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184 Original article

The efficacy of topical minoxidil 2% versus topical botanically

derived inhibitors of 5 alpha reductase in treatment of female
pattern hair loss by trichoscopy
Fairouz K. Badran, Rania E. Abd El Maksoud, Mona M. Ibrahim Moawad
Department of Dermatology, Venereology and
Andrology, Faculty of Medicine, University of
Alexandria, Alexandria, Egypt
Correspondence to Mona M. Ibrahim Moawad,
MD, Department of Dermatology, Venereology
and Andrology, Faculty of Medicine, University
of Alexandria, Alexandria, 21613, Egypt.
Tel: +20 122 999 2543;
e-mail: drranyah2002@icloud.com
Received 29 April 2018
Accepted 2 August 2019
Journal of the Egyptian Women's
Dermatologic Society 2019, 16:184–192
Background
Female pattern hair loss (FPHL) is a distressing common problem. Minoxidil is the
only FDA approved medical treatment for FPHL. However, the off-label botanically
derived 5-alpha reductase inhibitors (5αRIs) are commonly used despite insufficient
studies.
Objective
To determine the effectiveness of topical botanically 5αRIs in treating FPHL, by
comparing its results with topical minoxidil 2%.
Patients and methods
This study included 40 females with FPHL. Group 1 received topical minoxidil 2%
and group 2 received topical botanically 5αRIs. Patients were clinically assessed
via Savin scale; to compare between weeks 0 and 36. Change in hair diameter and
count in the target site were trichoscopically assessed at weeks 0, 16, and 36. Side
effects of both drugs were recorded.
Results
Minoxidil was effective in all disease stages, while 5αRIs were effective in early
disease onset and moderate cases. Both drugs produced a significant rise in hair
count and diameter, however; minoxidil had the superiority regarding the mean
increase of hair diameter. Side effects of minoxidil were more troublesome.
Conclusion
Minoxidil is recommended as a first line of therapy for patients with FPHL who want
a treatment with affordable price and could tolerate its side effects. Furthermore, it is
advised to shift to topical botanical 5αRIs as a second line therapy, in cases that
were nontolerant to minoxidil due to its fewer side effects. Likewise, the use of
trichoscopy for therapeutic follow up is strongly recommended.

Keywords:
botanical 5 alpha reductase inhibitors, female pattern hair loss, minoxidil 2%
J Egypt Women’s Dermatol Soc 16:184–192
© 2019 Egyptian Women’s Dermatologic Society | Published by Wolters Kluwer - Medknow
1687-1537

follow up could be aided by trichoscopy which is a

Introduction
noninvasive diagnostic tool [11].
Female pattern hair loss (FPHL) is hair follicle (HF)
miniaturization with characteristic progressive course
FPHL treatment by topical minoxidil 2% solution was
and pattern distribution [1]. FPHL pathophysiology is
approved by the FDA. Its active metabolite, minoxidil
not yet completely understood. The disease is
sulphate opens ATP-sensitive potassium channels in
multifactorial involving genetic, hormonal, and
cell membranes. Perifollicular angiogenesis is enhanced
possibly environmental factors [2]. 5-alpha reductase
by minoxidil by increasing the expression of vascular
enzyme converts testosterone to dihydrotestosterone
endothelial growth factor and hepatocytic growth
[3,4] Dihydrotestosterone is more potent than
factor, the latter being a hair growth promoter. It
testosterone and has greater affinity to androgen
causes prolongation of anagen duration and increase
receptors in HF, resulting in up regulation of genes
in hair count and weight [12]. Moreover, it enhances
of follicular miniaturization [5]. The androgen
hair growth by increasing prostaglandin E2 production
receptor/ectodysplasin A2 receptor locus on the X-
through stimulation of prostaglandin endoperoxide
chromosome has been identified to predispose to
synthase-1 enzyme [13]. It’s among the adverse
FPHL [6]. Furthermore, aromatase gene, micro-
RNAs, and Wnt/b-catenin pathway could also be
incriminated [7–9]. This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
Diagnosis of FPHL is based on the clinical picture, non-commercially, as long as appropriate credit is given and the new
patient’s medical and family history [10]. Therapeutic creations are licensed under the identical terms.

© 2019 Journal of the Egyptian Women's Dermatologic Society | Published by Wolters Kluwer - Medknow DOI: 10.4103/JEWD.JEWD_31_19
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Minoxidil 2% versus topical botanicals in female pattern hair loss Badran et al.
effects of minoxidil are contact dermatitis, facial
hypertrichosis, and temporary increasing hair
shedding [12].
Saw palmetto (Serenoa repens) is a small palm tree
native to the USA. The lipidosterolic extract of
serenoa repens contains 85–90% fatty acids and
phytosterols [14]. It has antiandrogenic mechanism
of action comprises two mechanisms: a direct one
which regards the dihydrotestosterone and
androstenediol cytoplasmic receptors; and an indirect
one which acts through the inhibition of 5-alpha
reductase enzyme types I and II [15,16].
However, the true efficacy of such topical botanical
products has not been sufficiently studied. Therefore,
this study was done to compare their efficacy versus a
‘standard’ approved protocol which is topical
minoxidil 2%.
Patients and methods
The present study included 40 FPHL patients with age
range of 18–52 years. The diagnosis was made on
clinical and trichoscopic basis.
For clinical diagnosis of FPHL, one of the following
different patterns were detected for diagnosis [1]:
(1) Diffuse thinning of the crown area preserving only
the frontal hairline.
(2) Thinning and widening of the central scalp part
with frontal hairline breech (Olsen scale:
Christmas tree pattern).
(3) Thinning accompanied by bitemporal recession
(Hamilton–Norwood type) [1].
Clinically patient staging was done according to Savin
scale [17–19] which is a system of eight computer
generated pictures of hair loss with progressive
severity. The pictures were simply a top view of the
scalp after parting of hair down the midline, in addition
to a special subcategory to detect frontal anterior
recession (Fig. 1) [19].
Stages I-1, I-2, I-3, I-4: demonstrate the hair density in
the female crown area. The first stage (I-1) shows a
woman with a central part in her hair without hair loss.
The part widens in images I-2, I-3, and I-4, denoting
thinning of hair across the top of the scalp and the
crown region as well.
Stages II-1, II-2: show progressively thin hair at the
scalp top as the hair loss advances.
185
Stage III: demonstrates a woman with severe FPHL,
focused at the top of the head as well as the region of
the crown.
Advanced: while seldom observed in clinical practice,
this picture shows a FPHL of a very advanced stage,
with almost no hair left on the top of the head or the
crown.
Frontal: denotes FPHL focused more at the forehead
area than the crown of the head and gradually moves
behind. This pattern is quite rare among women with
hair loss.
All patients were clinically diagnosed at the initial visit
prior to starting treatment. The study is a randomized
comparative double blinded trial where patients were
divided into three strata according to the disease severity
then random allocation by sealed envelope was done to
cases into two disease stage-matched treatment groups.
Group 1: were treated by topical minoxidil 2% spray
(Hair Back plus 2% scalp lotion; Minapharm, Elbardissi
street, taksim Asmaa Fahmy; Ard El Golf; Heliopolis,
Cairo, Egypt); in a dosage of 1 ml twice daily. Group 2:
were treated by topical botanically derived 5-alpha
reductase inhibitors (5αRIs) 9 (Revivogen scalp lotion;
Advanced Skin and Hair Company, 188 No 55, First
New Cairo; Cairo Governorate, Egypt); in a dosage of
1 ml twice daily to the affected area of the scalp for 36
weeks.
Informed written consent was taken from the patients
before the beginning of the study. The study protocol
had been approved by The Research Ethics Committee
of Alexandria. Exclusion criteria were: pregnancy or
lactation, patients who had previous sensitization to
minoxidil or botanically 5αRIs or who used topical or
systemic medications affecting hair growth, or using
cytotoxic drugs, anticonvulsant drugs, anti-thyroid,
tricyclic anti-depressant, anti-coagulant drugs, oral
antiandrogens or oral contraceptives and systemic
retinoids within the past 3 months. Furthermore, a
complete gynecological and obstetrical interrogatory
that included menarche, menstrual cycle hormone
replacement therapy, fertility treatment, problems in
getting pregnant as PCO, gynecological surgery,
pregnancies, births, miscarriages, and signs of
hyperandrogenism (excessive body hair growth, acne,
etc.) was taken to exclude influencing hormonal
dysregulations (e.g. hormone sensitive tumor).
Routine investigations including complete blood
count and serum ferritin were done for each patient
with exclusion of patients with abnormal values, likely
to influence study outcome.
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186 Journal of the Egyptian Women's Dermatologic Society, Vol. 16 No. 3, September-December 2019

Figure 1

Savin scale [19].

Also patients who had previous surgery or trauma with
excessive hemorrhage, severe emotional stress, fever in
the past 3 months, or with concomitant chronic
debilitating disease were excluded.
Skin phototype and the study patients were all veiled
with no difference in hair washing and styling routine.
The disease severity was classified according to Savin
scale [17–19]; patients were examined trichoscopically
using dermatoscope Dermlite DLIII (3Gen Inc. San
Juan Capistrano, California, USA). All cases were
viewed trichoscopically from frontal, vertex, temporal,
and occipital views and they were normal which showed
that all cases were solo androgenic alopecia without any
cases of associated telogen effluvium. Trichoscopic
images of each patient were taken using a Sony cyber-
shot 16.9 megapixel camera (Sony New Zealand
Limited, Ponsonby, Auckland, New Zealand)
mounted on the Dermlite DLIII dermoscope at 10-
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Minoxidil 2% versus topical botanicals in female pattern hair loss Badran et al.
fold magnification. These images were standardized for
light, angle, and position. Grading of the patients to
assess disease severity was done via Savin scale; to
compare between weeks 0 and 36. Two blinded
investigators did the evaluation by comparing between
the photos of weeks 0 and 36. Patients were considered to
have good improvement if they showed upgrading of
their alopecia by two stages, moderate improvement if
they showed upgrading by one stage and no or poor
improvement was used for patients maintaining the same
grade of alopecia or even worsening.
In order to check the same area at the follow up visits, a
fixed point was used as a land mark. The ‘V’ point
(Kang’s point) was used as a land mark. This ‘V’ point
represented the point of intersection between the mid-
sagittal line and the coronal line connecting the tips of
tragus of both ears. A plastic headband was used as a
land mark for this coronal line and a tapeline easily
showed the mid-sagittal line. The ‘V’ point, which was
located roughly 1–1.3 cm in front of the anterior
margin of the headband was measured by the
tapeline. Furthermore, for proper visualization of the
trichoscopic signs, another area was trimmed and
trichoscopic image was taken only at initial visit.
Furthermore, another area was trimmed and
trichoscopic image was taken only at initial visit.
Changes in hair density and hair shaft diameter in the
target site were trichoscopically assessed at weeks 0,
16, and 36. Trichoscopic images of each patient were
analyzed using simple morphometric software
(ImageJ, National Institutes of Health, Bethesda,
Maryland, USA). It analyses the trichoscopic
images interpreting them into terminal hair count
and vellus hair count (as markers of hair density)
and a software-aided count is displayed. This was
done by two blinded investigators. As for the
thickness, it gives the mean hair diameter by
measuring 30 hairs (of different shaft thickness)
cross-sectional, in 75% magnification of the
trichoscopic image. These variables were measured
in a larger surface area of (3 cm2) rather than per
1 cm2.
Statistical analysis
Data entry and analysis was carried out using Statistical
Package for the Social Sciences (version 18; SPSS Inc.,
Chicago, Illinois, USA). Qualitative data was coded
and code checking was carried out to check valid codes.
Data were presented using median, mean, and SD for
quantitative variables. On the other hand, for
qualitative variables frequency and percentage from
total was used.
187
Percent change was then estimated to measure the
increase in terminal hair count, diameter as well as
the decrease in vellus hair count.
For comparing studied variables for each group at
weeks 0, 16 and 36 after treatment, Freidman test
was used. Moreover for comparison between each two
times, Wilcoxon signed ranks test was used.
For comparing studied variables between the groups 1
and 2, χ 2; Fisher’s exact, and Monte-Carlo tests were
used for qualitative variables. For quantitative variables,
Mann–Whitney U test was used.
Spearman’s correlation coefficient was calculated to
estimate linear relationship between the terminal hair
count and duration of hair fall before starting treatment.
All statistical tests results were interpreted at 5% level
of significance.
Results
Clinical data
The minimum age of studied patients was 28 years,
while the maximum age was 52 years. The median age
for group 1 was 40 years (mean, 39.5±5.93 years)
compared to 42.5 years in group 2 (mean, 41.3±6.91
years) and this difference is statistically insignificant
(P=0.26). Also, the minimal disease duration was 3
years in both groups while the maximum was 15 years.
The median disease duration for group 1 was 5.5 years
(mean, 5.9±2.77years) compared to 6 years in group 2
(mean, 6.8±3.81 years), however this difference is
statistically insignificant (P=0.58).
Twelve (60%) patients in group 1 showed good clinical
improvement compared to four (20%) patients in group 2.
Eight (40%) patients in group 1 (minoxidil group)
reported moderate clinical improvement in response to
treatment compared to 12 (60%) patients in group 2
(topical botanically derived inhibitors of 5 alpha
reductase). Four (20%) patients in group 2 versus none
of group 1 patients reported poor improvement. It was
noted that there was statistically significant difference
between the studied groups regarding clinical
improvement in response to treatment (P=0.009)
(Table 1).
Trichoscopic examination
The baseline diagnostic trichoscopic signs were as
follows: anisotrichosis (100%), predominant single-
hair follicular unit (90%), brown peripilar sign (75%),
white peripilar sign (5%), honey comb pigmentation
(25%), yellow dots (25%), and white dots (40%).
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188 Journal of the Egyptian Women's Dermatologic Society, Vol. 16 No. 3, September-December 2019

Table 1 Difference between groups 1 and 2 regarding clinical response

Clinical response Group [n (%)] Monte-Carlo test
Minoxidil 5-alpha reductase inhibitor
Poor 0 4 (20) P=0.009*
Moderate 8 (40) 12 (60)
Good 12 (60) 4 (20)
Total 20 (100) 20(100)
Monte-Carlo test (qualitative variables). *Statistically significant if P value less than 0.05.

Table 2 Percent of change between groups 1 and 2 in trichoscopic hair parameters

Percentage change Group Mann–Whitney U test
Group 1 (N=20) Group 2 (N=20)
Percentage increase in hair diameter
Minimum–maximum (%) 25.53–70.97 2.56–44.19 Z=−3.466
Median (%) 44.23 30.34 P=0.001*
Mean±SD 47.88±15.16 27.01±13.35
Percentage increase in terminal hair
Minimum–maximum (%) 22.07–55.63 −16.3 to 96.82 Z=−0.866
Median (%) 32.12 26.57 P=0.386
Mean±SD 34.56±9.05 37.01±32.42
Percentage decrease in vellus hair diameter
Minimum–maximum (%) 14.63–52.55 13.21–55.86 Z=−1.3
Median (%) 23.35 34.62 P=0.194
Mean±SD 28.07±12.61 34.06±13.76
Mann–Whitney U test (quantitative variables). *Statistically significant if P value less than 0.05

Table 3 Correlation between disease duration and treatment outcome in terms of percent change
Group 1 Group 2
r P r P
Percent increase in diameter 0.068 0.78 −0.51 0.02*
Percent increase in terminal hair count 0.285 0.22 −0.09 0.68
Percent decrease in villous hair count 0.037 0.88 −0.006 0.78
r=Spearman correlation coefficient. Spearman correlation coefficient was calculated to estimate linear relationship between the terminal
hair count and duration of hair fall before starting treatment. *Statistically significant at P value less than or equal to 0.05.

When percent increase in terminal hair count and Side effects

diameter as well as percent decrease in vellus hair
count were compared among the two groups,
significant difference was noted only regarding the
percent increase in hair diameter. The latter was
significantly higher for group 1 compared to group 2
(P=0.02) (Table 2).
When disease duration was studied in relation to
treatment outcome in terms of percent change, a
significant inverse correlation was found in group
2 between percent increase in hair diameter and
disease duration. This signifies that the shorter the
duration the more the increase in hair diameter
(Table 3).
Figures 2 and 3 demonstrate clinical and trichoscopic
pretreatment and posttreatment images of patients of
groups 1 and 2, respectively both of which demonstrated
moderate response to treatment (Figs 2 and 3).
Regarding side effects, 12 (60%) patients of group 1
patients had some adverse effects as regards; scalp
irritation [four (20%) patients], hair dryness [four (20%)
patients], hirsutism [one (10%) patient], and headache
[one (10%) patient]. Alternatively, all group 2 patients had
a completely different range of side effects than group 1.
This means that all patients experienced unpleasant odor
[20 (100%) patients], brown staining of scalp in six (30%)
patients, itching in two (10%) patients, concomitant
brown staining and itching in two (10%) patients.
Discussion
FPHL is a progressive distressing nonscarring HF
miniaturization that occurs in genetically predisposed
women [20].
On comparing the two groups together, there was
statistically significant clinical improvement in group
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Minoxidil 2% versus topical botanicals in female pattern hair loss Badran et al. 189

Figure 2

A case of group 1. (a) Clinical picture at week 0 (stage II 1 by Savin scale). (b) Clinically at week 36 upgraded into stage I4 (moderate response to
minoxidil therapy). (c1) trichoscopic image at week 0 shows anisotrichosis. (c2) trichoscopic image after hair trimming at week 0 shows BPS,
SHFU, YDs, vellus hair, and honeycomb pigmentation. (d) Trichoscopic picture analyzed by imageJ software at week 36; red dots or Ctr 1 refers
to terminal hair count while blue dots or Ctr 2 refers to vellus hair count. (C2) Trichoscopic image after hair trimming shows BPS, SHFU, YDs,
vellus hair, and honeycomb pigmentation. (d) Trichoscopic picture analyzed by imageJ software at week 36; red dots or Ctr 1 refers to terminal
hair count while blue dots or Ctr 2 refers to vellus hair count. Red dots=terminal hair count, blue dots=vellus hair count. BPS, brown peripilar sign;
SHFU, single-hair follicular unit; YD, yellow dot.
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190 Journal of the Egyptian Women's Dermatologic Society, Vol. 16 No. 3, September-December 2019

Figure 3

A case of group 2: (a) Clinical picture at week 0 (stage II 2 by Savin scale). (b) Clinically at week 36 upgraded into stage II 1 (moderate response to
topical 5αRI therapy). (c1) trichoscopic image at week 0 shows anisotrichosis, (c2) trichoscopic image at week 0 after hair trimming shows BPS,
SHFU, YDs, and vellus hair. (d) Trichoscopic picture analyzed by imageJ software at week 36; red dots or Ctr 1 refers to terminal hair count while
blue dots or Ctr 2 refers to vellus hair count. (C2) Trichoscopic image after hair trimming shows honeycomb pigmentation, SHFU, WDs, YDs, and
vellus hair. (d) Trichoscopic picture analyzed by imageJ software at week 36. Red dots=terminal hair count, blue dots=vellus hair count. 5αRI, 5-
alpha reductase inhibitors; BPS, brown peripilar sign; SHFU, single-hair follicular unit; WD, white dot; YD, yellow dot.

1 and this was similar to previous results in the
literature [21–25]. Conversely, there was statistically
insignificant clinical improvement in group 2 when
compared to group 1; this was contrary to the results
reported by previous studies [17,26]. This could be
explained by the use of Savin scale that has a wide
category range of staging with small difference between
them.
Percent increase in terminal hair count and diameter
was noted in group 1. These findings were close to the
results reported by previous studies [21,24,27].
Likewise, group 2 showed percent increase of both
terminal hair count and thickness . However, when
both groups were compared together, significant
difference was noted in favor of group 1 in terms of
percent increase in hair diameter. This could be related
to the mechanisms of action of minoxidil including
increased expression of Vascular endothelial growth
factor mRNA in the DP (which induces angiogenesis
in the DP); activation of cytoprotective prostaglandin
synthase-1 (a cytoprotective enzyme that stimulates
hair growth) and increased expression of HGF m-
RNA (HGF is a hair growth promoter) [12].
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Minoxidil 2% versus topical botanicals in female pattern hair loss Badran et al.
Moreover, it was suggested that hair growth is induced by
increasing the production of PGE2 through stimulation
of prostaglandin endoperoxide synthase-1 [13].
The current study revealed that there was percent
decrease of vellus hair count. However, when both
groups were compared together in terms of difference
in percent decrease of vellus hair count, this difference
was statistically insignificant. This may be explained by
conversion of vellus hair into intermediate and terminal
hair. Moreover, similar results were reported by
Wessagowit et al. [26] after topical application of saw
palmetto. Conversely, Blume-Peytavi et al. [24] reported
an increase of vellus hair after minoxidil treatment but
they did not explain the reason.
There was statistically significant inverse relation
between posttreatment percent-increase in hair
diameter in group 2 patients and between disease
duration. These data suggest that 5αRIs are more
effective in early disease stages only and not in late
ones. Oppositely, no significant correlation was found
between disease duration and clinical response in terms
of percent change in group 1 signifying that minoxidil
is effective in all stages. Similar results were reported in
the literature regarding minoxidil efficacy irrespective
to disease severity [24].
To the best of our knowledge, no standardized
trichoscopic analysis was performed in the literature
comparing the efficacy of topical minoxidil 2% and
botanically derived 5αRIs in treatment of FPHL.
The present study revealed that local scalp irritation,
hair dryness, hirsutism, and headache were reported as
the most frequent side effects in group 1 patients. This
was also proved by previous studies [21,25,28]. No
other adverse effects were reported in this study
precisely, eye irritation, facial edema, or
cardiovascular manifestations which were reported by
Lucky et al [29] and Blume-Peytavi et al [21].
Conclusions
Topical minoxidil 2% is an effective in all disease stages,
well tolerated and relatively cheap line for treatment of
FPHL as well as it is superior to topical botanical 5αRIs
regarding increase of hair thickness, but with more adverse
effect profile. Topical botanical 5αRIs, contrariwise, are
slightly inferior, well tolerated modality with less side
effect profile but more expensive. Trichoscopy is an
effective objective tool for diagnosis and follow up, as
well as it is more accurate tool than other subjective ways
for therapeutic follow up.
191
Longer term studies on large scale and more varied
populations are recommended to draw conclusions and
guidelines on the placement of these modalities.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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