Laser therapies in androgenetic alopecia: Review and clinical experiences

Red light LLLT

Red light laser treatment (630–700 nm) has shown promising results in AGA therapy by strengthening hair, improving blood circulation, modulating oxidative stress, and promoting hair growth factors (GFs).²³ The 675 nm laser is highly effective in targeting collagen due to its selective absorption, minimizing interaction with vascular components and water, making it optimal for directly affecting collagen fibers without significantly impacting other chromophores. Its penetration depth exceeds 1 mm, creating a thermal column that diffuses heat to surrounding areas, thereby enhancing treatment effectiveness. In addition, red light at 660 nm stimulates the anagen phase of HFs, extending this active growth phase and delaying the transition to the catagen phase.¹² Furthermore, near-infrared light promotes cell proliferation and differentiation of stem cells, as indicated by increased expression of KI67, a biomarker of cell proliferation.^17,23

An in vivo study on C57BL/6 mice suggested a mechanism of red light (670 nm) that promotes vasodilation by triggering the release of a vasoactive substance, S-nitrosothiols (RSNO), from the endothelium, which operates in a NO-dependent but endothelial NO synthase-independent manner. This process involves the formation of extracellular vesicles containing RSNO, which exit the endothelium and induce smooth muscle relaxation. This study demonstrated enhanced vesicular trafficking and increased expression of CD63 in endothelial cells followed by exocytosis.²⁴ In an ex vivo study using 650-nm red light, Yang et al.²³ noted the promotion of HF proliferation, delayed the anagen-tocatagen transition, and involved processes like leukocyte migration. RNA-sequence revealed the specific gene signatures associated with these effects. Building on this, Sorbellini et al.²⁵ experimented with 675 nm laser efficacy in AGA patients. Results revealed a significant increase in hair shaft density and reduced miniaturization by 60% with no side effects. Further, research by Chandrashekar et al.,²⁶ observed a 17% increase in hair count and density and a 16.61% increase in hair thickness after 14 sessions, indicating improvements in hair growth and quality [Table 1].

Blue light laser

Blue light therapy (BLT) for AGA works through multiple biological pathways. It promotes hair growth by photolytically generating NO from nitrosated proteins, which enhances vasodilation and prolongs the anagen phase of HFs. BLT activates photoreceptors Opsin 2/rhodopsin (OPN2) and OPN3 (panopsin), expressed in human skin and anagen follicles, particularly through blue light at 453 nm, which has been shown to stimulate hair growth. In addition, BLT regulates melanogenesis by activating OPN3 and the tyrosinase-related protein complex involved in melanin synthesis and transfer to keratinocytes.^27,28 It also interacts with proteins like cytochrome C oxidase, which acts as a light acceptor, influencing enzymes and proteins such as nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase and calcium channels, thereby activating secondary messengers such as NO, ROS, cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and calcium ions. These combined mechanisms support HF regeneration and growth.^28-32

Lodi et al.³³ tested the efficacy of blue light-emitting diode (LED) light at 417 nm in AGA patients, observing an increase in hair density and shaft width in 90% of participants after 10 weeks, with 80% showing photographic improvement. No serious adverse events were reported, although two patients experienced hair darkening, potentially due to melanin stimulation by blue light. In addition, a study confirms that blue light at 453 nm induces the accumulation of cryptochrome 1 (CRY1) in human keratinocytes and HFs, where CRY1 is highly expressed in the anagen phase. Silencing CRY1 promotes catagen while stimulating it prolongs anagen, suggesting that CRY1 mediates blue light’s positive effects on hair growth.²⁷

Combination treatment-LLLT with microneedling (MN), platelet-rich plasma (PRP) , Growth factors (GFs), and exosomes

The primary limitation of LLLT for hair growth is its insufficient light penetration into the scalp. To address this, the concept of precision LLLT has been introduced, combining low-intensity lasers or LEDs with microneedling (MN). LLLT, through photobiomodulation, stimulates cellular activity, promotes healing, and activates the metabolism of HFs for regeneration and hair growth. While, MN creates micro punctures in the skin, initiating the wound healing process. This process releases factors such as Wnt3a, Wnt10b, and epidermal GFs, which activate HFs. The combined approach, often called “microneedle patch,” enhances hair regrowth by stimulating neocollagenesis, neovascularization, and GF release.³⁴

PRP is an established treatment for hair growth as a standalone therapy or combined with other treatments. Numerous studies support its efficacy. PRP treatment involves an autologous preparation of plasma with highly concentrated platelets. This plasma contains over 20 GFs crucial for hair regrowth and enhances the biological processes involved in HF regeneration. A retrospective case-series study evaluated the combined use of autologous non-activated PRP, LLLT (423–640 nm) and MN.³⁵ Eitta et al.³⁶ combined LLLT (650– 670 nm) with PRP and evaluated the trichogenic effects in AGA patients. The results showed significant improvements in hair diameter, vellus hair, terminal hair, and hair density after the initial three months of treatment. Although these improvements diminished somewhat after discontinuing the treatment, the results remained better than baseline levels.

Kittigul et al.³⁷ investigated the precision LLLT efficacy in C57BL/6 mice using different LED wavelengths – red (629 nm), green (513 nm), and blue (465 nm) – along with MN for 28 days. The combination treatment resulted in faster and greater hair growth than LED alone, with green light showing the most significant improvement. Histopathological analysis revealed increased HFs, collagen production, angiogenesis, and immune cell infiltration in treated areas. The green-light LED microneedle patch was most effective at triggering the telogen-to-anagen hair growth transition, with no serious side effects observed, suggesting its potential for treating AGA.

Building on this research, multiple studies investigated the efficacy of MN, LT (red light at 640 nm and blue light at 423 nm), and GFs.^38,39,41 Rattanapirat and Meephansan⁴⁰ conducted a pilot study, testing the safety and efficacy of green LED light (513 nm) and red light (629 nm) in combination with MN for AGA patients. All these approaches increased hair thickness, new hairs were noticed and significant scalp coverage was noted with no side effects.

Recent advancement of combined hair regrowth treatment involved MN patches decorated with hair nanoparticles and exosomes from human amniotic mesenchymal stem cells (hAMSCs), along with low-color-temperature yellow light (1900 K). The MNs facilitated drug delivery by penetrating the scalp, allowing hAMSC exosomes to activate HF stem cells and trigger the transition from telogen to anagen. Simultaneously, the yellow light alleviated HF inflammation, further promoting hair regrowth. Animal studies demonstrated significant hair regrowth within 7 days using this synergistic approach, with no adverse effects, highlighting its potential for clinical application.⁴²

Combination therapies such as these offer a beneficial option for AGA patients who are non-responders to FDA-approved drugs or achieve moderate results from other treatments. However, to establish standardized treatment protocols, prospective multicenter studies are necessary.

Fractional ablative CO₂

The fractional CO₂ laser, widely recognized for its skin rejuvenation properties, also shows potential in treating AGA by stimulating HFs through its wound-healing effects, as observed in murine models.⁵⁰ This laser creates microscopic thermal injury zones that can trigger the transition from the telogen to anagen phase, promoting new hair growth.⁴⁴ The mechanism underlying this effect, demonstrated in C57BL/6 mice, involves creating an inflammatory microenvironment, promoting VEGF-mediated angiogenesis, and activating the Wnt10b signaling pathway, all of which contribute to hair regrowth.⁵¹ More recently, Hasegawa et al.⁴⁷ demonstrated that CO₂ laser irradiation recruits Ccr2-positive macrophages, further supporting hair regrowth in a mouse alopecia model. These studies collectively enhance the understanding of the cellular and molecular mechanisms behind hair cycle initiation.

Clinical studies have consistently demonstrated the efficacy of fractional CO₂ lasers in treating AGA, particularly when used as a combination therapy. Rashed et al.⁴⁶ and Huang et al.⁴⁴ reported significant improvements in hair density, count, and thickness when fractional CO₂ laser treatments were combined with topical minoxidil or hair GFs. Salah et al.⁴⁵ further supported these findings, noting that patients treated with a combination of fractional CO₂ laser and minoxidil showed superior improvements in hair number and thickness in male AGA compared to those receiving monotherapy. Furthermore, Tawfik et al.⁴⁸ found that combining CO₂ laser therapy with PRP produced remarkable results in treating female pattern hair loss (FPHL), significantly improving hair density and hair quality, and effects were well-tolerated and long-lasting [Table 2].

Across these studies, fractional CO₂ laser therapy was consistently reported to be safe, with no serious adverse effects. The minimally invasive nature of the procedure, coupled with its durable results, positions the fractional CO₂ laser as an adjunctive treatment for AGA.

Fractional Erbium YAG: 2940 nm laser

The 2940-nm Er:YAG laser has garnered attention as a potential therapeutic tool for hair restoration and was initially introduced in 1995 for hair restoration. This laser promotes hair regrowth through several mechanisms. One of the primary pathways involved is the Wnt/β-catenin signaling pathway, which plays a critical role in the transition of HFs from the telogen (resting) phase to the anagen (growth) phase. The murine model study by Ke et al.,⁵² demonstrated that Er:YAG laser treatment significantly upregulates the expression of Wnt 10b and β-catenin, leading to accelerated HF cycling and increased hair growth. In addition, histological analyses have revealed an increase in HF density and an improved anagen-to-telogen ratio, further supporting the laser’s role in enhancing hair growth dynamics.^52,53

Moreover, the Er:YAG laser improves transdermal drug delivery by selectively ablating the stratum corneum, the main barrier to drug absorption. This enhances the penetration of topical agents like minoxidil through mechanisms such as skin barrier ablation, optical breakdown through photomechanical waves, and photothermal effects, creating temporary pathways for better drug absorption, crucial for treating AGA.⁵⁴

Clinical studies have consistently demonstrated the efficacy of the Er:YAG laser in treating AGA, both as a monotherapy and in combination with other therapies [Table 3]. In a study by Mokhtari et al.,⁵⁴ male patients with moderate-to-severe AGA showed significantly enhanced hair regrowth when treated with a combination of 2940-nm ablative fractional Er laser and 5% minoxidil, compared to those who received minoxidil alone. This improvement is attributed to the laser’s ability to stimulate HFs and improve drug delivery. Ahn⁵⁵ further corroborated these findings and reported effective hair regrowth with minimal side effects in patients treated with the Er:YAG laser and a hair growth-promoting solution through JetPeel^™, particularly in the frontal and vertex regions.

The efficacy of non-ablative Er:YAG laser therapy has also been explored. Day et al.⁵⁶ demonstrated that non-ablative Er laser, used as a monotherapy or in combination with PRP and minoxidil, significantly reduced AGA grades and improved hair quality in 93% of patients. This treatment was associated with high patient satisfaction and minimal discomfort. Similarly, Maksimov⁵⁷ reported substantial hair density restoration in a grade-3 AGA patient following a combination of non-ablative Er:YAG laser therapy and PRP injections, with sustained results and no adverse effects. In FPHL, Dekeyser⁵⁸ found that six sessions of ER: 2940 nm laser treatment effectively stabilized hair loss and increased hair density, with no reported side effects.

These findings collectively suggest that the Er:YAG laser, both in its ablative and non-ablative forms, whether used alone or in combination with other treatments, is a safe and effective option for improving hair regrowth and quality in AGA patients.

Fractional non-ablative 1550 and 1540 nm Er: glass lasers

The Er: Glass laser enhances cellular signaling and microenvironmental conditions conducive to HF activation and growth. This laser stimulates hair regrowth by enhancing hair density and shaft diameter, primarily through the modulation of GFs such as fibroblast growth factor, epidermal growth factor, insulin-like growth factor, and VEGF, which are crucial for wound healing and hair cycling.⁵⁹ In addition, the laser improves transdermal drug delivery, which elevates VEGF and prostaglandin E2 levels, helping to increase blood flow to HFs and further promoting hair growth.⁶⁰

Kim et al. (2011)⁶¹ demonstrated that a 1550-nm fractional Er laser could stimulate hair growth in both a murine model and a pilot human study, with improvements observed in hair density and growth rate. In addition, Lee et al.⁶² showed significant increases in hair density and thickness in South Korean women with FPHL after a 5-month course of 1550-nm Er laser treatments. Bertin et al.⁶³ reported positive outcomes in four patients treated with a 1550-nm Er laser followed by topical finasteride and GFs, showing enhanced hair regrowth and density without significant side effects. Suchonwanit et al.⁶⁰ found that combining 1550-nm Er laser therapy with topical 5% minoxidil significantly improved hair density and diameter compared to minoxidil alone in a 24-week study involving 30 men. Finally, Alhattab et al.⁶⁴ reported that the 1540-nm fractional Er laser effectively improved hair density and thickness in patients with AGA over 5 months [Table 4].

Collectively, studies highlight the potential of Er: lasers as a promising treatment for AGA, with notable improvements in hair regrowth and minimal adverse effects.

Fractional non-ablative pico: 1064-nm

Picosecond lasers stimulate hair growth by creating tiny, nonthermal micro-injuries in the scalp through Laser-Induced Optical Breakdown, triggering a wound healing response that releases GFs and activates HF stem cells. This process helps the transition of HFs from the resting phase to the growth phase, promoting hair regrowth. Furthermore, pico laser activates the Wnt/β-catenin signaling pathway, which is crucial for sustaining the hair growth cycle.^65,66

Lueangarun and Tempark⁶⁵ conducted a pilot study with five male participants using a 1064-nm fractional picosecond laser (FPL), demonstrating significant improvements in hair regrowth and patient satisfaction. The study employed standardized laser parameters and showed clinical and dermoscopic improvements with minimal adverse effects. In continuation, Lueangarun et al.⁶⁶ further explored the combined use of FPL and exosome therapy in a case study involving a patient with both AGA and poliosis circumscripta [Table 5]. The results showed noticeable hair regrowth and repigmentation of white hair patches, suggesting that combining FPL with exosomes could offer a new treatment avenue for both hair loss and pigmentation issues.

Fractional non-ablative thulium: 1927 nm

The fractional laser induces micro-injuries in the scalp, triggering a wound-healing response that stimulates stem cell proliferation and enhances the anagen phase of HFs, thereby promoting hair regrowth.^43,71 This treatment also disrupts the stratum corneum, improving transdermal absorption of topical GFs and medications like minoxidil, directly targeting the hair roots.⁴³

Clinical evidence supports the use of thulium lasers in treating AGA and pattern hair loss (PHL). Taub et al.⁷⁰ and Cho et al.⁶⁷ demonstrated that a 1927 nm fractional laser, combined with a GF solution, effectively increased hair density and diameter with minimal side effects in patients with AGA and PHL patients, respectively. Cho⁶⁷ showed that combining thulium laser with polydeoxyribonucleotide injections led to significant improvements in hair thickness and density. Finally, Brownell et al.⁶⁹ reported that thulium laser with PRP therapy resulted in substantial increases in hair density and mass index in male AGA patients, with few side effects. The research studies on thulium lasers in AGA treatment are summarized in Table 6.