ARTICLE
Auteur(s) : Ryoji Tsuboi1, Takao Tanaka2,
Tooru Nishikawa2, Rie Ueki3, Hidekazu
Yamada4, Kensei Katsuoka5, Hideoki
Ogawa3, Katsuyuki Takeda6
1Tokyo Medical University, Department of Dermatology,
Tokyo, Japan
2Taisho pharmaceutical Co., Ltd, Tokyo, Japan
3Juntendo University, School of Medicine, Department of
Dermatology, Tokyo, Japan
4Kinki University School of Medicine, Nara Hospital,
Department of Dermatology, Nara, Japan
5School of Medicine, Kitasato University, Department of
Dermatology, Kanagawa, Japan
6The University of Tokushima Graduate School, Institute
of Health Biosciences, School of Medicine, Professor Emeritus,
Tokushima, Japan
accepté le 18 Août 2006
Androgenetic alopecia, found both in men and in women, is also
known as male pattern hair loss. Androgenetic alopecia,
characterized by miniaturization of the hair follicles, is believed
to develop due to androgenic hormones or genetic factors [1, 2].
And the association between hair loss and androgen receptor gene
[3] or ageing is confirmed [4]. In Caucasians, it usually begins
between the ages of 12 and 40 in both men and women, and affects
approximately 50% of the population before the age of 50 [2, 5-7].
Its prevalence was reported to be lower and its severity less among
Asians, Native Americans, and African Americans [8]. Hair loss
observed in female androgenetic alopecia is usually mild, and the
area of baldness is not as clearly demarcated as in men [1, 2].
Although the exact prevalence of female androgenetic alopecia in
Japanese women has not been ascertained, the number of women who
worry about thinning hair has recently been increasing. There is
thus a growing demand for the treatment of thinning hair in Japan.
In countries other than Japan, 2% topical minoxidil has been used
not only for male androgenetic alopecia [9-17] but also for female
androgenetic alopecia [18-22]. In clinical comparative trials for
male androgenetic alopecia in Japan, 1% and 2% topical minoxidil
showed a similar degree of efficacy, although there was a higher
frequency of local side effects in the 2% solution [23, 24]. For
this reason, 1% topical minoxidil has been approved and used in
Japan for male androgenetic alopecia. However, no large-scale
clinical trials have been conducted to demonstrate the efficacy of
1% topical minoxidil in Japanese or other Asian women. We therefore
conducted the first double-blind, placebo-controlled study of
twice-daily application of 1 mL for 24 weeks to determine
whether 1% topical minoxidil is effective in treating androgenetic
alopecia in Japanese women.
Methods
Subjects
Women aged 20 or older with grade I or II hair loss on the Ludwig
scale [25] were included in this trial. During the trial period,
the patient’s hair style was left unchanged. As the alteration of
hair colour or hair condition affects the clinical evaluation,
patients were instructed to refrain from dyeing and perming their
hair. In cases where the patients were already in the habit of
doing so, they were permitted to continue as long as they did not
vary the frequency of these activities.
The following patients were excluded from this clinical
trial:
- – Patients with concomitant dermatological disorders on
the scalp other than androgenetic alopecia
- – Patients with serious heart diseases (angina pectoris,
myocardial infarction, etc.), renal diseases, or hepatic
diseases
- – Patients with pituitary diseases, thyroid diseases, or
collagen diseases (particularly systemic lupus erythematosus)
- – Patients receiving hormone replacement therapy
- – Patients who were pregnant or hoping to become pregnant,
patients within 12 months after delivery, or lactating mothers
- – Patients with drug hypersensitivity (including contact
dermatitis to cosmetics)
- – Patients wearing a wig (breathable wigs were acceptable)
and those with hair transplants
- – Patients previously treated with minoxidil
- – Patients without the ability to provide informed
consent
- – Patients judged by the investigator/subinvestigator as
otherwise being unsuitable for participation in this trial.
The trial protocol and informed consent forms were reviewed and
approved by the Institutional Review Board at each center. Each
patient received a full explanation of the trial and signed a
written informed consent form before participating in the
trial.
Design
After informed consent was obtained, patients eligible for the
trial were randomly allocated to either of two groups (n = 140 in
each group): a group receiving 1% topical minoxidil (lotion
containing 10 mg of minoxidil per mL: TMS group) or a group
receiving the placebo (lotion not containing minoxidil (vehicle
only): PBO group). Patients applied the drug to the bald area on
the scalp at a dose of 1 mL twice daily for 24 weeks.
The active drug and placebo were indistinguishable in appearance
and had indistinguishable packaging. The person responsible for
study drug allocation assigned patients to either the TMS or PBO
group at a ratio of 1: 1, and disclosed the allocation codes to no
one until the end of the trial.
Patients visited the hospital every 4 weeks for 24 weeks (and at
discontinuation of trial participation). At each visit, photographs
were taken to count the hairs using a CCD microscope system, the
investigators’ assessments were compared to the baseline (effect on
hair growth), and patients’ self-assessment (effect on hair growth
and effect on hair loss) was taken for efficacy evaluation.
Furthermore, patients underwent examinations for clinically adverse
events, blood and urinalysis tests, and blood pressure at each
visit.
Patients were not allowed to use other hair growth products or
topical products on the scalp. Hormone replacement therapy and the
use of non-breathable wigs as well as professional hair care were
prohibited, as well. It was specified that trial participation
would be discontinued for a patient if any adverse event occurred
and the investigator judged continuation of trial participation to
be impossible due to the adverse event.
This trial was conducted between January 2001 and February 2002
at three centers in Japan.
Efficacy evaluation
Hair count
Procedures for photography of hair with a CCD microscope
system
At the baseline, a template with an opening of approximately
1.5 cm2 was applied to the bald area in each
patient and all hairs in the opening were clipped to a length of 1
to 2 mm from the scalp. In this trial, tattoos were not used
as a means of identifying the same target area as at the baseline.
Instead, a non-elastic cord was applied between the right and left
ears via the area in which hairs had been clipped, and the distance
from the right ear to the clipped area was measured. The distance
from the midpoint between the two eyebrows to the clipped area was
also measured in the same manner. In addition, photographs of the
full head showing the location of the clipped area were taken. At
each visit (once every four weeks) after baseline, the same area as
at baseline was identified based on the record of the location of
the clipped area, photographs, and the stubble. The hair was again
clipped to 1 to 2 mm length in the same manner as at baseline
using the template. Final confirmation that the area chosen was the
same as that at baseline was made by comparing the photographs of
the clipped area with those taken at baseline.
For photography of the clipped areas, a microscope system
(MS-2000RS, MORITEX Corp.) equipped with a CCD camera incorporating
a computer was used. The magnification was fixed at 15×, and the
distance was fixed using a Contact dome (attachment for use with
the system only, MORITEX Corp.) fixed at the tip of the objective
lens. The tip of the Contact dome was applied to the clipped area
vertically against the scalp, and photographs were taken while
checking the image on the monitor. The images taken were directly
loaded into the computer and stored as digital image data.
The digital image data stored were sent to an independent
facility (EPS, Co., Ltd., Tokyo, Japan), where the hairs were
counted.
Hair counting procedures and parameters
The images with an area of approximately 1.5 cm2
that were obtained every 4 weeks from baseline to week 24 from each
patient were sent to the facility for hair counting. A person in
charge selected the site common to all images and cut out the
selected portion of each image with an area of 1cm2. The
person in charge superimposed the images by checking the positions
of the roots of all hairs, the characteristics of growth hairs from
each root, and the direction in which hairs grew from each root in
order to achieve “hair to hair” matching, in this fashion
confirming that all the cut-out images were those of the same
target area. These cut-out images, which were 1 cm2
in size, were used for hair counting. Three well-trained persons
independently counted hairs without knowledge of the treatment
group or the time at which the image was taken. They loaded the
image of a sample hair of 40 μm in diameter on the monitor,
compared the size of each hair with that of the sample, and marked
non-vellus hairs (hairs with a size of 40 μm or larger) and
vellus hairs (hairs less than 40 μm in size) separately for
counting. Total hair count (sum of non-vellus hair count and vellus
hair count) and percentage of non-vellus hair (proportion of
non-vellus hair count to total hair count) were calculated based on
the mean of three persons’ hair counts. The change from baseline in
non-vellus hair count (hair count increased) was chosen as the
primary variable for this trial.
Investigators’ assessments
Each investigator, who was a dermatologist, observed the status of
hair growth in the bald area every 4 weeks from baseline to week 24
(and at discontinuation of treatment), and assessed the effect on
hair growth by comparing the photographs taken at baseline using
the following 5-point scale: (1) markedly improved: dense hair
growth (bald area almost entirely covered with hair, of density
almost identical to that in the non-bald area); (2) moderately
improved: moderate hair growth (bald area partly covered with newly
growing hair, of density lower than that in the non-bald area; (3)
slightly improved: minimum hair growth (hair growth present, but
bald area clearly visible; (4) unchanged: no visual hair growth:
and (5) worsened: decreased hair growth.
Patients’ self assessments
Patients performed self-assessment of both the effect on hair
growth and the effect on hair loss compared to baseline every 4
weeks from baseline to week 24 (and at discontinuation of trial
participation).
They assessed the effect on hair growth using the following
5-point scale: (1) markedly improved: dense hair growth (hair
growth observed over almost the entire area); (2) improved:
moderate hair growth (partial hair growth easily noticeable); (3)
slightly improved: slight hair growth (hair growth slightly
noticeable); (4) unchanged: no visible hair growth; and (5)
worsened: decreased hair growth (bald area increased, with thinning
hair more noticeable than at baseline.) They assessed the effect on
hair loss using the following 3-point scale: (1) good: decreased
hair loss; (2) unchanged: no change in hair loss; and (3) worsened:
increased hair loss.
Safety evaluation
Patients underwent blood and urinalysis tests as well as blood
pressure measurements at baseline and every 4 weeks to week 24 (and
at discontinuation of treatment).
At baseline, each investigator examined the health of the
patient, checked for previous history of diseases, presence of
concomitant disease and drug hypersensitivity. Any unusual findings
(including abnormal changes in laboratory values and blood
pressure) that developed during the trial period were regarded as
adverse events.
Statistical analysis
The sample size was determined based on the value calculated
assuming a difference in mean change in non-vellus hair count of
9/cm2 using a significance level α of 0.05 (two-sided)
and a power (1 – β) of 0.8.
Analyses were performed on the full analysis set (FAS),
consisting of all patients administered at least one dose of study
drug and for whom any observations regarding efficacy or safety
after administration were available. However, those not eligible
for this trial due to violation of the inclusion criteria, etc.,
were excluded from efficacy analysis.
Change in non-vellus hair count (difference in non-vellus hair
count from baseline to the end of the trial) was examined as the
primary variable in this trial. A one-sample t-test was used for
intergroup comparisons, and a two-sample t-test for between-group
comparisons.
Investigators’ assessments, patients’ self assessments (effect
on hair growth and effect on hair loss), change in vellus hair
count, change in total hair count, and change in percentage
non-vellus count were examined as secondary variables.
Among secondary variables, investigators’ assessments, patients’
self assessments, and incidences of adverse reactions were compared
between groups using a contingency table χ2 test. All
hair count variables were analyzed in the same manner as change in
non-vellus hair count. For differences in change in hair count,
two-sided confidence intervals with 95% confidence are presented.
The two-sided significance level for tests was set at 5%.
Results
Patient characteristics
A total of 280 patients were enrolled in this trial. ( Figure 1 ) shows the
profile of the trial. One hundred forty patients each were enrolled
in the TMS group and PBO group. Eleven and 14 patients were
withdrawn due to adverse events, etc, respectively. The remaining
129 and 126 patients, respectively, completed this trial.
( Figure 2 )
shows the disposition of patients in the FAS evaluable for
efficacy. Three and 4 patients (with concomitant or suspected
thyroid disease) in the TMS group and the PBO group, respectively,
were ineligible for efficacy analyses and excluded from the FAS for
efficacy analysis. Therefore, the remaining 137 and 136 patients,
respectively, were included in at least one efficacy analysis. Some
of these patients had microscopic images with which hair counting
was impossible due to the small size or lack of clarity. Hair
counts for these images were excluded from tabulation. Accordingly,
analyses of actual hair counts were performed in 123 and 122
patients in the TMS group and PBO group, respectively. All enrolled
patients were included in safety analyses. Table 1( Table 1 ) shows the baseline demographics of
patients included in the FAS for efficacy analyses. Mean age at
baseline was 56.3 years for patients in the TMS group and 57.2
years for those in the PBO group. At baseline, 78 patients (56.9%)
had Ludwig’s grade I and 59 (43.1%) grade II in the TMS group, and
84 patients (61.8%) had grade I and 52 (38.2%) grade II in the PBO
group. The mean non-vellus count at baseline was approximately 134
in the TMS group and approximately 140 in the PBO group. There was
no significant difference between the two patient groups.
Table 1 Patient demographics at baseline
|
TMS group
|
PBO group
|
|
No. of patients*
|
137
|
136
|
|
Age (Mean ± SD)
|
56.3 ± 10.4
|
57.2 ± 9.7
|
|
History of hair loss (years)
|
6.86 ± 4.53
|
7.03 ± 5.62
|
|
Pattern of hair loss (Ludwig scale)
|
|
No. (%) of patients
|
Grade I
|
78 (56.9)
|
84 (61.8)
|
|
Grade II
|
59 (43.1)
|
52 (38.2)
|
|
Non-vellus hair count (Mean ± SD)§
|
133.75 ± 49.62
|
139.72 ± 46.45
|
|
Vellus hair count (Mean ± SD)§
|
55.53 ± 28.69
|
52.77 ± 27.82
|
|
Total hair count (Mean ± SD)§
|
189.27 ± 47.26
|
192.49 ± 40.85
|
Efficacy evaluation
Hair count
Table 2( Table 2 ) shows mean changes
from baseline in non-vellus hair count at the end of the trial (the
primary variable of this trial), as well as mean changes from
baseline in vellus hair count and total hair count.
Figures 3a, 3b, 3c shows the changes over time in each hair
count observed every 4 weeks. The change from baseline in
non-vellus hair count at the end of the trial was 8.15 in the TMS
group and 2.03 in the PBO group, with a significant difference in
both groups (one-sample t-test: p < 0.001 for the TMS group,
p = 0.042 for the PBO group). The difference between the groups in
change in non-vellus hair count was 6.12 (two-sided 95% CI:
3.29-8.96), with a significant increase in the TMS group compared
to the PBO group (two-sample t-test: p < 0.001).
In change from baseline in non-vellus hair count measured every
4 weeks, a significant increase was observed from week 12 in the
TMS group compared to the PBO group (two-sample t-test: p = 0.002)
(( figure 3a )).
Thereafter, significant differences were observed between the
groups at weeks 16, 20, and 24 (two sample t-test: p = 0.001,
p < 0.001, and p < 0.001, respectively).
The mean changes from baseline in vellus hair count at the end
of the trial (a secondary variable) were 7.00 and 0.83 in the TMS
group and PBO group, respectively. A significant difference was
found only in the TMS group (one-sample t-test: p < 0.001). The
difference between the groups in change in vellus hair count was
6.17 (two-sided 95% CI: 2.15-10.19) and significant (two-sample
t-test: p = 0.003). In change from baseline in vellus hair count at
every 4 weeks, a significant increase was observed from week 8 in
the TMS group compared to the PBO group (two-sample t-test:
p = 0.005) (( figure
3b )). Thereafter, a significant difference was observed up
to week 24 (two-sample t-test: p < 0.001, p = 0.042, p = 0.003,
and p = 0.002, respectively). The mean changes from baseline in
total hair count (sum of non-vellus and vellus hair counts) at the
end of the trial were 15.15 and 2.85 in the TMS group and PBO
group, respectively. A significant difference was found only in the
TMS group (one-sample t-test: p < 0.001). The difference between
groups in change in total hair count was 12.30 (two-sided 95% CI:
7.84-16.75) and significant (two sample t-test: p < 0.001) ((
figure 3c )). In
change from baseline in total hair count measured every 4 weeks, a
significant increase was observed from week 8 in the TMS group
compared to the PBO group (two-sample t-test: p < 0.001).
Thereafter, a significant difference was observed up to week 24
(two-sample t-test: p < 0.001 for all time points of
evaluation). The mean changes from baseline in percentage
non-vellus hair count at the end of the trial (one of the secondary
variables) were –1.02% and 0.08% in the TMS group and PBO group,
respectively. Neither between-group comparison nor within-group
comparison revealed a significant difference.
Table 2 Mean change from baseline in hair count at each
patient’s final visit(FAS)
|
Efficacy variable in hair count
|
Means ± SE
|
Difference in change*
|
|
TMS
|
PBO
|
|
(n = 123)
|
(n = 122)
|
|
Non-vellus hair count
|
8.15 ± 1.05
|
2.03 ± 0.99
|
6.12
|
|
(3.29-8.96)
|
|
p < 0.001
|
|
Vellus hair count
|
7.00 ± 1.43
|
0.83 ± 1.46
|
6.17
|
|
(2.15-10.19)
|
|
p = 0.003
|
|
Total hair count
|
15.15 ± 1.60
|
2.85 ± 1.60
|
12.30
|
|
(1.84-16.75)
|
|
p < 0.001
|
Investigators’ assessments
( Figure 4 )
shows investigators’ assessments of hair growth at the end of the
trial for each patient. The proportion of responders (defined as
patients exhibiting ‘slightly improved’ or better) was 68.6%
(94/137) in the TMS group and 60.3% (82/136) in the PBO group,
without significant difference between the groups. The proportion
of patients who exhibited ‘moderately improved’ or better was 29.2%
(40/137) in the TMS group and 11.8% (16/136) in the PBO group, with
a significant difference between groups (chi-square: p < 0.001).
The change over time in proportion of responders as assessed by
investigators every 4 weeks exhibited significant improvement from
16 weeks in the TMS group compared to the PBO group (chi-square:
p = 0.010) and a significant difference thereafter up to week 20
(data not illustrated). In the proportion of patients exhibiting
‘moderately improved’ or better, a significant difference was found
from week 16 between the TMS and PBO groups (chi-square:
p = 0.017), and continued to be observed thereafter up to 24 weeks
(data not illustrated).
Patients’ self assessments
( Figure 5 )
shows the effect on hair growth assessed by patients themselves at
the end of the trial. The proportion of responders (defined as
patients exhibiting ‘slightly improved’ or better) regarding effect
on hair growth was 75.2% (103/137) in the TMS group and 58.8%
(80/136) in the PBO group, with a significant difference between
groups (chi-square: p = 0.004). The population of patients who
exhibited ‘improved’ or better was 36.5% (50/137) in TMS group and
23.5% (32/136) in PBO group, with a significant difference between
groups (chi-square: p = 0.019). The change over time in effect on
hair growth assessed every 4 weeks revealed significant improvement
from week 16 in the TMS group compared to the PBO group
(chi-square: p = 0.038) (data not illustrated). Thereafter, a
significant difference was observed up to 20 weeks. In the
proportion of patients exhibiting ‘improved’ or better, a
significant difference was found from week 20 in the TMS group
compared to the PBO group (chi-square: p = 0.044), with significant
difference up to week 24. The proportions of responders regarding
effect on hair loss were 71.5% (98/137) and 64.0% (87/136) in the
TMS group and PBO group, respectively, with no significant
difference between groups.
Safety evaluation
Table 3( Table 3 ) shows a summary of
adverse events (adverse reactions) reported in this trial for which
a causal relationship with drugs could not be ruled out. The
incidence of adverse reactions was 13.6% (19/140) in the TMS group
and 12.1% (17/140) in the PBO group, with no significant difference
between groups (chi-square: p = 0.721). Main adverse reactions were
skin symptoms including irritation and contact dermatitis, the
incidence of which was similar in the two groups, at 7.9% (11/140)
and 6.4% (9/140) in the TMS group and PBO group, respectively.
Other events included headache, which was noted in 1.4% (2/140) in
the TMS group. The events were mild to moderate in severity, and
disappeared by the end of the trial. Myocardial infarction occurred
in one patient in the PBO group. Since the patient was found after
completion of the trial to have originally had heart disease, it
was judged that the myocardial infarction might have been due to
factors intrinsic to this patient. Abnormal changes in laboratory
values were noted in 2.9% (4/140: decreased lymphocyte ratio,
increased AST, increased ALP, and elevated uric acid in one
patient) in the TMS group and 3.6% (5/140: increased ALT in two
patients; and decreased leukocytes, increased eosinophil ratio, and
increased TSH in one patient) in the PBO group. All were mild
changes and judged by the investigator as being probably unrelated
to the trial. All patients recovered without treatment. No adverse
events related to blood pressure or the cardiovascular system
occurred in the TMS group.
Table 3 Adverse events related to investigational
drug
|
Group
|
TMS (n = 140)
|
PBO (n = 140)
|
|
Incidence of adverse events
|
19 (3.6)
|
17 (2.1)
|
|
Dermatological
|
Subtotal
|
11 (7.9)
|
9 (6.4)
|
|
Irritation
|
3 (2.l)
|
3 (2.1)
|
|
Contact dermatitis
|
2 (1.4)
|
2 (1.4)
|
|
Dermatitis
|
2 (1.4)
|
4 (2.9)
|
|
Pruritus
|
1 (0.7)
|
1 (0.7)
|
|
Eczema
|
0 (0.0)
|
1 (0.7)
|
|
Redness
|
1 (0.7)
|
0 (0.0)
|
|
Dermatitis
|
1 (0.7)
|
1 (0.7)
|
|
Dry feeling of hair
|
1 (0.7)
|
0 (0.0)
|
|
Desquamation
|
1 (0.7)
|
0 (0.0)
|
|
Discomfort application site)
|
0 (0.0)
|
1 (0.7)
|
|
Cardiovascular
|
Subtotal
|
0 (0.0)
|
1 (0.7)
|
|
Myocardial infarction
|
0 (0.0)
|
1 (0.7)
|
|
Neurological
|
Subtotal
|
3 (2.1)
|
1 (0.7)
|
|
Headache
|
2 (1.4)
|
0 (0.0)
|
|
Feeling strange
|
1 (0.7)
|
1 (0.7)
|
|
Others
|
Subtotal
|
1 (0.7)
|
1 (0.7)
|
|
Systemic malaise
|
0 (0.0)
|
1 (0.7)
|
|
Eye irritation
|
1 (0.7)
|
0 (0.0)
|
|
Abnormal laboratory test value
|
4 (2.9)
|
5 (3.6)
|
Discussion
In clinical trials conducted in the United States and other
countries, a method of evaluation by hair counting has been
employed to verify the efficacy of topical minoxidil [9-22]. In
Japan, however, global photographic assessment rather than hair
count has been employed to evaluate the efficacy of reagents for
androgenetic alopecia [23, 24, 26]. We used this method for the
first time in Japan for more objective evaluation of the efficacy
of 1% topical minoxidil. Hairs were counted and categorized as
vellus (< 40 μm in diameter) or non-vellus
(≥ 40 μm in diameter) with reference to reports by
Rushton et al. [27, 28] In addition, investigators’ assessments and
patients’ self assessments were performed, as in previous studies.
In the United States and other countries, a semi-permanent marker
(tattoo) is often used on the scalp as a means of locating the
target area for hair clipping at each visit [7, 17-22]. In Japan,
however, the use of tattoos is not socially accepted. Therefore, we
located the target area by means of a “hair to hair” matching
method by cross-referencing the macroscopic distance of the site
from fixed points, the trace of clipped hairs (stubble) and the
hair unit images preserved by a CCD camera.
The mean change from baseline in non-vellus hair
count/cm2, the primary efficacy variable, was 8.15 in
the 1% topical minoxidil group and 2.03 in the placebo group. The
difference between groups was 6.17 and significant (p < 0.001).
In clinical trials involving Caucasian women, 2% topical minoxidil
was compared with placebo, and results of these indicated that the
difference between groups in change in non-vellus hair
count/cm2 may be around 12 at weeks 24 to 32 [18, 20,
22]. In these clinical trials, technicians performing hair counting
visually classified hairs as vellus or non-vellus based mainly on
the presence or absence of pigmented hair [9, 11, 12, 17, 20]. The
present trial, on the other hand, was conducted using Japanese
women mostly with black hairs, and the hairs were classified by
diameter using 40 μm as a reference. The difference recorded
between the two groups might therefore be small but accurate.
Furthermore, since 2% topical minoxidil was used in aforementioned
trials, in comparison to the 1% solution in the present study, the
increase of hair count by about 6 in the present trial would appear
significant. In our trial, there were significant increases in mean
changes in vellus hair count and total hair count in the 1% topical
minoxidil group compared to placebo (p = 0.003 and p < 0.001,
respectively). The mechanism of action of minoxidil suggests that,
because vellus hairs change to non-vellus hairs, vellus hairs may
decrease in number and non-vellus hairs correspondingly increase.
Interestingly, in the present clinical trial, both vellus and
non-vellus hairs increased in number. The following may be reasons
for the increase in vellus hair count: hairs grew from hair
follicles that were in telogen phase at baseline; women originally
have thinner hair than men, and hairs originally too thin to be
visible became thick enough to be counted over the course of
treatment. Since both vellus hairs and non-vellus hairs increased
in number, both contributed to the increase in hair density.
In addition to the above findings of an increase in hair count,
favorable assessments made by investigators were obtained
concerning the status of hair growth over the entire area of hair
loss. The rate of slight improvement or better was 68.6% with 1%
topical minoxidil. For moderate improvement or better, the
improvement rate was 29.2%, and a significant difference was
observed compared to placebo (p < 0.001). In two clinical trials
in male pattern baldness conducted with Japanese men [23, 24], the
rates of slight improvement or better with 1% topical minoxidil
were 72.7% and 73.2%, respectively. Thus, 1% topical minoxidil may
be as effective in women as in men.
In patient assessment of effect of hair growth, the rate of
slight improvement or better was 75.2% with 1% topical minoxidil,
with a significant difference from placebo (p = 0.004). In the
present study, hair count increased, and patient self-assessment
was also favorable. Since androgenetic alopecia causes individuals
great concern regarding their appearance, these results indicate
that application of 1% topical minoxidil may be of great
therapeutic significance. In the present study, we were able to
objectively confirm the efficacy among Japanese women. The efficacy
observed was not inferior to that in Caucasian women, suggesting
that topical minoxidil may be effective in other Asian women, as
well.
The most common adverse reactions in the present trial were skin
symptoms (irritation, contact dermatitis, pruritus, etc.) The
incidence of such symptoms was 7.9% (11/140) for 1% topical
minoxidil and 6.4% (9/140) for placebo. Since the incidence with
minoxidil was similar to that with placebo, the skin symptoms
observed in this trial were probably due to the base used for
minoxidil, which consists of propylene glycol and ethanol. It was
likely that irritation by these alcohols caused skin symptoms. Use
of a less irritating base may be useful, in this regard. In a
placebo-controlled trial of 2% and 5% topical minoxidil conducted
in patients with female pattern hair loss in the United States, the
incidence of skin symptoms was 6% (10/154) for 2% topical
minoxidil, 14% (22/153) for 5% topical minoxidil, and 4% (3/74) for
placebo [20]. It appears that the incidence of dermatological
adverse reactions does not greatly differ between Caucasian and
Japanese women. Hypertrichosis (e.g., facial hair growth), which
has been seen in Caucasians, was not observed in the present trial.
No significant difference was detected between the groups in the
incidence of adverse reactions as a whole among Japanese women, and
the adverse reactions observed were all mild or moderate. Thus,
favorable tolerability of 1% topical minoxidil was confirmed.
In conclusion, we verified that 1% topical minoxidil solution is
effective and well- tolerated in the treatment of androgenetic
alopecia among Japanese women.
Acknowledgements
The authors would like to thank the following individuals for their
kind support: Shigeto Kanada, MD1, Shigeki Inui,
MD2, Tosiro Aoki,MD3,Mari Kaneda,
MD4,Masumi Sano, MD5,Haruyasu Itoh,
MD6,Tetsu Nakaji, MD7,Hiroyuki Suzuki,
MD8,Ai Kawamura, MD9,Mieko Kudo,
MD10,Chiyuki Matsumoto, MD11,Takayuki Ohta,
MD12,Yasuki Hata, MD13,Tooru Kuriyama,
MD14,Seiji Taguchi, MD15,Yasuyo Komine,
MD16,Haruko Anazawa, MD17,Ikuko Abe,
MD18,EPS Co.,Ltd.
1~6 OCROM Clinic,7~13 ToCROM
Clinic,14~18 Kasai Pediatrics.
The authors received financial support from: Taisho
Pharmaceutical Co.,ltd.
Conflict of interest: None.
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