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Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair Transplantation

  • SKINNOCENCE: The Skin Clinic & Research Centre, Gurgaon, INDIA

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Patterned hair loss (PHL) is one of the most commonly encountered problems for dermatologists. PHL at an early age is often cosmetically unacceptable, tends to be persistent and inflicts a profound negative impact on one's quality of life. Androgenetic alopecia (AGA) affects both genders in a distinctive pattern of hair loss from the scalp (MPHL for male PHL and FPHL or female PHL). The etiopathogenesis of AGA is complex, so far the major factor emphasized to be involved has been the undesirable androgen metabolism at the hair follicle level. In this review article, we shall dwell upon the relatively newly understood pathophysiological factors behind the genesis of AGA apart from the hormonal factors like the Wnt/β-catenin pathway, follicular micro-inflammation, prostaglandin imbalance, loss of extracellular matrix and oxidative stress. Based on the sound understanding of these factors we will be elaborating upon therapies for treatment of AGA beyong minoxidil, finasteride and hair transplantation. Amongst the therapeutic options discussed include topical 5alpha reductase (AR) inhibitors like finasteride, oral 5AR inhibitor – dual receptor antagonist dutasteride, botanical 5AR inhibitors, oral anti-androgens and estrogens for FPHL like spiranolactone, drospirenone etc. Wnt/β-catenin activators like topical valproic acid, hair stem cell based therapies, prostaglandin based therapies, tetrapeptides, nutritional and anti-oxidants and many more.
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Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil,
Finasteride and Hair Transplantation
Sidharth Sonthalia1*, Deepashree Daulatabad2 and Antonella Tosti3
1Consultant Dermatologist & Dermatosurgeon SKINNOCENCE: The Skin Clinic & Research Centre, Haryana, India
2Department of Dermatology and STD, University College of Medical Sciences & GTB Hospital, New Delhi, India
3Department of Dermatology and Cutaneous Surgery, University of Miami Hospital, Miami, FL, USA
*Corresponding author: Sidharth Sonthalia, Skinnocence: The Skin Clinic and Research centre, Sushant Lok-1, Gurgaon-122009, Haryana, India, Tel:
+91-124-4014661; E-mail:
Received date: December 19, 2015; Accepted date: January 20, 2016; Published date: January 23, 2016
Copyright: ©2015 Sonthalia S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Patterned hair loss (PHL) is one of the most commonly encountered problems for dermatologists. PHL at an early
age is often cosmetically unacceptable, tends to be persistent and inflicts a profound negative impact on one’s
quality of life. Androgenetic alopecia (AGA) affects both genders in a distinctive pattern of hair loss from the scalp
(MPHL for male PHL and FPHL or female PHL). The etiopathogenesis of AGA is complex, so far the major factor
emphasized to be involved has been the undesirable androgen metabolism at the hair follicle level. In this review
article, we shall dwell upon the relatively newly understood pathophysiological factors behind the genesis of AGA
apart from the hormonal factors like the Wnt/β-catenin pathway, follicular micro-inflammation, prostaglandin
imbalance, loss of extracellular matrix and oxidative stress. Based on the sound understanding of these factors we
will be elaborating upon therapies for treatment of AGA beyong minoxidil, finasteride and hair transplantation.
Amongst the therapeutic options discussed include topical 5alpha reductase (AR) inhibitors like finasteride, oral 5AR
inhibitor – dual receptor antagonist dutasteride, botanical 5AR inhibitors, oral anti-androgens and estrogens for
FPHL like spiranolactone, drospirenone etc. Wnt/β-catenin activators like topical valproic acid, hair stem cell based
therapies, prostaglandin based therapies, tetrapeptides, nutritional and anti-oxidants and many more.
Keywords: Hair restoration; Androgenetic alopecia; Minoxidil;
Finasteride; Hair transplantation
Hair loss not only constitutes one of the most commonly
encountered problems for dermatologists, it inicts a profound
negative impact on one’s quality of life [1, 2]. Advanced patterned hair
loss (PHL), especially at an early age is oen a source of depression in
young adults. Androgenetic alopecia (AGA) aects both genders in a
distinctive pattern of hair loss from the scalp (MPHL for male PHL
and FPHL or female PHL). Bitemporal recession aects 98.6% of men
and 64.4% of women; whereas mid-frontal hair loss aects nearly two
thirds of women and three quarters of men over the age of 80 years [3].
Loss of hair from the vertex is typical of MPHL, encountered in
majority of aected men. e hallmark of the condition is progressive
and gradual miniaturization of hair follicles (HFs), accompanied by
progressive decrease in the duration of anagen and reduction of
anagen to telogen ratio. Additionally in AGA, there is a delay between
the end of the telogen phase and the beginning of the new anagen
phase; a resting phase called kenogen during which the hair follicle
remains empty. e follicular miniaturization in AGA is an
asynchronous phenomenon even within a follicular unit (FU); with
aection of secondary follicles occurring in the initial phase and the
primary follicles in the last [4]. In contrast, the miniaturization process
is synchronous in alopecia areata (AA).
e etiopathogenesis of AGA is complex. e major factor involved
in the pathogenesis of AGA is the undesirable androgen metabolism at
the hair follicle level. Elevated activity of Type II isoform of the 5-alpha
reductase (5AR) enzyme, which metabolizes testicular testosterone
circulating in the blood into dihydrotestosterone (DHT) in the
genetically predisposed hair follicles of the temporal and vertex
regions, is the most signicant factor in MPHL. Decreased aromatase
activity (the enzyme that converts ovarian testosterone circulating in
the blood into 17 beta-estradiol) leading to elevated local
concentration of testosterone seems to be operative in FPHL [5]. Hair
follicles of the temporal and vertex areas of the scalp express androgen
receptors plentifully that bind to the increased local levels of DHT,
resulting in shortening of anagen and progressive miniaturization of
thick, pigmented terminal hair into thinner, non-pigmented vellus-like
hair [6]. Finasteride (FIN), the only United States Federal Drug
administration (FDA) approved oral agent for MPHL is a specic
inhibitor of 5AR, type II isoform. Minoxidil (MNX), the other FDA
approved topical agent (for MPHL as well as FPHL) apparently acts by
increasing follicular vascularity (as a potassium channel opener),
prolonging anagen and shortening telogen, and also by converting
partially miniaturized (intermediate) hair follicles to terminal hair [7].
Hair transplantation, of course remains one of the best and sometimes
the only therapeutic option in advanced AGA.
Essentially there is a four-fold reason to explore new therapies for
AGA. Firstly, the improvement with MNX and/or FIN is limited and
tends to plateau aer one to two years of continuous use. e success
rate of treatment for AGA barely exceeds 30% using either of these
agents; which brings the second reason to the fore, i.e., a high
possibility of other pathophysiologic pathways being involved in this
condition [8]. Indeed, there is now sucient evidence supporting the
role of factors other than hormones contributing signicantly to the
pathogenesis of AGA (
vide infra
). irdly, the sexual adverse eects
(SAEs) of FIN, whether sustained actually or due to the nocebo eect
[9], and the tediousness of twice-daily application of MNX oen
Journal of Cosmetology and
Trichology Sonthalia et al., J Cosmo Trichol 2016, 2:1
Review Article Open Access
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
reduce patient compliance, necessitating the development of novel
therapies. Lastly, despite the advantages of hair transplantation, many
patients who are candidates for the same prefer to avoid undergoing a
‘surgical’ procedure for hair restoration. In this review article, we shall
dwell upon the relatively newly understood pathophysiological factors
behind the genesis of AGA and discuss therapies for treatment of AGA
beyond minoxidil, nasteride and hair transplantation.
New Horizons in the Pathogenesis of AGA
Wnt/β-catenin pathway – A new yspeck in androgen-
mediated pathogenesis:
e relatively recent appreciation of the role of activation of Wnt
signaling for hair growth and wound healing [10] has literally
unleashed an altogether dierent approach to stimulating hair growth.
Hair follicle regeneration begins when signals from the mesenchyme-
derived dermal papilla cells (DPC) reach multipotent epidermal stem
cells in the bulge region [11]. Activation of Wnt/β-catenin signaling in
the epidermis leads to expansion of the stem cell compartment and
skews the keratinocytes in the interfollicular epidermis and sebaceous
glands (SGs) to dierentiate along the HF lineage. e activation of
Wnt signaling, especially Wnt10b is essential for hair follicle
development, hair cycling and hair growth [12,13]. Wnt has been
shown to be the rst trigger that stimulates DPC to induce hair growth
through induction and initiation of hair follicle formation, and
prolongation of anagen [13]. While the initiation of HF regeneration
seems to require only epidermal production of Wnt, the maintenance
and growth of these hair follicles needs subsequent interaction of Wnt
pathways between dermal and epidermal cells [12,14]. Although the
exact molecular mechanisms behind Wnt-induced hair follicular
stimulation to produce hair remain conjectural, activation of the Wnt/
β-catenin pathway seems to be contributory [14-16]. e importance
of the Wnt/β-catenin pathway in AGA is underscored by the recent
demonstration of molecular cross-talk between androgens and the
Wnt signaling in DPC, in patients with AGA. In a co-culture model
with human DPC from patients with AGA and HF stem cells, Leirós et
al.. demonstrated that androgens abrogate hair dierentiation,
evaluated by hair-specic keratin 6 expression [11]. Wnt signaling
activation restored the ability of androgen-treated DPC to induce
dierentiation. Androgen treatment revealed a profound reduction of
the cytoplasmic/total β-catenin protein ratio and upregulation of the
activity of glycogen synthase kinase-3β in DPC, indicative of canonical
Wnt pathway inhibition. us, it is becoming increasingly apparent
that androgens deregulate DPC-secreted factors involved in normal
HF stem cell dierentiation via the inhibition of the canonical Wnt
signaling pathway [11]. us, an understanding of these pathways has
clearly opened a new option of targeted treatments for AGA through
the modulation of the Wnt/β-catenin pathway. is includes drugs like
valproic acid and analogs like lithium chloride and beryllium chloride,
which have been shown to induce hair regeneration in murine model
and promote human hair growth in
culture model; and the
hair stimulating complex, a bioengineered human cell-derived
formulation containing Wnt7a protein that has shown promising
results in Phase I human clinical trials [10, 17-19].
Follicular micro-inammation
Follicular micro-inammation and brosis are being increasingly
recognized to play an important role in AGA, especially in the early
phases. Several studies have reported mild to moderate lympho-
histiocytic inammatory inltrate in the peri-infundibular region of
HF taken from subjects with AGA compared with controls [8]. e
term 'microinammation' has been proposed, to dierentiate the
gradual, subtle, and indolent process occurring in AGA from the
prominent inammation and brosis characteristically seen in classical
cicatricial alopecias. Morphometric studies in patients with MPHL
treated with MNX showed that 55% of those with micro-inammation
had re-growth compared to 77% in those patients without
inammation and brosis [20].
e exact trigger for this follicular micro-inammation remains
speculative. e detection of the perifollicular inltrate in the upper
follicle near the infundibulum of HF in AGA suggests the localization
of potential triggers to the peri-infundibular region; e.g.
sp., or other residential ora of the
follicular infundibulum, antigens of whom may be involved in the
generation of the inammatory response [21]. e role of
keratinocytes and Langerhans cells acting as antigen presenting cells
(APC) and inducing T lymphocyte inltration and proliferation
mediated by various pro-inammatory cytokines has been suggested.
Further, perifollicular brosis (appreciable on cross-sectional scalp
biopsy of scalp with AGA as ‘brotic streamers’) seems to result from
cytokine mediated activation of collagenases, such as matrix
metalloproteinases (MMPs) [8,21], and may end with complete
destruction of the aected follicles in advanced cases. Further support
for the role of micro-inammation in AGA has come from studies that
documented signicantly superior results in improving hair growth
with combinations of MNX with antimicrobials and/or anti-
inammatory agents (like zinc pyrithione, ketoconazole,
hydrocortisone, diclofenac, tea tree oil) compared with use of MNX
alone [22].
Prostaglandin imbalance
e recent discovery by Garza et al. of prostaglandin D2 (PGD2)
and its synthetase (PGD2S) being highly expressed in the scalp of
balding men with AGA, and the temporal relationship of the increased
levels of PGD2 with the initiation of miniaturization of hair follicles in
mice has serious implications for developing targeted interventions for
treating AGA [23]. PGD2 apparently inhibits hair growth by binding
to only one of its two receptors i.e. DP-2, located in the outer root
sheath of the HF [23,24]. e opposing role of prostaglandin E2
(PGE2), a known hair growth promoter was additionally conrmed by
detection of signicantly increased levels of PGE2 in hairy non-balding
scalp. is discovery emphasizes on the role of balance between PGE2
and PGD2 in controlling hair growth, dysregulation of which may be
responsible for hair loss in AGA. Logical extrapolation would favor the
therapeutic role of supplemental PGE2, and inhibitors of PGD2
signaling by DP-2 antagonists such as indole acetic acids, phenyl acetic
acids or tetrahydroquinolines [25,26].
Oxidative stress
Apoptosis of HF cells followed by early onset of the catagen phase
by lipid peroxides that generate free radicals has been demonstrated by
Naito et al. [27]. In the DPC culture study of Bahta et al., balding DPCs
not only demonstrated slower
growth (compared to
nonbalding scalp DPCs) but additionally showed increased nuclear
expression of markers of oxidative stress and DNA damage including
heat shock protein-27, super oxide dismutase, catalase, and
p16(INK4a)/pRB [28]. ese ndings further suggest that DPCs of
androgenetic HFs are more sensitive to environmental oxidative stress.
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 2 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
Indeed, pro-oxidant eects are suggested as the major mediators of
smoking and ultraviolet light induced exacerbation of AGA [21].
Loss of extracellular matrix (ECM)
In recent past, the loss of extracellular matrix (ECM) proteins in the
follicular bed contributing to progressive reduction in the size of the
hair follicle and loss of hair anchoring has gained attention as an
additional pathogenetic factor for AGA [29]. e ECM is the
extracellular part of tissue that usually provides mechanical and
structural support to the follicle cells. An appropriate amount of ECM
proteins, specically collagen type III, laminin and collagen VII is vital
to provide a good anchorage of the hair sha to the bulb [30]. In
addition, the ECM components regulate metabolic functions of the
cells surrounded by the matrix by - promoting anchorage of hair sha
in the HF, and modulating cell growth by binding and retaining
growth factors. Replenishment and re-modeling of these ECM
components by dermal broblasts is thus essential to ensure the
integrity of ECM and strong anchorage of the developing HF with the
bulb. Results from early DPC culture based studies by Randall et al.
have implicated an indirect role of androgens in altering the
production of regulatory substances such as growth factors and/or
ECM components acting via the cells of the dermal papilla, which is
their primary target [31].
In AGA, the naturally occurring tetrapeptide acetyl-N-Ser-Asp-Lys-
Pro (AcSDKP), a potent angiogenic factor has been demonstrated to
not only upregulate the synthesis of epidermal keratins, but also ECM
associated components including collagen III as well as the
glycoaminoglycans (GAGs). In the
ex vivo
-cultured hair follicles,
AcSDKP were found to promote hair sha elongation and induce
morphological and molecular modications culminating into
stimulation of hair growth [32]. Biomimetic peptides such as
acetyltetrapeptide-1 and 3, and their combination with botanical
extracts like
Trifolium pratense
ower extract, or biochanin-A (an
isoavone derived from red clover), enhance hair growth primarily by
stimulation of ECM protein synthesis in the vicinity of the hair follicle
[29]. Figure 1 summarizes salient points regarding these relatively
newer pathophysiological mechanisms implicated in AGA.
Wnt/β-catenin pathway
The activation of Wnt/β-catenin signaling essential for hair follicle development, hair cycling and hair growth
Wnt recently been shown to be the first trigger that stimulates dermal papilla cells (DPC) resulting in induction and initiation of hair follicle formation
Reduction of the cytoplasmic/total β-catenin protein ratio and upregulation of glycogen synthase kinase-3β in DPC – induced by androgens
Activators of Wnt/β-catenin signaling stimulate hair follicle (HF) formation in androgenetic alopecia (AGA)
Follicular microinflammation
Follicular microinflammation recognized to play pathogenetic role in early phases of AGA.
Mild to moderate lymphohistiocytic inflammatory infiltrate reported in the peri-infundibular region of HF of subjects with AGA, compared with controls
Potential triggers of follicular microinlammation – suspected to be localized to the peri-infundibular region; antigens of Propionobacterium sp., Malassezia sp., or other
residential flora may be involved in generating the inflammatory response.
Keratinocytes and Langerhans cells may be acting as antigen presenting cells (APC), inducing T lymphocyte infiltration and proliferation via pro-inflammatory
Perifollicular fibrosis contemplated to occur in later stages, plausibly a result of activation of collagenases, especially matrix metalloproteinases (MMPs); may lead to
complete destruction of HFs
Prostaglandin Imbalance
Increased expression of prostaglandin D2 (PGD2) and its synthetase (PGD2S) reported in scalp of men with AGA.
Increasing levels of PGD2 temporally related with initiation of miniaturization of HFs
PGD2 inhibits hair growth via DP-2 receptors located in the outer root sheath of the HF.
Prostaglandin E2 (PGE2) has a reverse effect and has hair growth promoting effects.
Imbalance of the levels (PGD2 > PGE2) seem to contribute to hair loss in AGA.
Oxidative Stress
Compared to non-balding scalp DPCs, the balding DPCs not only demonstrated slower in-vitro growth but aalso showed increased nuclear expression of markers of
oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase, catalase, and p16(INK4a)/pRB.
Pro-oxidant effects by free radical are suspected to be the major mediators of smoking and ultraviolet light induced exacerbation of AGA.
Figure 1: Insights from the recently understood pathogenesis of AGA.
Newer Drugs for Hair Growth (Other than Topical MNX and
Oral FIN)
Topical minoxidil and nasteride (5α reductase type II inhibitor) are
the only FDA approved treatments for MPHL. Both agents arrest
progression of hair loss and stimulate partial hair regrowth. Several
other drugs are also used o-label and a plethora of novel treatments
with partially substantiated hair growth claims are making inroads in
trichologists’ prescriptions. us, the knowledge of these alternative
drugs, their mechanism, dose protocol and adverse eects is exigent
for today’s practicing dermato-trichologist. Figure 2 summaries salient
points regarding major pathogenetic mechanisms.
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 3 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
Figure 2: Schematically outlines of the major pathogenetic mechanisms involved in AGA and important treatment options targeting the same.
Hormone Antagonists and Hormone Response
Topical 5AR inhibition
e use of anti-androgens in a topical formulation has always been
an attractive proposition, since it is expected to deliver some ecacy of
the oral drug, with minimal risk of systemic adverse eects. In a
randomized single center, open-label, parallel-group, exploratory study
conducted in 24 healthy men with AGA subjects received either
multiple scalp applications of the topical solution of FIN (0.25%)
twice-a-day or oral FIN 1 mg once-a-day for 7 days. A strong and
comparable inhibition of plasma DHT was observed in both the
groups, but the serum levels of nasteride were signicantly lower with
the topical application group [33]. e investigators, however did not
measure the scalp DHT levels. In a retrospective assessment of 50 male
patients aged 20-40 years with AGA, who had initially been treated
with topical MNX and oral FIN for a period of two years, and aer
which the oral FIN was replaced with combination of topical 5% MNX
fortied with 0.1% FIN, 84.44% maintained a good hair density
with topical combination therapy. us, topical nasteride can be
considered for hair density maintenance aer initial improvement with
oral nasteride, thereby obviating the indenite use of oral nasteride
Oral 5AR inhibition – Dual receptor antagonist dutasteride
In contrast with FIN, dutasteride, is a dual 5AR inhibitor and is
approximately 3 times more potent than FIN at inhibiting type II 5AR
and almost 100 times more potent at inhibiting type I isoenzyme [35].
e eect of dutasteride is dose dependent. A phase II randomized
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 4 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
placebo-controlled study of dutasteride versus nasteride showed
superiority of 2.5 mg of dutasteride over 5 mg nasteride in improving
scalp hair growth in men aged 21-45 years.[36]. e onset of hair
growth was also earlier in the dutasteride group. Improvement of hair
loss with dutasteride 0.5 mg has also been demonstrated in a lady who
failed to show any response to nasteride [37]. It has been safely
administered in women with FPHL in doses of 0.15mg per day for
three years [38]. Side eects including decreased libido, impotence and
gynecomastia are slightly higher with dutasteride than with FIN [36].
In addition, the nocebo eect, described for FIN [9] is also likely to be
encountered with dutasteride in the more educated and internet-savvy
patients. e long serum half-life of 4 weeks of dutasteride results in
persistent suppression of DHT level even aer dutasteride is ceased.
us, patients taking dutasteride should not donate blood until at least
6 months aer stopping their medication [36]. Currently, dutasteride
0.5mg dose is FDA approved for the treatment of benign prostatic
hyperplasia while its use in MPHL and FPHL remains “o-label”. It is
worth trying in patients with advanced PHL and when FIN delivers
Botanical 5AR inhibitors
Owing to the SAEs associated with FIN and dutasteride, extracts of
herbs with 5AR inhibitory eect have been explored as an alternative.
Saw palmetto berry (SPB) extract derived from the berry of the
American dwarf tree (
Serenoa repens, Sabal serrulata
) is the most
popular phytotherapeutic agent used in the treatment of AGA as well
as benign prostatic hypertrophy (BPH). e extracts from the ripe
berries of saw palmetto contain various phytosterols (e.g. β-sitosterol),
fatty acids, β-carotene and polysaccharides. SPB is being promoted as
the ‘herbal side-eect-free version of nasteride) for the treatment of
AGA. SPB acts as a multi-site inhibitor-cum-blocker of DHT [39]. It
blocks approximately 50% of the binding of DHT to ARs in the target
cells. It also blocks the nuclear uptake of DHT in target cells, and
strongly inhibits the action of the enzyme 5AR thereby reducing the
conversion of testosterone to DHT. Additionally, saw palmetto
increases activity of the 3α-hydroxysteroid-dehydrogenase, the enzyme
responsible for the metabolism of DHT into androstanediol, a weaker
While the principle molecules responsible for the aforesaid actions
of saw palmetto are phytosterols, their activity is enhanced in their
conjugated state with fatty acids. ß-sitosterol has been suggested to
result in local reduction of testosterone (the substrate for formation of
DHT) in the microenvironment of 5AR active tissues such as the
prostate and the hair follicle. us, the pharmacodynamics of saw
palmetto dier from that of FIN in the following ways 1) dual inhibitor
of both isoforms of 5AR 2) competitive as well as non-competitive
inhibition of the enzyme, and 3) multi-site eect, in addition to 5AR
inhibition. In terms of side-eects, multiple trials on BPH have
consistently shown SPB to be free of the SAEs typical of FIN and
dutasteride [40]. In a placebo-controlled, double-blind study
conducted in 26 healthy men aged 23-64 years with mild to moderate
AGA, subjects were randomly assigned to receive the active oral sogel
(consisting of saw palmetto extract 200 mg and ß-sitosterol 50 mg as
the major ingredients, with additional components to increase the
bioavailability such as lecithin, inositol, phosphatidylcholine, niacin,
and biotin) or a matching placebo; one sogel twice daily in both the
groups for 21 weeks duration. Out of the 26 subjects, 19 completed the
study. Treatment ecacy at the nal visit as per the investigative sta
assessment of change in the patient’s scalp hair growth from baseline
(‘improved’) was reported to be 60% vs 11% in the study group vs
placebo group respectively [41]. e adverse eects in the study group
were mild and transient. ough botanical 5AR inhibitors lack the
SAEs of FIN, their ecacy in improving hair growth in AGA is inferior
to their synthetic counterparts. is has been revealed in a 2-yr long
open label study of 100 male patients with AGA, in which the hair
growth score was higher in the group that received FIN 1 mg every
day, compared to the group that received
Serenoa repens
320 mg daily
for the same period. Moreover, the eect of
Serenoa repens
over the
front area was inferior to that of FIN [42]. us, larger and gender-
specic trials with better dened ecacy end points are needed to
discern the role of saw palmetto as a treatment option for AGA.
Oral anti-androgens and estrogens for FPHL
Androgen-dependent oral drugs for FPHL include 5AR inhibitors
and anti-androgens. Owing to their propensity to cause feminization
of the male fetus, they are contra-indicated in pregnant women. Use of
these drugs in combination with oral contraceptive pills (OCPs) oers
two advantages. Not only do they provide eective contraception to
prevent teratogenic eects of anti-androgens in a woman of
reproductive age group, the estrogen component of the pill has
additional hair growth stimulatory eects. It has been suggested that
estrogens act both directly (by prolonging the anagen phase acting via
follicular estrogen receptors) and indirectly (by increasing sex
hormone binding globulin (SHBG) production, which reduces
androgen levels by binding to them) [7,43]. Cyproterone acetate (CPA)
blocks androgen receptors and inhibits gonadotropin-releasing
hormone (GnRH). In many countries including India, it is available in
combination with estradiol as an OCP [44]. e benecial role of CPA
seems to be greater in patients with evidence of hyperandrogenism. In
two studies, combination therapy of CPA with estradiol resulted in
signicant decrease in shedding and thinning of hair in patients with
FPHL [45,46]. Spironolactone, another anti-androgen oen used for
treating hirsutism and acne, has also been found to be comparably
ecacious to CPA in a trial involving 80 FPHL patients [46]. e dose
used was 200 mg daily. Drospirenone, a 17α spironolactone derivative
possesses progestagenic, anti-androgenetic, and antialdosteronic
activities, but is devoid of uid retention property. Administered in a
dose of 3 mg/day in combination with 30 µg of ethinylestradiol during
a 21-day cycle, it has become a favoured pill for women with PCOS
and is expected to have benecial eects in FPHL [7]. Flutamide, a
selective anti-androgen has found to be eective in FPHL when given
for at least a year in dose of 250 mg/day [47]. Two randomized studies
reported greater improvements with utamide than spironolactone,
FIN, and CPA [46,48]. Unfortunately, the adverse eects of this drug,
especially dose-related severe hepatic dysfunction (seen in upto
3/10,000 patients) make it an unpopular choice for many trichologists.
Wnt/β-catenin Activation
Topical valproic acid
Valproic acid (VPA), a widely used antiepileptic, is known to
activate the Wnt/β-catenin pathway, which is associated
with hair growth cycle and anagen induction [17,18]. Aer initial
encouraging results from murine-model based studies, a recent
randomized, double-blind, placebo-controlled clinical trial was
conducted in 40 men with AGA of which 27 completed the trial.
Patients with moderate AGA received either VPA (8.3%) or placebo
spray for 24 weeks. Phototrichogram analysis was employed to evaluate
the primary end-point for ecacy, i.e., change in hair count during
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 5 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
treatment. e mean change in total hair count was signicantly
higher in the VPA group than in the placebo group [49]. Adverse
eects were mild and self-limited.
Hair stimulating complex (HSC)
Hair stimulating complex (HSC) is a bioengineered human cell-
derived formulation containing Wnt7a protein, epidermal growth
factors and follistatin, manufactured from naturally secreted growth
factors, proteins and other synergistic bioproducts that are derived
from culture of newborn cells grown in an oxygen-decient embryonic
environment. In phase I trial, intradermal application of 0.1 cc of HSC
resulted in signicantly increased hair sha thickness, hair density and
number of total terminal hair without any signicant adverse eects,
compared with placebo at 12 weeks [19]. Interestingly, the eect was
maintained aer 1 year of treatment at the HSC-treated sites. Phase II
trials are ongoing to gather more evidence in favour of HSC as a viable
therapeutic modality for PHL.
Stem cell-based therapies
Cross-species injection of antlerogenic stem cells in rabbits has
demonstrated increased number in hair follicles in the treated sites.
Moreover, these xenogenous stem cells induced an insignicant
immune response when compared with vehicle alone [50]. is
breakthrough, despite the need for substantiation with more studies,
has raised the possibility of using puried animal stem cells to promote
hair growth in humans [10]. Attempts to generate a follicular germ by
combining stem cells and dermal papillae followed by scalp
implantation of the germ have also proved fruitful with growth of a
viable hair follicle that was able to repeat the hair cycle, mingle with
the surrounding tissues and achieve piloerection [51]. ese results
invigorate the possibility of creating a functional hair follicle from
follicular stem cells, i.e., bioengineering hair for transplant. Trials are
ongoing to evaluate the possibility of creating new hair follicles by
injecting autologous dermal and/or epidermal cells.
Prostaglandin-Based erapies
Prostaglandin and prostamide analogues
Although drugs that block PGD2 signaling or enhance PGE2 are
under trial for evaluation of their ecacy and safety in AGA, other
prostaglandins also have therapeutic eects. e prostaglandin F2α
analogue latanoprost, and prostamide F2α analogue bimatoprost,
commonly used in treating glaucoma were serendipitously discovered
to be promoters of hair growth of eyelashes and eyebrows. ey result
in hair growth through modulatory action on the dermal papilla that
results in induction of the anagen phase in telogen hair follicles.
Bimatoprost is the only FDA-approved topical for hypotrichosis of the
eyelashes [52]. In anecdotal reports and few studies, these analogues
have resulted in modest hair regrowth in alopecia areata, involving the
eyebrows and eyelashes. ey are also used for cosmetic enhancement
of eyelashes. However, the use of these agents in PHL lacks robust
evidence. Following encouraging results from animal model-based
studies, a randomized comparison study that evaluated the use of
topical latanoprost 0.1% versus placebo (solutions applied daily to two
minizones of the scalp) in 16 men with Hamilton II–III patterned
alopecia revealed a signicant increase in hair density of both terminal
and vellus hair on the latanoprost-treated site at 24 weeks, compared to
baseline and to the placebo-treated site [53]. Fiy percent were dened
as having a “good clinical response” (treatment better than placebo in
at least two of the study criteria). Adverse events were limited to
folliculitis, erythema, and burning sensation on application. In
contrast, scalp injections of bimatoprost 0.03% weekly for 12 weeks
and then biweekly for 4 weeks attempted in a 59-year-old female with
FPHL failed to improve the condition [54]. us, it is premature to
comment on the ecacy of this group of drugs in PHL at present.
Direct Stimulation of Stem Cells and Dpcs
Marine protein supplements
Oral marine protein supplements (MPS) have been used for more
than 15 years as nutritional enhancers of hair growth in AGA. Viviscal®
(Hair Nourishment System; Lifes2good, Inc., Chicago, Illinois),
originally marketed under the brand name Hairgain® [Parexel Medstat
AS, Lillestrøm, Norway]) contains AminoMar C™ marine complex as
its most active principle, a proprietary blend of shark and mollusk
powder [55,56] Additional contents include an organic form of silica
derived from
sp. (horsetail), vitamin C derived from
Malpighia emarginata
(acerola cherry), microcrystalline cellulose
(E460), natural orange avor, magnesium stearate, hypromellose, and
glycerol [56]. Several studies, including randomized, controlled trials
have demonstrated the ecacy of Viviscal in the treatment of AGA in
men [55,57,58]. Signicant improvements, in terms of the physician-
assessed terminal hair counts as well as patient-perceived benets in
hair volume, scalp coverage, and thickness of hair shas have also been
reported in multiple double-blind, placebo-controlled studies
evaluating the ecacy of Viviscal supplement (given orally twice-a-day
for 3 months to 6 months) in women with self-perceived thinning hair
[56,59,60]. No AEs were reported in any study. Shell sh allergy is a
contraindication for this neutraceutical. e mechanism of Viviscal
seems to be the enhancement of proliferation of DPCs. It has been
postulated that Viviscal increases the alkaline phosphatase levels, a key
marker of anagen phase of the hair cycle, in DPCs [59]. Summarizing
from the above results, Viviscal may be an eective treatment option
both alone as well as a part of
a comprehensive hair restoration plan
e.g. in combination with MNX and/or FIN.
Platelet rich plasma
Platelet-rich plasma (PRP), an autologous preparation of plasma
with >1,000,000/μL platelets is gaining popularity across the globe as
an adjuvant treatment for PHL and to circumvent or delay the need for
hair transplantation. e platelet related growth factors (such as
platelet-derived growth factor (PDGF), transforming growth factor
(TGF), vascular endothelial growth factor (VEGF), broblast growth
factor (FGF), epidermal growth factor (EGF), and insulin-like growth
factor (IGF-1)) improve hair growth by multiple mechanisms -
stimulation of the bulge stem cells and dermal broblasts, proliferation
of dermal papilla cells, prolongation of anagen, and delaying the
progression into catagen [61]. ere are many important factors that
determine the ultimate ecacy of the therapy – e.g., the anti-coagulant
used in the collection tubes, centrifuge machine parameters (rotation
speed and total time), single-spin or double-spin method, manual
preparation or use of commercially available kits, temperature control,
addition of platelet activators etc. And more studies are warranted to
crystallize these concepts. e only adverse eect with PRP is the
procedure related pain and temporary scalp swelling. It should be
performed under topical anesthesia. Use of locoregional scalp blocks
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 6 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
are an alternate option to make the procedure painless, but needs
In a prospective cohort study that enrolled 18 males and 2 females
with PHL, PRP prepared by single-spin method in Regenlab SA kit was
injected in the androgen-related areas of scalp [62]. ree treatment
sessions, once-every-3-weeks and a booster session at 6 months were
delivered. At 3 months, reduction of hair loss was signicant and
hair density reached a peak at 3 months Improvement continued till
one year of the last treatment. Patients were satised with a mean
result rating of 7.1 on a scale of 1-10. In a recent randomized,
evaluator-blinded, placebo-controlled, half-head group study
compared hair regrowth with PRP versus placebo with the aid of
computerized trichograms. PRP, prepared from a small volume of
blood, was injected on half of the selected patients' scalps with PHL.
e other half was treated with placebo. ree treatments administered
at 30-day intervals protocol could be analyzed for 20 patients. Patients
were followed for 2 years. Of the 23 patients were enrolled, 3 were
excluded. At the end of the 3 treatment cycles, a signicant
improvement in the mean number of hair (mean increase of 33.6 hair
in the target area) and a mean increase in total hair density (of 45.9
hair per cm2) was observed compared with baseline values [63]. No
side eects were noted. In long term follow up, out of 20 patients, 4
(20%) reported progressive hair loss, which was more evident 16
months aer the last treatment. However, one must be aware of the
ner art of preparing and injecting PRP to optimize patient outcomes.
Readers are advised to refer to the article by Dhurat and Sukesh for
further reading on this aspect [64].
Microneedling involves the use of a microneedle-tipped instrument,
most commonly a dermaroller or a dermapen, available in models with
dierent or adjustable needle depths (usually ranging from 0.2-3.0
mm). Traditionally used for facial acne scars, facial rejuvenation, open
pores and striae (owing to its collagen stimulation and remodeling
eects), microneedling has recently been shown to enhance expression
of hair-related genes and stimulation of hair in mice by Jeong et al. and
Kim et al., [65,66]. A randomized evaluator blinded trial by Dhurat et
al. evaluated the eect of microneedling in 100 patients with MPHL
(grade III vertex or IV), with the Microneedling Group oered weekly
microneedling sessions along with twice daily 5% MNX lotion, and the
other group given only 5% MNX lotion twice daily. Dermaroller-MNX
treated group was statistically superior to MNX-alone treated group in
promoting hair growth in men with AGA for all 3 primary ecacy
measures of hair growth, including the mean change in hair count at
week 12 (91.4 vs 22.2 respectively), investigator evaluated visual
analogue scale scoring, and percentage of patients reporting more than
50% improvement (82% vs 4.5%) [67]. e hair re-growth induced by
microneedling is thought to result from the controlled wounding
induced by the dermaroller and the postulated mechanisms include -
release of growth factors like PDGF and EGF, direct activation of stem
cells in the hair bulge area, and increased expression of hair growth
related genes including β-catenin, Wnt3a, and Wnt10 b [65-67].
Stimulation of ECM components
e naturally occurring tetrapeptide AcSDKP, a potent angiogenic
factor was recently shown to stimulate the growth of human
keratinocytes, broblasts and follicle DPC. In the study by Hajem et al.,
topical treatment of
ex vivo
cultured skin explants with 10 M AcSDKP
not only increased the thickness of the epidermis and upregulated
keratin synthesis, it also stimulated production of ECM components
including bronectin, collagen III and IV, as well as the
glycoaminoglycans (GAGs) [32]. In the
ex vivo
-cultured hair follicles,
AcSDKP promoted hair sha elongation and induced morphological
and molecular modications, suggestive of hair growth induction. In a
randomized placebo-controlled study by Loing et al. conducted in 30
volunteers with early AGA, daily application of a cosmetic active
ingredient prepared by combining
Trifolium pratense
ower extract
and a biomimetic peptide for 4 months yielded a signicant increase in
anagen hair count (+13%), and the anagen/telogen (A/T) ratio (+46%)
over baseline, compared to application of placebo [29]. e postulated
mechanisms for hair growth stimulation include stimulation of ECM
protein synthesis, inhibition of 5 AR activity, and reduction of
follicular micro-inammation.
Diguanosine tetraphosphate (GP4G)
In the study by Severino et al., the eects of GpG formulation, a
liposomic solution of
Artemia salina
extract, on hair follicle structures
were evaluated. A 50% increase in hair length and a 30% increase in
the number of DPC were observed [68]. e mechanism seemed to be
an increase in skin blood vessels and broblast activation modied
collagen arrangement in dermal tissues. At the molecular level, cellular
activation induced by GpG evidenced by a 38% increase in the
intracellular ATP concentration and increases in the intracellular
concentration of tri- , di- , and monophosphate nucleosides, in two cell
culture lines - Hela and broblast cells. us GpG promises to be a
novel option worth further exploration for hair regrowth in AGA.
Nutritional and antioxidant therapy
In the past decade an increasing number of reports have provided
support for nutraceuticals as eective and safe treatment options for
hair loss in general. Furthermore, there seems to be a growing trend
towards supplementation compared with prescription or over-the-
counter (OTC) medications. Isolated reports have evaluated the
inuence of various dietary supplements such as millet extracts, biotin,
pantothenic acid and other B-complex vitamins, minerals like zinc and
iron, omega-3 and omega-6 fatty acids, and anti-oxidants like lycopene
in hair loss of various origins with variable results. However, the
studies have seldom focused on their ecacy in AGA.
Biotin, an essential vitamin is involved in vital physiological
functions like fatty acid synthesis, amino acid catabolism, and
gluconeogenesis. Additionally, it functions as a coenzyme for
mitochondrial carboxylases in hair roots. Absorption of biotin requires
the release of biotin from foods and biotin-containing peptides,
aected by the biotinidase (BTD) enzyme. An adequate intake (AI) of
30 µg/day has been suggested for adults. Genetic biotinidase
deciency, results in hair loss, in addition to a variety of systemic
symptoms such as seizures, mental retardation, dermatitis, and
aciduria, amongst others [69]. Important causes of acquired biotin
deciency include anticonvulsant therapy (especially valproate),
intestinal malabsorption and excessive alcohol consumption. Alopecia
is a common adverse eect of valproic acid, the pathogenesis of which
remains controversial. While earlier studies implicated reduced activity
of BTD leading to biotin deciency as the cause of valproate-induced
hair loss, newer studies have refuted this theory [70,71]. Irrespective of
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 7 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
the eect of valproic acid on serum biotin levels or BTD activity,
reversal of alopecia has been reported in few patients who were on
valproic acid therapy, with oral biotin (10 mg/day) administration.
[71,72]. Although robust evidence favouring the role of oral biotin in
arresting hair loss or stimulating regrowth is lacking, it remains one of
the most prescribed nutritional supplement for any kind of hair loss.
Biotin is also a frequent component of hair mesotherapy solutions.
However, there is a clear paucity of any evidence based on robust
research favoring the role of biotin in treatment of AGA.
e relation between zinc deciency and hair growth has been a
subject of debate for the past three decades. Zinc is a known potent
inhibitor of hair follicle regression, and also accelerates hair follicle
recovery [73]. Although, there have been arguments refuting the
relationship between zinc and hair loss [74], frank zinc deciency or at
least levels lower than control groups have indeed been documented in
almost all forms of non-cicatricial alopecia. Although, alopecia areata
(AA) and telogen euvium (TE) have been documented to be more
associated with low zinc levels [75,76], in a recent study, zinc levels
lower than the control group have also been documented in AGA [77].
In this case control study by Kil et al. that included 312 patients with
AA, MPHL, FPHL and TE, in each category of hair loss, the serum
zinc concentration was signicantly lower than that of the control
group. is included 161 patients of AGA (84 with MPHL and 77 with
FPHL). Expectedly, the ratio of the patients with serum zinc
concentration lower than the cut-o of 70 μg/dL was signicantly high
only in the AA group [77]. Zinc is also known to have some 5AR
inhibitory activity [78]. In conclusion, it is not surprising that zinc-
containing supplements have become a routine prescription by
trichologists for AGA patients as well.
Omega 3 fatty acids and antioxidants
In a recent randomized, comparative study conducted in 120
otherwise healthy female subjects with FPHL, compared to placebo, a
nutritional supplement containing omega 3 & 6 acids and antioxidants
given for 6-months resulted in statistically signicant and superior
improvement in hair growth parameters including photograph
assessment, reduction in telogen hair percentage, and increment in
non-vellus anagen hair [79]. Subjective evaluation by the women in the
supplemented group mirrored the objective results with reduction in
hair loss reported by 89.9%, improvement in hair diameter by 86.1%
and hair density by 87.3%.
Dietary supplements are popular over-the-counter products used
for hair loss by patients themselves. ese supplements contain
combinations of amino acids like L-cystine, L-lysine, L-methionine,
vitamins like biotin, calcium pantothenate and thiamine, minerals like
iron and zinc, and other substances such as Brewers yeast, in dierent
proportions. Oral supplementation with l-cystine, pantothenic acid,
thiamine nitrate, and medicinal yeast has been shown to increase the
anagen rate in apparently healthy women with telogen euvium in a
placebo-controlled study [80]. But none of these nutreceuticals have
been tested for ecacy in AGA patients. Since their general
mechanism of action seems to be induction of anagen, the use of these
multivitamin-mineral-antioxidant cocktail tablets/capsules has been
extrapolated as an adjuvant therapy in patients with AGA as well,
despite lack of evidence of ecacy in this particular type of alopecia.
Other Potential erapies for AGA
Ocinalis plant extracts – Enhancing microvascular supply
of DPC
e physiological activity of the pilosebaceous unit is linked to its
local microcirculatory system [81]. e anagen phase is accompanied
by angiogenesis. A recently launched commercial hair serum
containing extracts from 9
Carthamus tinctorius
Prunus persica
Zingiber ocinalis, Panax ginseng
Salvia ocinalis
Cuscuta epithimum
Carum petroselinum
Angelica archangelica
Capsicum annuum
has been suggested to be a hair growth stimulator
for TE, AA as well as AGA. e primary mechanism of action seems to
be an increase in the dermal papillary blood ow and nutrients supply,
with additional antioxidant and hydrating eects [81,82]. In the study
conducted by Gori et al. in 46 subjects with AGA (40 males, 6 females),
treated with the hair serum containing ocinalis plant extracts, once-
a-day for 3 months, 25 (54%) showed clinical signs of hair follicle
reactivation (anagen phase), with an initial or an appreciable regrowth
of terminal hair [82]. e local tolerance and cosmetic acceptance was
rated good by the users.
Caeine is evolving as a promising candidate
for hair growth stimulation. It possesses two activities of relevance for
hair growth – Indirect, via 5AR inhibition and direct, by stimulation of
hair growth parameters. Employing the hair organ culture model
wherein hair follicles from the vertex area of male AGA patients were
cultivated, Fischer et al. demonstrated that caeine in concentrations
of 0.001% and 0.005% not only counteracted the testosterone-induced
hair follicle growth suppression, but also induced signicant follicular
growth independently [83]. In their next study published recently,
Fischer et al. elaborated on caeine’s
eect at the cytokine
level in hair follicles cultivated from both men and women with AGA.
Caeine enhanced hair sha elongation, prolonged anagen duration
and stimulated hair matrix keratinocyte proliferation, with better
responses observed in female HFs [84]. Protein expression of TGF-β2
was reduced and IGF-1 increased in the matrix cells as well as outer
root sheath (ORS) keratinocytes in the HFs of both genders. With
discovery of such growth-promoting eects of caeine on human HFs,
the molecule has already found its way as a component of multi-
ingredient shampoos as well as some OTC as well as prescription hair
growth enhancing solutions.
Melatonin, the hormone secreted by the pineal gland is known to
have potent antioxidant activity. It acts as a direct radical scavenger
[21]. Melatonin’s eects on cell growth regulation have been shown in
human keratinocytes [85]. e antioxidative eects of melatonin have
been found to prevent UV-induced erythema in healthy humans,
prevent cell death of UVR irradiated leukocytes and have been
postulated to be instrumental in counteracting the detrimental eects
of environmental stressors on the aging-related parameters of skin and
hair [86,87]. Extensive research work by Fischer et al. has revealed
startling facts about the high potential of melatonin as a hair growth
agent. Human hair follicles have been shown to synthesize melatonin
and express melatonin receptors [88,89]. Human anagen hair follicles
in vitro in a culture medium with
a melatonin concentration
of 30 μM resulted in a signicantly faster rate of hair follicle growth
compared to the culture medium alone. [90]. Currently, MEL receptors
have been identied primarily in the root sheath of the hair, and have
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 8 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
been postulated to aect hair growth via receptor-mediated inuence
over the hair root sheaths. e hair growth eect of MEL may also
involve interaction with androgens and estrogens and their receptors,
as evidenced by the eects of MEL on inhibiting prostate enlargement.
Antiandrogenic eects of MEL on hair follicles include prolongation of
the hair cycle and decreased miniaturization.
It seems to be a promising candidate for halting hair loss and induce
growth in general hair loss as well as AGA, owing to its anti-oxidative
and antiandrogenic properties. Topically applied cosmetic hair
solution with 0.0033% melatonin content has been explored in many
studies to evaluate its ecacy in AGA in both the genders. In a detailed
analysis of ve clinical studies of MEL on hair loss, Fischer et al.
observed positive eects of topical MEL solution in the treatment of
AGA with good tolerability [91]. ese studies included both men and
women with early-stage AGA as well as generalized hair loss.
Signicant reduction in the percentage of patients with a 2- to 3-fold
positive hair-pull test, reduction of the overall severity of alopecia and
signicant increases in hair density were observed in these studies. e
duration of MEL application ranged from 3-6 months and ecacy
assessment was done by dierent methods in dierent studies
including questionnaires completed by investigators and patients, hair-
pull test, and digital soware-supported epiluminescence technique
(TrichoScan) treatment for AGA. Pharmacodynamics under once-
daily topical application in the evening showed no signicant inuence
on endogenous serum melatonin levels.
Topical roxithromycin
Roxithromycin, a macrolide antibiotic has recently been explored
for AGA based on its properties of inhibition of apoptosis of
keratinocytes (via suppressing the production of oxygen reactive
species) and suppression of the AR in human dermal broblasts
[92,93], with around 58% of the 13 men with AGA developing increase
in hair sha thickness, with no side eects following 6 months use of
3-5 mL of a 5% roxithromycin solution daily compared to the control
group in a randomized double-blinded trial [94].
Low-level laser/light therapy (LLLT)
Since the discovery of hypertrichosis as a possible paradoxical side-
eect of laser or light-based treatments for hair reduction in 2002 with
intense pulsed light therapy, this phenomenon has been estimated to
occur in 0.6% to 10% of patients treated with all laser types,
particularly when low uences are used [95,96]. e suboptimal
uencies, although too mild to induce thermolysis, are high enough to
stimulate follicular growth. e hypothesized mechanisms of action of
LLLT are increased adenosine tri-phosphate (ATP) production,
modulation of reactive oxygen species (ROS), and induction of
transcription factors. Cytochrome-c oxidase (COX) has been proposed
to be the cellular chromophore, with absorption peaks in the near
infrared light [97]. A complex biochemical process ensues following
the light-chromophore interaction leading to release of NO, which
further results in cellular proliferation, increased tissue oxygenation,
and modulation in the levels of cytokines and growth factors.
Devices based on the principle of LLLT include laser combs (e.g.,
the US-FDA approved HairMax Laser Comb®, available in three
models with 7, 9 and 12 diode-beams per comb) and machines with
helmet-like laser hoods. In a company-sponsored study of 110 male
patients, treatment with the HairMax Laser Comb® apparently resulted
in signicant increase in mean terminal hair density when compared
to a sham device [98]. Based on the favorable outcome of LLLT on hair
growth in an independent blinded study with seven patients, and
anecdotal experiences, a consensus paper by hair loss experts
suggested that while LLLT employing 650-900 nm wavelengths at 5
mW may be an eective and safe treatment option for patients with
AGA, more controlled, peer-reviewed studies validating current
devices were necessary [99-101]. In a 24-week, randomized, double-
blind, sham-device-controlled trial, Kim
et al.,
reported an increase of
hair density with the use of LLLT [102]. In a retrospective
observational study of 32 patients (21 female, 11 male) with AGA,
treated with the 655 nm-HairMax Laser Comb®, signicant
improvement was observed in 8, showed signicant, moderate
improvement in 20, and no improvement in 4, with no adverse
reactions reported in any patient [97]. Improvement was observed as
early as 3 months and was sustained up to a maximum observation
time of 24 months. Combination of LLLT with MNX and/or FIN was
suggested to have a synergistic eect in enhancing hair growth. In
another recent multicentric, randomized, sham device-controlled,
double-blind clinical trial that analyzed the ecacy of lasercomb in
103 male and 122 female subjects, whole scalp treatments were given
with a laser comb (trial groups) or sham device three times a week for
26 weeks. e mean terminal hair count of the target area at 26 weeks
in the lasercomb-treated subjects increased signicantly from baseline
(ranging from 18.4 to 25.7 per cm2), compared with minimal increase
noted in sham-treated subjects [103]. However, additional studies to
determine the long-term eects of LLLT on hair growth and to
Stem cell based treatment
Cell mediated treatments for AGA broadly include two main
approaches: the direct injection of cultured stem cells (SC) or the use
of cell secreted hair growth enhancing humoral factors. e premise of
cell-based treatment for AGA is that even till advanced stages of AGA,
the stem cell population is preserved, suggesting potential reversibility
of the condition [104]. e study of the HF stem cells (HFSCs) started
with the identication of epidermal SC in the HF bulge as quiescent
"label retaining cells". e research of these cells emerged rapidly aer
the identication of bulge cell molecular markers, such as keratin 15
and CD34 in mice and CD200 in humans, which allowed the isolation
and characterization of bulge cells from follicles [105]. Dermal Papillae
is a unique population of mesenchymal cells that regulates formation
of HF as well as the growth cycle. Although, DP cells were proposed as
the cell-based treatment for hair loss conditions like AGA,
unfortunately human DP cells are not suitable for this purpose because
they cannot be obtained in necessary amounts and rapidly lose their
ability to induce HF formation when cultured. During development
most DP cells are derived from mesoderm, however, functionally
equivalent DP cells of cephalic hair originate from neural crest (NC).
In the landmark study of Gnedeva et al., human embryonic stem cells
(hESCs) were directed to generate NC cells and then hair-inducing
DP-like cells in culture. ese hESC-derived DP-like cells (hESC-DPs)
express markers typically found in adult human DP cells and are able
to induce hair follicle formation when transplanted under the skin of
immunodecient nude mice [106]. e development of hESC-DPs
seemingly heralds a major breakthrough towards a cell-based
treatment for AGA and other hair loss disorders. Human hair follicle-
derived mesenchymal stem cells (HF-MSCs) are also capable of
dierentiating along multiple lineages. Addition of EGF and FGF to
the culture media enhance cellular pluripotency. Other cell lines
including epidermal keratinocytes, dermal broblasts and adipocytes
Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
Page 9 of 13
J Cosmo Trichol
ISSN:JCTT , an Open Access Journal Volume 2 • Issue 1 • 1000105
have also been explored for cell-based treatment of hair loss. Recently,
skin derived progenitor cells (SKPs) have been expanded
in vitro
the dermis and share certain characteristics of DP cells. SKPs are
highly plastic even aer long-term expansion
in vitro
and can
dierentiate into multiple lineages. SKPs are also able to induce HF
formation and they can be an ample source of inductive dermal cells
for HF regeneration [107]. Adipose tissue-derived stem cells (ADSCs)
and conditioned media of ADSCs (ADSC-CM) are reported to
promote hair growth
in vitro
. In a recent retrospective, observational
study of 27 patients with FPHL treated with ADSC-CM, application of
ADSC-CM showed ecacy in treating FPHL aer 12 weeks of therapy
[108]. ere was a signicant increase in hair density as well as
hair thickness, with no severe adverse reactions. e search for more
robust sources of generating a pool of human HF is ongoing and
hopefully, stem-cell based therapies shall occupy a prominent position
in the therapeutic armamentarium of AGA.
Future potential treatments that may be eective in AGA include:
Nitric oxide (NO) gel, which has been shown to promote hair
follicle formation through stem cell development, hair regeneration,
hair sha elongation and increased growth rate in rats and mice [10].
Vitamin D3: e Vitamin D receptor (VDR) is expressed in hair
follicle keratinocytes during late anagen and catagen. Additionally,
Vitamin D3 has also been shown to modulate Wnt10b gene expression
[109]. Studies based on VD3 gene knock-out and VD3
supplementation in nude mice has revealed encouraging hair growth
promoting eects of VD3 [10].
Nestin and noggin: Studies carried on patients with alopecia areata
showed that middle anagen and early anagen hair follicles with
growing cells were found to be nestin positive, suggesting a role of
nestin-positive in the regenerating hair follicles. Noggin is an inhibitor
of the bone morphogenetic protein-4 (BMP4), which physiologically
induces selective arrest of anagen development in the secondary hair
follicles [110]. Experimentally, the administration of noggin protein
was found to induce new hair growth phase in postnatal telogen skin
in vivo
e exact pathogenesis of AGA remains elusive and seems to
involve multiple players acting at dierent levels and stages. e
understanding of newer pathogenetic mechanisms contributing to
progressive miniaturization of hair in AGA such as the androgen-
mediated suppression of Wnt/β-catenin pathway, follicular
microinammation, perifollicular paracrine prostaglandin imbalance,
and oxidative stress have enhanced the possibility of development of
targeted therapies manifold. With MNX and FIN remaining the only
two US-FDA approved treatments for AGA that oen do not produce
desirable results, quest for such therapies and new avenues like hair
follicle bioengineering was logical. Hopefully, with improved
elucidation of molecular mechanisms underlying follicular
miniaturization, development of more ecacious treatment options
would ensue.
Conict of Interest:
Dr Antonella Tosti has in the past received honoraria as consultant
from the following companies-Incyte, Khytera, P and G, DS
Laboratories, Inneov Laboratories, Polichem.
Dr Sidharth Sonthalia has in the past received honoraria as
consultant from the following companies- Sun Pharmaceuticals, Cipla
Externa, H and H pharmaceuticals and Glenmark. He is also on the
medical advisory board of the South Asian Pigmentary Disorder
Forum (SPF) of GALDERMA.
However, none of the nancial associations of Dr Tosti or Dr
Sonthalia had in any way been an inuence on the contents of the
manuscript being submitted.
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Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
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Citation: Sonthalia S, Daulatabad D, Tosti A (2016) Hair Restoration in Androgenetic Alopecia: Looking Beyond Minoxidil, Finasteride and Hair
Transplantation. J Cosmo Trichol 2: 105. doi:10.4172/jctt1000105
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... 57 Finasteride has level 1 evidence for efficacy to prevent progression and improve hair loss in MPHL. 1,4,19,20,32,54,[56][57][58][59] Studies have revealed that the hair count and weight start show increase by approximately 6 months and the improvement continues at least for up to 5 years. 20,57 Treatment started earlier in the course of hair loss always responds better (►Figs. ...
... 1,4,20 Furthermore, change in the microbiome of the hair follicle, causing microinflammation in the perifollicular region, is thought to be one of the factors implicated in PHL. 1,59 Use of ketoconazole with its antifungal properties and antiinflammatory properties of zinc pyrithione has worked well in conjunction with topical minoxidil. 59 A few noncontrolled studies have shown benefits in MPHL as well as in FPHL with androgen excess. ...
... 59 A few noncontrolled studies have shown benefits in MPHL as well as in FPHL with androgen excess. 1,4,20,59 Saw Palmetto (Serenoa repens) Saw palmetto (SP), a botanical extract from the berries of Serenoa repens, is one among the many naturally occurring SRD5A inhibitors which has gained popularity as a magical remedy for MPHL. 59,109,110 Very few studies of efficacy of SP in PHL exist and most of the data on SP is from studies of its use in BPH. ...
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Pattern hair loss (PHL) is a condition that worsens with time and the only way it can be slowed down is with pharmacological intervention. Pharmacological treatments for PHL, from an evidenced-based perspective with respect to safety and efficacy, are limited to only two drugs, minoxidil and finasteride. However, there are a host of drugs being used, off-label with limited evidence. This article attempts to review the literature on this topic, and the authors add to this, with their experience of over two decades on incorporating pharmacologic treatments along with hair transplantation in their management of PHL.
... eir omnipresence and diverse functionality imply that any structural distortion or imbalance in the production and degradation of proteoglycans may lead to disorder. Typical examples are mucopolysaccharidosis, tumorigenesis, atherosclerotic plaque formation [4], osteoarthritis [5], and hair growth disorders [6]. e current review aims to present an up-to-date account on the roles of specific proteoglycans in the life cycle of the hair follicle and discuss their relevance to the pathophysiology of different types of hair loss. ...
... As stated earlier, proteoglycans form a specialised milieu around fibroblasts that regulates and governs almost all of the autocrine and paracrine signals being sent to the epithelial precursor cells; hence, their disrupted metabolism, especially within the DP, will affect the normal cycling behaviour of the hair follicle. It hence appears that a certain relative concentration of follicular proteoglycans is necessary for sustaining a normal anagen 6 Dermatology Research and Practice duration and preventing immature initiation of catagen. Evidence implies that even the slightest alteration in the concentration or composition of follicular proteoglycans can cause disproportionately large functional effects [23]. is can be observed at the end of anagen, when a shrinkage in the proteoglycan-rich, papillary ECM is the first morphological sign of catagen initiation [80]. ...
... Premature senescence of DP cells in PHL [83] may also contribute to this phenomenon. e newly recognised pathophysiological role of FHG and the ability of targeted treatments to address it have recently been outlined in an informative review by Sonthalia et al. [6]. Of note is that FHG in PHL has particularly been evidenced using versican as an archetypal bioactive proteoglycan. ...
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Follicular proteoglycans are key players with structural, functional, and regulatory roles in the growth and cycling behaviour of the hair follicles. The expression pattern of specific proteoglycans is strongly correlated with follicular phase transitions, which further affirms their functional involvement. Research shows that bioactive proteoglycans, e.g., versican and decorin, can actively trigger follicular phase shift by their anagen-inducing, anagen-maintaining, and immunoregulatory properties. This emerging insight has led to the recognition of “dysregulated proteoglycan metabolism” as a plausible causal or mediating pathology in hair growth disorders in both men and women. In support of this, declined expression of proteoglycans has been reported in cases of anagen shortening and follicular miniaturisation. To facilitate scientific communication, we propose designating this pathology “follicular hypoglycania (FHG),” which results from an impaired ability of follicular cells to replenish and maintain a minimum relative concentration of key proteoglycans during anagen. Lasting FHG may advance to structural decay, called proteoglycan follicular atrophy (PFA). This process is suggested to be an integral pathogenetic factor in pattern hair loss (PHL) and telogen effluvium (TE). To address FHG and PFA, a proteoglycan replacement therapy (PRT) program using oral administration of a marine-derived extract (Nourkrin® with Marilex®, produced by Pharma Medico Aps, Aarhus, Denmark) containing specific proteoglycans has been developed. In clinical studies, this treatment significantly reduced hair fall, promoted hair growth, and improved quality of life in patients with male- and female-pattern hair loss. Accordingly, PRT (using Nourkrin® with Marilex®) can be recommended as an add-on treatment or monotherapy in patients with PHL and TE.
... Hair shaft extension is sustained by highly proliferating cells of the hair matrix (HMs). These differentiate into several cell lineages, (among these cells of the outer (ORS) and inner (IRS) root sheaths) all differently specialized in the production and modification of hair keratins [1][2][3][4]. ...
... Patients affected by glaucoma and receiving PGF2α analogues, claimed side effects such as cutaneous hypertrichosis and hyperpigmentation of eyelashes [32]. PGF2α analogues latanoprost and bimatoprost are being tested in clinical trials for Patterned Hair Loss and Androgenic Alopecia and are showing promising results [4,31]. ...
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Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens. Nutraceuticals, on the contrary, have been shown to be safe and effective treatment options for hair loss. We here show that polyphenols from Malus Pumila Miller cv Annurca are endowed with hair growth promoting activity and can be considered a safe alternative to avoid CIA. In vitro, Annurca Apple Polyphenolic Extract (AAE) protects murine Hair Follicles (HF) from taxanes induced dystrophy. Moreover, in virtue of its mechanism of action, AAE is herein proven to be compatible with chemotherapy regimens. AAE forces HFs to produce ATP using mitochondrial β-oxidation, reducing Pentose Phosphate Pathway (PPP) rate and nucleotides production. As consequence, DNA replication and mitosis are not stimulated, while a pool of free amino acids usually involved in catabolic reactions are spared for keratin production. Moreover, measuring the effect exerted on Poly Unsaturated Fatty Acid (PUFA) metabolism, we prove that AAE promotes hair-growth by increasing the intracellular levels of Prostaglandins F2α (PGF2α) and by hijacking PUFA catabolites toward β-oxidation.
... 9,10 Nonscarring alopecia is classified into several types including androgenic alopecia (AGA), hair loss due to hormonal disorders, which is the most common type of alopecia that impacts both genders simultaneously and is caused by overproduction of dihydrotestosterone (DHT). 11 Hair loss may occur due to autoimmune disorders, namely, alopecia areata, alopecia totalis, and alopecia universal, depending on the affected body and scalp areas. 12 Hair loss also may occur due to stress, namely, telogen effluvium, 13 or it may occur from hair follicle trauma, namely, traction alopecia, which is common among children and young adults. ...
Alopecia or hair loss is a widespread issue that has significant effects on personal well-being for both genders nationally and internationally. In addition, alopecia causes extreme emotional stress and negatively impacts the psychological health and self-esteem of cancer patients suffering from chemotherapy-induced alopecia. Unfortunately, available synthetic medications are costly, invasive, or have extreme adverse effects. On the contrary, natural and herbal hair loss products are widely available in the local and international markets in variable pharmaceutical forms with different mechanisms of action, namely, androgen antagonists, nutritional supplements, vasodilators, and 5α-reductase inhibitors or dihydrotestosterone blockers. Thus, it is of great importance to encourage researchers to investigate these natural alternatives that can act as potent therapeutic agents having diverse mechanisms of action as well as limited side effects. Currently, natural remedies are considered a fast-rising pharmaceutical segment with demand from a wide range of consumers. In this study, we present a review of reported herbal remedies and herb combinations recommended for hair loss and their mode of action, along with an overview of available market products and formulations, their composition, and declared effects. In addition, a general outline of the different forms of alopecia, its causes, and recommended treatments are mentioned as well. This was all done with the aim of assisting further studies with developing standardized natural formulations for alopecia as many were found to lack standardization of their bioactive ingredients and efficiency confirmation.
... Besides, HFs are complex mini-organs undergoing cycles of anagen (growth), catagen (degeneration) and telogen (rest) 5 . A variety of genes and pathways are involved in the pathogenesis of AGA, including Wnt/β-catenin, immune and inflammatory responses, Janus-554 K Yang, et al activated kinase, sonic hedgehog, etc [5][6][7] . Among them, Wnt/ β catenin signalling pathway, which is specially important for the hair cycle and hair growth, has been shown to be negatively influenced by the increased androgen in AGA patients 8 . ...
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Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light. Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion: The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.
... Recently, peptides, which are short chains made up of amino acids, have been introduced to the market as topical and oral cosmetics in both contexts, i.e., hair health (15) and dermal rejuvenation (16). The efficacy of peptides in promotion of cellular turnover is conceded to be an adaptive response to 'signs' of tissue damage. ...
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One of the side‐effects of oral anti‐aging retinoids is increased hair shedding. Retinoids promote the expression of TGF‐β2 from fibroblasts, which stimulate collagen expression but silences keratinocytes. Since keratinocytes normally influence differentiation of dermal papilla cells at the base of the hair follicle, retinoids feasibly inhibit hair growth via the increased expression of TGF‐β2, which inhibits Wnt/β‐catenin signalling. Fortunately, the plant kingdom provides an array of alternatives as dual‐acting nutricosmetics and topicals that work independently of TGF‐β2 to confer dermal anti‐aging and hair health effects. These alternatives include ‘plant hormones’ such as cytokinins and phytoestrogens. Many cytokinins are agonists of the G‐coupled adenosine receptors. Partial agonism of adenosine receptors promotes collagen synthesis independently of TGF‐β2 signalling. Adenosine expression is potentially also the mechanism of minoxidil in promotion of scalp hair growth. Because of crosstalk between adenosine and cannabinoid receptors it makes sense to try combinations of specific CB2 agonists and cytokinins (or phytoestrogens). However, dual‐acting cosmetics including peptides with high numbers of positively charged amino acids, such as lysine or arginine, offer real potential as they can be processed from multiple botanical candidates, including almond, fenugreek, pea sprouts, soy, and seaweeds. The current review summarises much of what is known about retinoid alternatives in the plant kingdom and identifies potentially fruitful new areas of research.
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Androgenetic alopecia (AGA) is an exceedingly common condition that affects both men and women. It represents one of the commonest reasons that patients consult dermatologists. Ideally, early diagnosis and intervention are essential in management of AGA. The management of AGA is challenging and the choice of treatment depends on factors such as efficacy, risks and costs. Treatment modalities include medical or surgical management. Early intervention with topical and oral medications is important. The Validating minOxIdil by dermatologists ConsEnsus (VOICE) II is a survey conducted amongst Indian dermatologists to understand the various treatment modalities chosen for their patients suffering from hair loss with respect to different clinical grades and to determine their perceived patients’ expectations regarding treatment in terms of time taken to observe results.In this article, we evaluate such data including the different strengths of topical minoxidil recommended as monotherapy, on the following parameters: clinical diagnosis of the patient; grade of alopecia (MPHL/FPHL) and the treatment expectation of patients in terms of time taken to observe visible results.
Background: Monofilament thread therapy (PLLA) and minoxidil have been used as alternative treatments for female androgenetic alopecia. Aim: The aim was to determine the efficacy and safety of thread therapy combined with minoxidil in female androgenetic alopecia. Patient and methods: Twenty-seven women were enrolled in this randomized half-split study based on a left-head to the right-head pattern. Thread therapy (PLLA) treatment was unilaterally performed (once); minoxidil was bilaterally applied for 6 months. Global photographs and dermoscopy assessments were performed in the baseline and every 2 months till the end of treatment. Global photographs underwent blinded review by three independent dermatologists. Results: Mean hair density increased from 114 ± 27 to 143 ± 25/cm2 (P < .001) in the combined group and from 113 ± 24 to 123 ± 19/cm2 in the minoxidil group (P < .001). The mean change from baseline between the two groups was also compared (P = .003). Global photographs showed improvement in 93% (25/27) patients in the combined group and 52% (14/27) patients in the minoxidil group. Conclusion: Poly-l-lactic acid microthread therapy combined with minoxidil may improve hair density, hair thickness, and hair appearance better than minoxidil alone.
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More than 4 fibroadenomas in a single breast are uncommon. Repeated recurrences of supernumerary fibroadenomas, in multiple numbers, after excision, are extremely rare. The malignant potential of breast fibroadenoma increases significantly in women with complex fibroadenomas, proliferative disease or a family history of breast cancer. Such a condition poses a management dilemma to the surgeon. Prophylactic bilateral mastectomy is controversial, and requires a rigorous assessment of risk benefit ratio and a better assessment of psychosocial impact and ethical issues. More often than not, the patient prefers repeat excision and close surveillance as the most agreeable course of action; the relatively higher risk of malignancy notwithstanding. Repeated excision as new fibroadenomas appear seems to be a feasible option.
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Significance: Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, the results of a randomized, placebo-controlled, half-head group study to compare the hair regrowth with PRP versus placebo are reported. Hair regrowth was quantified by a blinded evaluator using computerized trichograms. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area and a mean increase in total hair density of 45.9 hairs per cm(2) compared with baseline values. No side effects were noted during treatment. The data clearly highlight the positive effects of PRP injections on male pattern hair loss and absence of major side effects.
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Human hair growth is cyclical but asynchronous. Women normally shed 50-150 hairs over a 24 hour period [1]. Most shedding goes unnoticed. Women who complain of excessive hair shedding, especially after washing their hair may have either an increase in the actual amount of hair falling or an increased awareness of their hair fall. Changes in actual amount of hair fall occur in anagen effluvium, acute and chronic telogen effluvium, alopecia areata, cicatricial alopecia and female pattern hair loss (FPHL) [1]. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of 'permanent cure' and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients' right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.
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An oral marine protein supplement (MPS) is designed to promote hair growth in women with temporary thinning hair (Viviscal Extra Strength; Lifes2good, Inc., Chicago, IL). This double-blind, placebo-controlled study assessed the ability of MPS to promote terminal hair growth in adult women with self-perceived thinning hair associated with poor diet, stress, hormonal influences, or abnormal menstrual cycles. Adult women with thinning hair were randomized to receive MPS (N = 30) or placebo (N = 30) twice daily for 90 days. Digital images were obtained from a 4 cm(2) area scalp target area. Each subject's hair was washed and shed hairs were collected and counted. After 90 days, these measures were repeated and subjects completed Quality of Life and Self-Assessment Questionnaires. MPS-treated subjects achieved a significant increase in the number of terminal hairs within the target area (P < 0.0001) which was significantly greater than placebo (P < 0.0001). MPS use also resulted in significantly less hair shedding (P = 0.002) and higher total Self-Assessment (P = 0.006) and Quality of Life Questionnaires scores (P = 0.035). There were no reported adverse events. MPS promotes hair growth and decreases hair loss in women suffering from temporary thinning hair. This trial is registered with Identifier: NCT02297360.
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The utility of platelet-rich plasma (PRP) has spanned various fields of dermatology from chronic ulcer management to trichology and aesthetics, due to its role in wound healing. Though PRP is being used over a long time, there is still confusion over proper terminology to define, classify and describe the different variations of platelet concentrates. There is also a wide variation in the reported protocols for standardization and preparation of PRP, in addition to lack of accurate characterization of the tested products in most articles on the topic. Additionally, the high cost of commercially available PRP kits, precludes its use over a larger population. In this article, we review the principles and preparation methods of PRP based on available literature and place our perspective in standardizing a safe, simple protocol that can be followed to obtain an optimal consistent platelet yield.
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Platelet-rich plasma (PRP) is defined as an autologous concentration of plasma with a greater count of platelets than that of whole blood. Its action depends on the released growth factors from platelets. It has been investigated and used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss. To evaluate the efficacy and safety of PRP injections in the scalp of patients with androgenetic alopecia. Prospective cohort study. 20 patients, 18 males and 2 females, with androgenetic alopecia were enrolled in the study. PRP was prepared using a single spin method (Regenlab SA). Upon activation, it was injected in the androgen-related areas of scalp. Three treatment sessions were performed with an interval of 21 days and a booster session at 6 months following the onset of therapy. Statistical analysis of the data was performed using the Statistical Package for the Social Sciences (SPSS), version 19.0 (IBM, NY, USA). Hair loss reduced and at 3 months it reached normal levels. Hair density reached a peak at 3 months (170.70 ± 37.81, P < 0.001). At 6 months and at 1 year, it was significantly increased, 156.25 ± 37.75 (P < 0.001) and 153.70 ± 39.92 (P < 0.001) respectively, comparing to baseline. Patients were satisfied with a mean result rating of 7.1 on a scale of 1-10. No remarkable adverse effects were noted. Our data suggest that PRP injections may have a positive therapeutic effect on male and female pattern hair loss without remarkable major side effects. Further studies are needed to confirm its efficacy.
The formation of the hair follicle and its cyclical growth, quiescence, and regeneration depend on reciprocal signaling between its epidermal and dermal components. The dermal organizing center, the dermal papilla (DP), regulates development of the epidermal follicle and is dependent on signals from the epidermis for its development and maintenance. GFP specifically expressed in DP cells of a transgenic mouse was used to purify this population and study the signals required to maintain it. We demonstrate that specific Wnts, but not Sonic hedgehog (Shh), maintain anagen-phase gene expression in vitro and hair inductive activity in a skin reconstitution assay.
Alopecia and thinning hair are highly prevalent conditions affecting a large proportion of men and women. Diffused hair loss is often more difficult to diagnose in women, mostly due to over-reliance on the assumption of hormonal influences, and it is commonly treated with a multi-therapy approach. Clinical studies have demonstrated the effectiveness of a nutraceutical supplement to provide essential nutrients that aid in stimulating existing hair growth and reducing hair shedding. The supplement Viviscal® contains a proprietary blend of proteins, lipids, and glycosaminoglycans derived from sustainable marine sources. We present here a summary of studies that have examined the safety and efficacy of this nutraceutical; as well as discussions on hair loss and current therapies from a recently convened expert panel in dermatology and plastic surgery. J Drugs Dermatol. 2015;14(suppl 9):s15-s22.
Female pattern hair loss (FPHL) is a common disorder but presents severe psychosocial problems in many female patients. Adipose tissue-derived stem cells (ADSCs) and conditioned media of ADSCs (ADSC-CM) are reported to promote hair growth in vitro. However, there are no clinical reports on the treatment of alopecia using ADSC-CM. This study evaluates our clinical experience in the use of ADSC-CM for the treatment of FPHL. A retrospective, observational study of outcomes in 27 patients with FPHL treated with ADSC-CM was performed. To evaluate the efficacy of the treatment, patients' medical records and phototrichographic images were analyzed. The application of ADSC-CM showed efficacy in treating FPHL after 12 weeks of therapy. Hair density increased from 105.4 to 122.7 hairs/cm(2) (P < 0.001). Hair thickness increased from 57.5 μm to 64.0 μm (P < 0.001). None of the patients reported severe adverse reactions. The application of ADSC-CM is a potential treatment option for FPHL. © 2015 The International Society of Dermatology.