Evaluating the Efficacy of Platelet Rich Plasma and 1550 nm Fractional Laser in Combination and Alone for the Management of Androgenetic Alopecia

Androgenetic alopecia (AGA) is the most common cause of hair loss, affects up to 70% of men and 40% of women over the course of their lifetime, and is known to advance with age.¹ AGA is a nonscarring diffuse alopecia due to hormonal and genetic influences. It is characterized by the progressive miniaturization of hair follicles, with the transformation of terminal hair into vellus hair.² AGA is believed to be attributed to genetic and environmental factors, while upregulating the enzyme perifollicular 5-alpha reductase.¹ Hair loss can cause considerable psychological and emotional distress with decreased quality of life. Therefore, developing a safe yet effective treatment modality can greatly benefit patients in a dermatology practice setting. Current treatment options include minoxidil, finasteride, spironolactone, nutritional supplementation, and hair transplantation surgery. Although topical minoxidil and oral finasteride are approved by the United States Food and Drug Administration (US FDA), they have drawbacks, including a limited degree of clinical improvement in some patients. The efficacy of new hair growth with current US FDA-approved therapies can be unsatisfactory, and significant improvement is not always observed.³ It is known that low level laser therapy or photobiomodulations, such as the US FDA-cleared HairMax Lasercomb^®, He-Ne laser, and excimer laser, are relatively affordable, user-friendly, safe, and effective forms of treatment for hair loss. While less is known about the effectiveness of fractional lasers for combating hair loss, research suggests that, by creating microscopic thermal injury zones, fractional lasers may cause an increase in hair growth from a wound healing process. As a result fractional laser therapies, including the 1550 nm nonablative fractional erbium-glass laser, the ablative fractional 2940 nm erbium:YAG laser, and the ablative fractional CO2 fractional laser, are a therapeutic option for alopecia.⁴ The nonablative fractional 1550 nm erbium-glass laser has been evaluated for the treatment of AGA in women and men because it can penetrate the scalp more effectively than other lasers without inducing bleeding. Like other fractional lasers, its method of action involves producing microcoagulative wounds in the dermis. Penetration depth and wound size while using this laser can be controlled with a fractional near-infrared laser.^5-7

The 1550 nm factional erbium-glass laser promotes increases in hair density, hair thickness, anagen: telogen ratio, and the rate of hair regrowth. Appropriate energy and density levels are needed to ensure proper treatment. Laser treatments set on excessively high energy levels or used beyond the recommended frequency may actually worsen the alopecia by stimulating fibrotic changes. The combination of the laser treatment with conventional treatments such as topical minoxidil and systemic medication, however, has been hypothesized to produce a synergistic effect on hair regrowth. Platelet-rich plasma (PRP) — the portion of the plasma fraction of autologous blood with platelet concentrations higher than the basal levels before centrifugation — is being used for multiple purposes in many fields of medicine. In dermatology, PRP has been shown to be beneficial in several areas, ranging from skin rejuvenation and acne scarring to hair loss.^8-10 The preparation of PRP begins with drawing the patient's blood. Centrifugation of the anticoagulated blood is used to separate the plasma containing the platelets from the red blood cells. Exogenous activating factors (such as calcium chloride) are added to stimulate the platelets. PRP is then injected into the target tissue located on the scalp in patients with AGA.^8-11 Platelets in PRP become activated when injected into the scalp, causing the release of these multiple growth factors, which stimulate hair growth by several potential mechanisms. These include apoptosis prevention, an anagen hair growth phase that is not only increased but also prolonged, delay of the progression from anagen to catagen hair growth phase, and increased viability and survival of the hair follicles. PRP has gained popularity for AGA due to its autologous nature, minimal invasiveness, absence of major side effects, and more affordable cost compared with hair restoration surgery. In this study, we report some cases of patients with male and female hair loss treated with PRP and/or 1550 nm fractional laser to evaluate the efficacy of both treatments alone and combined.

Participants Sixty patients with varying degrees of male pattern hair loss (MPHL) and female pattern hair loss (FPHL) were enrolled in the study. All subjects provided written informed consent prior to receiving any study-related procedures. Eligible patients were men and women, aged 20 to 60 years, with mild and moderate AGA. The diagnosis of AGA was established on the basis of a detailed medical history (any drugs causing hair loss), clinical examination, trichoscopic features (more than 20% variability in hair diameter between affected and uninvolved areas), and laboratory tests. Laboratory tests to exclude other hair loss causes such as anemia, poor nutrition, thyroid dysfunction, and syphilis included the following: complete blood cell count; measurement of serum levels of iron, serum ferritin, total iron-binding capacity, folic acid, T3, T4, antithyroid peroxidase, and testosterone; and a Venereal Disease Research Laboratory blood test for syphilis. Exclusion criteria included platelets disorders, thrombocytopenia, antiaggregating therapy, systemic treatments for alopecia in the previous 12 months (such as finasteride, dutasteride, and antiandrogens), bone marrow aplasia, uncontrolled systemic diseases, pregnant women, nursing mothers, and children. Patients with advanced stages of pattern hair loss and those who had used topical treatments for alopecia (eg, minoxidil, prostaglandin, analogs, retinoids, and corticosteroids) in the previous 12 months were also excluded. Study Design This was a randomized, prospective single-site study conducted in accordance with the principles of the Declaration of Helsinki, current Good Clinical Practice (GCP) guidelines, and Institutional Review Board (IRB) approval. Patients were randomized to 3 groups (n=20 per group): Group A received only fractional laser therapy application; Group B received only PRP injections; Group C received the application of laser therapy and subsequent application of PRP. Four treatments with 1550 nm fractional Er:Glass Laser and/or PRP injections were performed at a 1 month interval. Tricoscopy and global photographs were taken at baseline and at the end of the treatment. The photographs were then analyzed for changes in hair density. Global photographs underwent blinded review by 2 independent dermatologists using a 7‐point scale, while patients answered questionnaires assessing hair growth throughout the study (Table 1). Adverse effects were monitored and reported throughout the study. Treatment The PRP was processed in an appropriate procedure room, respecting all biosafety and asepsis standards. PRP was injected with a 1 mL syringe and 26 G1 / 2 needles, with intradermal points, at a distance of 1 cm to 2 cm between them, with 0.2 mL applied per point, over a predetermined extension. The volume of PRP processed was dependent on the size of the region being treated. The laser applied was the Fraxel Restore, a non-ablative erbium-glass 1550 nm fractional laser (low energy, high density settings: 7 mJ, level 3–9% coverage, 8 passes -120 mzt\cm²). Data Analysis The analysis of the data was based in the trichoscopy and photography comparison and the patient perception of improvement. Two medical observers, not involved in the research, were assigned to analyze the photographic data. Patients were assessed before starting the treatment and 1 month after the 4 sessions.

Statistical Analysis Association between group and evaluation variables were performed by Fisher's exact test or Pearson's chi-square test. The kappa coefficients of agreement were calculated with their respective 95% confidence intervals. The significance level adopted was 5% for all statistical hypotheses. Analyzes were performed using SPSS v.25 for Windows^®.

All 60 patients completed the 4-month schedule of treatments. By the evaluation of global clinical and trichoscopy images, important changes such as the emergence of new vellus hairs, as well as improvement of hair quality, color, and density, were noted in most cases in all 3 groups. None of the patients reported that their condition worsened after the first treatment session. No significant side effects were observed. The only side effects reported by the patients who received PRP treatment was mild to intense pain during the procedure, and mild pain the day after the treatment. Patients who were treated with laser reported only mild pain during the procedure. Interestingly, we noticed that younger patients had better and faster results, with many patients noting that their hair got darker at the end of the treatment. Table 1 presents the results of the distribution of evaluations according to group. No statistically significant associations were found between evaluations and groups according to each evaluator (P>0.05). Groups B and C had a higher proportion of improvement (moderate and excellent) compared with group A for all evaluators. Group A (only fractional laser therapy): 65% of the patients showed some improvement on hair density (Figure 1). Group B (only PRP injections): 70% of the patients showed some

improvement on hair density (Figure 2). Group C (laser therapy and subsequent application of PRP): 80% of the patients showed improvement in hair density (Figure 3).

PRP and 1550 nm erbium-glass fractional laser are effective yet safe treatment options for AGA, combined and alone. In our experience, patients showed better results when these 2 treatments were done together. We suggest that the wound healing process caused by fractional laser plus the effect of growth factors and cytokines from PRP act synergistically to stimulate hair growth.

The authors have no conflicts of interest to disclose.

1. Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. J Am Acad Dermatol. 2008;59(4):547-566; quiz 567-548. 2. Dinh QQ, Sinclair R. Female pattern hair loss: current treatment concepts. Clin Interv Aging. 2007;2(2):189-199. 3. Stevens J, Khetarpal S. Platelet-rich plasma for androgenetic alopecia: A review of the literature and proposed treatment protocol. Int J Womens Dermatol. 2019;5(1):46-51. 4. Perper M, Aldahan AS, Fayne RA, Emerson CP, Nouri K. Efficacy of fractional lasers in treating alopecia: a literature review. Lasers Med Sci. 2017;32(8):1919-1925. 5. Cho S, Choi MJ, Zheng Z, Goo B, Kim DY, Cho SB. Clinical effects of nonablative and ablative fractional lasers on various hair disorders: a case series of 17 patients. J Cosmet Laser Ther. 2013;15(2):74-79. 6. Kim WS, Lee HI, Lee JW, et al. Fractional photothermolysis laser treatment of male pattern hair loss. Dermatol Surg. 2011;37(1):41-51. 7. Yoo KH, Kim MN, Kim BJ, Kim CW. Treatment of alopecia areata with fractional photothermolysis laser. Int J Dermatol. 2010;49(7):845-847. 8. Elghblawi E. Platelet-rich plasma, the ultimate secret for youthful skin elixir and hair growth triggering. J Cosmet Dermatol. 2018;17(3):423-430. 9. Girijala RL, Riahi RR, Cohen PR. Platelet-rich plasma for androgenic alopecia treatment: A comprehensive review. Dermatol Online J. 2018;24(7). 10. Kramer ME, Keaney TC. Systematic review of platelet-rich plasma (PRP) preparation and composition for the treatment of androgenetic alopecia. J Cosmet Dermatol. 2018;17(5):666-671. 11. Alves R, Grimalt R. A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord. 2018;4(1):18-24.

Neil Sadick MD nssderm@sadickdermatology.com