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Microneedling and Its Use in Hair Loss Disorders: A Systematic Review
Microneedling and Its Use in Hair Loss Disorders: A Systematic Review
https://doi.org/10.1007/s13555-021-00653-2
REVIEW
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
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
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
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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