Oriainal Research Article

Drug Investigation 2 (I): 17-22. 1990

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Topical Minoxidil2% Solution ('Regaine') for Male

Pattern Baldness Among Filipinos
Georgina C. Pastorfide, Josephine G_ Chua, Jesus L. Garcia
and Guillermo T. Gutierez
Section of Dermatology, Department of Medicine, University of the Philippines-
Philippine General Hospital Medical Centre, Manila, The Philippines

Summary From a total of 50 healthy male Filipino subjects enrolled in the study, 34 completed
a IO-month open-label evaluation of 2% topical minoxidil. The remaining 16 withdrew
because of disinterest or noncompliance with the regular monthly follow-ups. Both ob-
jective measurement of hair growth by counting of indeterminate and terminal hairs in
the target balding area and subjective evaluation by subjects and investigators were made,
and photographs taken to document the efficacy of new hair growth.
52% of subjects noted minimal new hair growth, while 42% noted moderate new hair
growth. In comparison, the investigators rated 79% of subjects as having minimal new
hair growth and 21% as having moderate new hair growth. Overall, 70.5% of subjects
noted decreased shedding at the end of treatment. Furthermore, terminal hair counts at
the end of treatment showed statistically significant (paired t-test) growth. No significant
physical findings or laboratory abnormalities were seen.

An interest in the potential of topical minoxidil
as a hair growth stimulant in man was generated
by the high incidence, approximately 80%, of hy-
pertrichosis during clinical trials of oral minoxidil
tablets (Loniten®) in hypertensive patients. Short
exploratory studies of 5 to 14 weeks duration dem-
onstrated that minoxidil could stimulate vellus hair
growth, but that longer trials were required to bet-
ter define the nature and degree of the stimulated
hair growth. Subsequent trials in approximately
4000 volunteers investigated I, 2, 3 and 5% min-
oxidil in volunteers with male pattern baldness or
alopecia areata ranging from single patches to alo-
pecia totalis and alopecia universalis (Weiss et al.
1984). The major study in male pattern baldness
involved more than 2300 volunteers in 28 loca-
tions in the US (De Villez 1985; Olsen 1985): this
indicated that at least 4 months of continued use
may be required before evidence of hair growth can
be expected. Onset and degree of response was
variable, but the best results were obtained in sub-
jects with the least severe balding patterns. The
mechanism of action is not currently known.
The objective of this study was to evaluate the
safety and efficacy of topical minoxidil solution in
the treatment of male pattern baldness (alopecia
androgenetica) among Filipinos.
Subjects and Methods
This study was an open-label evaluation of 2%
topical minoxidil. Volunteers were seen monthly
for evaluation of hair growth and side effects.
18 Drug Invest, 2 (1) 1990

50 subjects, aged 21 to 49 years, were entered
into the study. All were in good general health, with
progressive premature thinning of the scalp hair,
otherwise known as male pattern baldness or alo-
pecia androgenetica. Subjects had had progressive
hair loss for 1 to 20 years duration, with no greater
hair loss than a type V male pattern alopecia [mod-
ification of Hamilton'S classification (1951)] (fig.
1)]. The study was approved by the Committee on
Research Implementation and Development of the
University of the Philippines College of Medicine
and informed consent was obtained from the
volunteers.
Excluded from participation in the study were
subjects with any of the following; hypertension
with sitting blood pressure above 140/90mm Hg;
cardiac disease of any kind including ischaemic
heart disease, congestive heart failure, arrhyth-
mias, etc.; liver, kidney and endocrine diseases;
oedema of any cause; psychiatric illness or emo-
tional instability; known sensitivity or allergy to
minoxidil, propylene glycol or alcohol; concomi-
tant therapy with steroids, cytotoxic agents, vaso-
dilators, antihypertensives or hair restorers; con-
comitant dermatological disorders of the scalp; and
use of an extemporaneous preparation of topical
minoxidil within the previous 5 months.
In an open-label fashion, subjects were advised
to apply the test medication comprising a 2% top-
ical minoxidil solution ('Regaine', Upjohn Com-
pany), supplied as a clear colourless to light yellow
solution containing 20mg minoxidil/ml in a 60ml
bottle. The subject was instructed to apply Iml of
the solution as a thin film to the affected areas of

~e ff+ e
Hamilton Scale

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-,- /J. .,"" f ., - g ' <,$'
I
~
" '
~I V
""';' ""
Ilia

,
-I \j

II
~e
-:-::-
-)
,- jl
J

III vertex
-'
.."..-
,I!'
....
~... , \J

~ ~e
~
. " f!
~fJt
::. 11.'
..:; I .:1

Iia IV VI

~~
•• ,03 III
~.," S
IVa
fig. 1. Hamilton scale for assessing male pattern baldness (after Hamilton 1951).
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' .:J'

VII
6
.-:~ ..:: .':'7:,.
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'J.'
Topical Minoxidil in Male-Pattern Baldness 19

the scalp twice daily. The total daily dose should Table I. Demographic profile of 34 subjects treated with topical
minoxidil
not exceed 2ml. If fingertips are used to facilitate
drug application, hands should be washed after- Parameter Number Percentage
wards. Use of a hair dryer to facilitate drying of Age (years)
the applied drug was not recommended as it may 21-28 12 35
decrease the effectiveness of the drug, but the hair 29-36 14 41
37-44 4 12
and scalp should be dried before application of > 45 4 12
topical minoxidil. The duration of treatment was Hamilton rating scale
40 weeks. II 6 18
III 13 38
All patients were cautioned of the potential for IV 9 26
systemic absorption of the drug. They were ad- V 6 18
vised to stop treatment if any of the following oc- Duration of baldne•• (years, n = 30)
<5 11 37
curred: rapid heart rate at rest (> 100 beats/min or 5-10 16 53
30 beats/min above baseline or frequent ectopic 10-20 1 3
beats greater than 10); unexplained weight gain of > 20 2 7
3kg or more; swelling or puffiness of hands, face,
ankles, or stomach; dizziness, lightheadedness or
fainting; new or worsening of pain in the chest, arm and listed as: vellus hairs (short, fine, nonpig-
or shoulder; redness, swelling or burning at the ap- mented); indeterminate hairs (hairs of intermedi-
plication site; diastolic blood pressure decrease from ate length, thickness and pigment); and terminal
baseline of ~ 15mm Hg. hairs (long, thick, pigmented hairs similar to those
Complete history and physical examinations on the nonbald areas of the scalp).
were repeated at monthly intervals during follow- The hairs in the target area were clipped to about
up visits. Subjective or objective findings were re- 0.6cm length to facilitate counting; this also aided
corded and referred for further evaluation to ap- the subsequent localisation of the study site. Hair
propriate specialties as needed. Chest x-ray, ECG counts were done by the same investigator at the
and other laboratory tests were obtained at the start start, middle and end of treatment. Photographs of
and end of treatment. the subjects' scalps were taken in a consistent man-
The subject's evaluations of the degree of new ner at the start, middle and end of treatment and
hair growth and of the degree of hair shedding were were used in assessing response to treatment.
recorded at weeks 12, 24, 36 and at the end of
treatment (10 months), using a numerical scale. Statistical Analysis
Physician's gross visual estimate of the degree
of new hair growth since the start of treatment in Hair growth in response to treatment was ana-
the target balding area was made at the end of lysed by paired Student's t-test, with p ~ 0.01 taken
treatment, also using a numerical scale. In addi- as significant.
tion, the investigators undertook a modified hair
counting procedure for documenting hair growth. Results
A circle lcm in diameter (target area) was marked
off over the balding area with a skin marker using The demographic profile of subjects and the de-
a template. The centre of the target was located by gree and duration of baldness are shown in table
a 3-point measurement with a tape measure, using I. In all, 34 men with male pattern baldness com-
the midpoint between the ears and a fixed distance pleted the 40 weeks of the study and were included
from the tip of the nose. These distances were re- in the analysis. 16 subjects withdrew due to lack
corded for future reference. Using a suitable mag- of interest, or noncompliance with regular monthly
nifier, the hairs in the marked off area were counted follow-ups. Our subjects tended to be young, with
20 Drug Invest. 2 (I) 1990

Table II. Laboratory data in 34 patients at the initial assessment these side effects were severe or continuous enough
and after treatment with topical minoxidil for 40 weeks
to require discontinuation of the test medication.
Parameter Normal Initial Final There were no significant physical findings or
Haemoglobin (gIL) 120-180 154.9 153.3
laboratory abnormalities that could be attributed
Haematocrit (L) 0.37-0.52 0.46 0.467 to the study medication.
wec (X 109 /L) 5-10 6.1 6.14
Platelets (X 109 /L) 150-400 235.6 240.5
Alkaline phosphatase 9-35 56.41 39.7 Discussion
(lUlL)
Glucose (mmoI/L) 3.3-6.05 4.51 4.75
Sodium (mmoI/L) 134-148 142 139.5 Minoxidil (Loniten®, Upjohn), a 2,4-diamino-
Potassium (mmoI/L) 3.6-5.0 3.97 4.37 6-piperidinopyrimidine 3-oxide, is a potent direct-
Chloride (mmoI/L) 98-109 104.78 101.7
acting peripheral vasodilator used in the treatment
Abbreviations : wec = white blood count. of hypertension. The fall in blood pressure triggers
sympathetic, vagal inhibitory and renal homeo-
static mechanisms that lead to increases in cardiac
minimal areas of baldness, and had been bald for rate and output and salt and water retention. Min-
5 to 10 years. Chest x-ray, blood chemistry, blood oxidil does not interfere with vasomotor reflexes
counts and urinalysis were all within normal lim- and therefore does not produce orthostatic hypo-
its, as shown in table II. tension. In contrast to effects following oral admin-
istration, topical application of minoxidil induced
Initial screening was done in order to obtain
no systemic effects related to absorption of the drug
baseline data and confirm eligibility. All chest x-
when compared with placebo in controlled clinical
rays were normal and except for a few minimal
trials. Topical minoxidil produced no effects on
electrical disturbances (not considered sufficient
blood pressure, pulse rate, bodyweight, or inci-
reason for exclusion), the ECG records were also
dence of oedema in either normotensive or un-
normal. These changes neither altered in pattern
treated hypertensive (diastolic blood pressure ~
or resolved during the study.
95mm Hg) patients.
Hair counts within the lcm target area were re- Following topical application, 2% minoxidil is
corded at the start of the study and periodically poorly absorbed from normal intact skin with an
thereafter. While indeterminate hair numbers at
beginning and end of treatment were almost the
same (27.2 vs 28.87), the number of terminal hairs
increased significantly (258 vs 945; p < 0.01).
Evaluation of hair growth at the end of treat-
ment by subjects and investigators is shown in fig.
2. Photographs taken before and after treatment
were used as a basis for this impression (fig. 3).
At the end of treatment 24 (70.5%) of the sub-
jects considered that they had decreased shedding;
7 (20.5%) noted no change; and 3 (9%) noted in-
creased shedding.
The adverse events reported by the subjects are
noted in table III. Four subjects complained of
headache: 3 during the first 2 weeks of treatment
and I at the third month of treatment. Three sub- Minimal hair growth Moderate No new hair growth
jects noted itchiness ofthe scalp between the third Fig.2. Evaluation of hair growth by investigator (.) and sub-
and sixth months of treatment. However, none of jects ~).
Topical Minoxidil in Male-Pattern Baldness 21

Diffuse type III-vertex

Fronto-vertex type V-a

Before Fronto-temporal type II-a After

Fig. 3. Photographs taken of 3 subjects before and after 10 months treatment with topical minoxidil.
22
Table III. Number of medical events occurring during treatment
with topical minoxidil for 40 weeks and percentage of total en-
rolled (some subjects had more than 1 symptom)
Event No. Percent
Headache 4 12
Mild scalp itching 3 9
Acneiform eruption 2 6
FOlliculitis 2 6
Scalp erythema 1 3
Burning sensation 1 3
Transient bipedal oedema 1 3
Tingling sensation 1 3
Mild palpitation 1 3
Increased scalp sweating 1 3
Arthralgia 1 3
average 1.4% (range 0.3 to 4.5%) of the total ap-
plied dose ultimately reaching the systemic circu-
lation (Franz 1985). Thus, 1ml of a 2% solution
delivering 20mg minoxidil to the skin would result
in absorption of approximately 0.28mg. After ces-
sation of topical administration, approximately 95%
of systemically absorbed minoxidil is eliminated
within 4 days.
The mechanism by which minoxidil can stim-
ulate hair growth remains to be elucidated. Hy-
pertrichosis has been associated with cutaneous va-
sodilation (Burton et al. 1975). Wester et al. (1984)
showed that topical minoxidil is capable of en-
hancing cutaneous blood flow in human balding
scalps. On the other hand, minoxidil may work
through a direct effect on follicular epithelium: in
vitro studies show that the drug has direct mito-
genic and morphological effects on epithelial cells
(Cohen et al. 1984). Minoxidil has been shown to
prolong the survival time of cultured epithelial cells
after confluence (Baden & Kubilus 1983).
From our study of 34 men with male pattern
baldness, we can conclude that 2% topical min-
oxidil does stimulate hair growth. Although the
majority of subjects belonged to the early male pat-
tern baldness group, 1 patient with baldness of more
than 20 years duration also had a positive re-
sponse. In the subjective evaluation, most patients
noted minimal hair growth. In contrast, a lower
Drug Invest. 2 (1) 1990
percentage of minimal hair growth was noted by
the investigators. Also, the majority of subjects
noted a decrease in hair shedding as early as the
third month of treatment.
Although 2 subjects who completed the study
believed that they had no apparent hair growth
while using study medication, and 3 patients
claimed to have increased shedding, no subjects had
a decrease in total target hairs from their baseline
counts. Furthermore, 18 (52%) showed a net de-
crease in the number of indeterminate hairs during
the study, but this was compensated for by an in-
crease in the number of terminal hairs at the end
of treatment.
There were local side effects with 2% topical
minoxidil, which consisted of some irritation in 7
subjects and mild systemic effects in 6 (table III).
However, in none of these subjects were the side
effects severe enough to warrant discontinuation of
the study medication. A definite cause and effect
relationship could not be ascribed to the topical
minoxidil. In addition, no significant physical or
laboratory changes were attributed to the study
medication.
References
Baden HP, Kubilus J. Effect of minoxidil on cultured keratino-:
cytes. Journal ofinvestigative Dermatology 81: 558-560, 1983
Burton JL, Schutt WH, Caldwell IW. Hypertrichosis due to di-
azoxide. British Journal of Dermatology 93: 707-711, 1975
Cohen RL, Alves MEAF, Weiss YC, et al. Direct effects of min-
oxidil on epidermal cells in culture. Journal of Investigative
Dermatology 82: 90-93, 1984
De Villez RL. Topical minoxidil therapy in hereditary androge-
netic alopecia. Archives of Dermatology 121: 197-202, 1985
Franz n. Percutaneous absorption ofminoxidil in man. Archives
of Dermatology 121: 203-204, 1985
Hamilton JB. Patterned loss of hair in man: types and incidence.
Annals of the NeW York Academy of Science 53: 70~728, 1951
Olsen EA. Topical minoxidil in early.male pattern baldness. Jour-
nal of the American Academy of Dermatology 13: 185-192,
1985
Weiss VC, et al. Alopecia areata with topical minoxidil. Archives
of Dermatology 120: 457-463, 1984
Wester RC, Maibach HI, Guy RH, et al. Minoxidil stimulates
cutaneous blood flow in human balding scalps: pharmacodyn-
amics measured by laser doppler velocimetry and photopulse
plethysmography. Journal of Investigative Dermatology 82: 5IS-
517, 1984
Authors' address: Dr Georgina C. Pastorfide, Section of Derma-
tology, Department of Medicine, Philippine General Hospital,
University of the Philippines, Manila, The Philippines.