Efficacy of Platlet Rich Plasma in Androgenic Alopecia: Systematic Review &
Meta-Analysis
Dr. Mayur J Gawande1,DrRajdeep Singh2,Dr.Ravikanth.P3,DrAshish Choudhary4,Dr.GowriSwaminatham Pendyala5,Dr. Ashwin Hiremath6 1. Assistant Professor, Department of Oral and Maxillofacial Surgery,
SwargiyaDadasahebKalmeghSmruti Dental College and Hospital, Wanadongri- Wadhamna Road, Hingna, Nagpur 441110, Maharashtra.
2. Reader, Department of Oral and Maxillofacial Surgery, chhattisgarh dental college and research institute, rajnandgaon, chhattisgarh.
3. MBBS DDVL, Senior resident ,Department of dermatology,venerology&leprosy, Meenakshi medical college &research institute ,Kanchipuram
4. Senior Research Associate, Department of Dentistry, AIIIMS Jodhpur.
5. Reader, Department Of Periodontics, Rural Dental College, Pravara Institute Of Medical Sciences, Loni, Ahmednagar, Maharashtra
6. Consultant Oral & Maxillofacial Surgeon, Redymed Cosmetic Surgery And Hair Transplant Center, Belgaum, Karnataka, India
1E mail: [email protected]
ABSTRACT
Introduction: Platelet-rich plasma (PRP) helps in hair growth by the release of growth factors and cytokines. Also it has multifactorial capabilities can also be used to treat aging skin, facial scarring, and acne. Hence in our current review we critically examine the success of PRP in the field of dermatology, specifically to the role of PRP in hair restoration. Where possible, meta- analyses were used to evaluate the efficacy of PRP.
Materials and methods: This review directed an electronic systematic literature search in MEDLINE (PubMed) and EmBase. Methodological quality was evaluated by using the Newcastle-Ottawa Scale tool. Odds ratio (OR) with 95% confidence interval (CI) was pooled to estimate the relative outcome of bruxism on dental implant failures. Statistical analyses done by using Review Manager 5.1.
Results: In androgenetic alopecia (AGA) patients, 3 monthly PRP injections showed exhibited greater efficacy over placebo as measured by change in total hair density (hair/cm2 ) over the treatment period (mean difference: 25.61, 95% CI: 4.45 to 46.77; P=.02). The studies included in the meta-analysis used a half-head design, that may have influenced the results because of the effects PRP can induce. Organized studies recommend that 2 to 4 sessions of PRP collective with traditional therapies and techniques can help minimize acne scarring and facial burns, improve
aesthetic results, and decrease recovery time. Nonetheless, data for these indications are lacking and are less robust in design.
Conclusion: It can be suggested that to achieve an improvement in hair restoration in patients with mild AGA, 3 initial monthly PRP injections should be given. Only upon completion of rigorous, randomized, controlled studies can standardized and effective PRP protocols for treating dermatology conditions such as acne scarring, facial burns, and aging skin be determined.
Keywords: PRP, Alopecia Areata, Facial Aesthetics, Meta-Analysis, Platelet-Rich Plasma
Introduction
Platelet-rich plasma (PRP) therapy includes concentration and administration of an autologous solution containing platelets found in whole blood. By the action of the growth factors and cytokines released from α granules found within platelets, PRP can promote cell survival, proliferation, and angiogenesis.1-3 PRP can be used widely in the dermatology-based applications because of its multifactorial capabilities and anti-inflammatory effects.4 The anti-inflammatory effect of PRP can combat localized micro-inflammation associated with hair loss conditions such as androgenetic alopecia (AGA).4,6,7 PRP also improves the density of collagen fibers by activating fibroblasts, that can smooth scarring and revitalize skin’s appearance.8,9,10 There are many questions surrounding the use of PRP such as its effectiveness in a dermatology setting, what protocols dermatologists should be using, and whether these protocols should change based on the condition being treated. Addressing these questions can be difficult as many protocol parameters could influence the efficacy of PRP including the frequency and number of PRP sessions, presence of an activator, and the exact specifications of the collection system. Our study will specifically observe the role of PRP in hair restoration by evaluating its efficacy in AGA, alopecia areata (AA), cicatricial alopecia (CA), along with other potential facial aesthetic applications.
Materials and methods
A literature search in MEDLINE (PubMed) and EMBASE was conducted. The ensuing search terms were used: PRP, platelet-rich plasma, hair, alopecia, facial scarring, skin revitalization, facial burns, and facial surgery. In vitro studies and case studies were excluded. Clinical trials that evaluated the direct injection of PRP as a monotherapy treatment for patients with AGA, CA, or AA (diagnosed prior to treatment) were included.
To generate a meta-analysis, we required a minimum of 3 studies reporting the mean change from baseline for the same outcome metric. A GRADEpro assessment, based on Cochrane methodology, was used to grade the quality of evidence for studies included in the meta- analysis.11 For hair restoration studies, outcome measures such as hair density (total hairs/cm2 ), hair count (total hairs/0.65 cm2 ), hair diameter (mm), hair shedding, and epidermal changes were examined. The meta-analysis was conducted using RevMan 5.3 (Copenhagen, Denmark).
Efficacy was calculated using the mean difference (MD) between outcome measures, and heterogeneity was evaluated using the percentage of variation across studies that is due to heterogeneity rather than chance (I2 statistic).12,13 The reported efficacy was compared with a control group and P < .05 was considered significant.
Results
In our review 23 met inclusion criteria and used PRP as a monotherapy for treatment of AGA (Table 1). Seven randomized, controlled trials (RCTs) were included14-20; all but one used a half- head design.11 Four studies evaluated the efficacy of PRP in female pattern hair loss (4/23 = 17%),14,15,21,22
10 studies evaluated the efficacy of PRP in male pattern hair loss (10/23 = 43%),17-19,23-27
and 8 studies evaluated PRP both in male and female pattern hair loss (9/23 = 39%).16,28-35 PRP was most commonly delivered once a month for 3 months (6/23 = 26% of studies)17-19,22,29,32,33,35
with 47% of studies (11/23) using some form of activation prior to injection (eg, calcium gluconate).15-19,22,25,28,31-33
Platelet concentrations within PRP solutions varied from 2 to 6 times baseline platelet count, with 3 times baseline platelet count the most common concentration reported (Table 1).
Eight studies reported the leukocyte status of their PRP solutions: Two studies used a PRP solution rich in leukocytes,21,34 3 studies used a leukocyte-poor PRP solution,16,32,35 Two studies used PRP solutions that might include leukocytes,17,18 and one study used a leukocyte-free PRP solution.14 Inter-follicular PRP injections (0.05 to 0.2 mL/cm2) were the most common method used.17,18,22,29,30
Approximately 50% of studies (6/12 = 50%) that reported needle gauge (G) used a 30-G needle when injecting PRP,17-19,29,32
Averaging across studies, each patient had a total of 3.9 sessions of PRP at 3.5-week intervals and were age 37.6 years.
Efficacy was measured among AGA studies using a wide array of outcomes including but not limited to hair count(total hairs/0.65 cm2),17,18 total hair density (total hair/cm2),16- 18 terminal hair density (terminal hairs/cm2),17,18 hair diameter (mm),15,22,30,32
hair shedding,14,26 and epidermal changes.17,18,32 Four included studies compared the impact of PRP (3 sessions at 1- month intervals) on mean change in hair count, as defined as total hairs/0.65 cm2 from baseline, with placebo-treated patients.14-18 Three of these studies found that PRP exhibited greater efficacy over placebo (all 3 studies P < .05),17,18 whereas 1 study did not find a significant difference amongst these 2 treatments (P > .05).16 Terminal hair density (terminal hairs/cm2) was evaluated in 3 placebo- controlled studies.17,18 In 2 of these studies, 3 PRP sessions administered at 1-month intervals exhibited greater efficacy over placebo with response to mean change in terminal hair density by end of treatment (P = .0003 for both studies).17,18 PRP also exhibited a greater efficacy over baseline measurements in hair diameter (mm) in 415,22,30,32 of the 5 studies that evaluated this endpoint (all studies P < .05).15,22,24,30,32
It was found both that interfollicular22,30 and intradermal injections15,24 made a significant impact in hair diameter.
Across all included studies that evaluated epidermal change (4 studies), PRP-treated patients had a statistically significant increase in epidermal thickness compared with baseline measurements (P<0.05 for all 4 studies).17,18,22,32
Half these studies reported the use of interfollicular injections, suggesting this depth may be required to create an epidermal change.17,18 Two included studies evaluated hair shedding by a self-assessment questionnaire.14,26 One study reported very little improvement in hair shedding 26 weeks post-treatment with 60% (9/15) of PRP-treated patients reporting no improvement, 13.3% (2/15) reporting some improvement, and 13.3% (2/15) reporting substantial improvement.14 Conversely, in a study by Borhan and colleagues,26 71%
(12/17) of patients reported a slight to moderate change in hair shedding 4 weeks posttreatment.
The major differences between these studies, such as time of evaluation and number of sessions, may have contributed to the differences in shedding improvement. PRP was found to exhibit a greater efficacy over placebo across all controlled studies that evaluated hair density (all studies P < .05).15- 18,27,29
Three of these studies used an interfollicular injection, 2 studies used an
intradermal injection, and 2 studies did not report injection depth.15,17,18,27,29
According to the meta-analysis conducted, 3 PRP sessions administered at 1-month intervals exhibited greater efficacy over placebo with response to mean change in total hair density (hairs/cm2) by end of treatment (MD: 25.61, 95% CI: 4.45 to 46.77;I2 = 23%, P = .02) (3 studies, pooled n = 58) (Figure 1).16-18
These results suggest that PRP is an effective treatment for AGA; however, the quality of evidence from these trials is low. Risk of bias and imprecision were judged as serious with inconsistency and indirectness considered not serious. Only one included study directly compared PRP with a comparator.30 In this study, PRP (2 sessions at 12-week intervals) was compared with placental extract in a nonrandomized fashion.30 A statistically greater level of improvement in hair thickness and overall clinical improvement was found with PRP-treated patients compared with placental extract–treated patients (P = .027 and P = .023, respectively).30 For Alopecia Areata: Three patchy AA studies met inclusion criteria; however, not enough quantitative data were included to conduct a meta-analysis.36-38 Only 2 studies (2/3 = 67%) were randomized and controlled, comparing PRP with a placebo and an active comparator (minoxidil or triamcinolone ace- tonide).36,37 One study used a half-head design,37 and PRP sessions were delivered monthly across all included studies (Table 1).36-38 Two studies evaluated the efficacy of PRP both in men and women,36,37 and one study did not report gender.38 Two studies also reported the use of activation (calcium gluconate)36,37 and only one study reported platelet concentration (3.5× whole blood).37 None of the studies included information on leukocyte status, needle gauge, or the collection system used. The depth of injection varied across studies reporting both intralesional injections 37 and subfollicular injections.38 Most studies used a single-spin technique (2/3 = 67%),36,37 with each patient on average receiving 4 PRP sessions.
The average age of the patient included in these studies was 24.6 years. Efficacy was measured across AA studies using hair regrowth and relapse rates.36-38
Across all studies that measured hair growth (2/3 = 67% of studies), patchy AA patients treated with PRP had a significantly greater improvement in hair growth compared with placebo-treated patients (both studies P < .05).36,37 Relapse rates reported in PRP-treated patients were low and ranged from 5% to 31%, 6 to 9 months post-PRP treat Minoxidil (P < .05).36 The lack of quantitative data limits the ability to understand how significant these data are and what factors could contribute to PRP’s success as an AA treatment. Further research in the use of PRP in AA is needed.
For Cicatricial Alopecia: No studies that met the inclusion criteria.
Discussion
We can propose from that from our findings in this meta-analysis, that 3 monthly PRP injections (1 PRP session every 4 weeks, 3 sessions in total) significantly enhanced hair density in AGA patients. In addition to total hair density, several AGA studies report a PRP-induced improvement in hair count, terminal hair density, hair shedding, and hair diameter.14,15,17,18,22,26,30,32
Various studies also suggested that PRP is an effective hair restoration treatment. PRP could also be a beneficial adjunct to hair transplantation. In a small, controlled study, incorporating PRP treatment into a follicular unit extraction procedure resulted in greater hair density compared with control (saline). This study also found that PRP treatment increased
skin recovery and reduced catagen loss of transplanted hair. An increase in hair density was also found with follicular units treated with PRP in a half-head study.
The conducted meta-analysis using monthly PRP studies included patients with Norwood Hamilton scores between II and V.16-18Maparet al19 suggest the failure to observe a positive effect of treatment may be due to hair loss severity. Thus, the development in hair restoration found with monthly PRP injections may not range to patients with more severe forms of AGA.
In addition, the studies captured by the meta-analysis included men and women alike using a half-head design. This trial design may influence the results found as PRP can cause angiogenesis and cross-signaling between growth factors, which can affect placebo sites.1,5 All 3 studies included in the meta-analysis used a total of 3 PRP sessions. The use of 3 sessions is recommended as a progressive effect of PRP from the first injection, which peaks after 3 to 5 injections and is attenuated with cessation of treatment. Thus, monthly PRP injections occurring for a minimum of 3 months may be necessary to ensure patients receive the optimal number of injections at an appropriate frequency.
There was a significant variability in the method of preparation and administration of PRP used across included hair loss studies such as activation, frequency, number of sessions, injection technique, and patient characteristics. Despite its frequent use, the role of activation remains unclear as a significant alteration in growth factor concentrations, which may influence outcomes, may not always occur.20Unfortunately, because of the limited number of studies, a meta-analysis comparing the results from monthly PRP injection with other injection frequencies (eg, PRP session every week) was not possible. However, a recently published study35 found monthly injections achieve better hair counts compared with quarterly injections (p < .001).
Based on the evidence, originally prescribing monthly PRP sessions may be necessary to attain an improvement in hair restoration parameters (eg, hair count, hair density).
Unfortunately, the included studies did not compare PRP with approved nonsurgical treatments.
Minoxidil was compared with PRP in AA patients; however, minoxidil is not an approved treatment for AA.36 PRP as a treatment for AGA has recently been compared with other approved nonsurgical AGA treatments in a network meta-analysis.In this analysis, low-level laser therapy was considered the superior treatment based on relative effects when compared with PRP, Finasteride, Minoxidil and Dutasteride. Further research using direct head-to-head studies are necessary to confirm this finding.
Conclusion
Based ontheevidence,monthlyPRPtreatments (3 sessions initiallyfollowed by a maintenanceregimen) can significantly improve hair density, hair count,hairshedding,andhairdiameter.Theseresultsmayberestricted to patients with mild AGA(Norwood Hamilton 11to V). Evidence has suggestedthat combiningPRP (2 to 3sessions) with traditional aesthetic therapies and procedurescanimproveoutcomes.Owingto inconsistentmeasurements and protocols, however, comparisons between studiesare limited.Withfurtherinvestigationusingrandomized,controlled studies, standardized and effective PRP protocolsfor dermatological conditionscouldbe determinedin thenearfuture.
References
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3658 http://annalsofrscb.ro
Table 1.Trial Characteristics of Studies Investigating the Efficacy of Platelet-Rich Plasma (PRP) as a Treatment for Hair Loss.
Centrifugation and Study TrialCharacteristics
Treatment GroupsAndrogenetic
Collectio n
SystemD etails
Characteristics of
PRP Solution Used Injection Details Patient Characteristics
1 PRP Session
Gentile etal,201717Not randomized Regen PRP Regen Blood Cell Activated(CG) 25-Gneedle N=6 men (Study2)
Puig etal,201614
2 PRP techniquesNot blinded
Randomized (TA)
Arthrex PRP PRP
Therapy Arthrex Angel System
Angel PRP system
5-fold increaseO WB
Leukocyte-free
1 mL per treatment section1 session Subcutaneous injection
Age: 40.8±11.3 HN IIIa to IIIv N=26 women Placebo-controlledDouble-
blinded(EandS) Saline Not activated
2.75 to3.4×PC 10 mL per
session1 session Age:≥18yearsLudwig II
PRPSessionEveryWee Leeetal,201521 k
Randomized (TA) CD34++PDRN SmartPReP2 platelet Leukocyte-rich Intraperifollicularinjection N=40 women 2 PRP techniquesSingle-
blinded(E) PRPPDRNP
RP concentrate system Not activated 0.05to0.1mL/cm212
or 13 sessions Age:33.2
Marwah et al,201423
Not randomizedNot
controlledNot blinded PRP Not reported Not reported 6 sessions N=10menII to III
Tawfik and
Osman, Randomized (TA) PRP 1200 g 15 mins Activated(CG) Intradermal injection N=30 women
201815 Placebo-controlled (1/2)Double-
blinded Saline 2000 g 10 mins 4 sessions Age: 29.3±6.56
Ludwig I toIII PRP Session Every 2 Weeks
Ayatollahi etal, Not randomized201724 Not controlled Not blinded Khatu etal,201425 Not randomized
PRP
PRP
RegenLab PRP Kit-Regen ACR 1500 g 5 mins 1500 rpm 6 mins
Not activated
Activated(CC)
Intradermal injection 0.05 ml per
area5 sessions 2 to 3 cc
N = 15
menAge:39±9.7HN III to VI
Hair loss: 36 months(median) N=11 men
Singhaletal,201528b
Not controlledNot blinded
Not randomized PRP
2500 rpm 15 mins
1500 rpm 6 mins Activated(CC)
4 sessions 8 to 12 cc
Age: 20 to 40H II to IV
N=16 men, 4 women Staraceetal,201822
ControlledNotblinded
Not randomized No PRP
PRP
2500 rpm 15 mins
My Cells system Not activated
4 sessions 25-Gneedle
Age: 25 to 35 N=10 women Not controlledNot
blinded 2500 rpm 10 mins Interfollicular
injection1cc per injection
Age:47.1 Ludwig I toIII Hair loss: 7.9 years
Table1.(continued)
Centrifugation and
Collection System Characteristics of
Study TrialCharacteristics Treatment Groups
Details PRP Solution Used
InjectionDetails Patient
Characteristics Gkinietal,201429d Not randomized PRP RegenKit BCT-3 Activated(CG) 27G needle N=20 men, 2
women
Not controlled 1500 g 5 mins 5.8×OWB 0.05 to0.1 mL/cm2 Age:
34±11.8
Single-blinded(E) 3 sessions HN II to V,
Ludwig I to 3 5.5×107to1.1×108
platelets/cm2
Kachhawa et al, Not randomized PRP 1200 rpm 4 mins Not reported 1 to2 cc per injection N=50 men 201727 Placebo-controlled
(1/2)
Saline 2400 rpm 4 mins Intradermal injection Age: 34
Not blinded 6 sessions NH III to VI
PRP Session Every 4 Weeks
Alvesand Grimalt, Randomized (LR) PRP Omnigrafter-Proteal Leukocyte- poor
30-Gneedle N=12 men,
13 women 201616 Placebo-controlled
(1/2)
Saline 460 g 8 mins Activated(CC) 0.15 mL/cm2per area Age: 39 Double-blinded(E and
S)
3×OWB 3 sessions HN II to V,
Ludwig I to III Anituaetal,201730e Not randomized PRP BTI System IV Leukocyte-
poor
30-Gneedle N=13 men, 6 women
Not controlled 580 g 8 mins Activated 3 to 4cm3 per
injection
Age: 45±11
Single-blinded(E) 2×OPB 5 sessions N III to VI,
Ludwig II 1.4×103to1.8×103
platelets/cm2 Cervelliet al, Randomized PRP Cascade-Selphyl-
Esforax
May include 0.1mL/cm2 N=10 men
201420 Placebo-controlled (1/2)
Saline 1100 g 10 mins leukocytes 3 sessions Age:
32.7±10.6
Single-blind(E) Activated(Ca+) HN IIa to IV
Ferrando et al, Not randomized PRP Omnigrafter Activated(CC) Intradermal injection N=19 men, 59 women
201731a,f Not controlled 460 g 1800 rpm 8
mins
0.1cc/cm2 Age: 18 to
72
Not blinded 6 sessions Ebling scale
II to IV Gentile etal,201832 Not randomized PRP 260 g 10 mins Not activated 30-Gneedle N=18 men, 5
women Placebo-controlled
(1/2)
Saline Interfollicularinjection Age: 21 to
70
Not blinded 0.2ml/cm2 HN I to V,
Ludwig I to II 3 sessions
Gentile etal,201717 Randomized (TA) PRP CPunT Preparation Not activated 30-Gneedle N=18 men (Study1) Placebo-controlled
(1/2)
Saline System Interfollicularinjection Age:
37.4±9.4 Double-blind(E and
S)
1200 rpm 10 mins 0.2mL/cm2 HN II to IVa
3 sessions Gentile etal,201517 Randomized (TA) PRP Cascade-Selphyl-
Esforax
May include 30-Gneedle N=23 men
Placebo-controlled (1/2)
Saline system leukocytes Interfollicularinjection Age:
34.7±11.7 Double-blind(E and
S)
1100 g 10 mins Activated(Ca+) 0.1mL/cm2 HN IIa to IV
Platelet-
richlipotransfer
3 sessions 1200 rpm 10 mins
Mapar etal,201619 Randomized (SQ) PRP PRP tube Tubex Activated(CG) 30-Gneedle N=19 men Placebo-controlled
(1/2)
Saline 3000 rpm 6 mins 3-foldincrease in
Deepdermis injection Age: 25 to 45
Single-blinded 3300 rpm 3 mins BPC 2 sessions N IV to VI
(continued)
Table1.(continued)
Centrifugation and
Collection System
Characteristics of
Study TrialCharacteristics Treatment Groups
Details PRP Solution Used
InjectionDetails Patient
Characteristics Hausauer and Randomized (TA) PRP Eclipse PRP kit Leukocyte-poor 32-Gneedle N=30 men, 10
women Jones,201835a,g 2 PRP techniques 3500 rpm 10
mins
Not activated Subdermalinjection Age:43.75
Singleblinded 4 to6×OWB 0.2to 0.5 mL per
aliquot
NH II to V, Ludwig I2 2 to 4 sessions to II1
Hair loss: 6.45 years
ElTaieb et al, Randomized (TA) PRP 3000 rpm 10 mins
Activated(CG) 3 sessions total N=39 men, 51 women
201736 Placebo-controlled Minoxidil Age:21.09
Comparator Panthenol Hair loss:28±16.15
Not blinded months
Trinketal,201337 Randomized (TA) PRP 70 g 8 mins Activated(CG) Intralesionalinjection N=20 men, 25
Abbreviations: 1/2, half-head design; 1/3, 3 lesions treated on each patient, 1 lesion per treatment; BPC, baseline platelet count; CC, calcium chloride; CG, calcium gluconate; E, evaluator; H, Hamiltonclassification;LR,leftorrightsideofscalp;Mins, minutes;N,Norwoodclassification;NH,NorwoodHamiltonclassification; Notblinded,openlabelorthestudydid notspecifythatblindingoccurred;OPB, over peripheral blood; OWB, over whole blood; PC, baseline platelet concentration; PDRN:
polydeoxyribonucleotide; SQ, square assignment; S, subject; TA, treatment allocation; TRA,triamcinolone acetonide.
aConcomitant hair loss treatment(s) wereallowed (or recommended) during studyprotocol (eg, finasteride).
bFifteen-day intervalbetweensessions.
cTreated every 3 weeks forthe first 3 sessions and6 weeks for thelast session, 4 sessions total.
dTreated every 3weeks fora total of3 sessions+1 boostersession atmonth 6.
eTwo additional reminderinjection doses wereadministered at months4 and 7.
fInjected in affected areas for 3 monthly sessions,followed by 3 bimonthly sessions and 2 or3 annual follow-up sessions.
gTwo different PRP regimensused: 3 monthly PRPsessions +1 boostersession 3 monthslater vs PRP sessionsevery 12 weeks (2sessions total).
women Placebo-controlled
(1/3)
TRA 3.5×OWB 3 sessions total Age:28.03
Comparator Placebo Hair loss: 4.52
years Double-blind(ES)
Singh,201538 Not randomized PRP Not reported Not reported Subfollicularinjection N=20
Not controlled 6 sessions total Age: 25 to 35
Not blinded
Figure 1: Three studies evaluated the impact of 3 monthly platelet-rich plasma (PRP) sessions (1 session per month) on hair density (total hairs/cm2) in patients with androgenetic alopecia (pooled N = 58 participants). Mean change from baseline to end of treatment was used as the unit of measure. IV indicates inverse variance.
