Am J Clin Dermatol
DOI 10.1007/s40257-013-0060-6

ORIGINAL RESEARCH ARTICLE

Efficacy and Safety of a Low-level Laser Device in the Treatmentof Male and Female Pattern Hair Loss: A Multicenter,
Randomized, Sham Device-controlled, Double-blind Study
Joaquin J. Jimenez • Tongyu C. Wikramanayake •Wilma Bergfeld • Maria Hordinsky • Janet G. Hickman •Michael R. Hamblin • Lawrence A. SchachnerÓ The Author(s) 2014. This article is published with open access at Springerlink.com

Abstract
Significance Male and female pattern hair loss are common, chronic dermatologic disorders with limited therapeutic options. In recent years, a number of commercial
devices using low-level laser therapy have been promoted,
but there have been little peer-reviewed data on theirefficacy.
Objective To determine whether treatment with a lowlevel laser device, the US FDA-cleared HairMax LasercombÒ, increases terminal hair density in both men andwomen with pattern hair loss.
Methods Randomized, sham device-controlled, doubleblind clinical trials were conducted at multiple institutional
and private practices. A total of 146 male and 188 female
subjects with pattern hair loss were screened. A total of 128
Trial Registration: All trials were registered with http://www.
clinicaltrials.gov. Trial #1 (registration #NCT00981461), ‘‘Treatmentof Androgenetic Alopecia in Females, 9 Beam’’; Trial #2(#NCT01016964), ‘‘Treatment of Androgenetic Alopecia in Females,
12 Beam’’; Trial #3 (#NCT00947505) and Trial #4 (#NCT00947219),‘‘Treatment of Androgenetic Alopecia in Males’’.
J. J. Jimenez (&)  T. C. Wikramanayake  L. A. Schachner
Department of Dermatology and Cutaneous Surgery, Universityof Miami Miller School of Medicine, Miami, FL 33136, USAe-mail: j.jimenez@med.miami.edu
W. Bergfeld
Department of Dermatology, Cleveland Clinic Foundation,
Cleveland, OH 44195, USA
M. Hordinsky
Department of Dermatology, University of Minnesota,
Minneapolis, MN 55455, USA
J. G. Hickman
The Education and Research Foundation, Inc., Lynchburg,
VA 24501, USA

male and 141 female subjects were randomized to receive
either a lasercomb (one of three models) or a sham device
in concealed sealed packets, and were treated on the whole
scalp three times a week for 26 weeks. Terminal hairdensity of the target area was evaluated at baseline and at
16- and 26-week follow-ups, and analyzed to determine
whether the hypothesis formulated prior to data collection,that lasercomb treatment would increase terminal hairdensity, was correct. The site investigators and the subjects
remained blinded to the type of device they dispensed/
received throughout the study. The evaluator of masked
digital photographs was blinded to which trial arm thesubject belonged.
Results Seventy-eight, 63, 49, and 79 subjects were randomized in four trials of 9-beam lasercomb treatment infemale subjects, 12-beam lasercomb treatment in female
subjects, 7-beam lasercomb treatment in male subjects, and9- and 12-beam lasercomb treatment in male subjects,
compared with the sham device, respectively. Nineteen
female and 25 male subjects were lost to follow-up. Among
the remaining 122 female and 103 male subjects in the
M. R. Hamblin
Wellman Center for Photomedicine, Massachusetts General
Hospital, Boston, MA 02114, USA
M. R. Hamblin
Department of Dermatology, Harvard Medical School, Boston,
MA 02115, USA
M. R. Hamblin
Harvard-MIT Division of Health Sciences and Technology,
Cambridge, MA 02139, USA

J. J. Jimenez et al.

efficacy analysis, the mean terminal hair count at 26 weeks
increased from baseline by 20.2, 20.6, 18.4, 20.9, and 25.7
per cm2 in 9-beam lasercomb-treated female subjects,
12-beam lasercomb-treated female subjects, 7-beam lasercomb-treated male subjects, and 9- and 12-beam lasercombtreated male subjects, respectively, compared with 2.8(p \ 0.0001), 3.0 (p \ 0.0001), 1.6 (p = 0.0017), 9.4(p = 0.0249), and 9.4 (p = 0.0028) in sham-treated subjects (95 % confidence interval). The increase in terminal
hair density was independent of the age and sex of thesubject and the lasercomb model. Additionally, a higher
percentage of lasercomb-treated subjects reported overall
improvement of hair loss condition and thickness and fullness of hair in self-assessment, compared with sham-treatedsubjects. No serious adverse events were reported in any
subject receiving the lasercomb in any of the four trials.
Conclusions and relevance We observed a statisticallysignificant difference in the increase in terminal hair density between lasercomb- and sham-treated subjects. No
serious adverse events were reported. Our results suggestthat low-level laser treatment may be an effective option totreat pattern hair loss in both men and women. Additional
studies should be considered to determine the long-term
effects of low-level laser treatment on hair growth andmaintenance, and to optimize laser modality.

1 Introduction
Male and female pattern hair loss is a common, chronic
dermatologic disorder. Male pattern hair loss (MPHL, or
androgenetic alopecia, AGA) affects 50 % of men by
50 years of age, and the frequency and severity increase
with age [1]. MPHL is characterized by a dihydrotestosterone-dependent process with miniaturization ofterminal hair follicles (HFs) into vellus HFs [2]. The frequency and severity of female pattern hair loss (FPHL) also
increase with age, with a prevalence of over 50 % in
women over the age of 80 years [3]. While the role ofandrogens in all cases of FPHL is less certain, FPHL also
undergoes follicular miniaturization [1]. Current medical
treatments for pattern hair loss include topical minoxidil(available in 2 % and 5 % solutions or 5 % foam, andsometimes combined with other active ingredients such astretinoin), finasteride, dutasteride (US FDA approved forthe treatment of benign prostatic hyperplasia, and prescribed off-label for treatment of MPHL), topical ketoconazole, anti-androgens and estrogens (for FPHL), andfollicular unit transplantation [4]. In addition, there are
numerous oral supplements and topical treatments claimed
to have hair growth-promoting or anti-hair loss effects thatare marketed directly to the consumers, without independent data supporting the claims.

In recent years, low-level laser/light therapy (LLLT), or
photobiomodulation or photobiostimulation, has been promoted to prevent hair loss and stimulate hair growth in both
MPHL and FPHL. There have been a number of commercially available devices designed for home use (daily orseveral times a week), and they are relatively inexpensive
compared with current medical treatment and hair transplantation surgery. However, there have been few peerreviewed data on efficacy [5]. In one published study, only
seven subjects with pattern hair loss (six female subjects andone male subject) were evaluated upon treatment with a laser‘‘hood’’ [6]. The study was not sham device-controlled andthe results did not reach statistical significance. A more
recent, randomized, double-blind, sham device-controlled
trial found ‘‘TOPHAT655’’ (a helmet-like device with lasers
and light-emitting diodes) treatment to increase terminal
hair count in pattern hair loss, but only male subjects were
included in the trial [7]. To date, the most comprehensive
published study is a randomized, double-blind, sham devicecontrolled clinical trial of 110 male subjects showing that the
HairMax LasercombÒ (Lexington International, LLC., Boca
Raton, FL, USA), FDA-cleared to treat pattern hair loss inmale subjects at the time, was effective in increasing terminal hair density after 26 weeks of treatment [8]. The
device has since been approved for treating FPHL, though
there has been only one published study supporting theefficacy, with limitations [9]. In this study, only sevenfemale subjects were included. They were given a lasercomb
to use for 6 months, and the terminal hair count was compared between baseline and at the end of the study. The FDA
considered the LaserCombÒ a medical device of ‘‘moderaterisk’’, therefore it only screened for safety, not efficacy.
Given the prevalence of MPHL and FPHL, their limited
medical treatment and the high costs of hair transplantation,and the ready availability and user friendliness of LLLT
home devices, it is important to determine whether LLLT
can provide an effective alternative for pattern hair loss,
especially FPHL, for which no randomized, controlled trials
have been published. The objective of this study was todetermine the efficacy of LaserCombÒ treatment of patternhair loss in both male and female subjects, in four randomized, multicenter, sham device-controlled, double-blindprospective trials. A total of 122 female and 103 male subjects were included in the efficacy analysis after 26 weeks oftreatment, and three lasercomb models were evaluated.

2 Methods
2.1 Patient Enrollment
The study protocol was evaluated under Good Clinical
Practice guidelines and approved by the authors’Lasercomb Treatment of Male and Female Pattern Hair Loss

Institutional Review Boards (IRBs) or the Chesapeake
Research Review, Inc. All trials were registered with http://
www.clinicaltrials.gov. Prior to participation in the trials,
each subject provided a written informed consent. Participants received free evaluations at baseline and at followups. They were compensated for each visit and were given alasercomb at the end of the study (26-week visit). Subject
screening, recruitment, and follow-up were carried out at
multiple study sites: Trial #1 (registration #NCT00981461),‘‘Treatment of Androgenetic Alopecia in Females, 9
Beam’’: International Dermatology Research, Inc. (Miami,
FL, USA), The Education & Research Foundation, Inc.
(Lynchburg, VA, USA); Trial #2 (#NCT01016964),‘‘Treatment of Androgenetic Alopecia in Females, 12
Beam’’: The Cleveland Clinic Foundation (Cleveland, OH,
USA), University of Minnesota (Minneapolis, MN, USA),
University of Miami Miller School of Medicine (Miami,
FL, USA); Trial #3 (#NCT00947505) and Trial #4(#NCT00947219), ‘‘Treatment of Androgenetic Alopecia in
Males’’: Dermatology Consulting Services (High Point,
NC, USA); Trials #1, #3, and #4: DermResearch, Inc.
(Austin, TX, USA), Skin Laser and Surgery Specialist(Hillsborough, NJ, USA), and Palm Beach Research Center(West Palm Beach, FL, USA). Full trial protocol is available upon request.
2.1.1 Study Inclusion/Exclusion Criteria
To be included in the trials, subjects must have been
healthy, 25–60 years of age, with active androgenetic hairloss (Norwood–Hamilton classification of IIa–V for malesubjects [10] and Ludwig/Savin classification of I-4, II-1,
II-2, or frontal for female subjects) [11–13] and haveFitzpatrick skin type I–IV [14]. Race/ethnicity information
was collected. Subjects must not have taken or used thefollowing medications within 6 months prior to screening:minoxidil, finasteride (or any other 5a-reductase inhibitors), medications with anti-androgenic properties (e.g.,
cyproterone acetate, spironolactone, ketoconazole, flutamide, bicalutamide), topical estrogen, progesterone, tamoxifen, anabolic steroids, medication that can potentiallycause hypertrichosis (e.g., cyclosporine, diazoxide, phenytoin, psoralens), oral glucocorticoids (inhaled glucocorticoids were permitted), lithium, phenothiazines, or othermedications at the discretion of the investigators. Other
excluded medications were phytotherapy (e.g., saw palmetto) within 8 weeks, isotretinoin within the past year,
and anticoagulation use [other than aspirin (\325 mg every
day, which was stable for 3 months)]. Subjects were
excluded if they had malignancy in the target area within
5 years, active infection on the scalp, chronic dermatologic
conditions (e.g., eczema, psoriasis, infection) of the scalp
other than pattern hair loss, a history of poor wound healingor keloid formation, a history of thyroid or other medical
condition that might influence hair growth and loss; humanimmunodeficiency virus infection, possession of a pacemaker, defibrillator, or other active implantable device; ahistory of drug and/or alcohol abuse within the past
12 months; or any other medical conditions at the discretion of the investigators. Pregnant female subjects or
female subjects planning on becoming pregnant during theduration of the study were excluded. Subjects with a history of photosensitivity to laser light, hair transplantation,
scalp reduction, radiation to the scalp or chemotherapy
within the past year, current hair weave or tattooing, as
well as subjects with hair shorter than one-half inch or withlight-blonde hair were also excluded.
2.2 The Lasercomb and Sham Devices
Three different lasercomb configurations were evaluatedfor similar laser dose rates. These models were designed tomeet varying marketing demands, and the FDA required
clinical studies on each model to ensure consistency of
results. The 7- and 9-beam lasercombs (HairMax LaserCombÒ, Lexington International, LLC) emit 7 or 9 redlaser beams (beam diameter \5 mm) at a wavelength of
655 nm (±5 %). The 12-beam dual model emits 6 beams at
a wavelength of 635 nm (±5 %) and 6 beams at 655 nm(±5 %). The lasers for each device were identical in power
output, and the treatment time was adjusted for similar
laser dose rates: 15 min for the 7-beam model, 11 min for
the 9-beam model, and 8 min for the 12-beam model. Twosham devices that emitted white light from light-emitting
diode bulbs had identical appearance as the 7- and 9-beamlasercombs, and were used as controls for the 7-, and 9- or
12-beam lasercombs, respectively.
2.3 Study Design
Four multicenter prospective trials were designed, to berandomized, sham controlled, and double blind. In Trials#1 and #2, subjects with FPHL used a 9-beam (#1) or adual 12-beam (#2) lasercomb and sham device. In Trials #3
and #4, subjects with MPHL used a 7- (#3) or a 9- or
12-beam (#4) lasercomb and sham device.
Each study protocol was approved by institutional or the
Chesapeake IRB. Each Clinical Study Sponsor confirmed
performance in compliance with Good Clinical Practice(GCP, as defined in CPMP/ICH/135/95), the Declaration of
Helsinki (with amendments), and local legal and regulatory
requirements. Lexington International LLC, as a company,
is and has been compliant and certified to ISO9001 andISO13485 Quality Standards. Lexington’s Clinical Study
Practices have been audited by the FDA and have confirmed to be in compliance with the FDA’s GCP. All

J. J. Jimenez et al.

studies were managed and audited by Palm Beach CRO(Clinical Research Organization) and validated to be incompliance with the approved protocol.
For subjects who met the inclusion and exclusion criteria, at the baseline visit, a ‘‘target site’’ in the affected
scalp area was chosen using a 25 mm 9 25 mm plastic
template, and hair within this target site (25mm 9 25mm)
was clipped. The target site was then marked with a semipermanent tattoo using a professional tattooing machine(K.P. Permanent Make-Up, Inc., Pomona, CA, USA), andphotographed.
Each subject was then provided with either a lasercomb
or a sham device. Randomization was generated by Eugene
R. Heyman (http://www.erhstats.com) using the SAS
PROC RAND method. For the 9- and 12-beam trial in malesubjects (#4), randomization was generated 1:1:1 with ablock size of 3. For all other trials, randomization was 2:1
with a block size of 3. The lasercomb and sham devices,along with instructions, were provided to the site investigators in sealed, sequentially numbered opaque packets in ablinded manner, and were dispensed sequentially. Both thesite investigators and the subjects remained blinded to thetype of device they dispensed/received throughout the
study.
The subjects were instructed to apply the device threetimes per week, with the beam on, to their entire scalp; theduration of treatment specific for each device and theirrespective sham control was included in the sealed packet(15 min for the 7-beam model, 11 min for the 9-beammodel, and 8 min for the 12-beam model). Each subject
was required to keep a diary of usage, which was reviewed
by the site investigator at the time of office visits. The
study duration was 26 weeks, with clinical monitoring
visits at 8, 16, and 26 weeks. Dermatology scalp assessment, safety assessment, global and macro digital imaging
after hair clipping, and computer-aided hair counts of thetarget sites were performed by blinded investigators at
weeks 16 and 26, and compared with baseline.
2.3.1 Efficacy Evaluation
Change of terminal hair density (hair count/cm2) at
26 weeks from baseline was used as the endpoint toevaluate the efficacy of lasercomb treatment in male andfemale subjects with pattern hair loss. The Canfield Epilume System was used for digital imaging of the target
sites at baseline and at weeks 16 and 26. All macro
photographs, with a 10-mm scale bar divided in 0.1-mm
increments, were labeled only by subject number anduploaded to an online database. An independent evaluator
not connected to the clinical trials analyzed the uploaded
images and performed computer-assisted hair counts,

using the TrichoScience software (Tricholog, Moscow,
Russia). The evaluator was a hair transplant surgeon with
20 years of experience in evaluation of hair counts, andwas blinded to which trial arm the subject belonged, as
well as which images were from baseline and which werefrom follow-up. Subjects also filled out questionnaires for
self-assessment of overall improvement of hair loss condition and thickness and fullness of hair at the 16- and26-week visits.
2.4 Statistical Analysis
Based on previous testing data on lasercomb use, change interminal hair count from baseline to study endpoint was
found to be a mean increase of just under 30 hairs/cm2 witha standard deviation of 18.6 hairs/cm2. For the sample size
calculation, the assumed standard deviation was 20 hairs/
cm2 and the treatment difference was assumed to be 17
hairs/cm2. Each trial had a planned enrollment of 60 subjects in a 2:1 allocation of lasercomb:sham device toachieve at least 80 % power while allowing a 10 % dropout rate. In Trials #1–3, subjects were randomized to a 2:1
allocation of the lasercomb:sham device. In Trial #4, subjects were randomized in a 1:1:1 allocation of the
9-beam:12-beam:sham device. For subject enrollment,
continuous variables (e.g., age) were analyzed with a oneway analysis of variance and categorical variables with theFisher’s exact test.
The primary efficacy endpoint was the change in terminal hair density within the target area at 26 weeks frombaseline, assessed in all subjects with baseline and at least
one post-randomization efficacy evaluation. The lasercomb-treated group was compared with the sham device
group using least squares mean with two-sided at a 5 %level of significance. The primary analysis of efficacy wasan analysis of co-variance, which modeled terminal hairdensity as a function of treatment group, study center, age(as a continuous variable), and Fitzpatrick skin type (as acategorical variable). The secondary efficacy endpoint was
the categorical change in terminal hair density from baseline, analyzed using the Cochran–Mantel–Haenszel row
mean score test with integer scores stratified by study site.
Cochran’s Q test was performed to analyze the homogeneity of results across genders, all trials, and all lasercomb
models. Subject self-assessment was also evaluated using
the Cochran–Mantel–Haenszel row mean score test withinteger scores stratified by site. The DerSimonian–Laird
approach was used to perform the meta-analysis homogeneity assessment. All statistical analyses were contracted toStat-Tech Services, LLC (Chapel Hill, NC, USA). For
evaluation of safety, adverse events were summarized andeach event was evaluated for frequency.

Lasercomb Treatment of Male and Female Pattern Hair Loss

3 Results

3.2 Analysis of Efficacy

3.1 Study Population

The trials were designed to be randomized and double
blind. Data from different study sites were pooled for statistical analysis. All the randomized subjects who had abaseline and at least one post-randomization evaluation
were included in the efficacy analysis (Fig. 1). To accountfor dropouts thereafter, all data are presented in last
observation carried forward for the analysis of covariancefor Trials #1 and #4.

Allocation
Follow-up
AnalysisFig. 1 Profile of the four
randomized, sham-controlled
trials of lasercomb treatment ofmale and female pattern hairloss. Dates of recruitments areindicated

Enrollment

A total of 188 female and 146 male subjects were screened,and 141 female and 128 male subjects were randomized toreceive the lasercomb or sham device. Of these subjects, 19
female and 25 male subjects were lost to follow-up, leaving
122 female and 103 male subjects completing at least one
follow-up. Sixty-five and 57 subjects (122 total) were
included in the efficacy evaluation for Trials #1 and #2 (thefemale trials evaluating the 9-beam and dual 12-beamlasercomb, respectively) (Fig. 1; Table 1), and 38 and 65
subjects (103 total) were included in the efficacy evaluation
for Trials #3 and #4 (the male trials evaluating the 7- andthe 9- or 12-beam lasercomb, respectively) (Fig. 1;
Table 2). There were no statistically significant differencesin demographic characteristics or hair loss features
between the lasercomb and sham group in any of the four
trials at baseline (Tables 1 and 2). The age of the subjects
was 25–61 years, and 94.7 % were Caucasian. The last
follow-up was conducted after 26 weeks of treatment, an
accepted standard for clinical trials on hair growth.

3.2.1 Primary Efficacy Analysis
In Trial #1, a significant difference in terminal hair densitychange from baseline was observed between the 9-beamlasercomb- and sham-treated female subjects at 26 weeks(p \ 0.0001) (Fig. 2a). The lasercomb-treated subjects
showed a much higher increase in terminal hair density
compared with sham-treated subjects, with a mean of 20.2(±11.2 standard deviation [SD]) versus 2.8 (±16.5 SD) per
cm2 (Fig. 2a). Similar improvement in terminal hair density was observed with the 12-beam lasercomb treatment in
Trial #2 (Fig. 2b). The lasercomb-treated female subjects

Study #1
Female, 9-beam

Study #2
Female, 12-beam

Study #3
Male, 7-beam

Study #4
Male, 9- or 12-beam

10/28/09 – 02/18/10

02/01/10 – 09/28/10

08/25/09 – 01/08/10

07/29/09 – 12/11/09

Subjects screened
N=117

Subjects screened
N=71

Subjects screened
N=57

Subjects screened
N=89

Did not meet criteria
n=39

Did not meet criteria
n=8

Did not meet criteria
n=8

Did not meet criteria
n=10

Randomized: n=78

Randomized: n=63

Randomized: n=49

Randomized: n=79

9-beam n=53,
Sham n=25

12-beam n=42,
Sham n=21

7-beam n=33,
Sham n=16

9-beam n=25,
12-beam n=28,
Sham n=26

16-week follow-up:
n=65
9-beam n=43,
Sham n=22
Lost to follow-up/
consent
withdrawal: n=13

16-week follow-up:
n=57
12-beam n=39,
Sham n=18
Lost to follow-up/
consent withdrawal:
n=6

16-week follow-up:
n=38
7-beam n=24,
Sham n=14
Lost to follow-up/
consent withdrawal:
n=11

16-week follow-up:
n=65
9-beam n=21,
12-beam n=22,
Sham n=22
Lost to follow-up/
consent withdrawal:
n=14

26-week follow-up:
9-beam n=42,
Sham n=21
Lost to follow-up:
n=2

26-week follow-up:
12-beam n=39,
Sham n=18
Lost to follow-up:
n=0

26-week follow-up:
7-beam n=24,
Sham n=14
Lost to follow-up:
n=0

26-week follow-up:
9-beam n=21,
12-beam n=19,
Sham n=21
Lost to follow-up:
n=4

Efficacy n=65

Efficacy n=57

Efficacy n=38

Efficacy n=65

J. J. Jimenez et al.
Table 1 Demographic characteristics of female subjects at baseline for the 9- and 12-beam lasercomb trials
Trial #1 (n = 65)

Number of subjects

Trial #2 (n = 57)

9-beam lasercomb

Sham

43

22

p valueAge (years)
Mean age (SD)

12-beam lasercomb

Sham

39

18

48.7 (10.2)

49.1 (8.3)

0.826149.3 (9.1)

49.8 (7.3)

0.9102

Median age

52

49

50

49

Range

29–60

37–60

26–61

33–60

39 (90.7 %)1 (2.3 %)

20 (90.9 %)0 (0 %)

37 (94.9 %)
1 (2.6 %)

18 (100.0 %)0 (0 %)

Race, n (%)
CaucasianAfrican American

1.00001.0000Native American

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

Alaska Native

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

Asia/Pacific Islander

2 (4.7 %)

1 (4.5 %)

1 (2.6 %)0 (0 %)Other

1 (2.3 %)

1 (4.5 %)0 (0 %)

0 (0 %)

Ethnicity, n (%)

0.27731.0000

Hispanic or Latino

13 (30.2 %)

10 (45.5 %)

10 (25.6 %)

4 (22.2 %)Not Hispanic or Latino

30 (69.8 %)

12 (54.5 %)

29 (74.4 %)

14 (77.8 %)
6 (33.3 %)Ludwig/Savin classification, n (%)

0.65130.2926I-4

12 (27.9 %)

3 (13.6 %)21 (53.8 %)II-1

11 (25.6 %)

7 (31.8 %)

11 (28.2 %)

6 (33.3 %)II-2

15 (34.9 %)

9 (40.9 %)

6 (15.4 %)

4 (22.2 %)Frontal

5 (11.6 %)

3 (13.6 %)

1 (2.6 %)

2 (11.1 %)Fitzpatrick skin type, n (%)

1.00000.7606III

0 (0 %)
15 (34.9 %)0 (0 %)
7 (31.8 %)2 (5.1 %)
11 (28.2 %)0 (0 %)
4 (22.2 %)III

20 (46.5 %)

11 (50.0 %)14 (35.9 %)

9 (50.0 %)IV

8 (18.6 %)4 (18.2 %)

12 (30.8 %)

5 (27.8 %)Mean baseline hair counta (SD)

162.6 (46.2)

155.7 (43.5)

142.2 (40.5)

168.4 (41.1)

ap value

Number of terminal hairs per cm2 in the target area

SD standard deviation

had a mean increase in terminal hair density of 20.6 (±11.6SD) compared with 3.0 (±9.3 SD) for the sham group(Fig. 2b). Overall, primary efficacy analysis showed thedifference in terminal hair density change at 26 weeks
from baseline between lasercomb and sham treatment was
highly significant (p \ 0.0001) in both female trials(Fig. 2a, b). Similarly, statistically significant improvement
was observed with lasercomb treatment compared withsham treatment in both male trials (Trial #3, 7-beamlasercomb vs. sham, p = 0.0017, Fig. 2c; Trial #4, 9- and12-beam lasercombs vs. sham, p = 0.0249 and
p = 0.0028, for the 9- and 12-beam lasercombs, respectively, Fig. 2d).
3.2.2 Secondary Efficacy Analyses
Secondary efficacy analyses included categorical summaries and covariate analyses of changes in terminal hairdensity from baseline. In Trial #1, 41 of 43 (95 %) of the

9-beam lasercomb-treated female subjects had hair density
improvement of [5 hairs/cm2 at 26 weeks while only 7 of
22 (32 %) sham-treated female subjects did (p \ 0.0001)(Fig. 2e). Additionally, none of the 43 lasercomb-treatedsubjects showed decreased hair density as opposed to 11 of
22 (50 %) sham-treated subjects (Fig. 2e). Analysis of datacollected at 16 weeks revealed similar results (data notshown). In Trial #2, 37 of 39 (95 %) of the 12-beamlasercomb-treated female subjects had hair density
improvement of [5 hairs/cm2 while only 6 of 18 (33 %)sham-treated female subjects did (p \ 0.0001) (Fig. 2f).
Although 7 of 18 (39 %) sham-treated subjects showeddecreased hair density, only 1 of 39 (3 %) lasercombtreated subjects did (Fig. 2f).
In Trial #3, 20 of 24 (83 %) of the 7-beam lasercombtreated male subjects had hair density improvement of [5hairs/cm2, while only 6 of 14 (43 %) sham-treated malesubjects did (p = 0.0033) (Fig. 2g). Additionally, only 2 ofthe 24 (8 %) lasercomb-treated male subjects showedLasercomb Treatment of Male and Female Pattern Hair Loss
Table 2 Demographic characteristics of male subjects at baseline for the 7-, 9-, or 12-beam lasercomb trials
Trial #3 (n = 38)

Number of subjects

7-beamlasercomb

Sham

24

14

Age (years)

Trial #4 (n = 65)
p value

9-beamlasercomb

12-beamlasercomb

Sham

21

22

22

0.03270.7100Mean age (SD)Median age

47.8 (9.0)
48

40.9 (9.5)
41.5

45.6 (9.3)
50

47.9 (9.6)
50.5

45.9 (10.4)
47

Range

26–59

25–55

26–58

26–59

30–61

23 (95.8 %)

13 (92.9 %)

21 (100.0 %)21 (95.5 %)

21 (95.5 %)Race, n (%)
Caucasian

1.00001.0000African American

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

Native American

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

Alaska native

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

Asia/Pacific islander

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

1 (4.5 %)Other

1 (4.2 %)

1 (7.1 %)0 (0 %)

1 (4.5 %)0 (0 %)

4 (19.0 %)

1 (4.5 %)0 (0 %)

17 (81.0 %)21 (95.5 %)

22 (100.0 %)Ethnicity, n (%)

0.6497

Hispanic or Latino

3 (12.5 %)

3 (21.4 %)Not Hispanic or Latino

21 (87.5 %)

11 (78.6 %)Norwood–Hamilton classification,
n (%)

0.041

0.91301.0000II

0 (0 %)

0 (0 %)

0 (0 %)

0 (0 %)

1 (4.5 %)III

10 (41.7 %)

5 (35.7 %)

10 (47.6 %)

10 (45.5 %)

10 (45.5 %)IV

9 (37.5 %)

5 (35.7 %)

8 (38.1 %)

9 (40.9 %)

7 (31.8 %)V

5 (20.8 %)

4 (28.6 %)3 (14.3 %)

3 (13.6 %)4 (18.2 %)2 (9.1 %)Fitzpatrick skin type (%)

0.79040.998

I

1 (4.2 %)0 (0 %)

3 (14.3 %)2 (9.1 %)II

3 (12.5 %)

3 (21.4 %)

9 (42.9 %)

10 (45.5 %)

9 (40.9 %)III

12 (50.0 %)5 (35.7 %)

7 (33.3 %)

8 (36.4 %)

9 (40.9 %)IV

8 (33.3 %)

6 (42.9 %)2 (9.5 %)2 (9.1 %)

2 (9.1 %)Mean baseline hair counta (SD)

211.5 (54.0)

216.6 (34.8)

163.3 (69.4)

151.5 (42.4)

171.4 (62.3)

ap value

Number of terminal hairs per cm2 in the target area

SD standard deviation

decreased hair density, while 6 of 14 (43 %) sham-treatedsubjects did (Fig. 2g). In Trial #4, lasercomb-treated malesubjects showed a higher percentage for hair density
improvement of [5 hairs/cm2 with either lasercomb model(86 % for the 9-beam model and 82 % for the 12-beammodel) than the sham-treated subjects (59 %) (Fig. 2h).
Whereas 9 of 22 (41 %) sham-treated subjects showeddecreased hair density, only 3 of 21 (14 %) 9-beam lasercomb-treated subjects and 4 of 22 (18 %) 12-beam lasercomb-treated subjects did (p = 0.0033) (Fig. 2h).
Overall, we observed significant categorical improvement in terminal hair density with lasercomb treatment
versus control (Fig. 2e–h). Taken together, all four trials
using three different lasercomb models in both male andfemale subjects showed improvement in terminal hairdensity that was highly statistically significant, as well as

categorical improvement, with lasercomb treatment compared with sham treatment at 26 weeks.
3.2.3 Subject Self-Assessment
A higher percentage of lasercomb-treated subjects reported
overall improvement of hair loss condition and thickness
and fullness of hair in self-assessment, compared withsham-treated subjects (Table 3). In Trial #1, statisticalsignificance was reached for the assessment of both theoverall improvement of hair loss condition and thickness
and fullness of hair. Results in Trial #2 did not reach statistical significance. In the pooled male subject trials,
assessment of the thickness and fullness of hair reachedstatistical significance, but not the overall improvement of
hair loss condition (Table 3).

J. J. Jimenez et al.

Changes in Terminal
Hair Density (per cm2)

ab
Changes in Terminal
Hair Density (per cm2)e

Trial #1. Female 9-beam
35
30
25
20
15
10
5
0
-5
-10
-15

35
30
25
20
15
10
5
0
-5
-10

Trial #1. Female 9-beam
60%

56%

50%
40%
20.2
14.8
1.3

2.8

sham

30%

9-beam

20%

40%

36%

sham

27%
14%

10%

0

0%

0%

0%

9-beam18%
5%5%
p<0.0001

p<0.0001
0

16 weeks 26 weeks

Categorical Change in Terminal Hair Density (count/cm2)f

Trial #2. Female 12-beam

Trial #2. Female 12-beam

60%

54%

50%
41%

40%
20.6
11.9

sham

30%

12-beam

20%

3.0

-0.8

28%

0%

p<0.0001

sham

28%

12-beam

11%

10%

0
0

28%

3%

0%

6%

3%

p<0.0001

16 weeks 26 weeks
Categorical Change in Terminal Hair Density (count/cm2)

Changes in Terminal
Hair Density (per cm2)

cg

Trial #3. Male 7-beam
35
30
25
20
15
10
5
0
-5
-10

Trial #3. Male 7-beam
50%

46%
43%

40%

38%

30%
17.7

18.4

2.8

1.6

sham

20%

7-beam

0

10%

21%

7-beam
14%
8%

4%

4%

0%

0%

p=0.0017
0

sham
21%

p=0.0033

16 weeks 26 weeks
Categorical Change in Terminal Hair Density (count/cm2)

Changes in Terminal
Hair Density (per cm2)

d
45
40
35
30
25
20
15
10
5
0
-5

h

Trial #4. Male 9- or 12-beam

80%

Trial #4. Male 9- or 12-beam
68%

60%
23.5
20.4

25.7

sham

20.9

9-beam12-beam

45%
38%

40%
20%

4.4
0

p=0.0249
p=0.0028

16 weeks 26 weeks

Fig. 2 a–d Mean changes in terminal hair density (count per cm2)from baseline in subjects treated with the lasercomb or sham device.
Bars indicate standard deviation. e–h Categorical changes in terminal

0%

0%

sham
9-beam12-beam

23%

9.4
0

48%

18% 14%14%
5%14%14%

p=0.0067
p=0.0033

Categorical Change in Terminal Hair Density (count/cm2)

hair density (count per cm2) from baseline to 26 weeks in subjects
treated with the lasercomb or sham device. Shown are p values at
26 weeks

LOCF last observation carried forward* Statistically significant

1 (2.3)

Worse/ minimally worse
p = 0.0321*

6 (14.0)36 (83.7)

No change

Improved/ minimally improved

Week 26 (LOCF), n (%)

0 (0)Worse/ minimally worse
p = 0.0149*

7 (16.3)

36 (83.7)

No change

Improved/ minimally improved

Week 16 (LOCF), n (%)

0 (0)11 (50.0)

11 (50.0)

1 (4.5)9 (40.9)

12 (54.5)

28 (65.1)

p = 0.0345*

0 (0)12 (27.9)

31 (72.1)

p = 0.0982

0 (0)15 (34.9)0 (0)12 (54.5)

10 (45.5)

0 (0)14 (63.6)

8 (36.4)

Sham(n = 22)p = 0.1713

2 (5.1)

11 (28.2)

26 (66.7)

p = 0.0546

3 (7.7)

11 (28.2)

25 (64.1)

Lasercomb(n = 39)

1 (5.6)6 (33.3)

11 (61.1)

2 (11.1)

9 (50.0)

7 (38.9)

Sham(n = 18)

Lasercomb(n = 43)

Lasercomb(n = 43)

Sham(n = 22)Overall improvementof hair loss condition

Thickness andfullness of hair

Overall improvementof hair loss conditionp = 0.1000

1 (2.6)

14 (35.9)

24 (61.5)

p = 0.2667

1 (2.6)15 (38.5)

23 (59.0)

Lasercomb(n = 39)

2 (11.1)

7 (38.9)9 (50.0)0 (0)10 (55.6)

8 (44.4)

Sham(n = 18)

Thickness andfullness of hair

Trial #2. Female 12-beam

Trial #1. Female 9-beam

Table 3 Subject self-assessment of efficacy (last observation carried forward)p = 0.0717

2 (3.0)25 (37.3)

40 (59.7)

p = 0.0706

1 (1.5)27 (40.3)

39 (58.2)

Lasercomb(n = 67)

3 (8.3)16 (44.4)

17 (47.2)

1 (2.8)23 (63.9)

12 (33.3)

Sham(n = 36)Overall improvementof hair loss conditionp = 0.0114*

1 (1.5)28 (41.8)

38 (56.7)

p = 0.2484

2 (3.0)28 (41.8)

37 (55.2)

Lasercomb(n = 67)

2 (5.6)21 (58.3)

13 (36.1)

2 (5.6)19 (52.8)

15 (41.7)

Sham(n = 36)

Thickness andfullness of hair

Trials #3 and #4. Male 7-, 9- and 12-beam (pooled)

Lasercomb Treatment of Male and Female Pattern Hair Loss

J. J. Jimenez et al.
Fig. 3 Male and female patternhair loss before and afterlasercomb treatment. Global
photographs of a female subject,
at baseline (a) and after
26 weeks (b) of the 12-beamlasercomb treatment.
Macrophotographs of a malesubject, at baseline (c) and after
26 weeks (d) of the 9-beamlasercomb treatment. Increased
hair count through conversionof vellus or intermediate
follicles to active follicles
producing terminal hair (ovals)
or resting telogen to active
anagen follicles (rectangles) ishighlighted

3.2.4 Meta-Analysis of the Effects of Lasercomb Model,
Study Duration, and GenderMeta-analyses were conducted to provide an overall
assessment of the individual study results. The overall
results showed the least squares mean difference of change
in terminal hair density of 15.27 (standard error 1.781) at
26 weeks from baseline between lasercomb- and shamtreated subjects, which was highly statistically significant(p \ 0.0001). The homogeneity assessment results were
non-significant (p = 0.6188). These results indicated thatcompared with sham treatment, lasercomb treatment
resulted in a statistically significant increase in terminal
hair density across the trials, independent of the lasercomb
model (7- and 9-beam 655 nm ± 5 % laser and 12-beam
635 nm and 655 nm ± 5 % laser) and the sex of thesubject.
Before and after global photographs (Fig. 3a, b) andmacrophotographs (Fig. 3c, d) demonstrated increases interminal hair density, most likely through the conversion ofvellus or intermediate follicles to terminal follicles or fromresting telogen follicles to active anagen follicles.
In summary, efficacy analysis showed a statisticallysignificant increase in terminal hair density after 26 weeksof lasercomb treatment compared with sham treatment.
The mean increase in terminal hair density was higher(statistically significant) in lasercomb-treated subjects thanin sham-treated subjects. Additionally, a higher percentageof lasercomb-treated subjects showed categorical hairdensity improvement ([5 hairs/cm2) at 26 weeks, compared with sham-treated subjects. Such improvement wasobserved in all four trials, and independent of the sex andage of the subject, and independent of the lasercomb model

when similar laser dose rates were delivered. A higher
percentage of lasercomb-treated subjects reported overall
improvement of hair loss condition and thickness andfullness of hair in self-assessment, though the results did
not always reach statistical significance.
3.3 Safety and Tolerability
No serious adverse events were reported in any subject
receiving the lasercomb in any of the four trials. Reported
lasercomb-related adverse events included dry skin(5.1 %), pruritus (2.5 %), scalp tenderness (1.3 %), irritation (1.3 %), and a warm sensation at the site (1.3 %). No
subjects experienced an adverse event that resulted in the
discontinuation of the study device, or interruption of thestudy. No adverse events had an impact on the study device
use. There were no significant differences in active device
adverse events as recorded by device type.

4 Discussion
Pattern hair loss may affect up to 70 % of men and 50 % of
women at some point in their lifetime [3, 4]. There has
been an urgent need to determine whether LLLT homedevices, which have been widely promoted for the treatment of MPHL and FPHL despite few randomized, controlled trials, can provide an effective alternative forpatients with pattern hair loss, especially female patients.
In this study, through four randomized, multicenter, shamdevice-controlled and double-blind clinical trials, we haveshown that 26 weeks of treatment with the FDA-cleared
HairMax LaserCombÒ, compared with sham treatment,

Lasercomb Treatment of Male and Female Pattern Hair Loss

resulted in a statistically significant terminal hair density
increase. Our results not only verified the effective treatment of MPHL reported previously [8], but also showedtreatment efficacy in female subjects, and demonstrated
that the treatment efficacy was independent of the laser
configurations tested when similar laser dose rates weredelivered. No serious adverse events were reported in any
subject receiving lasercomb treatment in any of the four
trials.
We have observed increased terminal hair density likely
through both conversion of vellus or intermediate follicles
to active follicles producing terminal hair and conversion ofresting telogen follicles to active anagen follicles (Fig. 3c,d). The exact mechanisms of such conversions by LLLT
remain unknown. Commonly used LLLT encompasses awavelength of 500–1,100 nm and delivers fluences of
1–4 J/cm2 with a power density of 3–90 mW/cm2, and has
demonstrated beneficial effects in various conditions
including wound healing, joint pain relief, mucositis prevention and treatment, and skin conditions [15–22]. Basedon anecdotal experience, LLLT of 650–900 nm wavelengths at 5 mW has been suggested to be an effective
treatment option for male and female patients with patternhair loss [23], though comprehensive studies evaluating
laser modality are lacking. Whereas the exact mechanismsof hair growth stimulation by LLLT remain unknown,
LLLT has been proposed to accelerate mitosis [24], andmay stimulate HF stem cells or activate follicular keratinocytes. Additionally, laser light may alter cell metabolism
through photodissociation of inhibitory nitric oxide from
cytochrome c oxidase [25] (unit IV in the respiratory chainof mitochondria), causing increased ATP production andcellular activity [26]. Furthermore, resolution of inflammation may be one potential mechanism of hair growth
stimulation by LLLT in AGA [27–32]. In vitro and in vivo
trials of LLLT have shown decreased inflammatory prostaglandin E-2 [32] and proinflammatory cytokines [30], andin contrast, increased anti-inflammatory cytokines transforming growth factor-beta 1 and interleukin-10 [27, 28].
Results from the present investigation are consistent
with the previous study of the 9-beam lasercomb in male
AGA subjects by Leavitt et al. [8]. Both studies demonstrated a higher increase in terminal hair density withlasercomb treatment versus sham treatment, which wasstatistically significant, with a positive safety profile for thedevice. However, the current study enrolled both male andfemale subjects, and tested a range of laser configurations(8 min of treatment for the 12-beam model, 11 min for the
9-beam model, and 15 min for the 7-beam model, so thatthe three models gave similar laser dose rates per treatment), making it a more comprehensive study. While wefound the lasercomb to be also efficacious in increasing

terminal hair count in female subjects, we feel we cannot
directly compare our results with another lasercomb studyof female subjects (n = 7) as the baseline hair counts were
too different (71–307/cm2 vs. 8–32/cm2) [9]. A recent
study described the high efficacy of treating MPHL using ahelmet-like low-level laser device, called TOPHATÒ, in arandomized, double-blind, controlled trial [7]. While the
TOPHATÒ study was for 16 weeks with treatment every
other day for a total of 60 treatments versus 78 treatments
in total in this lasercomb study, the laser dose rates pertreatment in the TOPHATÒ study were much higher (there
were 21 5-mW laser units). Future studies are required to
optimize laser modality and treatment regimen for hair
growth and maintenance.
The increase in terminal hair density per cm2 observedin our study is comparable to that observed in a 6-monthrandomized, investigator-blinded, controlled trial of 5 %minoxidil solution in MPHL [33], but lower than thatobserved in 48-week studies of 5 % and 2 % minoxidil
topical solution in MPHL [34] and FPHL [35]. Our resultsin the increase in terminal hair count are comparable to1 mg/day finasteride treatment in some MPHL trials [36,37], but less efficacious than longer term trials [38].
LLLT may provide a promising treatment option forpatients who do not respond to either finasteride orminoxidil, and who do not want to undergo hair transplantation. Additionally, while topical minoxidil solution
or foam is widely used to treat pattern hair loss and isgenerally well tolerated [39], the treatment needs to be
applied once or twice daily, and be in contact with the scalp
for at least 4 h. Such application can be impractical formany users, leading to noncompliance and reduced efficacy. As an alternative, the lasercomb treatment is safe andeasy to apply, with 8–15 min of treatment three times per
week, and leaves no residue on the scalp. Such user
friendliness of the lasercomb may lead to better patientcompliance and improved efficacy. Future studies tomodulate laser modality and treatment regimen will help
optimize hair growth stimulation and maintenance by lowlevel laser.

5 Conclusions
In four randomized, double-blind, sham-controlled trials of
MPHL and FPHL, we detected a statistically significant
increase in terminal hair density after 26 weeks of lasercomb treatment compared with sham treatment. Such
improvement was independent of the sex and age of thesubject, and independent of the lasercomb model whensimilar laser dose rates were delivered. A higher percentageoflasercomb-treatedsubjects
reportedoverall

J. J. Jimenez et al.

improvement of hair loss condition and thickness andfullness of hair in self-assessment, though the results did
not always reach statistical significance. Increase in terminal hair count was comparable to the short-term trials of
5 % minoxidil topical solution and 1 mg/day finasteride,
but less efficacious than longer term (C1 year) trials.
Further clinical trials are needed to define the optimal
duration of treatment, the duration of response, and the useof the lasercomb in other alopecia conditions.
Acknowledgments The authors would like to thank Zoe Draelos,
MD (Dermatology Consulting Services, High Point), David Goldberg,
MD (Skin Laser and Surgery Specialist, Hillsborough, NJ, USA;
Hackensack, NJ, USA), Michael Jarratt, MD (DermaResearch, Inc.,
Austin, TX, USA), Abe Marcadis, MD (Palm Beach Research Center,
West Palm Beach, FL, USA), and Jose Mendez, DO (International
Dermatology Research, Inc., Miami, FL, USA) for their participation.
Statistical analyses were contracted to Stat-Tech Services, LLC(Chapel Hill, NC, USA). Lexington International, LLC partially
funded the study, and provided the treatment and sham devices andequipment (including the digital imaging system). M.R. Hamblin hasreceived honorarium/consulting fees, and L.A. Schachner hasreceived fees for participation from Lexington International, LLC.
M. Hordinsky has received, on behalf of the Department of Dermatology at the University of Minnesota, a grant to conduct part of thisstudy. J.J. Jimenez, T.C. Wikramanayake, W.F. Bergfeld, and J.G.
Hickman have no conflicts of interest that are directly relevant to thisstudy. M.R. Hamblin was supported by a NIH grant R01AI050875.
The authors have full control of all primary data, and agree to allow
the journal to review their data if requested.
Open Access This article is distributed under the terms of theCreative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and the source are credited.

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