Original Contribution

Journal of Cosmetic Dermatology, 0, 1--4

The role of oxidative stress in early-onset androgenetic alopecia

Hilal Kaya Erdogan, MD,1 Isl Bulur, MD,1 Evin Kocaturk, MD,2 Bahadir Yildiz, MD,1
Zeynep Nurhan Saracoglu, MD,1 & Ozkan Alatas, MD3
1
Faculty of Medicine, Department of Dermatology, Eskisehir Osmangazi University, Eskisehir, Turkey
2
Department of Biochemistry, Eskisehir Yunus Emre State Hospital, Eskisehir, Turkey
3
Faculty of Medicine, Department of Biochemistry, Eskisehir Osmangazi University, Eskisehir, Turkey

Abstract Background Androgenetic alopecia (AGA) is the most common cause of alopecia in
men. In the literature, although there are in vitro studies investigating the
relationship between oxidative stress and AGA, any in vivo study does not exist.
Aim Our aim was to evaluate the oxidative stress status in male patients with early-
onset AGA by measuring total oxidant levels (TOS), total antioxidant levels (TAS),
and oxidative stress index (OSI).
Methods Our study included 33 male patients with early-onset AGA and 30 healthy
men between ages of 18 and 30 years old. TAS and TOS measurements were taken,
and OSI was calculated.
Results When TAS, TOS, and OSI levels were compared between patient and control
groups, there was no difference for TAS level, while TOS and OSI were significantly
higher in patient group. In patient group, correlation between TAS, TOS, and OSI
levels and age, and disease onset age and disease duration was evaluated. Highly
significant negative correlation was determined between TAS level and both age and
disease duration. When TAS, TOS, and OSI levels were assessed according to AGA
stage, there was no significant difference between groups, while OSI level was
significantly higher in patients with family history.
Conclusions We found increased oxidative stress in younger patients with early-onset
AGA. There is need for further molecular studies on the role of oxidative stress in the
etiopathogenesis of AGA. We also think that topical or systemic antioxidants can be
promising in treatment of AGA, especially for young patients.
Keywords: androgenetic alopecia, early onset, total oxidant capacity, total antioxidant

individuals. AGA is present in 50% of men in their fif-

Introduction
Androgenetic alopecia (AGA) is the most common
cause of alopecia in men, and it is triggered by the
effect of androgens in genetically predisposed
Correspondence: Hilal Kaya Erdogan, Department of Dermatology,
Eskisehir Osmangazi University, Buyukdere District, Osmangazi University
Meselik Campus 26040/ESKISEHIR/ Turkey. E-mail: hilalkayaerdogan@
yahoo.com
Accepted for publication November 7, 2016
ties, while 70% of men at older ages are affected.1
AGA is suggested to develop by reduced anagen
phase and prolonged telogen phase resulting from
binding of increased dihydrotestosterone (DHT) at scalp
pilosebaceous units to androgen receptors.2 DHT leads
to release of various factors causing hair follicle minia-
turization at dermal papilla (DP) and transformation of
terminal hair to vellus hair at vertex and temporal
region.3 Stress, anxiety, ischemia, smoking, sun expo-
sure, and oxidative stress are also related with the dis-
ease development in addition to genetic factors.3,4

2016 Wiley Periodicals, Inc. 1

Oxidative stress in androgenetic alopecia . H Kaya Erdogan et al.
Reactive oxygen species result from metabolic and
physiological process, and they are highly reactive
molecules damaging cell membrane, lipids, proteins,
and DNA. There are endogenous antioxidative defense
mechanisms to protect the organism. In certain cases,
oxidative equilibrium may be impaired due to increased
oxidants or decreased antioxidants. Oxidative stress is
considered to play role in more than a hundred dis-
eases. To determine the degree of oxidative stress, the
level of reactive oxygen species, nonenzymatic mole-
cules (glutathione, uric acid, melatonin, vitamins A, C,
and E) and antioxidant enzymes (superoxide dismutase,
glutathione peroxidase, catalase) can be measured.
However, these measurements do not reflect global
assessment of oxidative stress. Therefore in our study,
we globally evaluated the oxidative stress status by
measuring total antioxidant status (TAS) and total oxi-
dant status (TOS) via a newly developed method.46
In the literature, although there are in vitro studies
investigating the relationship between oxidative stress
and AGA, any in vivo study does not exist. In our
study, our aim was to evaluate the oxidative stress sta-
tus in male patients with early-onset AGA by measur-
ing TAS, TOS, and OSI levels.
Material and methods
Our study included 33 male patients with early-onset
AGA and 30 healthy men between ages of 18 and
30 years old. AGA, occurring before 30 years of age at
Hamilton-Norwood stage 3 and greater, is accepted as
early-onset AGA.7 Patients and volunteers with sys-
temic inflammatory disease, taking any systemic treat-
ment, antioxidants, food and vitamin supplements
within last 1 month, patients with skin disorder except
early-onset AGA and volunteers with dermatological
disease were excluded. In addition, smoking and alco-
hol consumption, diagnosis of metabolic syndrome,
and prolonged exposure to ultraviolet were also among
exclusion criteria.
Ethics committee approved the study protocol.
Patients and volunteers were informed, and informed
consent form was signed before being admitted to the
study.
The blood samples were centrifuged at 3000 g for
5 min within 30 min following sampling, and the
separated serum was stored at 40 C up to day
when TAS and TOS measurement was taken. Mea-
surements were taken colorimetrically by Roche/Hita-
chi Modular (Mannheim, Almanya) auto-analyzer.
TAS was measured using commercial kits of Rel
Assay (Rel Assay Kit Diagnostics, Turkey) developed
2 2016 Wiley Periodicals, Inc.
by Erel.6 Trolox, a water-soluble analogue of vitamin
E, was used as calibrator. Results were expressed as
mmol Trolox equiv./L. TOS level was measured using
commercial kits of Rel Assay (Rel Assay Kit Diagnos-
tics, Turkey) developed by Erel.5 Hydrogen peroxide
was used as calibrator. Results were expressed as
lmol H2 O2 equiv./L. The percentage expression of
the ratio of TOS level to TAS level was calculated as
OSI. Results were expressed as arbitrary unit (AU)
and calculated according to below formula: OSI= TOS
(lmol H2O2 equiv./L)/TAS, mmol Trolox equiv./L X
10.
SPSS 22.0 software was used for data analysis. Con-
tinuous quantitative data were expressed as n, mean,
and standard deviation, and qualitative data were
expressed as n, median, percentile 25, and percentile
75. Continuous data, composed from independent mea-
surements and showing normal distribution, were ana-
lyzed by independent-samples t-test, and variables
without normal distribution were analyzed by Mann
Whitney U-test. In order to demonstrate the correla-
tion between variables, Pearsons correlation test was
performed for variables with normal distribution and
Spearmans correlation test was performed for variables
without normal distribution according to normality
test results. Chi-square test was applied for categorical
data set. Probability value P < 0.05 was considered as
significant.
Results
The study included 33 men with AGA and 30 healthy
male volunteers. Mean age of patients was
24.94  2.83 years, and mean age for control group
was 23.63  2.57 years. There was no significant dif-
ference between groups in respect of age (P = 0.06).
HamiltonNorwood scale was stage 3 in 72.7% of
patients and stage 4 in 27.3%. Family AGA history
was present in 66.7% (22) of 33 patients. Mean age
for AGA onset was 19.51  2.87 years, and mean dis-
ease duration was 68.84  30.27 months.
When TAS, TOS, and OSI levels were compared
between patient and control groups, there was no dif-
ference for TAS levels, while TOS and OSI levels were
significantly higher in patient group (P = 0.536,
P = 0.045, P = 0.035, respectively) (Table 1).
In patient group, correlation between TAS, TOS, and
OSI levels and age, and disease onset age and disease
duration was evaluated. Highly significant negative
correlation was determined between TAS levels and
both age and disease duration (P = 0.013 r = 0.428,
P = 0.042 r = 0.356, respectively) (Table 2).
 Oxidative stress in androgenetic alopecia . H Kaya Erdogan et al.

Table 1 Comparison of TAS, TOS, and OSI levels in the patients Table 4 Comparison of TAS, TOS, and OSI levels in the patient
and control group group according to family history

Patient (n = 33) Control (n = 30) P Family History

TAS (mmol 1.88  0.14 1.86  0.13 0.536* Negative (n = 11) Positive (n = 22) P
Trolox equiv./L)
TOS (lmol 2.85 (2.353.80) 2.59 (2.023.20) 0.045 TAS (mmol 1.92  0.136 1.87  0.136 0.346*
H2 O2 equiv./L) Trolox equiv./L)

OSI (AU) 0.16 (0.130.20) 0.14 (0.110.15) 0.035 TOS (lmol 2.54 (2.332.88) 3.13 (2.545.44) 0.076
H2 O2 equiv./L)
TAS, total antioxidant status; TOS, total oxidant status; OSI, OSI (AU) 0.14 (0.120.15) 0.17 (0.140.29) 0.026
oxidative stress index.
*Independent-samples t-test (mean  SD), *Independent-samples t-test (Mean  SD).
*

MannWhitney U median (2575%). MannWhitney U median (2575%).

Discussion
Table 2 Correlation between TAS, TOS, and OSI levels and the
patient variables Oxidative stress results from disequilibrium between
systemic signs of reactive oxygen species and detoxify-
TAS TOS OSI
ing and repairing capacity of biological systems.8 Free
Age
radical production increases whereas endogenous
r 0.428* 0.033 0.101 defense mechanisms decrease with aging. A key role of
P 0.013 0.856 0.576 oxidative stress is also considered in hair graying and
Age of onset hair loss.4
r 0.018 0.137 0.116
P 0.919 0.446 0.522 Hair loss may due to nonandrogen signals in addi-
Duration tion to androgens at advanced age.9 In a study on
r 0.356* 0.242 0.088 AGA and oxidative stress, Bahta et al.10 determined
P 0.042 0.176 0.627
that the growth of cultured balding dermal papilla cells
*Spearmans correlation test.
(DPC) was slower than the cultured nonbalding DPC.
Premature aging was detected in cultured balding
DPC, and they suggested that this was related with
higher sensitivity of balding DHC to oxidative stress.
Table 3 Comparison of TAS, TOS, and OSI levels in patient Although cell aging does not directly lead to AGA
group according to AGA stage development, they suggested that balding DPC were
more sensitive to environmental stress than nonbald-
AGA Stage ing DPC and that even very small environmental alter-
ations could lead to hair miniaturization by affecting
3 (n = 24) 4 (n = 9) P
DPC function. Consequently, they indicated that drugs
TAS (mmol 1.88 (1.751.96) 1.93 (1.871.99) 0.331 targeting oxidative stress pathways could be beneficial
Trolox equiv./L) for treatment of AGA. In consistent with these results,
TOS (lmol 2.77 (2.373.47) 2.95 (2.236.39) 0.628 Upton et al. emphasized that the capacity to overcome
H2 O2 equiv./L)
OSI (AU) 0.15 (0.130.19) 0.16 (0.120.32) 0.731
the oxidative stress of nonbalding DPC was less.11
In our study, we also detected that TAS levels was
MannWhitney U median (2575%). significantly negatively correlated with age and disease
duration. This result shows that oxidative stress is
higher in younger ages, and this is important for rapid
When TAS, TOS, and OSI levels were assessed progression of AGA to HamiltonNorwood stage 34
according to AGA stage, there was no significant differ- disease.
ence between groups (Table 3). There was no signifi- Recent studies reported concomitant occurrence of
cant difference between patients family history and early-onset AGA and insulin resistance, metabolic syn-
TAS and TOS levels, but OSI level was significantly drome, and coronary artery disease1214; besides, Yang
higher in patients with family history (P = 0.026) et al. found that higher body mass index was signifi-
(Table 4). cantly associated with severity of early-onset AGA in

2016 Wiley Periodicals, Inc. 3

Oxidative stress in androgenetic alopecia . H Kaya Erdogan et al.
men.15 It is known that oxidative stress is associated
with insulin resistance, metabolic syndrome, coronary
artery disease, and obesity. So these studies can also
support the association between oxidative stress and
early-onset AGA.
In our study, we also found that OSI level was signif-
icantly higher in patients with family history. On the
other hand, Hillmer et al.16 showed that genetic vari-
ability in the androgen receptor gene was important
for the development of early-onset AGA. In the light of
these findings, we think that early-onset AGA patients
may be also genetically susceptible to oxidative stress.
Conclusions
Hair loss may be seen with advanced age due to
increased oxidative stress.9 However in our study, we
found increased oxidative stress in younger patients
with a short-time disease duration. Furthermore, family
history was found associated with early-onset AGA. We
think that there is need for further molecular studies on
the role of oxidative stress in AGA etiopathogenesis inde-
pendent from aging process. Besides, genetic studies
investigating the relationship between oxidative stress-
related genes and early-onset AGA are warranted. Also
we suggest that topical or systemic antioxidants can be
promising in treatment of AGA in the future.
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