Report

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International
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XXX2007 The
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of Dermatology
Society of Dermatology

Assessment of androgens in women with adult-onset acne

Androgens
Seirafi
report et al.in women with adult-onset acne

Hassan Seirafi, MD, Farshad Farnaghi, MD, Amir Vasheghani-Farahani, MD, Najmeh-Sadaat
Alirezaie, MD, Fatemeh Esfahanian, MD, Alireza Firooz, MD, and Seyedeh Zahra Ghodsi, MD

From the Department of Dermatology, Razi Abstract

Hospital, Tehran, Iran Background Acne is generally recognized as a disorder of young adults; however, the referral
of patients aged over 25 years with acne is increasing. Disturbed androgen production in the
Correspondence
ovaries or adrenal gland and impaired plasma transport of androgens in women with adult-
Hassan Seirafi, MD
Razi Hospital onset acne or acne associated with hirsutism have been described.
Vahdat Eslami Sq Methods Thirty-five white women with adult-onset acne (onset after the age of 25 years) and
Tehran hirsutism (A + H), 35 white women with adult acne without hirsutism (A H), and 35 age-
Iran matched white female controls were recruited in this casecontrol study. Serum levels of
E-mail: hassan_seirafi@yahoo.com
luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone,
dihydroepiandrosterone sulfate (DHEA-S), and sex hormone binding globulin (SHBG) were
determined in all patients and compared.
Results The mean SHBG, free androgen index (FAI), and DHEA-S were significantly different
between A + H and control subjects. The only significant difference between A H and control
subjects was observed for DHEA-S.
Conclusion DHEA-S plays a key role in the pathogenesis of adult-onset acne. Measurement
of circulating androgens, including DHEA-S, especially in patients presenting with adult-onset
acne and hirsutism, is helpful, and patients with elevated levels can benefit from hormonal therapy.

severe, of sudden onset, and associated with hirsutism or

Introduction
Acne vulgaris is a self-limited disease that affects the sebaceous
follicles. Acne is generally recognized as a disorder of young
adults; however, the referral of patients aged over 25 years
with acne is increasing. Post-adolescent acne is defined as the
presence of acne after the age of 25 years, regardless of the age
at onset. Late-onset acne appears for the first time after the
age of 25 years.1
Acne is a multifactorial disorder. Some important pathogenic
factors involved include hyperkeratinization and obstruction
of the sebaceous follicles as a result of abnormal keratinization
of the infundibular epithelium, androgenic stimulation of the
sebaceous glands, and microbial colonization of the piloseba-
ceous units by Propionibacterium acnes, and subsequent
perifollicular inflammation.2
Androgens impair the barrier function of the skin. As a
result, DNA synthesis is stimulated, which leads to epidermal
hyperplasia and follicular hyperkeratosis. Therefore,
androgens may facilitate acne formation through follicular
hyperkeratosis.3 Acne and hirsutism are common manifesta-
tions of hyperandrogenism.46 Nevertheless, acne or hirsutism
may be found in patients with normal androgenic parameters.7
Hyperandrogenism should be considered as a contributing
1188 factor to the development of acne in women whose acne is
irregular menstrual periods. A complete history and physical
examination to detect hyperandrogenism are therefore
helpful in these patients. If elevated androgen levels are
found, patients may benefit from various methods of
hormonal therapy, such as androgen receptor blockers
(antiandrogens) or inhibitors of androgen production by the
ovaries or adrenal gland.8
Disturbed androgen production in the ovaries or adrenal
gland and impaired plasma transport of androgens in women
with adult acne or acne associated with hirsutism have been
the focus of some investigations.9 Increased levels of serum
androgens have been shown in patients with acne;4,1013
however, many reports indicate no significant association
between acne and androgen levels.1416 Increased sensitivity
of the sebaceous end organ to androgen9 and increased
peripheral metabolism of androgens17,18 are other possible
mechanisms involved in the development of acne.
In addition to cosmetic concerns, acne may imply an under-
lying disorder. Some reports indicate a greater prevalence
of polycystic ovary syndrome (PCOS) in patients with acne.4
Hirsutism is the other common manifestation of hyper-
androgenism. An increased level of androgens or increased
sensitivity of the hair follicle end organ may be associated
with hirsutism.19

International Journal of Dermatology 2007, 46, 11881191 2007 The International Society of Dermatology
Seirafi et al.
Although two different end organs are associated with acne
and hirsutism, the level of circulating androgens should be of
greater importance in patients with concurrent acne and
hirsutism. In this study, we evaluated serum androgens in
patients affected by adult-onset acne alone or adult-onset
acne associated with hirsutism.
Materials and Methods
Thirty-five white women with adult-onset acne (appearance of
acne after the age of 25 years) and hirsutism (A + H), 35 white
women with adult-onset acne without hirsutism (A H), and 35
age-matched white women without acne, hirsutism, or menstrual
irregularity, as a control group, were studied. The mean ages of
A + H, A H, and control subjects were 28.7 3.5, 28.9 3.3,
and 29.2 3.6 years, respectively. None of the study subjects had
been treated with oral contraceptive pills, antiandrogens, systemic
antibiotics, or isotretinoin for 3 months prior to the study. A
questionnaire including the history of menstrual irregularity, marital
status, age at first acne development, weight, height, and age at
menarche was completed by all subjects. Physical examination to
determine acne severity was performed based on the William J.
Cunliffe criteria.20 Grading of hirsutism was recorded according to
the FerrimanGallwey method,21 and a score above eight was
defined as hirsutism. Blood samples for hormonal assessment
were obtained in the luteal phase in the early morning. Levels of
luteinizing hormone (LH), follicle-stimulating hormone (FSH), total
testosterone, dihydroepiandrosterone sulfate (DHEA-S), and sex
hormone binding globulin (SHBG) were determined, and the free
androgen index (FAI) was calculated as testosterone (nmol/L)/
SHBG (nmol/L) 100.
The 95th percentile around the mean was calculated for
hormonal parameters. Abnormal values were therefore
defined as LH > 9.02, FSH > 12.5, DHEA-S > 410, FAI > 5.48,
testosterone > 76.4, and androstenedione > 3.3. Sonography of
the ovaries was performed in all subjects.
Statistical considerations
The body mass index (BMI, kg/m2) was calculated. Values of age,
BMI, age at menarche, and serum hormone levels are presented
as the mean standard deviation (SD). Independent t-test was
used to compare mean values amongst the study groups. The
Table 1 Age, body mass index (BMI), and
Study group
age at menarche of patients with adult-
onset acne, with and without hirsutism,
Acne + hirsutism (n = 35)
and control subjects Acne hirsutism (n = 35)
Control (n = 35)
P NS
Values are depicted as mean standard deviation. NS, not significant.
*Significant difference was noted between patients with acne + hirsutism and controls.
2007 The International Society of Dermatology
Androgens in women with adult-onset acne Report 1189
upper 95th percentile of the blood sample values for the control
group was considered as the upper limit of normality. The
frequencies of hyperandrogenism based on the androgenic
parameters were compared using the chi-squared test. P values
of less than 0.05 were considered to be significant.
Results
The mean age of the subjects, BMI, and age at menarche are
shown in Table 1. The mean BMI of the A + H group was
greater than that of control subjects (P = 0.02). Menstrual
irregularity was observed in 28.6% of A + H and in 20% of
A H subjects. The results of serum hormone levels are
depicted in Table 2. The mean SHBG, FAI, and DHEA-S
levels were significantly different between A + H and control
subjects. The only significant difference in the hormonal
parameters between A H and control subjects was observed
for DHEA-S. Abnormal hormone levels were measured in all
groups of the study. Twenty subjects (57.1%) in the A + H
group, 10 subjects (28.6%) in the A H group, and three sub-
jects (8.6%) in the control group had at least one abnormal
androgenic parameter. Table 3 shows the values of the hor-
mone levels in patients with adult-onset acne (A + H and A
H groups) with regard to the severity of acne. The severity of
acne was not significantly correlated with BMI in either
group. FAI and SHBG were significantly different between
severe and mild acne in the A + H group (P = 0.044 and
P = 0.011, respectively). Sonography of the ovaries consistent
with PCOS was observed in two (5.7%), four (11.4%), and
10 (28.6%) patients in the control, A H, and A + H groups,
respectively.
Discussion
In this study, at least one abnormal (greater than the upper
limit) androgenic parameter was observed in 57.1% of
patients in the A + H group and in 28.6% of patients in the
A H group. Some studies in the literature reveal greater
values of hyperandrogenism in patients with adult-onset acne.
Maneschi et al.22 reported mild and heterogeneous hyper-
androgenism in 70% of women with adult acne (late onset
or persistent). Vexiau et al.23 reported hyperandrogenism in
Age (years) BMI (kg/m2) Age at menarche (years)
28.69 3.46 25.55 3.99 12.54 0.85
28.94 3.35 24.40 4.11 12.34 0.91
29.23 3.56 23.54 3.00 12.66 0.72
0.02* NS
International Journal of Dermatology 2007, 46, 11881191
1190 Report Androgens in women with adult-onset acne Seirafi et al.

Table 2 Serum hormone levels in patients with adult-onset acne, with and without hirsutism, and control subjects

Total Free
FSH LH LH to FSH testosterone SHBG androgen Androstenedione DHEA-S
Study group (mIU/mL) (mIU/mL) ratio (ng/dL) (nmol/L) index (ng/mL) g/dL)
(

Acne + hirsutism (n = 35) 7.01 3.05 5.49 2.60 0.83 0.30 50.06 23.0 46.46 19.54 4.99 3.88 2.29 0.94 280.83 135.56
Acne hirsutism (n = 35) 6.70 2.39 5.64 1.94 0.86 0.18 46.06 20.36 52.26 14.82 3.53 2.33 1.94 0.61 266.26 126.29
Control (n = 35) 6.35 3.06 5.19 2.14 0.86 0.20 42.51 18.93 58.00 17.11 2.75 1.37 2.05 0.70 201.14 120.32
P NS NS NS NS 0.01* 0.02* NS 0.01*, 0.03

DHEA-S, dihydroepiandrosterone sulfate; FSH, follicle-stimulating hormone; LH, luteinizing hormone; NS, not significant;
SHBG, sex hormone binding globulin.
Values are depicted as mean standard deviation.
*Significant difference was noted between patients with acne + hirsutism and controls.
Significant difference was noted between patients with acne hirsutism and controls.

Table 3 Androgenic parameters with regard to acne severity in acne patients with and without hirsutism

Severity of acne in acne + hirsutism patients Severity of acne in acne hirsutism patients

Mild Moderate Severe Mild Moderate Severe

(n = 15) (n = 13) (n = 7) P (n = 16) (n = 14) (n = 5) P

FSH (mIU/mL) 6.78 6.98 7.57 NS 6.52 6.91 6.70 NS

LH (mIU/mL) 4.82 5.65 6.60 NS 5.69 5.84 4.92 NS
LH to FSH ratio 0.77 0.85 0.94 NS 0.91 0.84 0.80 NS
Total testosterone (ng/dL) 45.87 49.08 60.86 NS 43.87 46.36 52.20 NS
SHBG (nmol/L) 54.07 44.31 34.14 0.011* 54.62 51.79 46.00 NS
Free androgen index 3.81 5.17 7.15 0.044* 3.07 3.82 4.22 NS
Androstenedione (ng/mL) 2.32 2.40 2.00 NS 1.97 1.78 2.32 NS
DHEA-S ( g/dL) 258.67 272.92 343.00 NS 241.31 273.78 325.00 NS

DHEA-S, dihydroepiandrosterone sulfate; FSH, follicle-stimulating hormone; LH, luteinizing hormone; NS, not significant;
SHBG, sex hormone binding globulin.
*Significant difference was noted between mild and severe acne in patients with acne + hirsutism.

86% of patients with persistent acne without signs of virilism.
Darley et al.13 and Slayden et al.24 reported abnormal levels of
androgenic markers in 76% and 55% of patients with adult
acne, respectively.
We have shown that the mean value of DHEA-S for A H
subjects is significantly greater than that of the control group.
This is consistent with some studies in the literature,2426 but
contrasts with the study by Walton et al.27 This androgenic
parameter was also increased significantly in patients in the
A + H group. Therefore, DHEA-S, that has its origin in the
adrenal gland, is the only androgenic marker increased in
both groups. Our study shows that the levels of androstene-
dione, SHBG, testosterone, and FAI are no different between
patients in the A H and control groups. This is consistent
with the study by Aizawa and Niimura.26 Darley et al.13
reported a 60% increase in the level of testosterone and
decrease in the level of SHBG in patients with late-onset or
persistent acne. Slayden et al.24 reported that nonhirsute
patients with acne demonstrated significantly lower levels of
SHBG and higher free testosterone and DHEA-S levels. In our
study, lower levels of SHBG, and higher levels of FAI and
DHEA-S, were evident in patients in the A + H and control
groups. Lawrence et al.28 reported similar results for testos-
terone. Ginsberg et al.29 reported an increase in DHEA-S in
48% of patients. They also showed that at least one androgen
amongst testosterone, DHEA-S, and androstenedione was
increased significantly in 61% of patients in the A + H group.
We found no overall correlation between hormonal levels
and acne severity. This is consistent with some reports in the
literature;16,30 however, others indicate that the severity of
acne is negatively correlated with the level of SHBG.31,32 We
found the same correlation only in patients in the A + H
group. FAI was also correlated positively with acne severity in
the same group. Such correlations were not found in patients
in the A H group.
In conclusion, DHEA-S, with its origin in the adrenal
gland, plays an important role in the pathogenesis of adult-
onset acne, and its measurement in patients with adult-onset

International Journal of Dermatology 2007, 46, 11881191 2007 The International Society of Dermatology
Seirafi et al.
acne can be helpful. If elevated levels of DHEA-S are found,
patients with adult-onset acne may benefit from hormonal
treatments, including inhibitors of ovarian or adrenal
androgen production or androgen receptor blockers. Acne
and hirsutism are commonly found in patients with hyper-
androgenism. As two different end organs are associated with
acne and hirsutism, it is highly recommended to screen for
circulating androgens, including DHEA-S, when patients
present with concurrent acne and hirsutism and, if elevated
androgens are found, specific hormonal therapy can be of
great benefit.
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