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Efficacy of 5% Minoxidil versus Combined 5% Minoxidil and 0.01% Tretinoin for Male Pattern Hair Loss

Authors:
  • Harvard Medical School, Cutaneous Biology Research center

Abstract

Background: 5% topical minoxidil solution has been widely used to stimulate new hair growth and help stop hair loss in men with androgenetic alopecia (AGA). However, it is not convenient for patients to continue applying the solution twice daily on a regular basis. Tretinoin is known to increase the percutaneous absorption of minoxidil and, therefore, to enhance the response of AGA to minoxidil. For this reason, it was assumed that tretinoin would be helpful in alleviating the inconvenience associated with the recommended twice-daily application of minoxidil. Objective: To compare the efficacy and safety of therapy using a combined solution of 5% minoxidil and 0.01% tretinoin once daily with those of the conventional 5% topical minoxidil therapy applied twice daily in the treatment of AGA. Methods: A total of 31 male patients (aged 28-45 years, mean 39.7+/-4.5) with AGA (Hamilton-Norwood classification type III-V) were randomly assigned into two groups, one in which 5% minoxidil was applied to the scalp twice daily and the other in which the combined agent was applied once daily at night together with a vehicle placebo in the morning. The efficacy parameters were: (i) changes in total hair count, non-vellus hair count, anagen hair ratio, linear hair growth rate, and mean hair diameter assessed by macrophotographic image analysis; and (ii) the patient's and investigator's subjective assessments. Results: After therapy, increases in the macrophotographic variables of total hair count and non-vellus hair count were shown in both treatment groups. There were no statistically significant differences between the two treatment groups with respect to changes in macrophotographic variables or scores on subjective global assessments by patients and the investigator. The incidence of adverse effects such as pruritus or local irritation was similar in the 5% minoxidil group (4 of 14 subjects) and the combined agent group (5 of 15 subjects). Conclusion: The efficacy and safety of combined 5% minoxidil and 0.01% tretinoin once-daily therapy appear to be equivalent to those of conventional 5% minoxidil twice-daily therapy for the treatment of AGA.
Am J Clin Dermatol 2007; 8 (5): 285-290
O
RIGINAL
R
ESEARCH
A
RTICLE
1175-0561/07/0005-0285/$44.95/0
© 2007 Adis Data Information BV. All rights reserved.
Efficacy of 5% Minoxidil versus Combined 5%
Minoxidil and 0.01% Tretinoin for Male Pattern
Hair Loss
A Randomized, Double-Blind, Comparative Clinical Trial
Hyo Seung Shin,
1
Chong Hyun Won,
2
Seung Ho Lee,
1
Oh Sang Kwon,
1
Kyu Han Kim
1
and Hee Chul Eun
1
1 Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
2 Department of Dermatology, Seoul National University Boramae Hospital, Seoul, Korea
Background: 5% topical minoxidil solution has been widely used to stimulate new hair growth and help stop
Abstract
hair loss in men with androgenetic alopecia (AGA). However, it is not convenient for patients to continue
applying the solution twice daily on a regular basis. Tretinoin is known to increase the percutaneous absorption
of minoxidil and, therefore, to enhance the response of AGA to minoxidil. For this reason, it was assumed that
tretinoin would be helpful in alleviating the inconvenience associated with the recommended twice-daily
application of minoxidil.
Objective: To compare the efficacy and safety of therapy using a combined solution of 5% minoxidil and 0.01%
tretinoin once daily with those of the conventional 5% topical minoxidil therapy applied twice daily in the
treatment of AGA.
Methods: A total of 31 male patients (aged 28–45 years, mean 39.7 ± 4.5) with AGA (Hamilton-Norwood
classification type III–V) were randomly assigned into two groups, one in which 5% minoxidil was applied to the
scalp twice daily and the other in which the combined agent was applied once daily at night together with a
vehicle placebo in the morning. The efficacy parameters were: (i) changes in total hair count, non-vellus hair
count, anagen hair ratio, linear hair growth rate, and mean hair diameter assessed by macrophotographic image
analysis; and (ii) the patient’s and investigator’s subjective assessments.
Results: After therapy, increases in the macrophotographic variables of total hair count and non-vellus hair
count were shown in both treatment groups. There were no statistically significant differences between the two
treatment groups with respect to changes in macrophotographic variables or scores on subjective global
assessments by patients and the investigator. The incidence of adverse effects such as pruritus or local irritation
was similar in the 5% minoxidil group (4 of 14 subjects) and the combined agent group (5 of 15 subjects).
Conclusion: The efficacy and safety of combined 5% minoxidil and 0.01% tretinoin once-daily therapy appear
to be equivalent to those of conventional 5% minoxidil twice-daily therapy for the treatment of AGA.
Androgenetic alopecia (AGA), the most common form of alo- US FDA. Minoxidil lengthens the duration of the anagen phase
pecia in men, is a genetically determined, cosmetic disorder usual- and shortens the latent period of the hair cycle.
[4]
In addition,
ly beginning from about the late twenties and affecting approxi- topical application of minoxidil increases the size of the hair
mately half of all adult males aged >50 years.
[1,2]
Shortening of the follicles.
[5]
However, the exact mechanism of action of the drug
anagen phase and miniaturization of the follicles are prominent in has not been fully elucidated.
[6]
AGA.
[3]
The effect of minoxidil correlates with the concentration and
Minoxidil, originally developed for the treatment of hyperten- amount of the applied agent. Olsen et al.
[7,8]
showed that twice-
sion, is the most popular topical agent for AGA approved by the daily application of minoxidil was superior to once-daily applica-
286 Shin et al.
tion for the treatment of AGA. Therefore, its application twice prepared by AmorePacific R&D Center (Gyeonggi-do, Korea) and
daily for the treatment of AGA has been generally recommend- distributed by our clinical research center pharmacy. The two
ed.
[9]
Regular application of minoxidil is an important factor in products were indistinguishable in terms of appearance, smell, and
effective treatment.
[10]
However, from a practical point of view, it viscosity. The patients were instructed to spray 1mL of the agent
is not easy for patients to regularly apply minoxidil daily. and massage their scalp softly twice daily. The test group applied
the placebo (vehicle, 95% alcohol plus 5% propylene glycol)
In a previous study,
[11]
the percutaneous absorption of 2%
without minoxidil or tretinoin in the morning and the combined
minoxidil was increased nearly 3-fold by 0.05% tretinoin, which
preparation in the evening. Therefore, the test group was treated
increases the permeability of the stratum corneum. When minox-
once a day, in contrast to the control group that applied 5%
idil combined with tretinoin was applied only once daily, the
minoxidil twice daily.
urinary excretion of minoxidil was significantly higher than that of
minoxidil alone applied twice daily.
[11]
Moreover, 0.5% minoxidil
Study Protocol
plus 0.025% tretinoin (95% alcohol plus 5% propylene glycol
vehicle) applied twice daily to the affected scalp area was reported
The patients visited the hospital a total of five times. At the first
to prolong the anagen hair ratio and induce new hair growth.
[12]
visit, a baseline global photograph of their scalp was taken, after
These findings suggest that tretinoin can be helpful in alleviating
which the scalp hairs on the transitional zone between the bald
the inconvenience associated with the recommended twice-daily
region and normal hairy region were shaved to create a round area
application of minoxidil. In this study, we compared the efficacy
1.5cm in diameter. The reference point was tattooed at the center
and safety of the combined 5% minoxidil and 0.01% tretinoin
of the shaved round area. Three days later, phototrichogram
topical preparation applied once daily with those of 5% minoxidil
images were obtained by taking close contact photographs with a
applied conventionally twice daily in the treatment of AGA.
digital camera (Coolpix 8400
®
,
1
Nikon Corporation, Tokyo, Ja-
pan) at a magnification of ×30 in the previously shaved region.
Patients and Methods
The camera was mounted with a rigid magnifying lens to ensure
that the images were always taken at the same distance from the
Patient Selection
scalp surface. After application of a drop of water to minimize
light scattering, the lens was pressed on to the shaved area so that
Thirty-one male patients ranging from 28 to 45 years of age
the newly grown hairs were flattened on to the scalp surface. We
(mean 39.7 ± 4.5 years of age) with a clinical diagnosis of AGA
recorded the exact time when shaving and taking of the photo-
type III–V (Hamilton-Norwood classification) volunteered to par-
trichogram were undertaken in order to calculate the exact dura-
ticipate in this study. Patients with other medical problems were
tion of new hair growth. Patients were than randomly assigned to
excluded. No patients had used any products or taken any drugs
one of the two treatment groups.
that might have affected hair growth for 6 months prior to this
At the 9-week visit, a global photograph was taken again, and
study.
the patient’s and investigator’s subjective assessments were made.
Patients were randomly divided into two groups (the test [n =
At the 18-week visit, the final global photograph was taken and
16] and control [n = 15] groups) by four-block randomization
final assessments were made by the patient and investigator. The
using a table of random sampling numbers. The random numbers
previously tattooed reference area was then shaved again in prepa-
and the allotment table were not made available to investigators
ration for the second phototrichogram. Three days later, on the last
and patients until after all study evaluations had been completed.
visit, the second phototrichogram for evaluation of the efficacy of
Written informed consent was obtained from all patients prior
the treatment was taken.
to participation in the study. The Institutional Review Board of
Seoul National University Hospital approved the conduct of the
Measurements
study.
Five biologic parameters of hair growth (total hair count, non-
Products Tested
vellus hair count, anagen hair ratio, linear hair growth rate, and
The 5% minoxidil solution and the combined topical prepara- mean hair diameter) at baseline and post-treatment were measured
tion consisting of 5% minoxidil and 0.01% tretinoin were transpar- by macrophotographic image analysis. Total hair count, linear hair
ent liquids in 95% alcohol plus 5% propylene glycol vehicle length, and hair diameter in the digitized images were measured by
1 The use of trade names is for product identification purposes only and does not imply endorsement.
© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (5)
Combined 5% Minoxidil and 0.01% Tretinoin for Hair Loss 287
Table I. Characteristics of study volunteers (n = 29)
No. of subjects Hamilton-Norwood classification
III IIIa IIIv V Va
Combined minoxidil and tretinoin 1 0 9 0 5
once-daily group (n = 15)
Minoxidil twice-daily group (n = 14) 2 1 8 1 2
Total (n = 29) 3 1 17 1 7
image analysis software (Image J 1.34s, Wayne Rasband, Bethes- Results
da, MD, USA). Hairs thicker than 40µm in diameter were counted
as non-vellus hair.
[13]
In addition, hairs with growth rates >200
Enrolled Patients
µm/day were classified as anagen hair, allowing the anagen hair
Initially, 31 otherwise healthy patients with AGA were en-
ratio (anagen hair count/total hair count) to be calculated.
[14]
rolled, but one patient in the control group and another patient in
At 9 and 18 weeks, patients were asked to rate the improvement
the test group withdrew after missing a follow-up visit. Thus, 15
in their hair loss on a 10-point scale, where 0 meant no change or
patients in the test group and 14 patients in the control group
worse and 10 indicated complete recovery. They also graded their
completed the study. No significant difference in the age of the
satisfaction with the result on a 10-point scale, where 0 meant
patients was observed between the two groups (mean ± SD 39.3 ±
complete disappointment and 10 indicated full satisfaction.
4.2 years for the test group vs 40.2 ± 4.8 years for the control
group). The most common AGA subtype was grade IIIv in the
The investigator’s assessment of the efficacy of the treatment
Hamilton-Norwood classification (table I).
was conducted by one designated investigator (HSS) and per-
formed by comparing global photographs obtained at the first visit,
Biologic Parameters of Hair Growth Characteristics
9 weeks, and 18 weeks. The results of the evaluation were rated
before Treatment
into five grades as follows: 4 = excellent (improved >75%); 3 =
good (improved 51–75%); 2 = fair (improved 26–50%); 1 = poor
No significant difference in total hair count, non-vellus hair
(improved <25%); 0 = no change or worse.
count, anagen hair ratio, linear hair growth rate, and mean hair
diameter was observed between the two groups before treatment
(table II).
Statistical Methods
Treatment Efficacy Within Each Group
A statistical analysis was performed using SPSS 11 software
(SPSS, Chicago, IL, USA) with a p-value of <0.05 being consid-
The total hair count and non-vellus hair count increased signifi-
ered significant. The non-parametrical Mann-Whitney test and
cantly after 18 weeks of treatment in both groups (p < 0.05). Mean
Wilcoxon signed rank test were used to evaluate differences in
hair diameter was also markedly increased in the control group (p
biologic parameters of hair growth characteristics and the patients’
< 0.05). In the test group the increase in mean hair diameter was of
and investigator’s assessments between the two groups.
borderline significance (p = 0.064). Neither anagen hair ratio nor
Table II. Biologic parameters of hair growth in the two treatment groups at baseline
Parameter Combined minoxidil and tretinoin once-daily group
a
Minoxidil twice-daily group
a
p-Value
Total hair count (n/cm
2
) 124.2 ± 8.5 124.0 ± 7.5 NS
Non-vellus hair count (n/cm
2
) 42.7 ± 5.8 33.4 ± 4.3 NS
Anagen hair ratio 0.554 ± 0.020 0.571 ± 0.025 NS
Linear hair growth rate (µm/d) 336.6 ± 10.6 302.2 ± 13.1 NS
Mean hair diameter (µm) 36.2 ± 1.3 34.8 ± 2.1 NS
a Values are mean ± standard error.
NS = not significant.
© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (5)
288 Shin et al.
Table III. Biologic parameters of hair growth at baseline and after 18 weeks of treatment in the two treatment groups
Parameter Baseline
a
After treatment
a
p-Value
Combined minoxidil and tretinoin once-daily group
Total hair count (n/cm
2
) 124.2 ± 8.5 142.4 ± 7.3 <0.05
Non-vellus hair count (n/cm
2
) 42.7 ± 5.8 48.8 ± 5.6 <0.05
Anagen hair ratio 0.554 ± 0.020 0.521 ± 0.037 NS
Linear hair growth rate (µm/d) 336.6 ± 10.6 331.1 ± 9.3 NS
Mean hair diameter (µm) 36.2 ± 1.3 38.1 ± 1.4 NS
Minoxidil twice-daily
Total hair count (n/cm
2
) 124.0 ± 7.5 139.9 ± 9.1 <0.05
Non-vellus hair count (n/cm
2
) 33.4 ± 4.3 47.4 ± 5.3 <0.05
Anagen hair ratio 0.571 ± 0.025 0.557 ± 0.035 NS
Linear hair growth rate (µm/d) 302.2 ± 13.1 317.7 ± 13.8 NS
Mean hair diameter (µm) 34.8 ± 2.1 37.4 ± 1.8 <0.05
a Values are mean ± standard error.
NS = not significant.
linear hair growth rate showed any significant differences after Safety Evaluation
treatment (table III).
Five patients in the test group (n = 15) and four patients in the
Treatment Efficacy between Groups
control group (n = 14) complained of scalp itching or prickling.
Among them, two patients in the control group had folliculitis on
No significant differences in percentage changes in biologic
their scalps. However, symptoms were mild in all cases and the
parameters of hair growth (total hair count, non-vellus hair count,
patients were able to continue application of the drugs. All adverse
anagen hair ratio, linear hair growth rate, and mean hair diameter)
effects were self-limiting and were no longer present after a few
were observed between the two groups after 18 weeks of treat-
days.
ment. The p-values all exceeded 0.05 (table IV).
Discussion
Patients’ and Investigator’s Subjective Assessments
The patient’s subjective assessment score and satisfaction score Among the various drugs used for the treatment of AGA, the
did not show any significant differences between the test group most popular topical agent, which is also approved by the FDA, is
and the control group during the study (table V). Similarly, the minoxidil. After application, minoxidil is converted to minoxidil
investigator’s subjective assessment score did not show any signif- sulfate, an active metabolite of the parent drug, by sulfotransferase
icant difference between the test group and the control group enzymes. Minoxidil sulfate opens an adenosine triphosphate-sen-
during the study (table VI). sitive potassium channel, which functions to relax vascular
Table IV. Comparison of changes in biologic parameters of hair growth between the two treatment groups
Change (%)
a
Combined minoxidil and tretinoin Minoxidil twice-daily group
b
p-Value
once-daily group
b
Total hair count 17.3 ± 3.8 12.9 ± 2.5 NS
Non-vellus hair count 23.4 ± 7.7 55.4 ± 19.6 NS
Anagen hair ratio
7.0 ± 4.1
2.9 ± 3.7 NS
Linear hair growth rate
1.3 ± 1.8 5.6 ± 3.1 NS
Mean hair diameter 5.4 ± 2.5 8.7 ± 3.4 NS
a Change (%) = (parameter at week 18 – parameter at baseline) / (parameter at baseline) × 100.
b Values are mean ± standard error.
NS = not significant.
© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (5)
Combined 5% Minoxidil and 0.01% Tretinoin for Hair Loss 289
Table V. Comparison of patients’ subjective assessment scores between the two treatment groups
Subjective score
a
Combined minoxidil and tretinoin Minoxidil twice-daily group
b
p-Value
once-daily group
b
Improvement (at 9wk) 3.1 ± 0.6 2.6 ± 0.6 NS
Improvement (at 18wk) 4.2 ± 0.6 3.7 ± 0.8 NS
Satisfaction (at 9wk) 3.0 ± 0.6 3.1 ± 0.7 NS
Satisfaction (at 18wk) 4.2 ± 0.6 3.9 ± 0.8 NS
a Graded on a 10-point scale, where a score of 0 means no change or complete disappointment and a score of 10 means complete recovery or full
satisfaction.
b Values are mean ± standard error.
NS = not significant.
smooth muscle. Therefore, increasing cutaneous blood flow has ies.
[8,19]
However, in contrast to previous studies that reported an
increase in anagen hair ratio with minoxidil therapy,
[4,19]
neither
been regarded as the main mechanism of action of minoxidil.
[15,16]
the combined agent nor conventional 5% minoxidil were found to
Tretinoin has been shown to alter the stratum corneum barrier
improve anagen hair ratio or linear hair growth rate in the current
and increase the percutaneous absorption of minoxidil which, in
study. Since minoxidil is reported to shorten the latent telogen
turn, enhances the response of AGA to minoxidil.
[11]
Moreover,
phase,
[4]
the lack of change in these parameters with treatment in
retinoic acid promotes the growth of hair follicles and the forma-
our study was not expected. It is possible that these results re-
tion of vessels via a molecular signaling pathway.
[17]
In addition,
flected seasonal variations in hair growth, as our study was per-
we have recently demonstrated that hair growth was significantly
formed between summer and autumn.
[20]
Otherwise, some exogen
enhanced by the combination of minoxidil plus retinol (vitamin A)
hair might have interfered with anagen hair growth by blocking its
compared with minoxidil alone via dual mechanisms: (i) activa-
path. These factors might at least partially explain why anagen hair
tion of extracellular signal-regulated kinase (Erk) and Akt signal-
ratio and linear hair growth rate were not significantly affected by
ing; and (ii) prevention of apoptosis by increasing the B-cell
treatment in this study.
leukemia/lymphoma (Bcl)-2/Bcl-2-associated X (Bax) protein ra-
Both groups demonstrated similar improvements in subjective
tio.
[18]
Therefore, enhancement of transepidermal absorption of
global assessment of therapy by patients and the investigator.
minoxidil and a direct stimulatory influence on hair growth have
The occurrence of adverse effects such as pruritus or local
been proposed as the mechanisms of action of tretinoin on hair
irritation was similar in both groups. Based on these results, it was
growth. However, it has not yet been determined which is more
inferred that the combined preparation is as safe as conventional
predominant in terms of promoting hair growth.
minoxidil.
In this study, we found that the application of the combined 5%
minoxidil and 0.01% tretinoin solution just once daily showed an
Conclusion
equivalent treatment effect to that of 5% minoxidil applied twice
daily in terms of changes in hair growth characteristics such as
This study was a randomized, double-blind, comparative
total hair count, non-vellus hair count, anagen hair ratio, linear hair
clinical trial designed to compare the efficacy of a combined
growth rate, and mean hair diameter. The increases in total hair
solution of 5% minoxidil and 0.01% tretinoin with that of conven-
count, non-vellus hair count, and mean hair diameter observed in
tional 5% minoxidil in the treatment of AGA. Topical tretinoin has
our study correlate well with those reported in previous stud-
been shown to increase the percutaneous absorption of minoxidil.
Table VI. Comparison of investigator’s subjective assessment scores between the two treatment groups
Subjective score
a
Combined minoxidil and tretinoin Minoxidil twice-daily group
b
p-Value
once-daily group
b
At 9wk 1.2 ± 0.2 0.9 ± 0.2 NS
At 18wk 1.6 ± 0.3 1.8 ± 0.4 NS
a Graded on a 4-point scale, where a score of 0 means no change or worse and a score of 4 means >75% improvement.
b Values are mean ± standard error.
NS = not significant.
© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (5)
290 Shin et al.
7. Olsen EA, DeLong ER, Weiner MS. Long-term follow-up of men with male
Therefore, we presumed that a combined solution of 5% minoxidil
pattern baldness treated with topical minoxidil. J Am Acad Dermatol 1987 Mar;
and 0.01% tretinoin would be effective for the treatment of AGA,
16 (3 Pt 2): 688-95
even when it is applied only once daily. There were no significant
8. Olsen EA, Dunlap FE, Funicella T, et al. A randomized clinical trial of 5% topical
differences in percentage changes in biologic parameters of hair
minoxidil versus 2% topical minoxidil and placebo in the treatment of androge-
netic alopecia in men. J Am Acad Dermatol 2002 Sep; 47 (3): 377-85
growth characteristics between the two groups after 18 weeks of
9. Olsen EA, Messenger AG, Shapiro J, et al. Evaluation and treatment of male and
treatment. There were also no statistical differences between the
female pattern hair loss. J Am Acad Dermatol 2002 Sep; 47 (3): 377-85
two groups in the subjective global assessment of treatment by
10. Buhl AE, Waldron DJ, Kawabe TT, et al. Minoxidil stimulates mouse vibrissae
patients and the investigator. The adverse effects of the combined
follicles in organ culture. J Invest Dermatol 1989 Mar; 92 (3): 315-20
solution were all mild. In conclusion, although this study had
11. Ferry JJ, Forbes KK, VanderLugt JT, et al. Influence of tretinoin on the percutane-
limitations, such as the small number of patients analyzed, the lack
ous absorption of minoxidil from an aqueous topical solution. Clin Pharmacol
of a placebo group, and the fact that no treatment group received
Ther 1990 Apr; 47 (4): 439-46
5% minoxidil once daily, our results suggest that the efficacy and
12. Bazzano GS, Terezakis N, Galen W. Topical tretinoin for hair growth promotion.
J Am Acad Dermatol 1986 Oct; 15 (4 Pt 2): 880-3
safety of combined 5% minoxidil and 0.01% tretinoin adminis-
13. Rushton DH. Chemical and morphological properties of scalp hair in normal and
tered once daily are equivalent to those of conventional 5%
abnormal states. Aberystwyth: University of Wales, 1988
minoxidil administered twice daily for the treatment of AGA.
14. Hayashi S, Miyamoto I, Takeda K. Measurement of human hair growth by optical
Since there is usually an inverse relationship between administra-
microscopy and image analysis. Br J Dermatol 1991 Aug; 125 (2): 123-9
tion frequency and compliance,
[21,22]
use of combined 5% minox-
15. Meisheri KD, Cipkus LA, Taylor CJ. Mechanism of action of minoxidil sulfate-
idil and 0.01% tretinoin once daily could be a useful alternative,
induced vasodilation: a role for increased K+ permeability. J Pharmacol Exp
with a high rate of compliance, for the treatment of AGA.
Ther 1988 Jun; 245 (3): 751-60
16. Winquist RJ, Heaney LA, Wallace AA, et al. Glyburide blocks the relaxation
response to BRL 34915 (cromakalim), minoxidil sulfate and diazoxide in
Acknowledgments
vascular smooth muscle. J Pharmacol Exp Ther 1989 Jan; 248 (1): 149-56
17. Madani KA, Bazzano GS, Chou AC. Effects of vitamin A status on cellular retinoic
acid-binding protein in rat skin and testes. Eur J Clin Chem Clin Biochem 1991
This study was financially sponsored by AmorePacific R&D Center,
May; 29 (5): 317-20
Gyeonggi-do, Korea. The authors have no conflicts of interest that are directly
18. Yoo HG, Chang IY, Pyo HK, et al. The additive effects of minoxidil and retinol on
relevant to the content of this study.
human hair growth in vitro. Biol Pharm Bull 2007 Jan; 30 (1): 21-6
19. Abell E. Histologic response to topically applied minoxidil in male pattern alope-
cia. Clin Dermatol 1988 Oct-Dec; 6 (4): 191-4
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© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (5)
... Probabilities were extrapolated from randomized controlled trials (RCTs) that evaluated the efficacy and safety of minoxidil monotherapy, minoxidil+PRP, or PRP monotherapy for men with AGA Hamilton-Norwood stages I-V [9][10][11][12][13][14][15]20,21]. Treatment response probabilities between health states were determined using physician assessments based on prospective clinical studies at six-month cycles. ...
... During the first cycle, 55% of patients improved with minoxidil+PRP [12], 53% of patients improved with PRP monotherapy [9], and 51% of patients improved with minoxidil monotherapy [10,14]. Following the first six-month cycle for those who improved, 99% of patients continued minoxidil+PRP [11], 97% of patients continued PRP monotherapy [15,20], and 91% of patients continued minoxidil monotherapy [11,13,14,20,21]. Over subsequent cycles, 98% of men who improved continued treatment, while 50% of men who did not improve continued treatment (Table 1) [1,[9][10][11][12][13][14][15]20,21]. ...
... During the first cycle, 55% of patients improved with minoxidil+PRP [12], 53% of patients improved with PRP monotherapy [9], and 51% of patients improved with minoxidil monotherapy [10,14]. Following the first six-month cycle for those who improved, 99% of patients continued minoxidil+PRP [11], 97% of patients continued PRP monotherapy [15,20], and 91% of patients continued minoxidil monotherapy [11,13,14,20,21]. Over subsequent cycles, 98% of men who improved continued treatment, while 50% of men who did not improve continued treatment (Table 1) [1,[9][10][11][12][13][14][15]20,21]. ...
Article
Background Androgenetic alopecia (AGA) is the most common cause of hair loss in men. In this study, we evaluated the cost-effectiveness of minoxidil monotherapy, minoxidil and platelet-rich plasma (PRP) combined therapy, and PRP monotherapy for the long-term treatment of early-onset AGA Hamilton-Norwood stages I-V in men. Methodology Markov modeling was performed to analyze the base-case parameters from 18 level I/II studies. The model base-case assumes a healthy 25-year-old man presenting to a dermatologist or plastic surgeon's office as a new patient for the evaluation and treatment of AGA Hamilton-Norwood stages I-V (non-severe AGA in men). Simulations began at an age of 25 years and ran over 35 years. Analyses were conducted from healthcare and societal perspectives. Outcomes included incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB). Willingness-to-pay (WTP) thresholds were set at $50,000 and $100,000. Deterministic and probabilistic sensitivity analyses were performed to evaluate uncertainty over 10,000 simulations. Results From a healthcare perspective, compared to minoxidil monotherapy, the ICER for minoxidil+PRP was $52,036/quality-adjusted-life-year (QALY) and the ICER for PRP monotherapy was $439,303/QALY. The NMB of minoxidil monotherapy was $914,887, minoxidil+PRP was $914,350, and PRP monotherapy was $904,572 at a WTP threshold of $50,000. When the WTP threshold was increased to $100,000, the NMB of minoxidil+PRP was $1,843,908, minoxidil monotherapy was $1,831,237, and PRP monotherapy was $1,822,246. Societal trends were similar. Conclusions Minoxidil 5% topical twice-daily monotherapy provided cost-effective treatment for men with AGA Hamilton-Norwood stages I-V at a WTP threshold of $50,000, whereas combining minoxidil 5% with PRP provided cost-effective treatment at a WTP threshold of $100,000. Level of evidence: Level II.
... Topical application of all-trans RA and other retinoids has been shown to produce minoxidil-like effects in C3H mouse models, namely, a prolonged growth phase and a shortened telogen period [62]. In addition, topical all-trans RA alone or in combination with 0.5% minoxidil has been shown to promote hair growth in patients with androgenetic alopecia [63,64]. The role of these small molecules in these signaling pathways is perhaps to promote the transformation of fibroblasts into DPC-LCs. ...
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The reprogramming of somatic fibroblasts into alternative cell linages could provide a promising source of cells for regenerative medicine and cell therapy. However, the direct conversion of fibroblasts into other functional cell types is still challenging. In this study, we show that dermal-papilla-cell-like cells (DPC-LCs) can be generated by treating fibroblasts, including L929 mouse fibroblast cell lines and somatic mouse fibroblasts, with small molecules. Based on alkaline phosphatase activity and other molecular markers, different compounds or their combinations are needed for converting the two different fibroblasts into DPC-LCs. Notably, we found that TTNPB alone can efficiently convert primary adult mouse fibroblasts into DPC-LCs. DPC-LCs generated from mouse fibroblasts showed a stronger hair-inducing capacity. Transcriptome analysis reveals that expression of genes associated with a hair-inducing capacity are increased in DPC-LCs. This pharmacological approach to generating functional dermal papilla cells may have many important implications for hair follicle regeneration and hair loss therapy.
... Based on the previous reports, it affects almost 50% of the population with the age over 50 years. [1,2] It was reported that it also affects 6%-38% of healthy females. [3] The reason behind the importance of treatment in these patients is the great discomfort, isolation, and reduction in quality of life this disease could cause. ...
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Background and Purpose: Using the commercially manufactured forms of minoxidil, the only approved topical drug preparation for hair regrowth in patients with androgenetic alopecia (AGA) comes across with challenges such as limited permeation through the superficial layers of the skin to reach the site of action and topical adverse reactions like itching and inflammation occur because of the ethanol in the formulations. In this study, a novel nanosuspension formulation with an aqueous base was prepared and evaluated to overcome the discussed challenges. Materials and Methods: The nanosuspension formulation was characterized by size, zeta potential, morphology, and in vitro release. Seventy patients were subjected to use either 1 mL of nanosuspension or the commercial product twice daily for six months and were then examined for changes in hair follicle diameter and hair density within a 1 × 1-cm2 area of the scalp as the primary endpoints besides any adverse reaction manifestation as the secondary endpoint. Results: The nanosuspension formulation showed uniform morphology, 200-nm particle size, and suitable zeta potential that ensures the stability. The in vitro release study exhibited almost 90% release in the first 6 h. It was observed that there were no significant differences between the efficacy of aqueous-based topical 2% nanosuspension of minoxidil and the commercial product in the treatment of AGA (P > 0.05). However, the aqueous-based topical 2% nanosuspension formulation showed better safety and tolerability compared to the marketed profile. Conclusions: It could be concluded that aqueous-based topical 2% nanosuspension is a suitable form with enhanced patient compliance compared to commercially manufactured products.
... 17 It helps to lengthen the anagen phase, increases the size of hair follicle and shortens the period of hair cycle. 18 Oral minoxidil was associated with certain side effects like weight gain due to retention of water but on further trials and investigation 5% topical solution showed no side effects and was better than oral minoxidil. 16 Platelet rich plasma (PRP) is being increasingly used in AGA.PRP is a product formed by the processing of autologous blood to produce concentration of platelets. ...
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Androgenic alopecia (AGA) is a type of progressive hairloss, where there is androgen mediated conversion of susceptible terminal hairs into vellus hairs, in genetically predisposed individuals. To compare efficacy of Topical 5% Minoxidil alone versus Topical 5% Minoxidil with Autologous Platelet Rich Plasma (PRP) therapy in patients with Androgenetic Alopecia. This is aProspective study conducted in Department of Dermatology GMERS Medical College, Gandhinagar, Gujarat. A convenience sample of 62 men in the age group of 20-40 with Grade 2-5 AGA according to Hamilton- Norwood Grading were selected and was divided into 2 groups of 31 each. Presitting digital photographs and dermoscopic photos were taken. Autologous PRP was prepared using 18 ml of patients blood after double spin centrifugation and injected by Nappage technique. Results were assessed at the baseline and at the end of each sitting on the basis of change in hair density, photographic evaluation and patient’s self satisfaction. Highly significant increase in hair density was achieved after 4 months of treatment. At T4 (Fourth Session of treatment) Group B showed higher hair density (42.97± 8.96) as compared to Group A (36.94 ± 11.57) which was statistically significant at P = 0.03 Group B showed better improvement as compared to Group A.PRP treatment has a positive therapeutic effect on male Androgenetic alopecia without major side effects.
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Even though a variety of treatments for androgenetic alopecia (AGA) currently have been using in clinical, satisfactory therapeutic methods are still lacking. We aimed to compare and rank these treatments for AGA according to their differences in efficacy via Bayesian network meta-analysis, suggesting the optimal therapy for clinical utility to refer. A systematic search of PubMed, Embase, Web of Science, and Cochrane Library database was performed and we included eligible randomized controlled trials. We compared differences in treatment effects of monotherapies and combination therapies using the Bayesian network model. The average difference in alteration from baseline of hair density and hair diameter, and variation value (Mean±SD) between the pre- and post-intervention were selected for main outcome measure and secondary outcome measure. Total 49 RCTs involving 3133 patients and 6 interventions were included. Regardless of based on hair density or hair diameter, topical/systemic combined with adjunctive therapeutics had the best treatment efficacy among all interventions (SMD: 40.11; 95% CrI 25.65–54.59), followed by topical combined with systemic medical therapeutics (SMD: 36.41; 95% CrI 17.54–55.24). In addition, in terms of hair density, treatment efficacy had significant difference sequentially among topical medical therapeutics (SMD: 22.15; 95% CrI 12.88–31.42), systemic medical therapeutics (SMD: 19.91; 95% CrI 6.504–33.22), and adjunctive therapeutics (SMD: 18.60; 95% CrI 8.020–29.10) compared to placebo. In recent years, combination therapies are showing significant promise as potential therapies. Taken together with the outcomes of this study, despite the specific mechanism of the effect of combination therapies was not clear and further studies are needed, it may be the best treatment for AGA. This article is protected by copyright. All rights reserved.
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Background Topical minoxidil 5% are effective in androgenetic alopecia. Spironolactone acts as an androgen antagonist by competitively blocking androgen receptors. Objectives studying the effect of topical minoxidil 5% gel and spironolactone gel 1% in management of AGA. Methods The study includes 60 patients diagnosed as AGA; (group I): treated with topical minoxidil gel 5%, (group II): with topical spironolactone gel 1% and group (III) treated with combined minoxidil 5% and spironolactone 1% gel. All patients were followed up monthly throughout the treatment period. Scalp biopsy was taken before and after 12 months. Results In group I, the clinical response was in 90% of patients with variable degrees in improvement, in group II, the clinical response was in 80% of patients, meanwhile, in group III the clinical response was in all patients (100%). Histopathological examination of skin biopsy after treatment revealed significant increase in anagen hair on the other hand, both telogen and vellus hair was significantly decreased meanwhile, the T/V ratio was significantly increased. Conclusions The results of this work revealed that topical minoxidil gel 5% and topical spironolactone gel 1% were effective in treatment of androgenetic alopecia, while the combination of two agents was better in treatment. This article is protected by copyright. All rights reserved.
Article
Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to 80% of men and 50% of women in the course of their life. AGA is caused by a progressive reduction in the diameter, length and pigmentation of the hair, resulting from the effects of the testosterone metabolite dihydrotestosterone (DHT) on androgen-sensitive hair follicles. Clinical presentation is different in men and women. Trichoscopy is used routinely in patients with androgenetic alopecia, for diagnosis and differential diagnosis with other diseases, allowing staging of severity and monitoring the progress of the disease and the response to treatment. Medical treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha reductase inhibitors and many other options. This guideline for the treatment of androgenetic alopecia has been developed by an Italian group of experts taking into account the Italian pharmacological governance. The article is adapted from the original of the European Dermatology Forum (EDF) in collaboration with the European Academy of Dermatology and Venereology (EADV). It summarizes evidence-based and expert-based recommendations (S3 level).
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Hair restoration in women involves mastering both the medical and the surgical treatment. Preoperatively, women should be thoroughly evaluated for biochemical causes of hair loss along with a complete history and physical examination taken. The physician must recognize the clinical presentation of scarring alopecias and maintain a low threshold for biopsy to rule out this condition. Postoperative hair shock loss is a common feature following hair transplant in women, and the surgeon should understand the preoperative counseling and preventative measures needed, the intraoperative methods to reduce the incidence, and the postoperative strategies to handle the situation.
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Nineteen healthy male volunteers completed a three-way, randomized, crossover study to determine the effect of the synthetic retinoid, tretinoin, on percutaneous absorption of minoxidil. Subjects received, for 20 days, twice-daily administrations of 1 ml of an aqueous 2% topical minoxidil solution either alone, with once-daily applications of a 0.05% tretinoin cream, or with once-daily applications of a vehicle control cream. When minoxidil was coadministered with tretinoin cream, minoxidil absorption was increased nearly threefold, compared with a 1.3-fold increase in absorption observed with coadministration of vehicle control cream. Transepidermal water loss measurements, which are sensitive to changes in stratum corneum function, were also significantly increased with tretinoin. No treatment-related changes in stratum corneum thickness were observed on the basis of skin biopsy analysis. The findings indicate that percutaneous minoxidil absorption is enhanced by tretinoin as a result of increased stratum corneum permeability.
Article
We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
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The need for a widely accepted, accurate, and reproducible standard of classification for male pattern baldness has increased with the advent and increasing popularity of hair transplant surgery. This report establishes such a classification, and reports its use in determining the incidence of male pattern baldness at various ages in 1,000 white adult male subjects. The action of testosterone as an incitant in male pattern baldness is well known, but this study points out the continued effect of time, even in later years. Since most hair transplant surgery is peformed on subjects with male pattern baldness, and because the success of hair transplant surgery is largely dependent on proper patient selection, a complete understanding of male pattern baldness is essential for consistently good results with hair transplantation.
Cellular retinoic acid-binding protein levels were determined in the skin and testes of normal and retinol-deficient rats. All-trans [3H]retinoic acid (1.1 TBq/mmol) was used to titrate the specific binding sites in tissue cytosol preparations. Scatchard plot analyses were used to determine the concentration of cellular retinoic acid-binding protein and its binding affinity (Kd) for all-trans-retinoic acid. In normal rat skin the concentration of cellular retinoic acid-binding protein was 3317 +/- 924 (SD) fmol/mg protein and the Kd was 1.98 +/- 1.0 x 10(-9) mol/l. In retinol-deficient rat skin the concentration of cellular retinoic acid-binding protein was 2584 +/- 1205 fmol/mg protein and the Kd was 3.30 +/- 3.4 x 10(-9) mol/l. In the normal rat testes the concentration of cellular retinoic acid-binding protein was 2965 +/- 1187 fmol/mg protein and the Kd was 2.30 +/- 2.1 x 10(-9) mol/l. In retinol-deficient rat testes the concentration of cellular retinoic acid-binding protein was 2439 +/- 383 fmol/mg protein and the Kd was 0.3 +/- 0.2 x 10(-9) mol/l. These findings indicate that there are no significant differences in the levels of cellular retinoic acid-binding protein between normal and deficient rat skin and testes (p greater than 0.1, by Wilcoxon rank sum test). We therefore conclude that the level of cellular retinoic acid-binding protein in skin and testes may not be controlled by the availability of vitamin A.
Article
We have developed a quantitative method for measuring hair growth using optical microscopy and image analysis, and have used this to investigate the rate of growth in subjects with and without alopecia. The hairs were cut from an area 7-8 mm in diameter and 24 h and 72 h later, images of the areas were obtained using an optical microscope and were recorded on a video disc. Measurements of the regrowing hairs, placed parallel to the scalp using a glass slide attached to the front of the microscope, were made using the image analyser. In subjects with little or no baldness there was a clear difference between fast-growing hairs and resting or slow-growing hairs. However, in subjects with alopecia there was no such difference and the growth rate of all the hairs showed a continuous distribution. Using this method other parameters such as the number of hairs per unit area and hair diameter as well as grouping of the hairs could be measured.
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Alopecia is a common problem affecting the scalp in both men and women. The vast majority of all cases of alopecia are of the androgenetic variety. The clinical and endocrinologic features of this disorder are reviewed. Potential therapies, including surgical and medical modalities, are mentioned.
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To explore an easily accessible and reproducible model for examining the effect of minoxidil on hair growth, we studied the effect of minoxidil on the natural hair cycles of rats from birth to 80 days of age. During the 1st and 2nd postnatal cycles, the hair follicles grew very rapidly and the size of anagen follicles were markedly enlarged. In the 3rd cycle (50 days to approximately 100 days of age), duration of the telogen phase lasted approximately 20 days. Topical minoxidil, 1%, 3%, or 5% solution, applied on the backs of the rats from 23 days (weaning) to 80 days, induced a remarkable shortening of the telogen phase in the 3rd cycle. Although the dose-dependent response was very minimal, rats treated with 3% or 5% minoxidil showed similar effects in the 4th cycle. Minoxidil, however, did not induce prolongation of the anagen phase, but increased the rate of DNA synthesis in the anagen bulb during the 2nd and 3rd cycles. These results suggest that minoxidil specifically stimulates the secondary germ of the telogen follicles, resulting in rapid progression to anagen follicles.
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BRL 34915 [6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl) 2H-benzo(b) pyran-3-ol], minoxidil sulfate and diazoxide may relax vascular smooth muscle via hyperpolarization due to an opening of membrane potassium channels. We therefore examined the effects of several potassium channel antagonists on the relaxation response to these vasodilators in isolated rat portal venous strips which were mounted in vitro for detecting changes in isometric force. BRL 34915 (IC50 = 4.7 X 10(-8) M), minoxidil sulfate (IC50 = 1.4 X 10(-7) M) and diazoxide (IC50 = 5 X 10(-6) M) elicited concentration-dependent relaxations of the spontaneous, myogenic contractions in venous strips. The relatively nonselective potassium channel antagonists tetraethylammonium ion (0.3-10 X 10(-3) M) and 4-aminopyridine (1-10 X 10(-3) M) caused concentration-dependent shifts (5- to 50-fold) in the relaxation responses to each vasodilator. Charybdotoxin (up to 10(-7) M) and apamin (up to 10(-7) M), known to be antagonists of high and low conductance calcium-activated potassium channels, respectively, had no inhibitory effect on the relaxation-response curves to BRL 34915, minoxidil sulfate or diazoxide. Glyburide (10(-7) to 3 X 10(-5) M), a sulfonylurea which has been shown to block the ATP-modulated potassium channel in insulin-secreting cells, caused concentration-dependent shifts to the right (up to 100-fold) of the IC50 value for BRL 34915 and diazoxide, and at 10(-6) M, abolished the relaxation response to minoxidil sulfate.(ABSTRACT TRUNCATED AT 250 WORDS)
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Minoxidil, a potent vasodilator, stimulates the growth of terminal hair from vellus or miniaturized follicles in balding scalp. To study minoxidil's action on isolated follicles we developed and validated an organ culture system using mouse whisker follicles. Control follicles cultured without minoxidil showed macroscopic changes including kinking of the hair shafts and bending of the follicles. Necrosis was evident in the differentiating epithelial elements forming the cuticle, cortex, and inner root sheath. These abnormalities were eliminated or greatly reduced in minoxidil-treated follicles. The morphology of these follicles was consistent with the production of new hair during culture. Direct measurement demonstrated that minoxidil-treated follicles grew significantly longer than control follicles during the 3-d culture. Minoxidil increased the incorporation of radiolabeled cysteine and glycine in follicles compared with control treatment. Doses of minoxidil up to 1 mM caused increased cysteine incorporation, while higher doses were inhibitory. Experiments with labeled thymidine indicated that minoxidil induced proliferation of hair epithelial cells near the base of the follicle. Autoradiography also showed that cysteine accumulated in the keratogenous zone above the dermal papilla. These studies demonstrate that organ cultured follicles are suitable for determining minoxidil's mechanism of action and may be useful for studying other aspects of hair biology. The results also show that minoxidil's effect on hair follicles is direct. This suggests that minoxidil's action in vivo includes more than just increasing blood flow to hair follicles.