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Journal of Pakistan Association of Dermatologists 2012;22:24-29.
Address for correspondence
Dr.
Mst. Laila Anjuman Banu,
Professor, Genetic & Molecular Biology,
6
th
Floor, Basic Medical Sciences Building
Bangabandhu Sheikh Mujib Medical University,
Dhaka, Bangladesh
Ph# 01911344673
Email: dr.lailabanu@gmail.com
Original Article
Polycystic ovarian syndrome in women with
acne
Sayera Begum*, M Zakir Hossain**, Md. Fashiur Rahman†, Laila Anjuman Banu‡
*Department of Dermatology & Venereology, Central Police Hospital, Dhaka.
**Department of Dermatology & Venereology, Sir Salimullah Medical College, Dhaka.
†Department of Dermatology& Venereology, Mymensingh Medical College, Mymensingh
‡Department of Genetic & Molecular Biology, Bangabandhu Sheikh Mujib Medical University,
Dhaka
Abstract
Background Acne is a common manifestation of hyperandrogenemia. Polycystic ovarian syndrome
(PCOS) is a common endocrine abnormality affecting reproductive aged women. In the female, the
most common cause of hyperandrogenemia is PCOS. The purpose of our study was to determine the
PCOS in women with acne.
Patients and methods In this observational, cross sectional study, 40 females, aged 15-40 years,
with various degree of acne who had not received hormonal treatment, including hormonal
contraceptive and antiandrogen therapy, for at least 3 months prior to study and 30 female
volunteers (aged 15-40 years) without acne or acne scars were enrolled as controls. The severity of
acne was graded as mild, moderate or severe. Clinical data including age, weight, height, body mass
index (BMI), menstrual history and androgenic sign (hirsutism, alopecia, acanthosis nigricans) were
recorded and hormonal assays and pelvic ultrasonography were done. Clinical parameters (acne
with menstrual irregularity) accompanied by other features of hyperandrogenism and/or elevated
level of luteinizing hormone (LH ) to follicle-stimulating hormone (FSH) ratio and/or ultrasound
picture based upon the presence of multiple small subcapsular cysts (diameter 2-8 mm) with dense
echogenic stroma, were used to diagnose PCOS.
Results 7.5% patients were obese in case group, which was statistically significant. No statistically
significant differences were observed in hormonal profiles (serum LH and serum FSH) but
significant differences seen in serum testosterone level and pelvic ultrasound to visualize the
polycystic ovary in women with acne. There were 11 (27.5%) women with PCOS among the 40
women with acne; 8 showed PCO picture on ultrasound. 10 cases with elevated LH to FSH ratio.
Out of 11 women with PCOS, 1 case was diagnosed only clinically. Control group had also one
PCOS (3.3%). Prevalence of PCOS with acne was higher in studied cases than control group, which
is statistically significant in our population.
Conclusion All women with acne should be considered for underlying PCOS and asked about their
menstrual patterns and examined for other sign of hyperandrogenism. Those who have menstrual
disturbances should have hormonal profile determination as well as pelvic ultrasonography for
ovarian visualization. Early diagnoses and treatment can avoid the possible complications.
Key words
Acne, hyperandrogenemia, polycystic ovarian syndrome.
Introduction
Acne is a chronic inflammatory disease of
pilosebaceous units. Acne vulgaris remains
one of the most common conditions affecting
adolescents. The pathogenesis of acne is
multifactorial and complex.
1
There are four
major factors in etiology of acne are seborrhea,
Journal of Pakistan Association of Dermatologists 2012;22:24-29.
comedo formation, colonization of sebaceous
duct with Propionibacterium acnes and
inflammation. Seborrhea or increased
sebaceous gland activity, dependent on
androgenic sex hormone mainly of adrenal or
ovarian origin.
2
Classic acne vulgaris is usually gradual in
onset but an abrupt onset of acne should be
further questioned to explore an underlying
etiology. Hyperandrogenism should be
considered in the female acne patient whose
acne is severe, sudden in onset, or associated
with hirsutism or irregular menstrual periods.
In general laboratory workup is not indicated
unless hyperandrogenism is suspected.
3
An
appropriate, thorough history and physical
examination will identify evidence of
androgen excess. Laboratory screening for
hormonal abnormalities is imperative when
clinical signs of hyperandrogenism are
present.
4
Androgen levels in patients with acne
are higher than those in controls. Acne is a
clinical manifestation of some endocrine
diseases.
The polycystic ovary syndrome (PCOS) has
the highest prevalence in acne.
5
The PCOS is a
heterogeneous condition which is defined by
the presence of two out of the three criteria:
oligo- and/or anovulation, hyperandrogenism
(clinical and/or biochemical), polycystic
ovaries (with the exclusion of other etiology).
6
The pathogenesis of PCOS is unknown.
However it is a complex multigenetic disorder
characterized by abnormal gonadotropin
release and dysregulation of steroidogenesis. It
is a combination of genetic abnormalities
combined with environmental factor, such as
nutrition and body weight, which then affect
the expression of syndrome.
6
The clinical
definition of PCOS changed in recent years
and includes one of its cardinal criteria, the
dermatological manifestation of
hyperandrogenism chiefly acne vulgaris,
hirsutism, alopecia and acanthosis. Any one of
these dermatological features may provide
early clinical clues to recognition of PCOS. If
the condition is unrecognized or untreated, the
patient faces increased risk of reproductive,
metabolic, cardiovascular, psychological and
neoplastic squelae.
7
It is one of the most
common causes of anovulatory infertility.
8
Acne is a common manifestation of
hyperandrogenemia.
9
Therefore, acne may not
pose only cosmetic concern, but may also be
sign of underlying disease. In females, the
most common cause of hyperandrogenemia is
PCOS. Therefore, all women presenting with
acne should be considered for underlying
PCOS and asked about their menstrual pattern.
Those who have menstrual disturbance should
have hormonal profile, pelvic ultrasound
which will help early diagnosis of PCOS.
However, confirmation of diagnosis and
provision of detailed information to the
affected women together with the availability
of interdisciplinary treatment help to
improving PCOS-related symptoms and avoid
its possible consequences. It may help in the
better management of acne and to reduce their
psychological distress.
Patients and methods
This was a hospital-based, observational,
cross-sectional study which was carried out in
the out-patient Department of Dermatology
and Venereology of Dhaka Medical College
Hospital (DMCH), Dhaka from November
2007 to October 2008 over a period of 12
months. A total of 70 females, 40 female
patients with various degree of acne and 30
female volunteers without acne or acne scars
aged from 19-40 years were enrolled as
controls. Purposive sampling method was
done as per inclusion and exclusion criteria.
Inclusion criteria included: female acne
patients, aged 15-40 years who consented to
participate in the study and undergo pelvic
USG and blood tests; female acne patients
who had not received hormonal treatment,
Journal of Pakistan Association of Dermatologists 2012;22:24-29.
including hormonal contraceptives and
antiandrogen therapy for at least 3 months
prior to study; female acne patients with
menstrual irregularity; and obese female acne
patients. Patients with some co-existing
systemic illness or those who were on
hormonal, steroid or oral contraceptive therapy
were excluded from the study.
The severity of acne was graded as mild,
moderate or severe.
10
Clinical data, including
age, weight, height, body mass index (BMI),
menstrual history and androgenic signs were
recorded. Hormonal assays and pelvic
ultrasonography were done.
Operational terms and definitions
Acne
Acne is a chronic inflammatory disease of
pilosebaceous follicles characterized by
comedone, papules, pustules, nodules and
often scars.
11
Acne was graded as mild:
comedone, papules/pustules; moderate:
papules, pustules/nodules; and severe:
nodulocystic/acne conglobata (severe acne
with many abscesses, cysts, marked scarring
with sinus).
10
Body mass index (BMI)
The BMI was calculated as weight in
kilograms divided by the square of height in
meter; thin= BMI<18.5; normal range= BMI
18.5-24.9; overweight= BMI 25-29.9; obese=
BMI>30 (according to WHO classification).
Menstrual history
Menstrual factors such as cycle length
(minimum/ maximum), cycle irregularities, the
duration of menstrual bleeding or the absence
of bleeding without being pregnant were
examined.
Menstrual irregularity
Fewer than 9 periods a year or periods longer
than 40 days apart.
11
Ultrasound examination
Pelvic USG were performed in all subjects
either transabdominally or transvaginally (in
married women). Either a 3.5 MHz
transabdominal (full bladder technique) or a 5
MHz transvaginal probe was used. The
ovarian morphology was carefully visualized.
Polycystic ovary (PCO) diagnosis was based
upon the presence of multiple small
subcapsular cysts (diameter 2-8 mm) with
dense echogenic stroma. PCO was not
diagnosed in cases with multiple small cysts
scattered throughout the ovary without dense
echogenic cores.
Hormonal assays
Blood samples were drawn from all subjects
for estimation of serum concentration of
testosterone, luteinizing hormone (LH) and
follicle-stimulating hormone (FSH). Sera were
frozen at -20ºC until the time of assay.
Measurements of the hormones were
performed by radioimmunoassay.
Polycystic ovarian syndrome (PCOS)
The PCOS is a heterogeneous condition which
is defined by the presence of two out of the
following three criteria: i) Oligo- and/or
anovulation;
ii) h
yperandrogenism (clinically
or biochemically); and
iii) p
olycystic ovary,
with exclusion of other etiology.
6
Diagnostic criteria for PCOS
The diagnostic criteria for PCOS was acne
with menstrual disturbances accompanied by a
clinical feature of hyperandrogenism/ratio of
LH to FSH equal to or greater than 2 and/or
and by ultrasonic findings of PCO.
9
Data analysis
Descriptive statistics were calculated,
including mean, standard deviation (SD). The
chi-square test and unpaired t-test were used to
determine the statistical significance. P values
less than 0.05 were considered statistically
significant. All statistical calculations were
Journal of Pakistan Association of Dermatologists 2012;22:24-29.
done by computer using the program SPSS
(Statistical Package for the Social Sciences)
version 11.0.
Results
The study included 70 subjects out of which
40 (57.1%) were in case and 30 (42.9%) were
in control group No statistical significant
(p>0.05) difference was found in menstrual
history between case and control in chi square
test (Table 1). Obesity was found only in case
group, in which 3 (7.5%) patients were obese
(Table 1), p<0.05. In USG, polycystic ovary
was found in 20.0% and 3.3% in cases and
controls, respectively (p<0.05), Table 1. The
mean levels of LH and FSH were not different
in two groups, however, serum testosterone
levels were significantly lower in controls
(p=0.001), Table 2.
There were 11 females with PCOS among the
40 patients with acne (case group) and 1
(3.3%) PCOS case amongst 30 controls (Table
3), (p<0.05). Out of 11 PCOS patients in case
group, 8 were diagnosed PCOS by acne (A) +
menstrual irregularities (MI) + PCO on
ultrasound + LH:FSH (>2:1), 2 cases by
A+MI+LH:FSH with hyperandrogenism
(hirsutism, alopecia, acanthosis nigricans) and
1 case diagnosed by A+MI+
hyperandrogenism.
Table 3 compares different characteristics in
PCOS cases in two groups. The mean BMI
and S. testosterone were statistically
significant (p<0.05) in chi square, however
others were not statistically significant
(p>0.05).
Discussion
In this study, prevalence of PCOS in acne
patients was 27.5%, which was significant.
PCOS is a common endocrine disorder. Its
etiology remains uncertain, and the diagnostic
Table 1 Menstrual history of the study population
(n=70).
Case
(n=40) Control
(n=30)
N (%) N (%)
Menstrual history
Irregular 12 (30) 13 (43.3)
NS
Regular 28 (70) 17 (56.7)
NS
Body mass index
Normal 18 (45.0) 16 (53.3)
NS
Overweight 19 (47.5) 14 (46.7)
NS
Obese 3 (7.5) 0 (0.0)
S
USG of uterus with adnexal
Polycystic ovary 8 (20.0) 1 (3.3)
S
Normal ovary 32 (80.0) 29 (96.7)
NS
NS=not significant (p>0.05), S=significant
(p<0.05).
Table 2 Mean distribution of biochemical
parameters of the study population (n=70).
Biochemical
parameters
Case
(n=40) Control
(n=30)
Mean±SD Mean±SD
LH (nmol/l) 13.4 ±13.0 11.3±9.2
NS
(2.72-83.77) (1.75-42.68)
FSH (nmol/l) 8.9±6.4 8.9±5.9
NS
(1.26-30.06) (1.89-26.6)
Serum testosterone 81.0±38.0 46.7±25.3
S
(nmol/l) (3.2-183) (0.20-106.2)
NS=not significant (p>0.05), S=significant (p <
0.05) with unpaired t test.
FSH=serum follicle-stimulating hormone,
LH=serum luteinizing hormone.
Table 5 Characteristics in PCOS patients in case
and control groups.
Mean values Cases
(n=11) Controls
(n=1)
Age (years) 21.5±4.8 24.7±5.9
Weight (kg) 63.0±8.8 58.2±6.5
BMI (kg/m
2
) 27.5±3.6 24.4±3.1
S
LH (nmol/l) 15.8±7.0 12.5±14.7
FSH (nmol/l) 7.8±3.0 9.3±7.3
Testosterone (nmol/l) 115.5±7.3 67.5±30.3
S
S=significant (p < 0.05), BMI=body mass index,
FSH=serum follicle-stimulating hormone,
LH=serum luteinizing hormone.
criteria are still debated. This syndrome has a
wide spectrum of clinical, biochemical and
ovarian morphological features.
9
The clinical
definition of PCOS has changed in recent
years and includes as one of its cardinal
criteria the dermatological manifestation of
hyperandrogenism, chiefly acne vulgaris,
Journal of Pakistan Association of Dermatologists 2012;22:24-29.
hirsutism and androgenic alopecia.
7
In this
study, the mean age of respondent was
23.8±5.7 years. The result of the observation
was similar with the study done in Italy,
12
where mean age of respondents were
23.6±6.06 years.
12
In our study, 47.5% patients
were overweight and 7.5% acne patients were
obese according to WHO criteria. The mean
BMI status of PCOS with acne was 27.5±3.6
kg/m² and without PCOS was 24±3.1 kg/m².
BMI status in PCOS with acne was
significantly higher than acne without PCOS
in our study. This finding was similar with the
previous data.
9
Patient with PCOS typically
have menstrual disorder, obesity, hirsutism
and often acne. This study found that almost
30% female acne patient had menstrual
irregularities. 40% female acne patient had
also menstrual irregularity in previous study.
9
While assessing an individual patient of acne,
a detailed history of menstrual disorder
especially oilgo- and amenorrhea is
mandatory.
13
Hirsutism and alopecia may also
be seen in women with acne due to
hyperandrogenemia.
13
No statistically
significant differences were observed in
hormonal profiles (serum LH and FSH)
between case and control groups in our study.
However, serum testosterone level
significantly tends to be higher in patient with
PCOS with acne. The limitations of the
hormone assays are also due to differences and
variation in the assay techniques. Even in
typical PCOS cases, the LH to FSH ratio
might not be higher than usual.
9
In the present
study, the LH to FSH ratio was also not higher
in PCOS cases. These are consistent with the
results by Timpatanapong and Rojanasakul
study.
9
PCO was visualized by ultrasonography in
about 20% of case group and 3.3% of control
group in our study, which was significant.
However, Timpatanapong and Rojanasakul
found PCO only in cases, not in control
group.
9
There is substantial heterogeneity of
symptoms and signs among women with
PCOS. In addition to different diagnostic
criteria used, the ethnic background of women
with PCOS may affect the clinical and
hormonal condition.
14
Clinical parameters (acne with menstrual
irregularity) accompanied by other features of
hyperandrogenism (hirsutism/acanthosis
nigricans/alopecia) with or without elevated
level of LH to FSH ratio (equal to or greater
than 2) and/or ultrasound picture were used in
this study to diagnose PCOS. PCOS found
higher in case (n=11) than control group (n=1)
among the study subjects. However, the
prevalence of PCOS in women with acne in
our study is lower than other studies. Other
researcher found 37.3% and 45.37% acne
patient had PCOS in their studies,
9,12
except for
the a study
15
which found that only 19% acne
patient had PCOS.
We conclude that all female patients with acne
should be screened for PCOS by history and
examination and if necessary, pelvic
ultrasound and hormonal assays should be
done.
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