Comparing the therapeutic efficacy of topical minoxidil and finasteride with topical minoxidil and oral finasteride in androgenetic alopecia: a randomized trial

Abstract

p class="abstract"> Background: There is an increased interest in the development and use of topical finasteride for treating androgenic alopecia (AGA) due to growing evidence of side effects from oral finasteride. In this study we aimed to compare the treatment outcomes of topical 5% minoxidil with 0.1% finasteride and topical 5% minoxidil with oral 1 mg finasteride.
Methods: 50 patients of stage III and IV of Hamilton-Norwood scale were randomly assigned to either Group A receiving topical 5% minoxidil and oral finasteride 1 mg and Group B receiving topical 5% minoxidil and topical 0.1% finasteride. After taking uninterrupted treatment for 12 months, patients were assessed for hair regrowth and maintenance using global photography and trichoscopy and compared with baseline parameters. Patients in both the groups were assessed for any adverse effects as well.
Results: At baseline, patients in both the treatment groups were similar with respect to their age at the time of presentation, family history of hair loss and Hamilton Norwood scale. In group A, three discontinued treatment and of the rest 65% maintained a good hair density and reduced hairfall. In group B, five discontinued treatment, of the rest 83% patients demonstrated good improvement in hair density (p<0.05).
Conclusions: The results of this study strongly support the use of topical finasteride in combination with topical 5% minoxidil for AGA and this may obviate the need of taking long term oral finasteride.</p

Full text

International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 386
International Journal of Research in Dermatology
Rai PB et al. Int J Res Dermatol. 2018 Aug;4(3):386-390
http://www.ijord.com
Original Research Article
Comparing the therapeutic efficacy of topical minoxidil and finasteride
with topical minoxidil and oral finasteride in androgenetic alopecia:
a randomized trial
Priyam Bhaskar Rai, Pragya Khushwaha*, Nitish Jain, Swati Gupta
INTRODUCTION
Androgenic alopecia, commonly referred to as male-
pattern hair loss in men or as female-pattern hair loss in
women, affects at least half of all men by the age of 50
years, and more later in life.1 This androgen-dependent
hair loss is heritable and occurs in a specific pattern. It
has been hypothesised that the genetically predisposed
hair follicles undergo miniaturization after being
stimulated by androgens, which result in gradual
replacement of large and pigmented hairs by thin and
depigmented hairs (vellus).2 Scalp biopsy on histological
examination reveals that perifollicular lymphocytic
infiltration is very common and culminates in fibrosis of
the follicle. The mechanism explaining the microscopic
follicular inflammation resulting in fibrosis has been
poorly understood.
Minoxidil, developed as an anti-hypertensive agent,
promotes hair growth through increasing the duration of
anagen.3 Finasteride is a competitive inhibitor of type 2
5- reductase and inhibits the conversion of testosterone
ABSTRACT
Background:
There is an increased interest in the development and use of topical finasteride for treating androgenic
alopecia (AGA) due to growing evidence of side effects from oral finasteride. In this study we aimed to compare the
treatment outcomes of topical 5% minoxidil with 0.1% finasteride and topical 5% minoxidil with oral 1 mg
finasteride.
Methods:
50 patients of stage III and IV of Hamilton-Norwood scale were randomly assigned to either Group A
receiving topical 5% minoxidil and oral finasteride 1 mg and Group B receiving topical 5% minoxidil and topical
0.1% finasteride. After taking uninterrupted treatment for 12 months, patients were assessed for hair regrowth and
maintenance using global photography and trichoscopy and compared with baseline parameters. Patients in both the
groups were assessed for any adverse effects as well.
Results:
At baseline, patients in both the treatment groups were similar with respect to their age at the time of
presentation, family history of hair loss and Hamilton Norwood scale. In group A, three discontinued treatment and of
the rest 65% maintained a good hair density and reduced hairfall. In group B, five discontinued treatment, of the rest
83% patients demonstrated good improvement in hair density (p<0.05).
Conclusions:
The results of this study strongly support the use of topical finasteride in combination with topical 5%
minoxidil for AGA and this may obviate the need of taking long term oral finasteride.
Keywords: Androgenic alopecia, Finasteride, Minoxidil, Outcomes
Department of Dermatology, Venereology and Leprosy, Muzaffarnagar Medical College and Hospital, CCS
University, Muzaffarnagar, Uttar Pradesh, India
Received: 13 April 2018
Accepted: 15 May 2018
*Correspondence:
Dr. Pragya Khushwaha,
E-mail: dr.pragya28@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20183163

Rai PB et al. Int J Res Dermatol. 2018 Aug;4(3):386-390
International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 387
to dihydrotestosterone (DHT).4 DHT, by binding to the
androgen receptors in the dermal papillae of the hair
follicles, causes miniaturization of follicles, reduced
duration of anagen phase and decreased anagen to telogen
ratio. This presents clinically as decreased hair density.5
Though, oral finasteride is well tolerated, numerous
preclinical and clinical studies have reported significant
sexual adverse effects like decreased libido, erectile
dysfunction, ejaculation disorders, and orgasm disorders
etc.6,7 Given the concerning efficacy and side-effects of
oral finasteride, there is an interest in the development of
a better tolerated topical formulation. Since, hair follicles
widely home in 5α-reductase, topical formulations of
finasteride in comparison to its oral formulations are
expected to potentially reduce its systemic adverse
effects. In this study we aimed to compare the treatment
outcomes of topical 5% minoxidil with 0.1% finasteride
with topical 5% minoxidil with oral 1 mg finasteride.
METHODS
Study design
An interventional, prospective, double blinded
randomized clinical trial.
Participants
Patients in the age group of 18-45 years whose primary
complaint of androgenic alopecia and had stage III and
IV of Hamilton-Norwood scale were included in the
study. The diagnosis of androgenic alopecia was made
based on the history given by the patient and the clinical
examination. All patients taking treatment for androgenic
alopecia from the outpatient Department of Dermatology,
Venerology and Leprosy at Muzaffarnagar Medical
College, Muzaffarnagar (UP) from March 2017 till
March 2018 were included in the study. The patients
were in good general health with no evidence of any
major systemic disease. We excluded patients who were
known to be hypersensitive to minoxidil or finasteride or
were using other therapies for restoring hair or taking any
other systemic medications (like steroids, cytotoxic drugs
etc.). Informed written consent was taken from all the
patients enrolled after explaining study drugs, its benefits
and side effects and further approval from Institutional
Ethical Committee was obtained.
Inclusion criteria
We included patients who were not taking any treatment
from last 3 months; patients of age group 18-45 years;
patients who will give written informed consent; patients
with androgenetic alopecia stage III-IV Hamilton-
Norwood classification in male.
Exclusion criteria
Exclusion criteria were below 18 years and more than 45
years; androgenic alopecia associated with other
dermatological conditions; patients with alopecia other
than androgenetic alopecia.
Interventions
Patients were randomized into two groups. Group A
received topical 5% minoxidil and oral finasteride 1 mg.
Group B received topical 5% minoxidil and topical 0.1%
finasteride. Examined patients were blinded to the type of
treatment being given to the patient. The patients were
assigned to either of the two groups using the random
number method with 1:1 allocation ratio.
Outcomes
Patients in both the groups received treatment for 12
months. Primary endpoint was photographic score at the
end of 12 months from baseline. Standardized digital
photographs of the frontal and parietal region were taken
every three months with the patient’s head in a similar
position to ensure consistency of photography. Secondary
endpoint was trichoscopy examination done by two
doctors blinded to the treatment. Quality of life
assessment was done according to the male androgenetic
alopecia quality-of-life (QoL) Questionnaire.8 Safety
evaluations were done on every visit by asking patients
about any adverse event related to medication. Routine
investigations were ordered as and when required.
Assessment criteria
 Photographic assessment at every visit.
 Trichoscan (measurement of hair density and
diameter).
 Patients overall satisfaction at the end of treatment.
Statistical analysis
Using SPSS version 23 treatment outcomes were
compared using the chi square or Fisher’s exact test. P
value less than 0.05 was considered statistically
significant.
RESULTS
During the study period, 50 men with androgenic
alopecia were enrolled and were allocated to the
treatment arms. The age of the patients ranged from 18 to
45 years, with an average of 29.4±3.62 years. At baseline,
patients in both the treatment groups were similar with
respect to their age at the time of presentation, age when
hair loss began, family history of hair loss and Hamilton
Norwood scale (Table 1). In Group A three patients
discontinued treatment and the remaining 22 patients who
received an uninterrupted treatment, 14 patients’ hair
density was moderately maintained, as shown in Figure 1.
5 patients in Group B discontinued treatment, and of the
remaining patients 20 demonstrated good hair growth and
maintenance. The rate of favourable treatment outcome
was slightly higher in receiving topical finasteride (Group
B) (p value less than 0.05). The findings of digital

Rai PB et al. Int J Res Dermatol. 2018 Aug;4(3):386-390
International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 388
photography and trichoscopy are as shown in Figure 2.
Adverse events encountered in both the groups are shown
in Table 2, most interesting side effects of oral finasteride
in our patients facial edema (3 patients) and dryness of
mouth (5 patients). Mean quality of life was comparable
in both groups at baseline (Table 3) (p=0.72), but it was
significantly higher in patients of Group A as compared
to patients of Group B at final follow up (46.27 vs. 40.53;
p<0.05). At the end of study period, six cases in Group A
and only one patient in Group B were labelled as non-
responders to the treatment (Table 4).
Table 1: Baseline characteristics of the patients
included in the study.
Group A
Group B
Number of patients
25
25
Age at the time of
presentation to hospital
28.5±4.4
29.2±4.9
Age when hair loss began
23.2±5.1
24.6±5.3
Family history of hair loss
18
17
Hamilton Norwood scale
Stage 3
14
12
Stage 4
11
13
Table 2: Side effect of finasteride in patients.
Side effect
Group A
(%)
Group B
(%)
Erectile dysfunction
2 (8)
0 (0)
Ejaculatory dysfunction
2 (8)
0 (0)
Anxiety/depression
4 (16)
0 (0)
Loss of libido
3 (12)
0 (0)
Facial edema
3 (12)
0 (0)
Dryness of mouth
5 (20)
0 (0)
Itching
0 (0)
5 (20)
Erythema (over scalp)
0 (0)
4 (16)
Heaviness
0 (0)
3 (12)
Mood changes
2 (8)
0 (0)
Table 3: Comparison of improvement in quality of life
of patients.
Quality of Life
Group
Mean
SD
P value
Baseline
A
38.60
11.17
0.72
B
34.67
10.02
6 months
A
46.27
13.10
<0.05
B
40.53
12.53
Table 4: Distribution of patients as per response of
treatment.
Response
Group
Total
A (n=22)
B (n=20)
Responders
16
19
35
72.72%
95%
79.54%
Non responders
6
1
7
27.27%
5%
0.7%
Total
22
20
42
P value less than 0.05.
Figure 1: Bar graph comparing the treatment
outcomes in the two groups.
Group A: Topical 5% minoxidil + Oral finasteride 1 mg; Group
B: Topical 5% minoxidil + Topical finasteride 0.1%; P value
using chi square less than 0.05.
Figure 2: Digital photography and trichoscopy
comparing the treatment outcomes in the two groups:
(A) Group A patients, (B) Group B patients.
DISCUSSION
Oral 1 mg finasteride was FDA approved in year 1997 for
androgenetic alopecia of males. Since then no new drug
was introduced except dutasteride this drug has been
approved for the treatment of scalp hair loss in South
65% 83%
35% 17%
0%
20%
40%
60%
80%
100%
120%
Group A Group B
Percentage of patients
Treatment groups
Comaprison of clinical improvement
No clinical
improvement seen
Clinical
improvement seen
B
A

Rai PB et al. Int J Res Dermatol. 2018 Aug;4(3):386-390
International Journal of Research in Dermatology | July-September 2018 | Vol 4 | Issue 3 Page 389
Korea since 2009 and in Japan since 2015.9,10 It has not
been approved for this indication in the United States.
Androgenetic alopecia is more of cosmetic concern rather
than a disease. It has tremendous psychological effect on
young adult males. To maintain better density of hair
over scalp almost lifelong treatment with oral finasteride
is required, though side effects are thought to be very less
with oral medication but still present. Till now various
studies have been done on oral finsteride for its efficiency
and side effects, but few on topical finasteride. Sintov et
al studied the effects of the topical base formulation for
finasteride and flutamide on the growth of human hair in
a murine transplantation model.11 According to them the
effective topical delivery of flutamide and finasteride for
alopecia is feasible, giving similar results to those
obtained with oral finasteride that is with no systemic
side effects as demonstrated by Testosterone/
Dihydrotestosterone monitoring.
Another double blind randomized study done by
Hajheydari et al demonstrated similar effectiveness of 1%
finasteride in increasing total hair content, after 6 months
of treatment, topical finasteride response was better in
2nd, 3rd and 4th months of treatment, but equated that of
oral formulation of finasteride in the 5th and 6th month of
treatment, we have also demonstrated similar results in
our study.12
Study done by Chandrashekar in cases previously treated
with oral finasteride, followed by topical finasteride their
study shows that topical medication alone is beneficial in
maintaining hair growth density as well as improving hair
growth.13 There are two school of thought about sexual
side effects of oral finasteride.
Some studies say that these are as minimal as with
placebo, and according to FDA, there is no clear cause
and effect relationship between finasteride and sexual
adverse events that continued after stopping the drug.
While other state that, for some patients the adverse
effects were manifested in loss of libido, diminished
libido, erectile dysfunction and in some cases
contemplating suicide.14-18
In our study, patient with oral finasteride presented with
erectile dysfunction (2 patients 8%), ejaculatory
dysfunction (2 patients 8%) and loss of libido (3 patients
12%). These side-effects were not present in patients with
topical drug and hair growth was comparable in both the
groups at 6 months. Other interesting side effects
observed in our study were facial edema (in 3 patients)
and dryness of mouth (in 5 patients). Our study also show
that sexual side effects do exist with oral finasteride.
For this IADVL therapeutic guidelines committee also
recommend that in apprehensive patients, lower doses of
finasteride 0.2 mg/day can be started as this dose gives
adequate suppression of DHT in the scalp skin and
serum.19
CONCLUSION
Among different studies there are controversies about
sexual dysfunction associated with oral finasteride.
Sexual side effects either significant or not, they do exist
and vary with patient’s psychological state because of
easy availability of information about everything on
internet and media, patients are more conscious about
side effects of drugs. They should be properly counselled
and informed about the drug, especially younger ones
who are going to marry in near future. Higher therapeutic
efficacy of topical minoxidil and finasteride was
demonstrated as compared to topical monixidil and oral
finasteride for androgenic alopecia.
The results of this study strongly support the use of
topical finasteride in combination with topical minoxidil
especially in younger ones and this may obviate the need
of taking lifelong oral finasteride. Further long term
studies on larger samples at multiple centers are required
to support the results of this study.
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: The study was approved by the
institutional ethics committee
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Cite this article as: Rai PB, Khushwaha P, Jain N,
Gupta S. Comparing the therapeutic efficacy of topical
minoxidil and finasteride with topical minoxidil and
oral finasteride in androgenetic alopecia: a randomized
trial. Int J Res Dermatol 2018;4:386-90.