Survey of Cutaneous Manifestations in Adolescents Suffering from Poly Cystic Ovarian Syndrome
Mohammad H. Dabbaghmanesh,
The adolescents suffering from Poly Cystic Ovarian Syndrome (PCOS) are concerned
about weight gain, menstrual irregularities and cutaneous manifestation (hirsutism,
acne and alopecia). The present study aimed to investigate the prevalence of cutaneous
manifestations in 14-18 year old female high school students based on PCOS. This
descriptive-analytical study was conducted on 3200 female students between 14
and 18 years old in 2009. The intensity of hirsutism was determined using modified
Ferriman-Gallwey scale. In addition, the intensity of acne was classified based
on the classification consensus conference on acne. Finally, alopecia was assessed
using Ludwigs scale based on scalp and forehead line hair density. Experiments
(prolactin, TSH, DHEAS, total testosterone and free testosterone), hyperandrogenism
clinical features and sonography were performed. Then, the data were analyzed
using Chi-square test. The prevalence of hirsutism, acne and alopecia were 3.2,
5 and 4.2%, respectively. The results revealed no significant relationship between
the mean of androgens as well as suffering from PCOS and hirsutism and alopecia
(p>0.05). However, a significant relationship was found between menstrual irregularities
and hirsutism (p<0.001). Also, a significant relationship was observed between
the testosterone level and PCOS (p<0.001). Among the cutaneous manifestations,
severe acne and androgen level were significantly related to PCOS. Considering
the consequences of acne in the girls lives, hormonal screening and sonography
are recommended to be performed in the girls with average acne and normal menstrual
cycles, as well.
Received: November 27, 2013;
Accepted: December 21, 2013;
Published: February 03, 2014
Poly Cystic Ovarian Syndrome (PCOS) affects 5-10% of the women in the reproductive
age. This disorder which is one of the most prevalent endocrine disorders in
women is identified by high androgen and insulin levels (Lee
and Zane, 2007). This complex, multispecialty disorder is more prevalent
in the individuals with menstrual irregularities, obesity, insulin resistance,
acanthosis nigricans, type II diabetes, dyslipidemias, hypertension, non-alcoholic
liver diseases and obstructive sleep apnea (Lowenstein,
2006). Moreover, PCOS is the most common cause of hyperandrogenism. Evidence
has shown that PCOS begins at puberty. Yet, disorders in ovarian androgens production
may occur at puberty, childhood and even at the time of fetal growth (Franks,
2002; Vuguin, 2010).
In general, acne, hirsutism, alopecia, obesity and acanthosis are the cutaneous
manifestations of PCOS. The clinical hyperandrogenism symptoms, such as hirsutism,
acne and male features, occur in almost 66% of the adolescents suffering from
PCOS. Hirsutism is the most prevalent clinical signs of hyperandrogenism in
PCOS (Warren-Ulanch and Arslanian, 2006). Thus, the
incidence of hirsutism in an adolescent directs the diagnosis towards PCOS (Plouffe,
2000). The prevalence of hirsutism has been reported to vary from 5-5% in
various societies (Azziz, 2003; Azziz
et al., 2000). Some studies have also estimated the prevalence of
hirsutism to be 5-25% among the premenopausal women (Azziz
et al., 2000). The incidence of hirsutism depends on the concentration
of blood androgens as well as the genetic sensitivity of the hair follicles
to androgens. Thus, anovulation and androgens increase can leave no sign of
hirsutism (Speroff and Fritz, 2005). The study by Ferriman
and Gallwey showed that only 5% of the society members had obtained scores of
6 or above (Ferriman and Gallway, 1961).
Acne vulgaris is one other common cutaneous manifestation of hyperandrogenism
(Addor and Schalka, 2010). One of the most important
features of such patients is development of several closed comedones changed
into tenders, lumpy nodules in the lower half of face and jaw-line (V distribution).
The incidence of acne usually lasts for 5-7 days and it is also possible to
occur before the menstrual cycle. In addition to face, acne can also present
on the chest, shoulder and back. Moreover, the individuals with acne may also
have evidence of hirsutism and alopecia as well as a family history of PCOS
(Archer and Chang, 2004). In one study, the incidence
rate of acne was reported as 83 and 19% in the women with PCOS and control women,
respectively. Besides, almost 80% of the women with severe acne, 50% of those
with average acne and 30% of the women with mild acne showed increase in the
blood androgen level (Bunker et al., 1989).
In the study increase in the androgen level was detected in all the patients
with acne; however, only 19% of them suffered from PCOS (Borgia
et al., 2004).
Nonetheless, Female Pattern Hair Loss (FPHL) may not have androgenic origin
in all the cases (Olsen, 2001). Thus, diagnosis of
hair loss is quite difficult in the patients suffering from PCOS and those with
other causes of hyperandrogenism.
Various clinical manifestations of alopecia have been described by Ludwig (diffuse),
Hamilton (male pattern) and Olsen (frontal accentuation) (Olsen,
2001). Increase in androgen is usually detected in the women with FPHL.
Hormonal effects lead to conversion of terminal hair to vellus hair eventually
leading to baldness.
Alopecia is another cutaneous manifestation of PCOS. In female androgenic alopecia,
diffuse thinning of hair is detected all over the scalp at first. In addition,
nearly 40% of the women with androgenic alopecia suffer from a type of hyperandrogenism
(Olsen, 2001). The results of one study showed the
prevalence of hyperandrogenism to be 38.5% in 109 women who suffered from average
to severe alopecia. Besides, 43% of these patients had the criteria of PCOS
(Futterweit et al., 1988). Acanthosis nigricans
which is defined as dark velvety hyperpigmentation of skin is the first sign
of insulin resistance particularly in obese individuals. Acanthosis nigricans
is mainly detected on the neck, armpit and groin (Madnani
et al., 2013).
The present study aims to determine the prevalence of cutaneous manifestations
in 14-18 year old girls as well as their relationship with the amount of androgenic
hormones and polycystic ovaries.
MATERIALS AND METHODS
This descriptive, cross-sectional study was conducted on 3200 female high school
students between 14 and 18 years old. According to the study in Isfahan and
considering CI = 95% and loss rate of 30%, a 3200-subject sample size was determined
for this study (p = 3.5%, d = 0.7).
In this study, 800 students in 3-4 high schools were randomly selected from
each educational district. The inclusion criteria of the study were being 14-18
years old, being willing to take part in the study, signing the written informed
consents and not suffering from adrenal and thyroid problems as well as hyperprolactinemia.
At first, the researcher completed the study questionnaire including the demographic
information and assessment of hirsutism, acne and alopecia. Then, by observing
the ethical principles, the students were examined on face, back and chest in
a room with sufficient light.
The intensity of hirsutism was determined at 9 anatomic areas based on the
modified Ferriman-Gallwey scale. Accordingly, the scores of 0-6, 6-9, 10-14
and 15 and above were considered as no, mild, average and severe hirsutism,
respectively (Ferriman and Gallway, 1961).
In addition, acne was categorized based on the classification consensus conference
on acne. According to this classification, acne is categorized into mild, average
and severe groups. It should be mentioned that comedones, a large number of
papules and pustules, nodules, cysts and scars exist in the severe form of acne.
In this study, the severe form was considered as acne (Pochi
et al., 1991).
Regarding alopecia, in addition to the above-mentioned criteria, the following
were taken into account, as well: Not having referred to treatment centers due
to hair loss, pregnancy, childbirth and lactation during the last year, scalp
disorders, kidney failure, cardiovascular diseases, uncontrolled insulin-dependent
diabetes, history of using finasteride or 5-alpha reductase inhibitors during
the past 12 months, recent consumption of pencillamine, isotretinoin, zydovirax,
interferon and dutasteride, treatment by specific plants from the past 2 months,
consumption of minoxidil, topical estrogen and progesterone, tamoxifen, anabolic
steroids, lithium and phenothiazine, consumption of hypertrichosis causing drugs,
such as cyclosporine, diazoxide, phenytoin and psoralen and consumption of anti-androgenic
drugs, such as cyproterone acetate, spironolactone, ketoconazole, flutamide
and beclotamide, in the past 6 months.
In this study, alopecia was defined by average and severe scalp as well as
forehead line hair density according to Ludwigs classification (Ludwig,
Pelvic ultrasound was performed for the patients suffering from hirsutism,
acne and alopecia. In this way, the ovaries were scanned in longitudinal and
transverse planes and their volume was measured using the formula for computing
an ovals volume. Afterwards, PCOS was determined based on the criteria
of Adams et al. (1986) and Berker
et al. (2004) the most important of which being the existence of
10 small peripheral follicles. It should be mentioned that the sonography specialist
was not aware of the results of the patients clinical examinations and
biochemical tests. Thus, in case the patients showed 10 or more 2-8 mm cysts
in the peripheral view or several 2-4 mm cysts in the diffuse view, they were
diagnosed with PCOS (Adams et al., 1986; Swanton
et al., 2010). Also, in case the subjects had the clinical or biochemical
symptoms of hyperandrogenism or PCOS-related menstrual irregularities while
presenting no other causes of androgen increase, they were considered with PCOS
(Takahashi et al., 1994).
After providing the subjects with sufficient information about the hormonal
and biochemical experiments, the experiments were performed at the Endocrine
and Metabolism Research Center, Namazi hospital, Shiraz, Iran. The patients
hormonal evaluation was performed using morning blood including prolactin (for
rejection of hyperprolactinemia), dehydroepiandrostenedione sulphate (for rejection
of adrenal disorders), total and free testosterone and TSH (for rejection of
hypothyroidism). In case the amount of testosterone was twice as much the normal
level, the necessary measures were taken towards rejection of neoplasm (Franks,
After all, the collected data were analyzed using descriptive statistics, Fishers
test, chi-square test and frequency distribution tables. All the statistical
tests were performed considering CI = 95% and α = 0.05.
In this study, most of the participants (30.2%) were 17 years old. The prevalence
of hirsutism was 3.2%. In addition, the mean of total (0.685+0.354) and free
testosterone (1.647+0.835) was higher in the patients suffering from hirsutism
compared to the normal subjects; however, the difference was not statistically
significant (p>0.05) (Table 1 and 2).
The results of the present study showed menstrual irregularities in 12.1% of
the subjects 88.2% of whom had mild to severe hirsutism. In addition, a significant
relationship was observed between menstrual irregularities and hirsutism (p<0.001)
|| Distribution of cutaneous manifestations in population
|CM: Cutaneous manifestations
|| Mean testosterone and free testosterone levels in patients
with hirsute, acne and alopecia in the study population
|CM: Cutaneous manifestations
|| Correlation of hirsute, menstrual patterns in the study population
|X2 = 60.65, Df: 6, p = 0.001
|| Distribution of alopecia, hirsute and polycystic ovarian
|| Distribution of facial and body acne and polycystic ovarian
According to the results of Fishers
test, a significant difference was found between the subjects with hirsutism
and PCOS and those suffering from hirsutism but not PCOS (p<0.001) (Table
In this study, the frequency of severe acne on face and body was 0.5% (143
subjects) and 3.2% (103 subjects), respectively (Table 1).
Besides, the mean of total testosterone (0.775+0.250) was higher in the participants
with acne compared to those without acne. On the other hand, the mean of free
testosterone (1.469+0.544) was lower in the subjects with severe acne compared
to those without acne. However, the results of independent T-test revealed no
significant difference between the two groups (Table 2).
Furthermore, 59 subjects with acne on their faces (82%) showed PCOS in ultrasound,
which was significantly different from the subjects with acne who did not have
PCOS (p<0.05) (Table 5).
Also, 75 participants (75%) with acne on their bodies showed PCOS in ultrasound.
According to Fishers test, a
significant difference was found between the participants with body acne and
PCOS and those suffering from acne but not PCOS (p<0.05) (Table
Based on Ludwigs classification,
135 study participants (4.2%) had average to severe alopecia. Considering the
features investigated for alopecia, 612 subjects (3.7%) had average to severe
scalp hair loss, 38 ones (1.2%) had average and severe hair loss at temples
and 45 participants (1.4%) had average and severe hair loss at forehead line
(Table 1). However, no significant relationship was observed
between total and free testosterone levels and alopecia hair loss pattern (p>0.05)
In this study, none of the study participants had prolactin and adrenal disorders.
In addition, 34 subjects presented hypothyroidism and were referred to an endocrinologist
for treatment. The results of Fishers
test revealed no significant difference between the subjects with alopecia and
PCOS and those suffering from alopecia but not PCOS (p = 0.2) (Table
In this study, the prevalence of hirsutism was 3.2% (almost 100 subjects).
Some studies have reported the frequency of hirsutism as 2-8% (Ehrmann,
2005; Arslanian and Witchel, 2002). In addition,
the review study conducted by Escobar-Morreale et al.
(2012) in several countries showed the prevalence of hirsutism to be 4.3-10.8%.
They also stated that the prevalence of hirsutism was lower in Asian countries
(Knochenhauer et al., 1998).
In females, ovarian and adrenal secretions and metabolism of prohormones secreted
in peripheral tissues, such as fat, are androgenic sources. Overall, 70-80%
of the patients with increase in androgens present hirsutism. Yet, genetic and
racial differences can change the effects of androgens on the skin (Speroff
and Fritz, 2005; Ludwig, 1977). One other reason
for increase in hirsutism can be the sensitivity of the final organ to 5-alpha
reductase activity (increase in conversion of testosterone to dihydrotestosterone).
This enzyme is affected by genetic and racial factors and plays a role in the
incidence of hirsutism (Escobar-Morreale et al.,
The findings of the current study showed no significant relationship between
PCOS and hirsutism. In other studies, however, PCOS was shown to be the most
common reason for increase in hirsutism (Greep et al.,
1986). In that study, 91 and 92% of the patients had PCOS. Among the girls
with hirsutism in the present study, on the other hand, 33.3% had cystic ovaries
and 26.5% lacked ovarian cysts. This lower prevalence might be due to the difference
in sonography method. These results are on the contrary to those obtained in
the study performed in United Arab Emirates (90%) as well as the one conducted
by Adams et al. (1986) in England (Ibanes
and de Zegher, 2004; Gatee et al., 1996).
In general, vaginal sonography provides a better image of the ovaries, particularly
in obese girls; however, it is not possible to be used in adolescents (Moran
et al., 1994). Moreover, 20-30% of the normal women show PCOS in
sonography during the reproductive ages (Azziz, 2006).
In case hirsutism does not result from PCOS, it may be due to the type of testosterone
measurement. In fact, free testosterone plays the key role in hirsutism and
other hyperandrogenism symptoms. On the other hand, total testosterone can be
within the normal range in the women with hirsutism because the active part
of testosterone increases in these women and the free part increases from 1-2%
(Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop
In the present study, 12.1% of the subjects with hirsutism had menstrual irregularities.
This rate was lower compared to that reported in other studies which might be
due to the lower prevalence of hirsutism in the study population. Menstrual
cycles without ovulation during adolescence can lead to irregular menstrual
cycles, as well. It should also be noted that regular menstrual cycles cannot
reject PCOS and adrenal hyperplasia (Rasgon et al.,
2003; Carmina and Lobo, 2001). For instance, Gattis
study showed that 25.2% of the PCOS patients had regular menstrual cycles (Michelmore
et al., 1999).
In this study, the prevalence of severe face and body acne was 5%. In the study
by Kilkenny et al. (1998), mild acne was detected
in 83% of the subjects, while average and severe acne was observed in 17% (Gatee
et al., 1996). In Oktans study (Aktan
et al., 2000) also, 8.8% of the girls had average to severe acne
(Kilkenny et al., 1998). Moreover, Karciauskiene
et al. estimated the prevalence of acne as 73% in female adolescents
and considered weight gain and obesity as the most important risk factor (Aktan
et al., 2000). In general, the prevalence of acne varies from 0-90%
in various countries and communities (Karciauskiene et
al., 2013; Lehmann et al., 2002; Cordain
et al., 2002; Poli et al., 2001).
The results of the current study indicated a significant relationship between
acne and PCOS in sonography. The study by Timpatanapong
and Rojanasakul (1997) showed that 19 out of the 51 study women with acne
(37.3%) had PCOS (Smithard et al., 2001). In
another study, the incidence rate of PCOS was 29.9% in the subjects with acne
compared to 8.5% in the control group (Timpatanapong and
Rojanasakul, 1997). Other studies have also reported acne to be accompanied
by PCOS (Timpatanapong and Rojanasakul, 1997; Kelekci
et al., 2010).
In this study, high androgenic hormones levels were significantly related to
the incidence and severity of acne. In the same line, the results of the study
by Chen et al. showed high dihydrotestosterone levels in the PCOS patients
with acne (6.01+3.45 vs. 4.87+4.29 μmol L-1; p = 0.002) (Maluki,
2010). However, the results obtained by Bunker
et al. (1991) and Puzigaic et al. (1991)
were on the contrary to those of the present research (Chen
et al., 2011; Bunker et al., 1991).
Basically androgens increase acne and provide proper conditions for colonization
of microorganisms, such as propionibacterium, through stimulation of sebum production
(Puzigaic et al., 1991). Of course, since a
positive family history increases the probability of acne, genetic backgrounds
should also be taken into account in investigation of the incidence of acne
(Burkhart and Gottwald, 2003). Furthermore, some researchers
have stated that the prevalence of acne is not certainly higher in PCOS patients
compared to the normal population (Cunliffe and Simpson,
1998) because some forms of acne present in adolescents as well as 50% of
the above 25 year old females (Azziz et al., 2006).
The findings of the present research indicated the prevalence of androgenic
alopecia among the 14-18 year old girls to be 4.2%. Some studies have mentioned
that alopecia is a weak predicator of hyperandrogenism since alopecia and hair
loss depend on various factors (Cunliffe and Simpson, 1998;
Azziz et al., 2006; Goulden
et al., 1999). These factors include age androgens increase during
menopause, food diet concerning iron and other mineral and protein compounds
(Barth et al., 2007), stress, stressful life
experiences, negative body image, adjustment disorder (Sinclair,
1998) and genetic factors. The studies conducted on twins have also shown
that potential, age, pattern and speed of hair loss all depend on genetic factors
(Bolduc and Shapiro, 2000; Stough
et al., 2002).
Furthermore, several studies have revealed a relationship between hair loss
and iron deficiency (Nyholt et al., 2003). In
this study, however, the subjects hemoglobin level was not assessed. Thus,
hair loss in some study subjects might have resulted from iron deficiency anemia.
The results of this study showed no significant relationship between total
and free testosterone levels and PCOS as well as alopecia hair loss pattern
(p>0.05). One study reported the prevalence of hyperandrogenism to be 38.5%
in 109 females with average to severe alopecia. In addition, 43% of the patients
with hyperandrogenism had the criteria of PCOS (Cook, 2005).
One other study also showed that the prevalence of PCOS was 67% among the women
with androgenic alopecia compared to 27% in the control group. Besides, the
prevalence of hirsutism was higher in the women with alopecia in comparison
to the control group (Essah et al., 2006).
Based on what was mentioned above, testosterone level and PCOS increase in
the patients suffering from androgenic alopecia. Yet, the difference between
the results of the present study and those of other studies might be due to
the age of the research population (14-18 years old), hemoglobin level (which
was not assessed in this study) and other problems which might present in females
in higher reproductive ages.
In this study androgenic hormones levels were higher in the patients with acne
and were significantly related to the incidence of PCOS. However, no significant
relationship was observed between hirsutism as well as alopecia and androgenic
hormones levels and PCOS. This might be due to the differences in genetic factors,
race, nutrition, type of sonography, sonography equipment and age of the research
community. Thus, further studies are recommended to be conducted on 20-25 year
old subjects and on the females with regular menstrual cycles.
The present article was extracted from Ms. Tahere Naderis
M.Sc. thesis. The study was financially supported by the Research Vice-chancellor
of Shiraz University of Medical Sciences, Shiraz, Iran. Hereby I would like
to thank community based nursing and midwifery research center and Research
Improvement Center of Shiraz University of Medical Sciences and Ms. A. Keivanshekouh
are appreciated for improving the use of English in the manuscript.
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