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Originl Article Access this rticle online Wesite: www.ijtrichology.com DOI: 10.4103/0974-7753.1584 Quick Response Code: Use of Low Level Lser Therpy s Monotherpy or Concomitnt Therpy for nd Androgenetic Alopeci Andréi Munck, Mri Fernnd Gvzzoni, Rlph M Trüe 1 Institute of Dermtology Prof. R.D. Azuly, Rio de Jneiro, Brzil, nd 1 Center for Dermtology nd Hir Diseses, Bhnhofpltz, Wllisellen, Switzerlnd ABSTRACT Address for correspondence: Prof. Rlph M. Trüe, Center for Dermtology nd Hir Diseses, Bhnhofpltz 1A, CH 8304 Wllisellen, Switzerlnd. E mil: r.truee@ derm hrceter.ch Bckground: Androgenetic lopeci (AGA) is the most common form of hir loss in men nd in women. Currently, minoxidil nd finsteride re the tretments with the highest levels of medicl evidence, ut ptients who exhiit intolernce or poor response to these tretments re in need of dditionl tretment modlities. Ojective: The im ws to evlute the efficcy nd sfety of low level lser therpy (LLLT) for AGA, either s monotherpy or s concomitnt therpy with minoxidil or finsteride, in n office sed setting. Mterils nd Methods: Retrospective oservtionl study of mle nd femle ptients with AGA, treted with the 655 nm HirMx Lser Com, in n office sed setting. Efficcy ws ssessed with glol photogrphic imging. Results: Of 32 ptients (21 femle, 11 mle), 8 showed significnt, 20 moderte, nd 4 no improvement. Improvement ws seen oth with monotherpy nd with concomitnt therpy. Improvement ws oserved s erly s 3 months nd ws sustined up to mximum oservtion time of 24 months. No dverse rections were reported. Conclusions: LLLT represents potentilly effective tretment for oth mle nd femle AGA, either s monotherpy or concomitnt therpy. Comintion tretments with minoxidil, finsteride, nd LLLT my ct synergistic to enhnce hir growth. Key words: Androgenetic lopeci, concomitnt therpy, HirMx Lser Com, low level lser therpy, monotherpy INTRODUCTION The ility of lsers to induce hir growth ws incidentlly noted s erly s 1967 when Mester et l. used low level lser therpy (LLLT) to tret cncer in mice with shved cks. [1] Since then, hypertrichosis hs een recognized to e possile side effect of lser tretment. First descried in 2002 with intense pulsed light therpy, [2] this phenomenon hs now een widely cknowledged to occur with n incidence rte rnging from 0.6% to 10% with low fluences nd ll lser types. [3] It is thought to e the result of suoptiml fluences tht re too low to induce thermolysis, ut high enough to stimulte folliculr growth. Eventully, LLLT hs een developed for the tretment of ndrogenetic lopeci (AGA). As opposed to other currently mrketed systems, the lser com utilizes hir prting teeth for optiml delivery of lser energy to the exposed sclp. In 2007, the HirMx Lser Com (Lexington Interntionl, LLC) received 510 (k) clernce from the Food nd Drug Administrtion (FDA) for the tretment of AGA for men, nd 2011 for women. This clernce mens tht the device is considered moderte risk medicl device y the FDA nd is therey solely screened for sfety. The HirMx Lser Com hs een tested in compny sponsored study of 110 mle ptients with the clim of significnt increse in men terminl hir density when compred to shm device. [4] Avrm nd Rogers conducted the first independent linded study nd hir growth with seven ptients nd found tht on verge, there ws decrese in the numer of vellus hirs, n increse in the numer of terminl hirs, nd n increse in shft dimeter. [5] A consensus written y hir loss experts sttes tht sed on necdotl experience, LLLT, prticulrly 650-900 nm wvelengths t 5 mw, my e n effective tretment option for ptients with AGA. [6] In recent times, Kim et l. reported n increse of hir density with the use, when compred to the shm device in 24-week, rndomized, doule lind, shm device controlled tril. [7] To evlute efficcy of the 655 nm HirMx Lser Com either s monotherpy or s concomitnt therpy for Interntionl Journl of Trichology / Apr-Jun 2014 / Vol-6 / Issue-2 45

tretment of mle nd femle AGA, we performed retrospective oservtionl study of glol photogrphic ssessments of ptients in n office sed setting. MATERIALS AND METHODS The study design ws retrospective nd oservtionl. Ptients who hd purchsed HirMx Lser Com etween July 2011 nd July 2013 for tretment of AGA t the Center for Dermtology nd Hir Diseses Prof. Trüe were retrieved for ssessment of glol photogrphic imges performed t follow up visits. Ptients on concomitnt tretment hd een treting with topicl minoxidil or orl finsteride for t lest, efore strting therpy with the HirMx Lser Com. Ptients used the HirMx Lser Com t home ccording to instructions 3 times weekly etween 8 nd 15 min depending on the model purchsed (Advnced 7, Lux 9, or Professionl 12). Glol photogrphs were performed t 3, 6, 12, nd 24 months of tretment follow up in stndrdized mnner with stereotctic cmer device of Cnfield Scientific Inc., in which the ptient s chin nd forehed re fixed nd on which digitl cmer nd flsh device re mounted, ensuring tht view nd lighting re the sme t consecutive visits, thus enling precise follow up of the sme sclp re of interest with frontl nd vertex views. Glol photogrphs were evluted y two of the uthors (AM nd RMT), nd scored s significnt, moderte, or no improvement. In the cse of diverging opinions, the inferior score ws given. RESULTS In totl, 32 ptients with AGA were involved in the study, of which 21 were femles, ged 22-73 (men: 43.6 ± 15.19 stndrd devition [SD]), nd 11 were mles, ged 20-70 (men: 39 ± 15.01 SD) totl men: 42 ± 15.1 SD. The durtion of hir loss in yers for men nd women ws men 7.1 ± 5.2 SD. The durtion in months for men nd women ws men 8.7 ± 5.2 [Tle 1]. The ptient chrcteristics, with respect to gender, ge, clssifiction of AGA ccording to Ludwig nd Hmilton-Norwood scles, durtion of hir loss, nd concomitnt tretments re recorded in Tle 2. The results for the scoring of the glol photogrphic ssessment in reltion to tretment durtion with the HirMx Lser Com re demonstrted in Tle 3. In summry, eight ptients (three femle, five mle) showed significnt improvement, 20 ptients (14 femle, six mle) moderte improvement, nd four ptients (four femle, zero mle) no improvement [Figure 1]. Of 32 ptients, the HirMx Lser Com ws used s monotherpy in six ptients (two femle, four mle), nd s concomitnt therpy in 26 ptients (19 femle, seven mle). In the monotherpy group, two ptients (one femle, one mle) showed significnt improvement [Figure 2], four ptients (one femle, three mle) moderte improvement, nd zero ptients no improvement [Tle 3]. In the concomitnt therpy group, six ptients (two femle, four mle) showed significnt improvement [Figures 3 nd 4], 16 ptients (13 femle, three mle) moderte improvement, nd four ptients (four femle, zero mle) no improvement. There ws no sttisticl significnt difference etween LLLT monotherpy nd concomitnt therpy with either minoxidil nd/or finsteride (P = 0.829), nd regrding mle or femle AGA (P = 0.091) [Tle 4]. Tretment ws well tolerted nd no serious dverse events were reported. DISCUSSION Androgenetic lopeci is the most common form of hir loss in men nd in women. Currently, topicl 2% nd 5% minoxidil solution nd 1 mg orl finsteride re Tle 1: Improvement of lopeci in reltion to the vriles: Age, durtion of hir loss, nd durtion Vriles Sttistics Totl Improvement P vlue of Numer Moderte Significnt Kruskl- Wllis test Age (yers) Durtion of hir loss* (yers) Durtion (months) n 32 4 20 8 0.1 Men 42.0 33.0 44.8 39.6 Stndrd devition 15.1 6.8 16.4 13.5 Minimum 20.0 25.0 22.0 20.0 Mximum 73.0 40.0 73.0 62.0 n 24 4 13 7 Men 7.1 7.3 7.0 7.4 0.892 Stndrd devition 5.2 3.9 5.8 5.6 Minimum 0.5 3.0 0.5 1.5 Mximum 20.0 11.0 20.0 16.0 n 32 4 20 8 Men 8.7 12.0 8.0 8.8 0.549 Stndrd devition 5.2 8.1 3.7 6.9 Minimum 2.0 6.0 2.0 3.0 Mximum 24.0 24.0 18.0 24.0 LLLT Low level lser therpy 46 Interntionl Journl of Trichology / Apr-Jun 2014 / Vol-6 / Issue-2

Tle 2: Ptient chrcteristics Gender Age Clssifiction Durtion of hir loss Concomitnt tretments 25 Hmilton-Norwood III NOS* Nil** 54 Hmilton-Norwood IV 20 yers Nil** 34 Hmilton-Norwood IV 10 yers Nil** 70 Hmilton-Norwood III NOS* Nil** 28 Hmilton-Norwood IV 9 yers 5% minoxidil solution 32 Hmilton-Norwood IIIv 2 yers 5% minoxidil solution 56 Ludwig pttern 7 yers 5% minoxidil solution 20 Hmilton-Norwood IIIv 18 months 1 mg orl finsteride 1 mg+5% minoxidil solution 34 Hmilton-Norwood IIIv NOS* 1 mg orl finsteride 1 mg+5% minoxidil solution Hmilton-Norwood V 16 yers 1 mg orl finsteride 1 mg+5% minoxidil solution Hmilton-Norwood IV 12 yers 1 mg orl finsteride 1 mg+5% minoxidil solution 73 Ludwig II Nil** 62 Ludwig I-II 2 yers Nil** 71 Ludwig II 12 yers 0.025% estrdiol solution Ludwig II NOS* 5% minoxidil solution 31 Ludwig II 3 yers 5% minoxidil solution 39 Ludwig II NOS* 5% minoxidil solution 44 Ludwig I 15 yers 5% minoxidil solution 30 Ludwig I 10 yers 5% minoxidil solution 52 Ludwig II 3 yers 5% minoxidil solution 40 Ludwig I 3 yers 5% minoxidil solution 40 Ludwig I 30 months 5% minoxidil solution 37 Ludwig I 3 yers 5% minoxidil solution 37 Ludwig I 5 yers 5% minoxidil solution 25 Ludwig I 11 yers 5% minoxidil solution 50 Ludwig I 4 yers 5% minoxidil solution 33 Ludwig II 8 yers 5% minoxidil solution 22 Ludwig I NOS* 5% minoxidil solution 24 Ludwig I 4 yers 5% minoxidil solution 69 Ludwig I 8 yers 5% minoxidil solution 45 Ludwig I NOS* 5% minoxidil solution 53 Ludwig I NOS* 5% minoxidil solution *NOS Not otherwise specified; **NIL Nothing in vriety of indictions more thn 30 yers, [9] it hs only recently found the ttention of the scientific community for the tretment of AGA. [6,10,11] Figure 1: Grphic summry of results the tretments with the highest levels of medicl evidence, [8] ut ptients who exhiit intolernce or poor response to these tretments re in need of dditionl tretment modlities. Although low level energy lsers hve een therpeuticlly used in medicine for photoiostimultion We hve chosen the 655 nm HirMx Lser Com for severl resons: First, it represents the device with the most clinicl study reports regrding its efficcy, [4,5,12] secondly, the cost of the device is ffordle, nd thirdly, the device is simple enough for ptients to use t home. Finlly, the fct tht the device is sfe, for which it received 510 (k) clernce from the FDA for the tretment of AGA, ws lso n importnt considertion. Our study demonstrtes clinicl efficcy of the device for tretment of mle nd femle AGA, oth s monotherpy Interntionl Journl of Trichology / Apr-Jun 2014 / Vol-6 / Issue-2 47

[PDF Purchsed from http://www.ijtrichology.com on Fridy, August 29, 2014]ce Munck, et l.: Low level lser therpy Tle 3: Scoring of glol photogrphic ssessment in reltion to tretment durtion Gender Age Durtion No Moderte Significnt improvement improvement improvement 25 4 months 54 [Figure 2] 34 70 28 4 months 32 56 3 months 20 10 months 34 24 months 5 months 73 2 months 62 0 71 31 3 months 39 44 30 52 40 40 8 months 37 37 24 months 25 50 33 5 months 22 24 69 45 18 months 53 [Figure 3] c Figure 2: Monotherpy in 54-yer-old mle () Before tretment, nd improvement fter (), nd (c) of low-level lser therpy [Figure 4] Figure 3: Concomitnt tretment with topicl 5% minoxidil in 55-yerold mle dding on low-level lser therpy (LLLT) to 4 yer pretretment with 5% topicl minoxidil solution () Before, nd () After 3 months of dded LLLT LLLT Low level lser therpy Tle 4: Comprtive ssessment of efficcy etween monotherpy nd concomitnt for mle nd femle ndrogenetic lopeci Totl (n (%)) Improvement (n (%)) P vlue of Numer Moderte Significnt Fisher test Gender 11 (34.4) 21 (65.6) 4 (100.0) 0 6 (30.0) 5 (62.5) 14 (70.0) 3 (37.5) 0 Concomitnt 26 (81.3) 4 (100.0) therpy 4 (20.0) 2 (25.0) 16 (80.0) 6 (75.0) 48 c Figure 4: Concomitnt tretment with topicl 5% minoxidil nd 1 mg orl finsteride in 34-yer-old mle () Before, () After tretment with 1 mg orl finsteride nd topicl 5% minoxidil solution id, nd (c) After 3 months fter dding on low-level lser therpy 0.091 Therpy Monotherpy 6 (18.8) 0.829 nd s concomitnt therpy, in terms of cliniclly relevnt improvement of ppernce of hir. Of 32 ptients, eight ptients (25%) showed significnt improvement, nd 20 ptients (62.5%) showed moderte improvement in glol photogrphic ssessments. The effect ws oserved Interntionl Journl of Trichology / Apr-Jun 2014 / Vol-6 / Issue-2

s erly s 3 months of tretment, nd ws sustined up to mximum oservtion time of 24 months. The technology ppers to work etter for some thn for others, nd predictive fctors which will most enefit from LLLT re to e determined. It seems though, tht ptients with intermedite lopeci (Hmilton-Norwood III nd IV, nd Ludwig I nd II, respirtory) respond est, since effective photoiostimultion depends on minimum of hir for effective photoiostimultion, nd on mximum of hir for the lser em to rech the sclp without sorption or interference from existing hirs. The hypothesized mechnisms of ction re incresed denosine tri phosphte (ATP) production, modultion of rective oxygen species (ROS), nd induction of trnscription fctors. The proposed cellulr chromosphere responsile for the effect of visile light is cytochrome c oxidse (CO) with sorption peks in the ner infrred, nd mitochondri the likely site for the initil effects. It is elieved tht LLLT displces nitric oxid from CO llowing n influx of oxygen to ond to CO nd progress forwrd in the respirtory process to ATP production nd ROS signling. These effects in turn led to incresed cellulr prolifertion, modultion in levels of cytokines, growth fctors nd inflmmtory meditors, nd incresed tissue oxygention. While the effects of these iochemicl nd cellulr chnges hve rodly een studied in oth niml models nd clinicl studies with ptients, nd hve shown enefits in diverse conditions, such s incresed heling in chronic wounds, improvements in sports injuries nd crpl tunnel syndrome, pin reduction in rthritis nd neuropthies, nd meliortion of dmge fter hert ttcks, stroke, nerve injury nd retinl toxicity, [7,9] the effects on hir growth stimultion hve only recently gined the ttention of the scientific community. CONCLUSIONS From our own oservtions, we shre with other uthors the opinion tht LLLT represents sfe nd potentilly effective tretment option for ptients with AGA who do not respond or re not tolernt to stndrd tretment of AGA. [6,7] Moreover, comining LLLT with topicl minoxidil solution nd orl finsteride my ct synergistic to enhnce hir growth. Due to the known eneficil effect on wound heling, it is conceivle tht LLLT s n djunctive therpy in hir trnsplnt surgery my lso reduce postopertive shedding, reduce heling time, nd increse grft ptency. The scientific sis for such n pproch is given, ut there is need for controlled studies with higher numer of ptients to estlish n increse in efficcy of comintion regimens. [13] REFERENCES 1. Mester E, Szende B, Gärtner P. The effect of lser ems on the growth of hir in mice. Rdioiol Rdiother (Berl) 1968;9:621 6. 2. Moreno Aris G, Cstelo Brnco C, Ferrndo J. Prdoxicl effect fter IPL photoepiltion. Dermtol Surg 2002;28:1013 6. 3. Bernstein EF. Hir growth induced y diode lser tretment. Dermtol Surg 2005;31:584 6. 4. Levitt M, Chrles G, Heymn E, Michels D. HirMx LserCom lser phototherpy device in the tretment of mle ndrogenetic lopeci: A rndomized, doule lind, shm device controlled, multicentre tril. Clin Drug Investig 2009;29:283 92. 5. Avrm MR, Rogers NE. The use of low level light for hir growth: Prt I. J Cosmet Lser Ther 2009;11:110 7. 6. Avrm MR, Leonrd RT Jr, Epstein ES, Willims JL, Bumn AJ. The current role of lser/light sources in the tretment of mle nd femle pttern hir loss. J Cosmet Lser Ther 2007;9:27 8. 7. Kim H, Choi JW, Kim JY, Shin JW, Lee SJ, Huh CH. Low level light therpy for ndrogenetic lopeci: A 24 week, rndomized, doule lind, shm device controlled multicenter tril. Dermtol Surg 2013;39:1177 83. 8. Blumeyer A, Tosti A, Messenger A, Reyggne P, Del Mrmol V, Spuls PI, et l. Europen Dermtology Forum (EDF) Evidence sed (S3) guideline for the tretment of ndrogenetic lopeci in women nd in men. J Dtsch Dermtol Ges 2011;9 Suppl 6:S1 57. 9. Chung H, Di T, Shrm SK, Hung YY, Crroll JD, Hmlin MR. The nuts nd olts of low level lser (light) therpy. Ann Biomed Eng 2012;40:516 33. 10. Gupt AK, Digle D. The use of low level light therpy in the tretment of ndrogenetic lopeci nd femle pttern hir loss. J Dermtolog Tret 2014;25:162 3. 11. Ghnt M. Types of hir loss nd tretment options, including the novel low level light therpy nd its proposed mechnism. South Med J 2010;103:917 21. 12. Stino JL, Mrkou M. Hir regrowth nd incresed hir tensile strength using Hir Mx Lser Com for low level lser therpjy. Int J Cosmet Surg Aesthet Dermtol 2003;5:113 7. 13. Rjput RJ. Controversy: Is there role for djuvnts in the mngement of mle pttern hir loss? J Cutn Aesthet Surg 2010;3:82 6. How to cite this rticle: Munck A, Gvzzoni MF, Trüe RM. Use of low-level lser therpy s monotherpy or concomitnt therpy for mle nd femle Androgenetic lopeci. Int J Trichol 2014;6:45-9. Source of Support: Nil, Conflict of Interest: Rlph M. Trüe performs consultnt ctivity for Lexington Interntionl LLC. This study represents n integrl prt of Andréi Munck s trineeship in trichology t the Center for Dermtology nd Hir Diseses Prof. Trüe. Interntionl Journl of Trichology / Apr-Jun 2014 / Vol-6 / Issue-2 49