one factor, this overlap suggests unifying
TABLE 1
Clinical and biochemical characteristics of the study participants.
Characteristic PCOS (n [1,062) Non-PCOS (n [1,887) P value
a
P value (BMI-adjusted)
Age (y) 24 5 26 5 <.01 <.01
BMI (kg/m
2
) 22.3 3.9 21.1 2.8 <.01
WC (cm) 75.1 9.8 72.4 7.4 <.01 .463
SBP (mm Hg) 108 9 107 9 <.01 .256
DBP (mm Hg) 70 8 69 8 <.01 .225
SHBG (nmol/L) 70.6 40.3 106.6 59.3 <.01 <.01
TT (ng/dL) 66.3 19.8 45.9 14.7 <.01 <.01
FT (ng/dL) 0.84 0.4 0.41 0.20 <.01 <.01
FAI 4.7 4.0 1.9 1.2 <.01 <.01
FPG (mg/dL) 85 11 85 7 .165 .249
PPG (mg/dL) 103 30 97 22 <.01 <.01
FI (mIU/L) 8.9 7.4 4.1 4.6 <.01 <.01
PI (mIU/L) 61.4 59.3 29.1 28.9 <.01 <.01
HOMA-IR 1.96 1.95 0.87 1.01 <.01 <.01
TC (mg/dL) 179 30 175 28 <.01 <.01
TG (mg/dL) 85 50 74 35 <.01 <.01
HDL-C (mg/dL) 51 12 51 11 .169 <.01
LDL-C (mg/dL) 111 26 109 24 .100 <.01
OV volume (cm
3
) 9.2 3.7 5.7 2.3 <.01 <.01
OV follicle no. 10.6 3.8 6.9 2.5 <.01 <.01
Oligomenorrhea 926 (87.2) 388 (20.6) <.01 <.01
Hyperandrogenemia 645 (60.7) 191 (10.1) <.01 <.01
Hirsutism 266 (25.1) 324 (17.2) <.01 <.01
Polycystic ovary 894 (84.3) 279 (14.8) <.01 <.01
Note: Data are presented as mean SD or number (percentage). WC waist circumference; SBP systolic blood pressure; DBP diastolic blood pressure; TT total T; FT free T; FPG fasting
plasma glucose; PPG postload 2-hour plasma glucose; FI fasting insulin; PI postload 2-hour insulin; TC total cholesterol; TG triglycerides; HDL-C HDL cholesterol; LDL-C low-density
lipoprotein cholesterol; OV ovarian.
a
The c
2
test was used for categoric variables (oligomenorrhea, hyperandrogenemia, hirsutism, and polycystic ovary), and the t test was used for continuous variables.
Sung. Hyperandrogenemia in polycystic ovary syndrome. Fertil Steril 2014.
TABLE 2
Factor analysis of the metabolic and reproductive variables in women with and without PCOS.
Factor
Factor matrix
Women with PCOS (n [1,062) Women without PCOS (n [1,887)
1 2 3 4 1 2 3 4
BMI 0.780
a
0.265 0.313 0.07 0.559
a
0.170 0.438
a
0.343
WC 0.778
a
0.247 0.323 0.053 0.524
a
0.168 0.424
a
0.367
TG 0.578
a
0.043 0.188 0.052 0.122 0.726
a
0.012 0.018
HDL-C 0.605
a
0.156 0.147 0.019 0.041 0.269 0.147 0.816
a
HOMA-IR 0.699
a
0.039 0.141 0.141 0.132 0.461
a
0.018 0.203
FPG 0.702
a
0.187 0.033 0.141 0.076 0.616
a
0.046 0.017
PPG 0.724
a
0.117 0.113 0.016 0.045 0.555
a
0.302 0.024
FT 0.521
a
0.451
a
0.145 0.118 0.026 0.064 0.798
a
0.077
Menses/y 0.013 0.873
a
0.021 0.059 0.082 0.017 0.672
a
0.282
SBP 0.209 0.066 0.908
a
0.076 0.896
a
0.094 0.047 0.070
DBP 0.227 0.019 0.915
a
0.066 0.880
a
0.110 0.066 0.031
OV volume 0.018 0.038 0.162 0.763
a
0.119 0.064 0.224 0.081
OV follicle no. 0.028 0.017 0.036 0.830
a
0.160 0.040 0.028 0.016
TC 0.145 0.122 0.069 0.019 0.076 0.303 0.033 0.758
a
mFG score 0.068 0.052 0.061 0.016 0.055 0.013 0.102 0.009
Note: Abbreviations as dened in text and Table 1.
a
Factor loading R0.4.
Sung. Hyperandrogenemia in polycystic ovary syndrome. Fertil Steril 2014.
VOL. 101 NO. 3 / MARCH 2014 843
Fertility and Sterility
commonalities between each domain. This analysis method
has never been used to analyze the complex phenotypes of
women with PCOS. In our study four components were
identied by factor analysis in women with PCOS, and the
central component consisted of BMI, waist circumference,
triglycerides, HDL cholesterol, HOMA-IR, fasting glucose,
postload 2-hour glucose, and free T. The number of menses
per year was indirectly linked to the central component via
free T. Metabolic disturbances and oligomenorrhea were
linked via a mutual association with hyperandrogenemia.
The cosegregation of free T in both the metabolic and oligo-
menorrhea factors represents the central role of hyperandro-
genemia in women with PCOS. Interestingly, in our study
there was no direct relationship between ovarian morphology
and metabolic disorders, suggesting that ovarian morphology
was distinct fromthe central component. These results concur
with the view of the Androgen Excess and PCOS Society,
specically the view that the absence of clinical or biochem-
ical hyperandrogenism makes a diagnosis of PCOS less
certain, regardless of the presence of ovulatory or menstrual
dysfunction or of polycystic ovaries (19). In PCOS, hyperinsu-
linemia stimulates ovarian androgen production. The etiology
of insulin resistance in PCOS has been shown to involve both
intrinsic and acquired defects in insulin action. The androgen
excess contributes to insulin resistance in the adipose cells
and skeletal muscle of women with PCOS (3), potentially
establishing a vicious cycle whereby hyperinsulinemia causes
increased androgen production, which in turn contributes to
insulin resistance. Interestingly, a novel nding of this study
is that hyperandrogenemia was clustered with oligomenor-
rhea and obesity and not with other metabolic components
in women without PCOS. A possible explanation for the
different clustering between PCOS and non-PCOS is the
distinction of mechanisms related to the reproductive and
metabolic pathway. These data demonstrated that hyperan-
drogenemia can play an important role in metabolic
abnormalities in women with PCOS.
Recently a consensus statement by the Androgen Excess
and PCOS Society suggests that a cutoff value of R3 be
applied to Far East and South East Asian women (12). In the
present study the prevalence of hirsutism was 25.1%, which
is lower than that in Caucasian women with PCOS (20), and
hirsutism was not directly related to the metabolic or repro-
ductive variables. Most Caucasian women and black women
of African descent with PCOS exhibit excess hair growth
(21), whereas Asians typically have less hair than European
Americans, which may be explained by low 5a-reductase
activity in the skin of Asians (22).
We compared the anthropometric, metabolic, and repro-
ductive variables according to the presence of hyperandroge-
nemia. The women with PCOS with hyperandrogenemia
exhibited higher BMIs, greater waist circumferences, and
elevated cardiovascular riskfactors, including highblood pres-
sure, dyslipidemia, and insulin resistance. Additionally, hyper-
androgenemia was signicantly associated with metabolic
syndrome after adjusting for age, BMI, HOMA-IR, and the
number of menses per year in women with PCOS. Hyperandro-
genemia is a well-established contributor to the etiology of
PCOS and is detected in approximately 60%80% of all cases
(23). In a previous study, free T was found to be an independent
risk factor for the development of metabolic syndrome (24),
and women with PCOS with metabolic syndrome exhibited
signicantly higher free T levels than women with PCOS
without metabolic syndrome after adjusting for BMI (17).
TABLE 3
Characteristics of women with PCOS with or without
hyperandrogenemia.
Characteristic
Women with
PCOS with
hyperandrogenemia
(n [645)
Women with
PCOS without
hyperandrogenemia
(n [417)
Age (y) 24 4 24 4
BMI (kg/m
2
) 23.0 4.3
a
21.1 2.8
WC (cm) 77 10
a
72 7
SBP (mm Hg) 110 10
a,b
106 8
DBP (mm Hg) 71 8
a
69 7
FT (ng/dL) 1.06 0.44
a,b
0.50 0.17
mFG score 1.8 3.0 2.1 3.4
TC (mg/dL) 183 30
a
174 29
TG (mg/dL) 94 59
a,b
73 31
HDL cholesterol
(mg/dL)
51 13 52 11
FPG (mg/dL) 86 14
a
84 7
PG (mg/dL) 107 35
a
97 19
FI (mIU/L) 9.5 7.7
a,b
5.6 4.2
PI (mU/mL) 65.0 62.0
a,b
40.4 33.1
HOMA-IR 2.09 2.05
a,b
1.20 0.91
Metabolic
syndrome
97 (15.1)
a
11 (2.7)
Note: Values are mean SDor number (percentage). The c
2
test was used for categoric vari-
ables (metabolic syndrome), and the t test was used for continuous variables. Abbreviations
as dened in text and Table 1.
a
P<.05 vs. women without hyperandrogenemia.
b
P<.05 after adjusting for BMI.
Sung. Hyperandrogenemia in polycystic ovary syndrome. Fertil Steril 2014.
TABLE 4
Logistic regression analysis of the predictors of metabolic syndrome in women with PCOS.
Factor
Unstandardized coefcients
Standardized
coefcients
b P value Condence interval B SE
Hyperandrogenemia 1.874 0.325 6.513 <.01 3.44612.311
Age-adjusted 1.860 0.327 6.422 <.01 3.38612.179
Age- and BMI-adjusted 1.113 0.387 3.106 <.01 1.4546.633
Age-, BMI-, and HOMA-IR-adjusted 1.572 0.742 4.817 .034 1.12420.638
Age-, BMI-, HOMA-IR-, and menses-adjusted 1.568 0.745 4.797 .035 1.11520.641
Sung. Hyperandrogenemia in polycystic ovary syndrome. Fertil Steril 2014.
844 VOL. 101 NO. 3 / MARCH 2014
ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY
The main strengths of this study are the large sample size
and the comprehensive assessment of the subjects, which was
sufcient to identify the factors that represent both the meta-
bolic and reproductive features of PCOS. We found that
hyperandrogenemia is implicated in both the metabolic and
reproductive morbidities through our factor analysis. This
analysis method has not been previously used to investigate
the complex components of PCOS, and it re-established the
importance of hyperandrogenemia. The results from the
factor analysis were limited by differences in the ethnicity
of the patients studied, the number of included risk variables,
the sample size, and the loading cutoff points set by the inves-
tigators (10). Our study population was limited to young
Asian women; therefore, extrapolation of these results to
other age or ethnic groups should be undertaken with caution.
Free T is the most accurate marker in hyperandrogenemia, but
the reference measurement method for free T is a time-
consuming, complex, and not very accurate procedure in
women. Therefore, we used total T and calculated androgen
parameters (calculated free T, FAI) for our analysis, and
only free T may present the reproductive and metabolic
components. That was another limitation of our study.
Additionally, we performed transabdominal ultrasonography
in 701 virgin women. In Korea, women who are not sexually
active tend to be reluctant to have an ultrasound probe
inserted in their vagina. Thus, we were compelled to perform
transabdominal ultrasonography in women who refused
transvaginal ultrasonography.
In summary, factor analysis identied four underlying
domains among the metabolic and reproductive variables in
women with PCOS. It is remarkable that hyperandrogenemia
was related to the anthropometric, metabolic, and oligome-
norrhea variables. Therefore, this study suggests that hyper-
androgenemia is a common link between the metabolic and
reproductive disease manifestations, and the identication
of hyperandrogenemia in women with PCOS should prompt
a search for metabolic abnormalities.
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