efficacy of off-label topical treatments for the
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Gupta, Aditya K., Mays, Rachel R., Versteeg, Sarah G., Shear, Neil H., Piguet, Vincent and
Piraccini, Bianca Maria 2019. Efficacy of off-label topical treatments for the management of
androgenetic alopecia: a review. Clinical Drug Investigation 39 (3) , pp. 233-239. 10.1007/s40261-
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1
EfficacyofOff-LabelTopicalTreatmentsfortheManagementofAndrogeneticAlopecia:a
SystematicReview
AdityaK.GuptaM.D.,Ph.D.1,2,RachelR.MaysB.Sc.
1,SarahGVersteegM.Sc.
1,NeilH.ShearM.D.
2,3,
VincentPiguetM.D.,Ph.D.2,4,5
andBiancaMariaPiracciniM.D.6
1MediprobeResearchInc.,London,Canada
2DivisionofDermatology,DepartmentofMedicine,UniversityofTorontoSchoolofMedicine,Toronto,Canada
3DivisionofDermatology,SunnybrookHealthSciencesCentre,Toronto,Canada
4DivisionofDermatology,Women'sCollegeHospital,Toronto,Canada
5DivisionofInfectionandImmunity,CardiffUniversitySchoolofMedicine,Cardiff,UnitedKingdom
6Dermatology,DepartmentofExperimental,DiagnosticandSpecialtyMedicine,UniversityofBologna,Italy
CorrespondingAuthor:
A.K.Gupta
MediprobeResearchInc.
645WindermereRoad
London,Ontario,CanadaN5X2P1
Phone:519-851-9715
Fax:519-657-4233
Email:[email protected]
CompliancewithEthicalStandards
Funding:Thispaperwasnotfunded.
Conflictofinterest:Dr.PiguetreportsreceivingeducationalgrantsinhisroleasDepartmentDivision
Director,Dermatology,UniversityofToronto(onbehalfoftheDivisionofDermatologyResidency
Program)fromAbbvie,Celgene,Janssen,Naos,Lilly,Sanofi,Valeant,andnon-financialsupportfromLa
Roche-Posay,outsidethesubmittedwork.
2
Abstract
Androgeneticalopecia(AGA)ischaracterizedbynon-scarringfollicleminiaturization.Despitethe
successofapprovedtherapies,commonlyreportedsideeffectsandtheneedforcontinualusehasled
totheinvestigationofalternativetherapies.Theaimofthispaperistocriticallyreviewthesuccessof
off-label,topicalmonotherapiesfortreatmentofAGAinmen.Aliteraturesearchwasconductedto
obtainrandomized,controlledandblindedstudiesthatinvestigatedoff-label,topical,monotherapiesin
malepatients.Hairdensity,hairdiameterandhairgrowthwereusedtoevaluatetreatmentsuccess.
Fourteenoff-labeltopicaltherapieswereinvestigatedamongthe16studiesthatmetinclusioncriteria.
Nineoff-labeltherapieswerereportedtoproduceasignificantlygreaterimprovementinhair
restorationparameters(e.g.,meanchangefromhaircountandhairdiameter)ascomparedtoplacebo
(p<0.05foralltreatments).Intwostudies,procyanidinoligomersexhibitedgreaterefficacyovervehicle
withresponsetomeanchangeinhairdensity(hairs/cm2)(ps<0.0001atweek24).Inconclusion,
prostaglandinanalogsandpolyphenols,suchaslatanoprostandprocyanidinoligomers,canimprove
hairrestorationparametersinmaleAGApatients,possiblythroughtargetingmechanismsproposedin
theetiologyofAGA.Thecurrentevidencesuggestsshortterm(24weeks)usemayprovidebenefitfor
hairlosspatients;however,long-termefficacyandsafetydataarerequired.
KeyPoints
• Duetothepotentialsideeffectsandtheneedforcontinualuseofapprovedtherapies,thereisa
needtoexploretheefficacyofoff-labeloptions.
• Eightoff-labeltopicaltherapies,includingprostaglandinanalogsandpolyphenols,werefoundto
improvehairdensity,whileoneadditionaltherapyimprovedhairdiameter.
Keywords:androgeneticalopecia,off-labeltherapies,prostaglandinanalogs,polyphenols
3
1.0Introduction
Androgeneticalopecia(AGA)isacommonhairlossdisordercharacterizedbynon-scarring
follicleminiaturization1.TheetiologyofAGAismultifactorialandpolygenetic,withandrogensplaying
apivotalrole2,3.Finasteride,anoral5-αreductaseinhibitor,andminoxidil,atopicalvasodilator,are
FDAandHealthCanadaapprovedfortreatmentofAGA4–7.Despitetheirsuccess,theseapproved
therapieshaveseveraldrawbacks.Theirimprovementinhairrestorationparameterstendstoplateau
afterafewyearsofcontinueduse.Inaddition,theseapprovedtherapieshavebeenassociatedwithside
effectssuchasskinirritationandsexualdysfunction4–7.Thus,thereisaneedfornew,safeandeffective
treatmentsforAGA.Theaimofthispaperistocriticallyreviewthesuccessofoff-label,topical
therapiesfortreatmentofandrogeneticalopeciainmen.
2.0MethodsofLiteratureSearch
AliteraturesearchinPubMed,MEDLINE(Ovid),Embase(Ovid),andCINAHLwasconducted
usingthefollowingsearchterms:‘androgeneticalopecia’,‘malepatternbaldness’,‘AGA’and
‘randomizedcontrolledtrial’(February2018).Randomized,controlled(placeboorvehicle)andblinded
(single,doubleortriple)trialsthatinvestigatedtopicaloff-labelmonotherapiesforthetreatmentof
androgeneticalopeciainmalepatientswereincluded.Studiesthatinvestigatedoralorcombination
therapies,includedonlyfemalepatients,and/orincludedalopeciaconditionsotherthanandrogenetic
alopeciawereexcluded.Eligiblestudieswererequiredtoevaluatetreatmentsuccessusinghairdensity
(hair/cm2),hairdiameter(mm)orhairgrowth(mm/cm
2).Clinicaloutcomesvarywidelyamongstudies;
weselectedarangeofquantitativemeasurementstobeasinclusiveandobjectiveaspossible.
3.0ResultsofLiteratureSearch
Sixteenstudiesmetinclusioncriteria(Figure1)8–23
.Atotalof1,709maleparticipantswere
includedwithanaverageageof40years.Fourteenoff-labeltopicaltherapieswereinvestigated:a
4
penta-peptide(Gly-Pro-Iie-Gly-Ser),adenosine,bimatoprost,Curcumaaeruginosaextract,dabao,
fulvestrant,aherbalextract,latanoprost,anon-steroidalanabolichormonegel,procyanidinoligomers,
pyrithionezinc,roxithromycin,sodiumvalproateandviprostol(Tables1-3)8–23
.Treatmentduration
rangedfrom4weeks23to52weeks
21with24weeksthemostcommonduration(10/16=63%)
9,12,15–19,21–
23.Investigatedtherapieswereadministeredinawidearrayofformulationsincludingcream(herbal
extract11),gel(non-steroidalanabolichormones
18),lotion(adenosine,penta-peptide,dabao,
roxithromycin12-14,17
),shampoo(pyrithionezinc8),solution(bimatoprost
22-23,latanoprost
9,Curcuma
aeruginosaextract20,fulvestrant
10,procyanidin
16,21,viprostal
19),andspray(sodiumvalproate
15).
3.1HairDensity
Fifteenincludedstudiesusedhairdensitytoevaluatetreatmentsuccessofoff-labeltherapiesin
AGApatients8–11,13,15-23
.Themeanchangeinhairdensity(hairs/cm2)frombaselinetoendoftreatment
foroff-labeltherapiesrangedfrom-4hairs/cm2to54hairs/cm
2(Table1).Eightoff-labeltherapies
(pyrithionezincshampoo,latanoprost,aherbalextract,adenosine,sodiumvalproatespray,procyanidin
oligomers,dabao,andanon-steroidalanabolichormonesolution)hadasignificantlyhighermean
changefrombaselineascomparedtoplacebo(p<0.05foralltreatments)8,9,11,13,15–18,21
.Thehighestmean
changeinhairdensity(hairs/cm2)after24weeksoftreatmentwasfoundwithlatanoprost(Figure2)
9.
Twostudiesreportedprocyanidinoligomertreatmentexhibitedgreaterefficacyovervehiclewith
responsetomeanchangeinhairdensity(hairs/cm2)byendof24weeksoftreatment(ps<0.001)
16,21.
3.2HairDiameter
Twoincludedstudiesusedchangesinhairdiametertoevaluatetreatmentsuccessofoff-label
therapiesinAGApatients(Table2)8,12
.Meanchangeinhairdiameter(mm)ascomparedtobaselinewas
significantlyhigherwithroxithromycinascomparedtovehicleafter24weeksoftreatment(p<0.01)12,
whereas,26weeksofpyrithionezinctreatmentwasnotsignificantlydifferentfromplacebotreatment8.
5
3.3HairGrowth
Threestudiesmeasuredtheimpactofoff-labeltopicaltherapyonmeanchangeinhairgrowth,
asdefinedasmm/cm2frombaseline,comparedtovehicletreatedpatients(Table3)
10,22,23.Bimatoprost
treatmentonceortwiceadayproducedameanchangeinhairgrowthafter24weeksoftreatmentof
0.76mm/cm2and0.92mm/cm
2,respectively
22,23.Asignificantlylowermeanchangeinhairgrowthwas
foundwithfulvestrantascomparedtominoxidilafter16weeksoftreatment(p<0.001)10.
4.0Discussion
Inrecentyears,manynoveltreatmentsfortreatingAGAandotherhairlosshavebeen
investigated.Theobjectiveofthisreviewwastoevaluatetherapeutic,off-labeloptionsavailabletotreat
AGA.TheexistingpharmaceuticaltherapiesforAGAareoralfinasterideandtopicalminoxidil;someof
theoff-labeltreatmentsdiscussedinthisreviewworkviasimilarmechanisms.Eightoff-labeltherapies
(pyrithionezincshampoo,latanoprost,aherbalextract,adenosine,sodiumvalproatespray,procyanidin
oligomers,dabao,anon-steroidalanabolichormonesolution)producedsignificantincreasesinhair
density,whileroxithromycinsignificantlyincreasedhairdiameter8,9,11-13,15–18,21
.Apartfrom
placebo/vehicle,minoxidil5%wasusedasanactivecomparatorinthreestudies,whereitwas
significantlybetterthanfulvestrant10,numericallysimilartopyrithionezincshampoo
8andC.aeruginosa
extract20,andnumericallybetterthanbimatoprostformulations
22.Althoughsafetywasnotafocusof
thisreview,allbutfourstudies8,17-19
monitoredadverseevents.Therewerenoadverseeventsor
adverseeventsrelatedtotreatmentforherbalextract,adenosine,procyanidinoligomers,and
roxithromycin.Studiesofbimatoprost,latanoprost,fulvestrant,herbalextract,valproate,andCurcuma
aeruginosareportedmildskin-relatedadverseeventssuchaserythema,pruritus,urticarial,or
dermatitis.Mostofthetreatmentsappeartobewell-toleratedandsafeintheshort-term.
6
Ofthe24weektreatments,latanoprost,aprostaglandinanalogantagonist,wasfoundtohave
thehighestmeanchangeinhairdensity(hairs/cm2)9.Prostaglandinanalogs,whichincludelatanoprost,
bimatoprostandviprostol,canstimulatekeratinocyteandmelanocyteactivity,enhancinghairgrowth
andpigmentation24.Interestingly,viprostol,asyntheticprostaglandininhibitor,wasnotaneffective
treatment19.Thisfindingcouldbeduetothesyntheticnatureofviprostol,thehairlossseverityof
includedpatients(IIIvtoV)orthedosageused.
Intwostudies,procyanidinoligomersexhibitedagreaterefficacyovervehiclebyendof
treatmentwithresponsetomeanchangeinhairdensity(hairs/cm2)16,21
.Procyanidinoligomers,and
otherpolyphenols,mostlikelypromotehairgrowthvianitricoxide,agasproducedintheliningofveins
whichpromotesvasodilationandreducescholesterolbuild-up.Polyphenolshavealsobeenshownto
inhibit5α-reductaseactivitywhichhasbeentheorizedtoplayaroleinthepathogenesisofAGA25.
Regardlessofthesepromisingeffects,moreclinicaltrialsneedtobeconductedbeforetheuse
oftheseoff-labeltreatmentsissanctioned.Ofparticularnoteisthatthecurrentevidenceforoff-label
treatmentsisfromclinicalstudiesthatareshortinduration,with24weeksthemostcommon.Long-
termefficacyandsafetydataarenotavailableandwearethusunabletodrawcomparisonswith
approvedtherapies.Whileimprovementcanplateauovertimewithfinasterideandminoxidil,thelong-
termefficacyofoff-labeltreatmentsisunknown.Thepatientsintheincludedstudieswere
predominantlymaleanddifferencesintreatmentefficacybetweenmalesandfemalesshouldbekeptin
mind.Therapieswithmulti-factorialcapabilitiesmaybemoreappropriatefortreatingfemalepattern
hairloss,whereas,malepatternhairlosspatientsbenefitmorefromadirectanageneffect2.
Additionally,animportantlimitationwhenevaluatingefficacyofhairlosstreatmentsisthe
varietyofoutcomemeasuresusedtomeasuresuccessfulhairgrowth;thereisnoacceptedindustry
standard.Assessmentofglobalphotographsbyanexpert,haircountsusingphototrichogram,and
7
manualhaircountsusingclippingsorhairdensityinatargetareawereallreportedinstudies.Global
assessmentsbasedonphotographs,forexample,canofferusefulinsight,buttheyarenotthesameas
blindedquantitativemeasurement.Haircountcanbeconvertedintohairdensitywhenatargetareais
providedbytheauthors,butnotallauthorsdisclosedthisinformation.Thisshouldbeapointof
considerationinthedevelopmentofnewtrialsasaconsistentquantitativeoutcomemeasurecanaidin
comparingdifferenttreatments.Patient-centredoutcomessuchassatisfactionarealsoimportant.
Whilethereporteddata(Tables1-3)certainlyshowanincreaseinhairparameters,increasesmaynot
benoticeableorsatisfactoryforpatientstojustifytreatmentor,patientsmayexpresssatisfaction
despitelittletonoclinicalimprovement.Evenifpatientsbelieveatreatmentisbeneficial,acasecanbe
madethatcliniciansshouldnotencourageuseoftreatmentsthatdonotobjectivelyimprovehairloss.
5.0Conclusion
Preliminaryevidencesuggeststhat,intheshort-term,eightoff-labeltherapiessuchas
prostaglandinanalogsandpolyphenolscansignificantlyimprovehairdensity8,9,11,13,15–18,21
.Furtherstudy
ofhairlosspatientsenrolledinrandomized,controlledandblindedstudiesisneededtoexpandonthe
efficacyandsafetydatathathasbeencollectedtodate.Inthemeantime,cliniciansmaywishtouse
off-labeltherapiesastheymayprovidebenefittopatients.Hairlossneedsshouldbeaddressed
individuallyasbothoff-labelandapprovedtreatmentthatworksforonepersonmaynotworkfor
another.
8
6.0References
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11
FigureCaptions:
Figure1:StudySelectionProcess
Figure2:MeanChangeinHairDensity(hairs/cm2)after24weeksofOff-LabelTopicalTherapy
8,9,13–22.
BimatoprostA,B,andC:Detailsonthesetreatmentgroups(e.g.,percentageofbimatoprost)notyet
releasedonclinicaltrials.gov;Dabao:50%ethanol,42%water,8%Chineseherbalextracts(saffron
flowers,mulberryleaves,stemonaroot,fruitsofthepepperplant,sesameleaves,theskinofthefruitof
Sichuanpepper,gingerroot,Chineseangelicaroot,barkofthePseudolarix,fruitsofthehawthorn);
Latanoprost:50%ethanol,20%propyleneglycolwater;Non-steroidalanabolichormones(NSAH):
CMM,madeofinsulin,thyroxinandgrowthhormonegelledin1.5%hydroxyethylcellulose;Procyanidin
B-2:70%ethanol,10%1,3-butyleneglycol,0.5%N-acetylglutamine-isostearylester,
0.25%polyoxyethyleneglycerylmonopyroglutamatemonoisosterate,0.1%dl-α-tocopherol,0.05%d-
biotin,0.1%ascorbylpalmitate,0.001%β-carotene,0.1%sodiumcitrateand17.899%purifiedwater;
ProcyanidinMix:7.3%procyanidinB-1,26.2%procyanidinB-2,7.7%procyanidinC-1,40%other
oligomericprocyanidins,70%ethanol,3%1,3-butyleneglycol,0.15%N-acetylglutamineisostearylester,
0.067%citrate-sodiumcitratebuffer,0.05%sodiumbisulfite,purifiedwater;SodiumValproate:8.3%
sodiumvalproateusinga27%ethanolsolutionasthevehicle.
12
Table1:ImpactofOff-LabelTopicalTherapyonHairDensity(hairs/cm2)byEndofTreatment
Study Characteristics TreatmentDetails MeanChangeFromBaseline
Bergeretal.20038
N:200
Age:40
Severity:IIIvtoIV
Duration:26wks
PlaceboShampoo(1xday) -1hairs/cm2
PyrithioneZincShampoo(1%,1xday) 6hairs/cm2*
PyrithioneZincShampoo(1%,1xday)+Minoxidil(5%,2xday) 6hairs/cm2*
Minoxidil(5%,2xday)+PlaceboShampoo(1xday) 12hairs/cm2*
Blume-Peytavietal.20129
N:16
Age:(23-35)
Severity:IItoIII
Duration:24wks
Placebo(50µL/day) 8hairs/cm2
Latanoprost(0.1%,50µL/day) 51hairs/cm2*
Gassmuelleretal.200810
N:102
Age:38
Severity:IIItoVa
Duration:16wks
Vehicle(2xday) 8hairs/cm2
Fulvestrant(70mg/mL,42mg/day) 8hairs/cm2
Minoxidil(20mg/mL,12mg/day) 25hairs/cm2**
Greenberg&Katz199611
N:24
Age:43
Severity:IIItoIV
Duration:40wks
Vehicle(1xday) 6hairs/cm2
HerbalExtract(1xday) 54hairs/cm2*
Iwabuchietal.2016a13
N:38
Age:42
Duration:24wks
Vehicle -10hairs/cm2
Adenosine(0.75%) 12hairs/cm2*
Joetal.201415
N:40
Age:38
Severity:IIIvtoV
Duration:24wks
Vehicle(0.8mL/dose,2xday) -1hairs/cm2a
SodiumValproateSpray(0.8mL/dose,2xday) 23hairs/cm2a*
Kamimuraetal.200016
N:30
Age:47
Duration:24wks
Placebo(1%,1.8mL2xday) 4hairs/cm2
ProcyanidinB-2(1%,1.8mL2xday) 28hairs/cm2*
Kesselsetal.199117
N:396
Duration:24wks
Placebo(1.7mL,2xday) 22hairs/cm2
Dabao(1.7mL,2xday) 27hairs/cm2*
Lindenbaumetal.200318
N:56
Age:28
Severity:IItoIV
Duration:24wks
Placebo(1-3mL/day) 16hairs/cm2
Non-SteroidalAnabolicHormones(1-3mL/day) 30hairs/cm2*
NCT0132533722
N:307
Duration:24wks
Vehicle(1xday) 4hairs/cm2b
BimatoprostFormulationB(1xday) 6hairs/cm2b
BimatoprostFormulationC(1xday) 6hairs/cm2b
BimatoprostFormulationA(1xday) 13hairs/cm2b
Minoxidil(5%,1xday) 22hairs/cm2b
NCT0190472123
N:244
Duration:7-24wks
BimatoprostSolution1(2xday) 13hairs/cm2b
BimatoprostSolution2(2xday) 9hairs/cm2b
Vehicle(2xday) 6hairs/cm2b
Olsen&DeLongetal.
199019
N:72
Age:38
Severity:IIIvtoV
Duration:24wks
Vehicle(0.3mL/dose,2xday) -8hairs/cm2
Viprostol(120µg,0.3mL/dose,2xday) -4hairs/cm2
Placebo(0.3mL/dose,2xday) -3hairs/cm2
Pumthongetal.201220
N:89
Age:39
Severity:II-VII
Duration:24wks
Vehicle(2xday) 20hairs/cm2
Curcumaaeruginosaextract(5%,2xday) 31hairs/cm2
Minoxidil(5%,2xday) 31hairs/cm2
Minoxidil(5%,2xday)+Curcumaaeruginosaextract(5%,2x
day)33hairs/cm
2
Takahashietal.200521
N:49
Age:(27-58)
Duration:24-52wks
Vehicle(2mL2xday) -8hairs/cm2
Procyanidin(0.7%,2mL2xday) 6hairs/cm2*
*p<0.05ascomparedtoplacebo/vehicle;**p<0.05ascomparedtocomparator;a:medianchange;b:terminalhairswereused;Age(years):Mean(range);Severity:
BasedonHamilton-NorwoodScaleandeligibilitycriteria;Wks:weeks;Latanoprost:50%ethanol,20%propyleneglycolwater;Herbalextract:7.5%extractoffennel,
13
polygonum,mentha,chamomile,thujaandhibiscusinawater-basedcream;SodiumValproateSpray:8.3%sodiumvalproateusinga27%ethanolsolutionasthevehicle;
ProcyanidinB-2:70%ethanol,10%1,3-butyleneglycol,0.5%N-acetylglutamine-isostearylester,0.25%polyoxyethyleneglycerylmonopyroglutamatemonoisosterate,
0.1%dl-α-tocopherol,0.05%d-biotin,0.1%ascorbylpalmitate,0.001%β-carotene,0.1%sodiumcitrateand17.899%purifiedwater;Procyanidin:7.3%procyanidinB-1,
26.2%procyanidinB-2,7.7%procyanidinC-1,40%otheroligomericprocyanidins,70%ethanol,3%1,3-butyleneglycol,0.15%N-acetylglutamineisostearylester,0.067%
citrate-sodiumcitratebuffer,0.05%sodiumbisulfite,purifiedwater;Dabao:50%ethanol,42%water,8%Chineseherbalextracts(saffronflowers,mulberryleaves,
stemonaroot,fruitsofthepepperplant,sesameleaves,theskinofthefruitofSichuanpepper,gingerroot,Chineseangelicaroot,barkofthePseudolarix,fruitsofthe
hawthorn);Non-steroidalanabolichormones:CMM,madeofinsulin,thyroxinandgrowthhormonegelledin1.5%hydroxyethylcellulose;BimatoprostA,B,C,1and2:
Detailsonthesetreatmentgroups(e.g.,percentageofbimatoprost)notyetreleasedonclinicaltrials.gov
14
Table2:ImpactofOff-LabelTopicalTherapyonHairDiameter(mm)byEndofTreatment8,14
Study Characteristics TreatmentDetails MeanChangefromBaseline
Bergeretal.20038
N:200
Age:40
Severity:IIIvtoIV
Duration:26wks
PlaceboShampoo(1xday) -0.04mm
PyrithioneZincShampoo(1%,1xday) -0.04mm
PyrithioneZincShampoo(1%,1xday)+Minoxidil(5%,2xday) -0.01mm
Minoxidil(5%,2xday)+PlaceboShampoo(1xday) -0.01mm
Itoetal.200912
N:24
Age:48
Severity:IItoIIIV
Duration:24wks
Vehicle 0.0004mm
Roxithromycin 0.309mm*
*p<0.01ascomparedtobaseline;Age(years):Mean(range);Severity:BasedonHamilton-NorwoodScaleandeligibilitycriteria;Wks:weeks;Roxithromycin:0.5%
Roxithromycin,65%ethylalcohol,5%propyleneglycol,39.5%distilledwater
15
Table3:ImpactofOff-LabelTopicalTherapyonHairGrowth(mm/cm2)byEndofTreatment
10,24,25
Study Characteristics TreatmentDetails MeanChangefromBaseline
Gassmuelleretal.200810
N:102
Age:38
Severity:IIItoVa
Duration:16wks
Vehicle(2xday) 0.7mm/cm2
Fulvestrant(70mg/mL,42mg/day) 0.84mm/cm2
Minoxidil(20mg/mL,12mg/day) 2.9mm/cm2*,^
NCT0132533722 N:307
Duration:24wks
BimatoprostFormulationC(1xday) 0.12mm/cm2
Vehicle(1xday) 0.13mm/cm2
BimatoprostFormulationB(1xday) 0.25mm/cm2
BimatoprostFormulationA(1xday) 0.76mm/cm2
Minoxidil(5%,1xday) 1.29mm/cm2
NCT0190472123 N:244
Duration:7-24wks
Vehicle(2xday) 0.05mm/cm2
BimatoprostSolution2(2xday) 0.67mm/cm2
BimatoprostSolution1(2xday) 0.92mm/cm2
*p<0.05ascomparedtoplacebo/vehicle;^p<0.05ascomparedtoinvestigatedoff-labeltopicaltherapy;Age(years):Mean;Severity:BasedonHamilton-NorwoodScale
andeligibilitycriteria;Wks:weeks;BimatoprostA,B,C,solution1andsolution2:Detailsonthesetreatmentgroups(e.g.,percentageofbimatoprost)notyetreleasedon
clinicaltrials.gov
16
Figure1.
Recordsidentifiedthroughdatabases
(N=1004)
Recordsaftertitleandabstractexclusion
(N=113)
Recordsafterfulltextexclusion
(N=42)
Recordsincludedinreview
(N=16)
Titleandabstract
exclusion
(N=891)
Fulltextexclusion
(N=71)
Exclusionduring
dataextraction
(N=26)
17
Figure2
-4
6 6 68
12 13
23
27 2830 31
51
-10
0
10
20
30
40
50
60
MeanChangeinHairDensity(hairs/cm
2)