doi: 10.1111/1346-8138.

13159 Journal of Dermatology 2016; 43: 567–570

CONCISE COMMUNICATION
Topical adenosine increases the proportion of thick hair in
Caucasian men with androgenetic alopecia
Tokuro IWABUCHI,1 Ritsuro IDETA,1 Ritsuko EHAMA,1 Haruyo YAMANISHI,1
Masato IINO,1 Yosuke NAKAZAWA,1 Takashi KOBAYASHI,2 Manabu OHYAMA,3
Jiro KISHIMOTO1
1
Shiseido Research Center, Yokohama, 2Department of Dermatology, Teikyo University Medical Center, Chiba, 3Department of
Dermatology, Keio University School of Medicine, Tokyo, Japan

ABSTRACT
Adenosine is an effective treatment for androgenetic alopecia (AGA) in Japanese men and women. Adenosine
exerts its effects by significantly increasing the proportion of thick hair. In this study, we assessed the clinical
outcome of adenosine treatment for 6 months in 38 Caucasian men. The change in proportion of thick hair
(≥60 lm) compared with baseline in the adenosine group was significantly higher than that in the placebo group
(P < 0.0001). The change in vellus hair proportion (<40 lm) was significantly lower in the adenosine group than
that in the placebo group (P = 0.0154). The change in hair density compared with baseline of the adenosine group
was also significantly higher compared with that of the placebo group (P = 0.0470). No adverse effects due to
treatment were noted during this study by dermatological evaluation. Adenosine is effective in increasing the
proportion of thick hair in Caucasian men with AGA as well as in Japanese men and women.

Key words: adenosine, androgenetic alopecia, Caucasian, hair growth.

INTRODUCTION METHODS
Study design
Minoxidil is a well-known hair growth stimulator for both men
A total of 38 Caucasian male volunteers with AGA participated
and women.1–4 However, its mode of action has not been
in this study. This clinical study was conducted on all subjects
totally elucidated. Previous report proposed that minoxidil
during the same 6-month study period. All volunteers were ran-
exerts its effects via the action of adenosine.5 Adenosine has
domized into two groups: one group used 0.75% adenosine
been shown to improve hair loss in Japanese men and
lotion while the other group used lotion without adenosine.
women, which supports a sex independent mechanism of
Details for randomization are supplied in the Appendix S1.
minoxidil.6,7 Clinical studies on adenosine indicate that it
increases the thick-to-thin hair ratio in both men and
women.6,7 Hair loss in androgenetic alopecia (AGA) is thought Assessment of baldness grade
to mainly result from a decrease in the proportion of thick Baldness grade was evaluated by comparison with reference
hair.8 Adenosine stimulates the expression of fibroblast pictures according to the method described by Ishino et al. by
growth factor-7 (FGF-7)/keratinocyte growth factor (KGF) in dermatologists. Hair diameter and hair density were measured
cultured human dermal papilla cells,9 and organ culture assay by the phototrichogram technique.8
indicated its stimulator role on hair growth,9,10 suggesting that Details are described in the Appendix S1.
minoxidil acts through FGF-7/KGF via adenosine-mediated
signaling pathway.6,7 Regarding the responsiveness of hair- Safety evaluation and statistical analysis
growing agents, while it is known that the effectiveness of Details are described in the Appendix S1.
topical minoxidil treatment for AGA are slightly different
between Caucasian and Mongoloid subjects,2,3,11 all the effi-
RESULTS
cacy data of adenosine were taken in the Mongoloid popula-
tion,6,7 and not in the Caucasian population. In this study, we Baseline characteristics
investigated the efficacy and safety of topical adenosine use A total of 38 male volunteer patients with AGA completed
as a treatment for hair loss in Caucasian men. treatment using adenosine (19 volunteers) or placebo (19

Correspondence: Jiro Kishimoto, Ph.D., Shiseido Research Center, 2-2-1 Hayabuchi, Tsuzuki, Yokohama, Kanagawa 224-8558, Japan. Email: jiro.
[email protected]
This paper is dedicated to the memory of Dr Takashi Kobayashi, who passed away in April 2014.
Received 10 June 2015; accepted 25 August 2015.

© 2015 Japanese Dermatological Association 567

volunteers) over a period of 6 months. At baseline, the volun- the adenosine group was significantly higher than in the
teers were randomized into two groups equal in age, baldness placebo group (P = 0.0494). In Figure 1(b), significant increase
grade and hair density, as well as in the proportions of thick of hair was observed after treatment of adenosine.
hair, thin hair and vellus hair. No significant differences in base-
line characteristics, including age (P = 0.8620), baldness grade Treatment effect on overall hair appearance
(P = 0.6187), hair density (P = 0.4749), thick hair (≥60 lm in Overall improvement in hair loss was assessed by a dermatolo-
diameter) proportion (P = 0.4778), thin hair (40–60 lm in diam- gist. Although there was no significant improvement in overall
eter) proportion (P = 0.1948), and vellus hair (<40 lm in diame- hair loss in the adenosine group compared with the placebo
ter) proportion (P = 0.0741), were observed between the two group (P = 0.3955), some people showed significant improve-
groups (Table 1). ment by adenosine application as shown in global photographs
in Figure 1(c).
Treatment effect on hair diameter and density
Hair diameter was compared between the adenosine group and Safety
the placebo group after 6 months (Table 2). The change in thick No causal adverse effects due to the application of adenosine
hair proportion (classified as hair ≥60 lm in diameter) was sig- or placebo lotion were noted in any subject throughout this
nificantly different between the two groups (P < 0.0001). The study by dermatological evaluation.
proportion of thick hair in the adenosine group was significantly
higher than in the placebo group at 6 months. The proportion of
DISCUSSION
thin hair (classified as hair 40–60 lm in diameter) at the end of
the study was not significantly different between the two groups Adenosine significantly increased the proportion of thick hair
(P = 0.1113). The proportion of vellus hair (classified as hair compared with the placebo group. Furthermore, a lower pro-
<40 lm in diameter) between the two groups was significantly portion of vellus hair was seen in the adenosine group com-
different (P = 0.0154), with significantly less vellus hair noted in pared with the placebo group. Previous clinical studies in
the adenosine group compared with the placebo group. Fig- Japanese men and women revealed that adenosine increases
ure 1(a) shows the close-up photos of significant improvement the amount of thick hair.6,7 In fact, adenosine is a potent acti-
of hair thickness after treatment of adenosine. vator of hair thickness in both sexes and has been shown to
Hair density was compared between the adenosine group significantly stimulate hair density in Caucasian men. However,
and the placebo group at the end of this study. Hair density in previous studies showed that hair density in Japanese men

Table 1. Baseline characteristics of randomized subjects

Test solutions
Placebo Adenosine P value*
No. of subjects 19 19
Age (years, mean  SD) 41.2  5.4 41.5  5.7 0.8620
Baldness grade† 6.1  2.4 5.7  2.5 0.6187
Hair density (n/cm2, mean  SD) 256.6  66.4 243.1  46.8 0.4749
Proportion
Thick hair (%, mean  SD) (at least 60 lm in diameter) 19.2  13.8 22.0  12.9 0.4778
Thin hair (%, mean  SD) (40–60 lm in diameter) 37.0  13.8 42.9  13.6 0.1948
Vellus hair (%, mean  SD) (<40 lm in diameter) 43.8  13.4 35.2  15.4 0.0741

*Non-paired Student’s t-test except baldness grade which was analyzed by Mann-Whitney U-test. †See Appendix S1. SD, standard deviation.

Table 2. Hair diameter and density at 6 months of treatment compared with baseline

Mean  SD (%)
Efficacy end points Placebo Adenosine P value*
Change in vellus hair proportion 6.6  9.0 1.4  10.3 0.0154
(less than 40 lm in diameter)
Change in thin hair proportion (40–60 lm in diameter) 1.9  11.3 4.1  11.5 0.1113
Change in thick hair proportion 8.5  4.3 5.5  6.4 <0.0001
(at least 60 lm in diameter)
Change in hair density† 3.8  14.2 4.9  13.9 0.0494
Change in baldness grade (assessed by M.D.) 0.179  0.421 0.350  0.412 0.3955

*Non-paired Student’s t-test except change in baldness grade which was analyzed by Mann-Whitney U-test. †Change in hair density was calculated
by assessing the difference in hair density after treatment with the baseline value (as 100%). SD, standard deviation.

568 © 2015 Japanese Dermatological Association

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Figure 1. Examples of significant improvement of hair density, hair diameter and overall appearance after adenosine treatment on
Caucasian men. Significant increase of (a) hair diameter, (b) hair density (c) and global appearance 6 months after adenosine treat-
ment compared with starting time point. (a,b) Phototrichogram and (c) global photograph.

and women did not significantly change following adenosine higher than in the placebo group at 12 months, but not at
treatment.6,7 Caucasians have a greater hair density than Mon- 6 months.7 However, Faghihi et al.14 reported that 6-month
goloids.12 Therefore, hair density changes may have a wider topical adenosine was effective in treating hair loss. Longer
range in Caucasians than in Mongoloids and adenosine is treatment of adenosine may be needed to impact hair loss in
expected to be more effective in increasing the proportion of Caucasian men. Adenosine also did not cause any causal
thick hairs in Caucasian men with AGA than in Japanese peo- adverse effects on Caucasian men as well as Japanese men
ple. On the other hand, in this study, adenosine treatment and women such as irritant reaction including redness, which
showed no advantage in improving overall hair thickness com- is a common side-effect of minoxidil treatment.15 Because
pared with placebo, although significant improvement has been Caucasians tend to have easily noticeable redness of the skin
reported in Japanese men and women.6,7 This can be due to relatively thinner scalp skin thickness, adenosine may
explained by several possibilities. First, Caucasian hair is thin- be a useful alternative to minoxidil.
ner than Mongoloid hair,13 and may therefore be associated
with a more narrow range of change. Second, the present
study assessed short-term changes within 6 months of treat- ACKNOWLEDGMENTS: We are grateful to Dr Keiko Terai
ment. A previous study on Japanese women showed that the for professional advice. The authors would also like to acknowledge
proportion of thick hair in the adenosine group was significantly Yoshiharu Tsuji for valuable discussions throughout this work. We also

© 2015 Japanese Dermatological Association 569

thank Takako Matsumoto, Keiko Naito, Tomie Tsuji, and Yuka Shishi- loss: a pilot, double-blind, randomized, placebo-controlled trial. J
kura for their technical support. Dermatol 2008; 35: 763–767.
8 Ishino A, Takahashi T, Suzuki J, Nakazawa Y, Iwabuchi T, Tajima
M. Contribution of hair density and hair diameter to the appearance
CONFLICT OF INTEREST: M. O. was funded to complete and progression of androgenetic alopecia in Japanese men. Br J
this clinical study on the safety of adenosine and received a commis- Dermatol 2014; 171: 1052–1059.
sion fee from Shiseido. 9 Iwabuchi T, Goetinck PF. Syndecan-4 dependent FGF stimulation
of mouse vibrissae growth. Mech Dev 2006; 123: 831–841.
10 Iino M, Ehama R, Nakazawa Y et al. Adenosine stimulates fibroblast
growth factor-7 gene expression via adenosine A2b receptor signal-
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570 © 2015 Japanese Dermatological Association