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Dermatol Ther (Heidelb) (2022) 12:41–60

https://doi.org/10.1007/s13555-021-00653-2

REVIEW

Microneedling and Its Use in Hair Loss Disorders:


A Systematic Review
Robert S. English Jr. . Sophia Ruiz . Pedro DoAmaral

Received: November 8, 2021 / Published online: December 1, 2021


Ó The Author(s) 2021

ABSTRACT investigations totaling 911 androgenic alopecia


(AGA) subjects, MN improved hair parameters
Introduction: Microneedling (MN) is a mini- when paired with 5% minoxidil, growth factor
mally invasive procedure involving the induc- solutions, and/or platelet-rich plasma (PRP)
tion of percutaneous wounds with medical- topicals, or when introduced to subjects whose
grade needles. In this literature review, we hair count changes had plateaued
investigate clinical data on MN for the treat- for C 6 months on other treatments. Across
ment of hair loss disorders. four investigations on 201 alopecia areata (AA)
Methods: A literature search was conducted subjects, MN improved hair parameters as a
through PubMed up to November 2021 to standalone therapy versus cryotherapy, as an
identify original articles evaluating the use of adjunct to 5-aminolevulinic acid and photody-
MN on hair loss disorders. The database was namic therapy, and equivalently when paired
searched using the following keywords: ‘‘mi- with topical PRP versus carbon dioxide laser
croneedling,’’ ‘‘micro needling,’’ ‘‘micro needle,’’ therapy with topical PRP. Across 657 subjects
‘‘microneedle,’’ ‘‘needle,’’ ‘‘dermaroller’’ and receiving MN, no serious adverse events were
‘‘alopecia,’’ ‘‘hair loss,’’ ‘‘alopecia,’’ ‘‘areata,’’ ‘‘ci- reported.
catricial,’’ or ‘‘effluvium.’’ Conclusions: Clinical studies demonstrate
Results: A total of 22 clinical studies featuring generally favorable results for MN as an adjunct
1127 subjects met our criteria for inclusion. therapy for AGA and AA. However, data are of
Jadad scores ranged from 1 to 3, with a mean of relatively low quality. Significant heterogeneity
2. As an adjunct therapy, MN improved hair exists across interventions, comparators, and
parameters across genders and a range of hair MN procedures. Large-scale randomized con-
loss types, severities, needling devices, needling trolled trials are recommended to discern the
depths of 0.50–2.50 mm, and session frequen- effects of MN as a standalone and adjunct
cies from once weekly to monthly. Across 17 therapy, determine best practices, and establish
long-term safety.
Supplementary Information The online version
contains supplementary material available at https:// Keywords: Microneedling; Alopecia; Hair loss
doi.org/10.1007/s13555-021-00653-2.

R. S. English Jr. (&)  S. Ruiz  P. DoAmaral


Perfect Hair Health, 2021 Fillmore, Ste 98, San
Francisco, CA 94115, USA
e-mail: rob@perfecthairhealth.com
42 Dermatol Ther (Heidelb) (2022) 12:41–60

rates high [4]. Consequently, there remains


Key Summary Points demand for novel and effective hair loss
treatments.
Why carry out this study? Microneedling (MN) is a minimally invasive
procedure involving the induction of percuta-
There is growing interest in the use of neous wounds with 0.25–5.00 mm medical-
microneedling as a standalone and grade needles. First described by Orentreich in
adjunct therapy for hair loss disorders. 1995 for the use of wrinkles and atrophic scars,
This literature reviews summarizes a body MN purportedly releases platelet-derived
of clinical evidence on microneedling for growth factor and vascular endothelial growth
hair loss disorders to evaluate hair loss factor to promote wound-healing responses,
outcomes, evidence quality, limitations in improve angiogenesis, and attenuate or par-
research, and areas of opportunity for tially reverse fibrosis resulting from acute injury
future investigations. and skin aging [5, 6]. MN can be administered
at-home or in-clinic, with devices ranging from
What was learned from the study? needling stamps, manual rollers, and auto-
Microneedling improves hair loss mated pens with or without fractional
parameters across a range of hair loss radiofrequency. Across a range of devices,
types, needling devices, needling depths, needling depths, and session frequencies, MN
session frequencies, and combination has demonstrated clinical improvements as a
therapies. standalone and/or adjunct therapy for patients
with atrophic scars, actinic keratoses, and pig-
While evidence suggests that mentation disorders such as vitiligo and mel-
microneedling might improve hair loss, asma [6, 7].
clinical data are of relatively low quality. In the last decade, studies have demon-
With better study designs and efforts to strated that MN may enhance transdermal
standardize best practices, microneedling delivery, promote anagen-initiating Wnt/b-
could become a staple adjuvant to US catenin signaling, and improve dermal papillae
Food and Drug Administration (FDA)- stem cell proliferation—thus potentiating ther-
approved hair loss treatments. apeutic effects for a variety of hair loss disorders
[8–10]. In 2013, the landmark study by Dhurat
et al. on 100 AGA subjects found that over a
12-week period, once-weekly MN combined
with twice-daily 5% minoxidil increased hair
counts significantly versus minoxidil
INTRODUCTION monotherapy [11]. Since then, investigators
have continued to assess the effects of MN as
Alopecia is a common cosmetic concern affect-
both a standalone and adjunct therapy for hair
ing over 50% of adults throughout a lifetime [1].
loss.
Hair loss disorders are typically categorized into
In this systematic review, we investigate the
scarring and nonscarring alopecias, with treat-
use of MN as a standalone, adjunct, and com-
ments dependent on the pathogenesis and
parator therapy on hair loss disorders. We
diagnosis determined during dermatological
evaluate patient populations, interventions,
evaluation [2]. While drug and nondrug inter-
comparators, MN procedures, outcomes, and
ventions often help to improve many hair loss
adverse events—as well as evidence quality
disorders, treatments for androgenic alopecia
using Jadad scoring. We discuss possible mech-
(AGA) are typically relegated to stopping the
anisms by which MN may improve hair loss
progression of the condition [3]. Moreover,
disorders as a monotherapy and an adjunct
treatments for alopecia areata (AA) and alopecia
intervention. Finally, we identify limitations in
totalis (AT) remain limited, with recurrence
Dermatol Ther (Heidelb) (2022) 12:41–60 43

the current body of research and provide rec- Table 1 PICOS inclusion and exclusion criteria
ommendations for future clinical trials.
Parameter Inclusion criteria Exclusion criteria
Patients Patients of any age
METHODS treated for scalp
hair loss
Literature Search
Intervention MN as a standalone MN devices with
A broad literature search was conducted or adjunct therapy needle-releasing
through PubMed up to November 2021 to drugs, acupuncture
identify original articles that evaluate the use of needles
MN on hair loss disorders. The database was
Comparator How effective is
searched using combinations of the following
keywords: ‘‘microneedling,’’ ‘‘micro needling,’’ MN at improving
‘‘micro needle,’’ ‘‘microneedle,’’ ‘‘needle,’’ ‘‘der- hair loss
maroller’’ and ‘‘alopecia,’’ ‘‘hair loss,’’ ‘‘alopecia,’’ outcomes?
‘‘areata,’’ ‘‘cicatricial,’’ or ‘‘effluvium.’’ This arti- Outcomes Primary endpoints: Any study not
cle is based on previously conducted studies and
phototrichogram, designed to
does not contain any new studies with human
investigator, and/ adequately test for
participants or animals performed by any of the
authors. or patient the standalone or
assessments additive effect of
Inclusion and Exclusion Criteria MN
Study design Prospective studies Retrospective design,
All search hits were screened and examined for case series,
relevant titles and abstracts. Full texts were literature reviews,
reviewed to determine eligibility. Articles were or nonhuman
included if they featured all of the following:
subjects; studies
(a) human subjects with scalp hair loss, (b) MN
with fewer than
as a standalone or adjunct therapy, and
(c) endpoint measurements related to scalp hair. five patients;
Articles were excluded if they did not feature ongoing clinical
(a) original data, (b) human data, (c) endpoint trials; Jadad scores
measurements for hair parameters, and/or lower than 1
(d) designs that adequately evaluated the effects
A table summarizing the inclusion and exclusion criteria in
of MN on hair. This literature review is based on
our systematic review for clinical studies investigating the
previously conducted studies and does not
use of MN for the treatment of hair loss disorders
contain any new studies with human partici-
pants or animals performed by any of the
authors. Full inclusion and exclusion criteria
can be found in Table 1. selections, and/or Jadad scores were discussed
RE and SR each independently identified 367 by RE and PD and resolved by RE.
records for screening. RE, SR, and PD each
independently screened all 367 titles and
abstracts to assess eligibility, and the 42 full RESULTS
texts to determine inclusion. RE, SR, and PD
each independently assessed Jadad scores. Any Of the 42 full texts accessed to assess eligibility,
disagreements in identifications, screenings, 20 were excluded on the basis of the wrong
intervention (n = 2), outcome (n = 4), or study
44 Dermatol Ther (Heidelb) (2022) 12:41–60

Fig. 1 PRISMA flowchart. A PRISMA flowchart detailing the process of eligibility for all records reviewed for the literature
review, as well as the number of studies identified, screened, excluded, and included

design (n = 14). A total of 22 clinical studies met AGA


our criteria for inclusion: 17 trials with ran-
domization and 5 nonrandomized prospective Patients
cohorts (Fig. 1). Jadad scores ranged from 1 to 3, Within studies featuring AGA subjects, enroll-
with a mean score of 2 (Table S1). ment ages ranged from 18 to 70 years, with a
Of the 22 studies, 16 were conducted on AGA subject-weighted average of 33.75 years. Of the
subjects, 4 on alopecia areata subjects, 1 on 15 studies with male AGA subjects, 1 did not
alopecia totalis subjects, and 1 on both AGA enroll subjects based on a classification system,
and telogen effluvium (TE) subjects. A total of while 14 included males with hair loss based on
1127 subjects (856 males and 269 females) were the Norwood–Hamilton scale: I (0.0%), II
included featuring the following hair loss types: (46.7%), III (93.3%), IV (93.3%), V (60%), and
AGA (n = 911), AA (n = 201), AT (n = 8), and TE VI (26.7%). Of the seven studies with female
(n = 7) [11–32]. AGA subjects, one did not enroll subjects based
on any classification system, one enrolled based
on Sinclair scores, and five enrolled females
with hair loss determined by the Ludwig scale: I
(80.0%), II (60.0%), and III (60.0%) (Table 2).
Table 2 Parameter summaries for studies assessing the use of MN on AGA subjects
Androgenic alopecia (AGA)

Author Total subjects (sex); alopecia type Study type Treatment regimen MN procedure No. of MN Treatment Endpoints Effectiveness Adverse Jadad
(year) sessions duration events score

Ramadan n = 126 (46 m, 80 f); AGA Combination: PRP, Group 1: medications ? PRP MN automated 6, once 6 months Hair counts, hair Yes, in both sexes No serious 2
et al. 5% minoxidil, injections pen, 2.00 mm every diameters, events
Hair density
[12] 2.50 mg needles, session month photographic reported
Group 2: increased in
finasteride (men), endpoints evaluation
medications ? MN ? topical group 2 versus Twenty-three
200 mg marked as three
PRP group 1; larger subjects
spironolactone passes followed
effect for reported
(women) Group 3: medications by PRP
groups 1 and 2 transient
application
versus group 3 pain after
Dermatol Ther (Heidelb) (2022) 12:41–60

PRP
Sohng n = 29 (24 m, 5 f); AGA Combination: 5% Group 1: home-use MN MN stamp, 52, twice 6 months Hair counts, self No No serious 2
et al. minoxidil 0.25 mm spiral weekly assessments events
Group 2: home-use MN ? 5%
[13] needles, reported;
minoxidil
endpoint mild and
Group 3: 5% minoxidil sessions marked transient
as gentle pruritus
tapping 20 noted in
times in target one subject
area
Burns n = 11 (f); AGA Combination: 5% 5% minoxidil ? MN twice per MN automated 6, twice 3 months Photographic Yes No serious 1
et al. minoxidil ? MN month added to ongoing hair pen, session every evaluation, events
Investigators
[14] added to ongoing loss treatments endpoints month self reported
noted that
hair loss marked as two assessments
11/11 subjects
treatments passes across the
improved at
frontal, crown,
least 1–1.5
vertex, and
Sinclair scores
upper-parietal
scalp
Gowda n = 90 (m); AGA Combination: 5% Group 1: 5% minoxidil MN roller, 4, once 4 months Hair counts, Yes No serious 1
et al. minoxidil, PRP 1.50 mm every photographic events
Group 2: 5% minoxidil ? MN Hair counts
[15] needles, session month evaluation reported in
increased in
Group 3: 5% minoxidil ? PRP endpoints MN group
groups 1, 2,
injections marked as
and 3;
passes
investigators
longitudinally,
noted
vertically, and
improvements
diagonally until
in group 3
pinpoint
bleeding noted
45
46

Table 2 continued
Androgenic alopecia (AGA)

Author Total subjects (sex); alopecia type Study type Treatment regimen MN procedure No. of MN Treatment Endpoints Effectiveness Adverse Jadad
(year) sessions duration events score

Shome n = 50 (25 m, 25 f); AGA Combination: Group 1: intradermal QR678 MN roller, 8, once 12 months Hair counts, hair Yes No serious 2
et al. intradermal versus Neo(Ò) 1.50 mm every diameters, events
Hair counts and
[16] MN delivery of needles, session 3 weeks photographic reported;
Group 2: MN ? QR678 hair diameters
growth factor endpoints evaluation, transient
Neo(Ò) topical increased in
solution marked as 4–5 self scalp
groups 1 and 2;
passes assessments itchiness
no difference
longitudinally, higher in
in changes to
vertically, and group 2
hair counts and
diagonally until
diameters in
light erythema
group 1 versus
noted
2
Ozcan n = 62 (m); AGA Combination: PRP Group 1: PRP injections MN automated 4, once 10 weeks Hair counts, hair Yes No events 2
et al. solution pen, 1.50 mm every diameters, reported
Group 2: MN ? PRP solution Hair counts and
[17] needles two pull tests,
hair diameters
weeks photographic
increased in
then evaluation,
groups 1 and 2;
once self
changes to
after assessments
anagen:telogen
1 month
hairs increased
in group 2
versus group 1
Yu et al. n = 40 (m); AGA Combination: 5% Group 1: saline ? MN MN roller 16, once 16 weeks Hair counts, hair Yes No serious 3
[18] minoxidil, growth weekly diameters, events
Group 2: 5% minoxidil ? MN Hair density
factors photographic reported
increased in
Group 3: growth factors ? MN evaluation,
groups 2, 3, Three subjects
Group 4: 5% self
and 4 developed
minoxidil ? growth assessments
mild
factors ? MN erythema
which
alleviated
after
24 hours
Dermatol Ther (Heidelb) (2022) 12:41–60
Table 2 continued
Androgenic alopecia (AGA)

Author Total subjects (sex); alopecia type Study type Treatment regimen MN procedure No. of MN Treatment Endpoints Effectiveness Adverse Jadad
(year) sessions duration events score

Bao et al. n = 75 (m); AGA Combination: 5% Group 1: 5% minoxidil MN automated 8, once 24 weeks Hair counts, hair Yes Twelve events 3
[19] minoxidil pen, every diameters, related to
Group 2: MN Hair counts
1.00–2.00 mm 3 weeks photographic scalp
increased in
Group 3: 5% minoxidil ? MN needles, session evaluation irritation
groups 1, 2,
endpoints were noted;
and 3; hair
marked as all resolved
density
hemorrhage within
increased in
and redness 4 days; no
groups 2 and 3;
Dermatol Ther (Heidelb) (2022) 12:41–60

differences
larger
in
improvements
occurrence
for group 3
across
versus groups 1
groups
and 2
Aggarwal n = 30 (m); AGA Split scalp: MN, PRP Side 1: MN MN roller, 4, once 6 months Hair counts, hair Yes No serious 3
et al. 1.50–2.00 mm monthly diameters, self events
Side 2: MN ? PRP injections Hair counts and
[20] needles, session assessments reported
hair diameters
endpoints
increased in
marked as
sides 1 and 2;
gentle rolling
no difference
until pinpoint
in change of
bleeding
hair counts and
hair diameters
in side 1 versus
side 2
47
48

Table 2 continued
Androgenic alopecia (AGA)

Author Total subjects (sex); alopecia type Study type Treatment regimen MN procedure No. of MN Treatment Endpoints Effectiveness Adverse Jadad
(year) sessions duration events score

Faghihi n = 59 (29 m, 30 f); AGA Combination: 5% Group 1: 5% minoxidil MN automated 6, once 12 weeks Hair counts, hair Yes More pain 2
et al. minoxidil pen, 1.20 or every diameters, reported
Group 2: 5% minoxidil ? MN Hair counts and
[21] 0.60 mm 2 weeks photographic from MN
1.2 mm diameters
needles, session evaluation, in group 2
increased in
Group 3: 5% minoxidil ? MN endpoints self versus 3
groups 1, 2,
0.6 mm marked as assessments
and 3; change
pinpoint
in hair counts
bleeding
and diameters
greater in
group 3 versus
group 1;
change in hair
diameters
greater in
group 2 versus
group 1
Starace n = 50 (14 m, 36 f); AGA, TE Combination: MN MN every 3 weeks added to MN roller, 3, once 6 months Hair counts, hair AGA: yes, in No serious 1
et al. added to ongoing ongoing hair loss treatments 1.50 mm every diameters, both sexes events
[22] hair loss needles, 4 weeks photographic reported
TE: yes
treatments 20–25 minute evaluation,
sessions, session self Hair counts and
endpoints assessments hair diameters
marked as eight increased
passes
longitudinally,
vertically, and
diagonally in
affected regions
or until mild
erythema and
pinpoint
bleeding noted
Dermatol Ther (Heidelb) (2022) 12:41–60
Table 2 continued
Androgenic alopecia (AGA)

Author Total subjects (sex); alopecia type Study type Treatment regimen MN procedure No. of MN Treatment Endpoints Effectiveness Adverse Jadad
(year) sessions duration events score

Kumar n = 60 (m); AGA Combination: 5% Group 1: 5% minoxidil MN roller, 8; four 12 weeks Hair counts, Yes No serious 2
et al. minoxidil 1.50 mm sessions photographic events
Group 2: 5% minoxidil ? MN Hair counts
[23] needles, session (month evaluation, reported
increased in
endpoints 1), two self
group 2 versus
marked as sessions assessments
group 1; higher
passes (month
self assessment
longitudinally, 2), two
scores in group
vertically, and sessions
2 versus group
Dermatol Ther (Heidelb) (2022) 12:41–60

diagonally in (month
1
affected regions 3)
until pinpoint
bleeding noted
Yu et al. n = 19 (m); AGA Split scalp: 5% Side 1: 5% minoxidil Fractional 5, once 5 months Hair counts, hair Yes No serious 3
[24] minoxidil radiofrequency every diameters, events
Side 2: 5% Hair counts and
MN, 1.50 mm 4 weeks photographic reported
minoxidil ? fractional hair diameters
needles evaluation,
radiofrequency MN increased in
self
sides 1 and 2;
assessments
changes to hair
counts and
diameters
greater in side
2 versus 1
Bao et al. n = 60 (m); AGA Combination: 5% Group 1: 5% minoxidil MN automated 12, once 24 weeks Hair counts, hair Yes No serious 3
[25] minoxidil pen, every diameters, events
Group 2: MN Hair counts
1.50–2.50 mm 2 weeks photographic reported;
increased in
Group 3: 5% minoxidil ? MN needles, session evaluation, no
groups 1, 2,
endpoints self differences
and 3; hair
marked as 3–4 assessments in adverse
counts, hair
passes until event
diameters,
redness and/or reporting
photographic
hemorrhaging across
evaluations,
noted groups
and self
assessments
better in group
3 versus groups
1 and 2
49
50

Table 2 continued
Androgenic alopecia (AGA)

Author Total subjects (sex); alopecia type Study type Treatment regimen MN procedure No. of MN Treatment Endpoints Effectiveness Adverse Jadad
(year) sessions duration events score

Shah n = 50 (m); AGA Combination: 5% Group 1: MN roller, 6, once 6 months Photographic Yes No events 2
et al. minoxidil, PRP 1.50 mm monthly evaluation, reported
5% minoxidil Photographic
[26] needles, session self
evaluations
Group 2: 5% endpoints assessments
better in group
minoxidil ? MN ? PRP marked as eight
2 versus group
injections passes
1
longitudinally,
vertically, and
diagonally in
affected regions
or until mild
erythema
Dhurat n = 100 (m); AGA Combination: 5% Group 1: 5% minoxidil MN roller, 12, once 3 weeks Hair counts, Yes No serious 3
et al. minoxidil 1.50 mm weekly photographic events
Group 2: 5% minoxidil ? MN Hair counts
[11] needles, session evaluation, reported
increased in
endpoints self
groups 1 and 2;
marked as assessments
hair counts
passes
increased in
longitudinally,
group 1 versus
vertically, and
2; higher
diagonally in
photographic
affected regions
evaluations and
until mild
self assessments
erythema
in group 1
versus 2
Lee et al. n = 11 (f); AGA Split scalp: growth Side 1: growth factor MN automated 5, once 5 weeks Hair counts, self Yes No events 1
[27] factor solution solution ? MN pen, 0.50 mm weekly assessments reported
Hair counts
needles
Side 2: saline ? MN increased in
side 1 versus
side 2

A table summarizing all included studies assessing the use of MN on AGA subjects. Each study summary features parameters regarding author, year of publication, total subjects, gender, study type, treatment regimen, MN procedure,
number of MN sessions, treatment duration, assessment endpoints, effectiveness, adverse events, and Jadad score
Dermatol Ther (Heidelb) (2022) 12:41–60
Dermatol Ther (Heidelb) (2022) 12:41–60 51

Interventions and Comparators Of the seven studies testing MN with 5%


In total, 536 subjects received MN therapy, minoxidil, six found statistically significantly
while 375 received other hair loss interventions. increased hair counts versus 5% minoxidil
Across all study groups, MN was included as a alone, and for a range of devices and needle
standalone therapy in 6 groups (n = 105). As an lengths: rollers, automated pens, and fractional
adjunct therapy, MN was evaluated alongside radiofrequency devices with depths from 0.60
topical minoxidil in 10 groups (n = 234), pro- to 2.50 mm [11, 15, 18, 19, 21, 23, 25]. How-
prietary topicals and/or growth factor solutions ever, Sohng et al. tested 5% minoxidil with a
in 3 groups (n = 46), PRP in 2 groups (n = 61), 0.25 mm needling stamp twice-weekly and
continued medication use in 1 group (n = 50), found no effect on hair parameters [13]. When
PRP and systemic medications in 1 group comparing 5% minoxidil with 0.60 mm or
(n = 42), PRP with topical minoxidil in 1 group 1.20 mm needle lengths, Faghihi et al. found
(n = 25), topical minoxidil and continued that 0.60 mm needle lengths led to significant
medications in 1 group (n = 11), and topical hair count and diameter increases versus 5%
minoxidil alongside growth factors in 1 group minoxidil, whereas 1.20 mm needle lengths
(n = 10) (Table 2). only saw hair count increases versus 5%
minoxidil [21].
MN Procedures All three studies testing MN alongside pro-
MN devices tested included manual rollers prietary topicals and/or growth factors noted
(n = 8), automated pens (n = 7), manual stamps increases to hair counts [16, 18, 27]. Lee et al.
(n = 1), and automated fractional radiofre- and Yu et al. demonstrated improved hair
quency pens (n = 1). Needle lengths ranged parameters but no differences across groups
from 0.25 to 2.50 mm, with a mean needle when comparing MN use with topical versus
length of 1.39 mm. intradermal delivery of proprietary products
The frequency of MN sessions ranged from and/or growth factors [18, 27]. Conversely,
twice weekly to once monthly, with a mean Ozcan et al. found that MN alongside either
session frequency of once per 2.64 weeks. The topical or injectable PRP significantly increased
number of MN sessions ranged from 3 to 52, hair counts and diameters similarly across
with a mean of 9.53 MN sessions per study. groups, but that subjects receiving MN along-
Treatment durations averaged 20.01 weeks. side topical PRP saw greater improvements to
While four studies did not specify MN ses- anagen:telogen hairs [17]. Interestingly, in a
sion endpoints, 13 studies standardized end- split-scalp study, Aggarwal et al. showed that
points by a number of passes, directions, and/or both MN and MN with PRP injections increased
taps (n = 3), mild erythema (n = 3), a number of hair diameters and density equivalently—with
passes and/or bleeding (n = 3), or passes until no significant differences noted across groups
hemorrhage (n = 4) (Table 2). [20].
Two studies tested the introduction of MN
Outcomes alongside ongoing hair loss medications
In total, 15 of 17 studies assessed hair parame- [14, 22]. Burns et al. found that twice monthly
ters through phototrichograms (i.e., hair MN combined with 5% minoxidil improved
counts, hair diameters, and/or hair densities). Ludwig scores for 11/11 females who had pre-
Of the 17 studies, 6 included MN-only groups, viously plateaued for C 6 months on other hair
whereas all studies tested MN alongside other loss treatments [14]. Starace et al. showed that
hair loss interventions. the addition of MN improved hair counts in
Of the six MN monotherapy groups, two those already using hair loss treatments
noted significant increases to total hair counts, for [ 1 year (Table 2) [22].
one found significant increases to hair diame-
ters and total hair density, and three showed no Adverse Events
effect [13, 18–20, 25, 27]. Across 536 subjects receiving MN, no serious
adverse events were reported. Of mild adverse
52 Dermatol Ther (Heidelb) (2022) 12:41–60

events, transient pain, scalp irritation, and mild mean session frequency of once every
erythema were most commonly reported. 3.46 weeks. The number of MN sessions ranged
Withdrawal rates across MN groups were low from three to six, with a mean of 4.40 MN ses-
and comparable to non-MN groups. sions per study. Treatment durations averaged
14.20 weeks.
AA and AT While one study did not specify MN session
endpoints, four studies standardized endpoints
Patients by a number of passes (n = 2), a number of
Of the five studies with AA and AT subjects, passes and/or mild erythema (n = 1), or minutes
enrollment ages ranged from 16 to 45 years, of passes in affected areas (n = 1) (Table 3).
with a subject-weighted average of 28.34 years.
Three investigations enrolled subjects with hair Outcomes
loss gradients according to Severity Of Alopecia In total, two of five studies assessed hair
Tool (SALT) score, one study enrolled on the parameters through objective measurements
basis of severe AA, and one study enrolled on (i.e., phototrichograms or 4 mm punch biop-
the basis of AT (Table 3). sies). Subjective measurements for the remain-
ing three studies included Severity of Alopecia
Interventions and Comparators Tool (SALT) scores (n = 2), Lesional Area &
In total, 114 subjects received MN therapy while Density (LAD) scores (n = 1), and/or a four-
95 received other hair loss interventions. Of the point scale (n = 1).
five studies featuring AA and AT subjects, three Of the three studies testing standalone MN
compared treatments across patients (n = 181), groups, Aboeldahab et al. and Abdallah et al.
while two compared treatments across lesions showed that MN alone increased hair density
within the same patients (n = 28). and improved SALT scores, respectively [28, 30].
Across all study groups, MN was included as However, Giorgio et al. demonstrated no chan-
a standalone therapy in three groups (n = 68). ges to hair parameters using a four-point scale
As an adjunct therapy, MN was evaluated to evaluate MN alone [31].
alongside a PRP topical in one group (n = 20), When comparing MN with cryotherapy,
and with 5-aminolevulinic acid or methyl Aboeldahab et al. found significant increases to
5-aminolevulinic acid alongside photodynamic hair counts and hair densities across both
therapy in two groups (n = 25). As a compara- interventions, with MN demonstrating greater
tor, MN was included as a control against changes to SALT scores versus cryotherapy [28].
cryotherapy in one group (n = 40), PRP injec- Conversely, Abdallah et al. found that triamci-
tions in one group (n = 20), fractional CO2 laser nolone acetonide injections with and without
alongside a PRP topical in one group (n = 20), 5% intradermal minoxidil led to greater
triamcinolone acetonide injections in one improvements to SALT and LAD scores versus
group (n = 20), 5% minoxidil injections in one controls than MN alone [30].
group (n = 20), and 5-aminolevulinic acid or As an adjunct therapy, Giorgio et al. showed
methyl 5-aminolevulinic acid alongside photo- that MN alongside 5-aminolevulinic acid and
dynamic therapy in two groups (n = 23) photodynamic therapy improved 94% of AA
(Table 3). lesions versus 53% of lesions receiving only
5-aminolevulinic acid and photodynamic ther-
apy [31]. However, Yoo et al. found that in AT
MN Procedures
subjects, methyl 5-aminolevulinic acid and
MN devices tested included manual rollers
photodynamic therapy with and without MN
(n = 3) and automated pens (n = 2). Needle
led to no hair parameter improvements
lengths ranged from 1.00 to 5.00 mm, with a
according to 4 mm punch biopsies [32].
mean needle length of 2.25 mm.
Finally, Ragab et al. demonstrated that, over
The frequency of MN sessions ranged from
a 3-month period, MN alongside topical PRP
once every 2 weeks to once monthly, with a
improves SALT scores similarly to fractional
Table 3 Parameter summaries for studies assessing the use of MN on AA and AT subjects
Alopecia areata (AA), alopecia totalis (AT)

Author Total subjects Study type Treatment regimen MN procedure No. of Treatment Endpoints Effectiveness Adverse Jadad
(year) (gender); MN duration events score
alopecia type sessions

Aboeldahab Comparison: cryotherapy Group 1: cryotherapy MN automated pen, 6, once 12 weeks Hair counts, hair Yes No adverse 3
et al. n = 80 (50 m, 30 f); versus MN 1.00–2.00 mm every density, events in
Group 2: MN Hair counts, hair density,
[28] alopecia areata (AA) needles, session 2 weeks Severity of group 2
SALT scores,
endpoints marked Alopecia Tool
photographic
as 4–5 passes (SALT)
evaluation, and self
longitudinally, scores,
assessments improved
vertically, and photographic
Dermatol Ther (Heidelb) (2022) 12:41–60

in groups 1 and 2;
diagonally evaluation,
higher changes to
self
SALT scores in group
assessments
2 versus 1

Ragab et al. Combination: PRP Group 1: PRP injections MN roller, 1.50 mm 3, once 3 months SALT Yes No serious 3
[29] n = 60 (48 m, 12 f); solution needles, session monthly events
Group 2: fractional CO2 SALT scores improved in
AA endpoints marked reported;
laser ? PRP topical groups 1, 2, and 3; no
as 4–5 passes pain
difference in SALT
Group 3: MN ? PRP longitudinally, higher in
scores across groups
topical vertically, and group 1
obliquely until versus
mild erythema group 3
noted

Abdallah Intrapatient comparison: Patch 1: triamcinolone MN roller, session 4, once 16 weeks SALT, Lesional Yes No serious 2
et al. n = 20 triamcinolone acetonide injections endpoints marked every Area & events
SALT and LAD scores
[30] (19 m, 1 f); AA acetonide injections, as 4–5 passes 4 weeks Density reported
Patch 2: 5% minoxidil decreased in patches 1,
minoxidil 5% longitudinally, (LAD) scores
injections 2, 3, and 4; largest
injections vertically, and
differences seen in
Patch 3: triamcinolone diagonally
patches 1 and 3 versus
acetonide
patch 5
injections ? 5%
minoxidil injections

Patch 4: MN

Patch 5: control
53
54

Table 3 continued
Alopecia areata (AA), alopecia totalis (AT)

Author Total subjects Study type Treatment regimen MN procedure No. of Treatment Endpoints Effectiveness Adverse Jadad
(year) (gender); MN duration events score
alopecia type sessions

Giorgio Combination: Group 1: MN MN automated pen, 6, once 18 weeks 4-point scale Yes No events 1
et al. n = 41 (17 m, 24 f); 5-aminolevulinic acid 1.00 mm needles, every reported
Group 2: No change in group 1;
[31] AA photodynamic therapy session endpoints 3 weeks
5-aminolevulinic improvements noted in
marked as
acid ? photodynamic 53% of group 2 and
5 minute of passes
therapy 94% of group 3
on AA-affected
Group 3: MN ? 5- areas
aminolevulinic
acid ? photodynamic
therapy

Yoo et al. Split scalp: Side 1: MN ? methyl MN roller, 5.00 mm 3, once 12 weeks Histological No No serious 1
[32] n = 8 (2 m, 6 f); 5-aminolevulinic 5-aminolevulinic needles every assessments events
alopecia totalis (AT) acid ? photodynamic acid ? photodynamic 4 weeks (4 mm punch reported
therapy therapy biopsy)

Side 2: methyl
5-aminolevulinic
acid ? photodynamic
therapy

A table summarizing all included studies assessing the use of MN on AA and AT subjects. Each study summary features parameters regarding author, year of publication, total subjects, gender, study type, treatment regimen, MN
procedure, number of MN sessions, treatment duration, assessment endpoints, effectiveness, adverse events, and Jadad score
Dermatol Ther (Heidelb) (2022) 12:41–60
Dermatol Ther (Heidelb) (2022) 12:41–60 55

CO2 laser therapy alongside topical PRP topical minoxidil [38]. However, two of the
(Table 3) [29]. subgroups were a part of split-scalp studies
assessing MN versus PRP injections or topical
Adverse Events growth factor solutions [20, 27]. Therefore, the
Among 114 subjects receiving MN, no serious possibility of percutaneous treatment diffusion
adverse events were reported. Of mild adverse across scalp zones cannot be discounted.
events, transient pain and mild erythema were Animal models suggest that MN may pro-
most common. Of the five studies, no with- mote anagen-initiating Wnt/b-catenin signaling
drawals were reported in MN or non-MN and dermal papillae stem cell proliferation. In
groups. particular, percutaneous wounds from MN
appear to activate hair follicle stem cells, plate-
let-derived growth factor, and vascular
DISCUSSION endothelial growth factor—potentiating the
initiation of angiogenesis, neocollagenesis, and
Clinical studies demonstrate generally favorable a new anagen cycle [5–7, 9, 10]. Clinical data
results for MN as an adjunct therapy for AGA show that MN reduces scarring and improves
and AA. However, data are of relatively low the density and thickness of epidermal and
quality and should be interpreted with caution. dermal skin layers [39, 40]. In two randomized
Due to significant heterogeneity across inter- controlled clinical trials, Bao et al. found that
ventions, comparators, and MN procedures (i.e., MN alone increased terminal hair counts—with
devices, needle lengths, session frequencies, and their latter study analyzing biopsies from a
session endpoints), we could not conduct a subset of AGA subjects showing that MN alone
meta-analysis. Here we discuss the proposed upregulated protein levels of both FZD3 and
mechanisms of MN, limitations in the current LEF-1 but not b-catenin [19, 25]. However, RT-
body of research, and design considerations for PCR testing revealed no statistical increases to
future studies. mRNA expression—with the authors postulat-
ing that the inconsistent results might be due to
Mechanisms small sample sizes, infrequent needling ses-
sions, shallow needling depths, and/or post-
AGA transcriptional modifications [25].
In AGA-affected hair follicles, dihydrotestos- As an adjunct therapy, MN may improve
terone dysregulates the Wnt/b-catenin path- AGA by enhancing transdermal delivery, and by
way, induces transforming growth factor b1, improving sulfation and Wnt pathway expres-
and triggers apoptosis in dermal papillae and sion when paired with topical minoxidil. Henry
epithelial cells. This leads to a shortened anagen et al. demonstrated in vitro that 0.15 mm nee-
phase, reductions to dermal papillae cell cluster dles inserted into human skin for 10 seconds
sizes with each re-entry into anagen and, con- enhanced transdermal permeability of calcein
sequently, microvascular degradation alongside by more than 1000-fold [41]. These effects may
progressive hair follicle miniaturization [33–36]. partly explain the equivalent and/or additive
In mid-to-late stages of miniaturization, peri- improvements to hair parameters from intra-
follicular fibrosis is often observed and may dermal growth factors or PRP injections versus
reduce the effectiveness of both systemic and MN alongside their topical applications [16, 17].
topical AGA treatments [37]. Additionally, MN may enhance topical minox-
As a monotherapy for AGA, data on MN are idil activation. Topical minoxidil is a pro-drug
limited, and the mechanisms by which MN that requires sulfation by sulfotransferase
might improve AGA remain speculative. In a enzymes in the outer root sheath of hair folli-
pooled linear regression across six subgroups, cles [8]. Goren et al. demonstrated that reduced
Gupta et al. found that MN significantly sulfotransferase activity in hair follicles pre-
increased total hair counts, by more than 5% dicted topical minoxidil nonresponders [42].
More recently, Sharma et al. found that, over
56 Dermatol Ther (Heidelb) (2022) 12:41–60

21 days, once-weekly microneedling led to a does not include a meta-analysis and cannot
median increase in sulfotransferase activity of establish best practices for MN procedures.
37.5% [8]. Finally, Bao et al. demonstrated that Faghihi et al. found hair parameters
MN with 5% minoxidil upregulated the improved more when pairing 5% minoxidil
expression of FZD3, LEF-1, and b-catenin in with fortnightly MN using an automated pen
mRNA and protein more than MN or 5% with needle lengths of 0.60 mm versus 1.20 mm
minoxidil monotherapy—suggesting that the [21]. Faghihi et al. postulated that puncture
addition of MN might amplify the effects of depths of 0.60 mm still generate enough of an
minoxidil on the Wnt pathway [19]. inflammatory response for stem cell and growth
factor recruitment, but without damaging the
AA and AT hair follicle bulge residing 1.00–1.80 mm from
AA and AT are autoimmune forms of alopecia the skin surface [43]. Interestingly, Sasaki found
resulting from the collapse of immune privilege that with MN automated pens, needling lengths
in affected hair follicles. In particular, peribul- matched penetration depths up to 1.50 mm
bar lymphocytic infiltrates appear to induce [44]. Due to user pressure variability and needle
apoptosis in hair follicle keratinocytes—leading entry angulation, Lima et al. estimated that a
to inflammation, impaired hair shaft produc- 3.00 mm MN manual roller only penetrates to
tion, and sometimes hair shaft miniaturization skin depths 50–70% of its needle length [45].
within the same hair cycle. While the histologic Taken together, equivalent MN penetration
features of AA and AT are well studied, their depths of 0.60–0.80 mm may be achievable
underlying pathogenesis remain poorly under- with MN automated pens and MN manual
stood—with researchers speculating the rollers set to needle lengths of 0.60–0.80 mm
involvement of immunological shifts related to and 1.25–1.50 mm, respectively. Relatedly, Fer-
genetic and environmental factors [4]. nandes postulated that MN device preferences
As a monotherapy for AA and AT, data on do not matter so long as the skin is penetrated
MN are unrobust. While Aboeldahab et al. and to the same depths [46]. Regardless of stan-
Abdallah et al. noted improvements to AA from dardizations for MN devices or needle lengths,
MN alone, these results should be interpreted additional methodological considerations—i.e.,
with caution due to relatively small sample session durations, frequencies, and endpoints—
sizes, as well as the 50% spontaneous recoveries still likely exert influence over the degree of
observed in many AA studies with adequate inflammation induced, and thereby the mag-
controls [28, 30]. Moreover, Giorgio et al. found nitude of outcomes across a variety of hair
no effect from MN alone in AA subjects [31]. As parameters. As such, no procedural best prac-
an adjunct therapy, Giorgio et al. suggested that tices can be ascertained with the current body of
the release of growth factors from MN may evidence.
induce immunosuppressive actions that While 8 of 22 clinical studies on MN inclu-
amplify the effects of substances such as ded groups to evaluate MN alone (n = 174),
5-aminolevulinic acid [31]. Ragab et al. found only 1 study compared MN monotherapy
that MN alongside topical PRP improved hair against an untreated control patch for AA
parameters similarly to PRP injections, and (n = 20). Moreover, 21 of 22 clinical studies on
suggested that MN may also enhance transder- MN assessed hair parameter changes over peri-
mal delivery for AA [29]. ods of less than 52 weeks. Study durations of
less than 52 weeks often do not allow investi-
Limitations gators to separate the effects of any intervention
against seasonal fluctuations to hair cycling—
particularly in the absence of untreated control
Due to significant heterogeneity across MN
groups [47, 48].
studies regarding interventions, comparators,
Finally, 4 out of 22 clinical studies utilized
MN devices, needle lengths, session frequencies,
split-scalp study designs to evaluate MN against
and session endpoints, our systematic review
or as an adjuvant to topicals and/or injectables.
Dermatol Ther (Heidelb) (2022) 12:41–60 57

Since MN is suspected to enhance transdermal ACKNOWLEDGEMENTS


drug delivery, split-scalp study designs leave
open the possibility of percutaneous drug dif-
fusion across scalp zones, thus limiting the Funding. No funding or sponsorship was
interpretability of endpoint assessments. received for this study or publication of this
article.
Recommendations
Authorship. All named authors meet the
Large-scale, randomized, placebo-controlled International Committee of Medical Journal
clinical trials assessing the use of MN for hair Editors (ICMJE) criteria for authorship for this
loss are needed. Future investigations should article, take responsibility for the integrity of
consider study durations of at least 12 months, the work as a whole, and have given their
include groups for MN as a monotherapy, and approval for this version to be published.
evaluate MN against a placebo (i.e., manual
Author Contributions. RE contributed to
rollers with removed needles, automated pens
the concept/design, systematic review process,
with uninstalled needle cartridges, and/or an
and writing of the manuscript. RE, SR, and PD
untreated control group). Split-scalp studies
contributed to the systematic review process.
should be avoided, particularly when evaluating
MN against or as an adjuvant to topicals and/or
Disclosures. Robert S. English, Sophia Ruiz,
injectables. Finally, studies evaluating the use of
and Pedro DoAmaral have nothing to disclose.
MN across different procedural standards (i.e.,
shorter needle lengths and more frequent ses- Compliance with Ethics Guidelines. This
sions versus longer needle lengths and less fre- article is based on previously conducted studies
quent sessions) will help toward establishing and does not contain any new studies with
best practices. human participants or animals performed by
any of the authors.
CONCLUSION Data Availability. Data availability is not
applicable to this article as no datasets were
Among 22 clinical studies featuring 1127 sub-
generated or analyzed during the current study.
jects, MN as an adjunct therapy improved hair
parameters across genders as well as a range of Open Access. This article is licensed under a
hair loss types, hair loss severities, needling Creative Commons Attribution-NonCommer-
devices, needling depths of 0.50–2.50 mm, and cial 4.0 International License, which permits
session frequencies from once weekly to once any non-commercial use, sharing, adaptation,
monthly—with no serious adverse events distribution and reproduction in any medium
reported. However, results should be interpreted or format, as long as you give appropriate credit
with caution due to significant heterogeneity to the original author(s) and the source, provide
across study interventions, comparators, and a link to the Creative Commons licence, and
MN procedures (i.e., devices, needle lengths, indicate if changes were made. The images or
session frequencies, and session endpoints). other third party material in this article are
Large-scale randomized controlled trials are included in the article’s Creative Commons
needed to discern the effects of MN as a stan- licence, unless indicated otherwise in a credit
dalone and adjunct therapy, determine best line to the material. If material is not included
practices for MN procedures, and establish long- in the article’s Creative Commons licence and
term safety data. Study designs should consider your intended use is not permitted by statutory
12-month durations, include groups using MN regulation or exceeds the permitted use, you
as a monotherapy, and evaluate MN against a will need to obtain permission directly from the
placebo and/or untreated group. copyright holder. To view a copy of this licence,
58 Dermatol Ther (Heidelb) (2022) 12:41–60

visit http://creativecommons.org/licenses/by- 12. Ramadan WM, Hassan AM, Ismail MA, El Attar YA.
nc/4.0/. Evaluation of adding platelet-rich plasma to com-
bined medical therapy in androgenetic alopecia.
J Cosmet Dermatol. 2021;20(5):1427–34.

13. Sohng C, Lee EH, Woo SK, Kim JY, Park KD, Lee SJ,
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