Is There a Rationale for the Use of an Alpha-Melanocyte-Stimulating Hormone Analog to Improve Gray Hair Repigmentation?

Dear Editor,

Hair color plays an important role in human society [1]. Hair graying is a natural age- and genetic-related biological process [2, 3]. Dyeing is an alternative to mask aging signs, but it may damage the hair shaft and is temporary [1].

Recently, palmitoyl tetrapeptide 20 (PT-20), an α-melanocyte-stimulating hormone analog, has been described to stimulate melanogenesis in hair follicles, possibly restituting the original hair color [4]. This study aimed to discuss the rationale behind it based on our clinical experience.

We proposed daily treatment with 2 mL of 2% PT-20 lotion applied all over the scalp to 14 patients for 6 months. Global photographs were taken before and after the treatment. Three independent dermatologists evaluated the images. The gray level was defined as low (5–25%), moderate (25–50%), and extensive (> 50%), whereas the result was rated as no improvement, partial (< 50%), and extensive (> 50%). Table 1 shows the results. Images can be seen in Figure 1.

Table 1.

Summary of the assessment of 14 patients undergoing PT-20

/WebMaterial/ShowPic/1472215Fig. 1.

Clinical images from 2 male patients with gray hair before treatment (a, c) and after 6 months undergoing Palmitoyl Tetrapeptide-20 topic lotion 2% (b, d). The first patient showed a good outcome (b) while the second patient showed no response (d).

/WebMaterial/ShowPic/1472213

Most of the patients were male (78.6%), phototype III (42.9%), and Caucasian (64.3%). The mean age at first evaluation was 45.5 (33–56 years old) and at the beginning of graying was 31.8 (24–43 years old). The mean duration of graying was 13.9 (1–26 years old).

The level of graying was low or moderate for 42.9% and 35.7% of patients, respectively. Only one used tobacco (7.1%), and another had comorbidity (7.1%). A total of 78.5% reported regular physical activities. Parental history of graying was common for all, but 1 patient (92.9%) and most patients had no alopecia (78.6%). Above 50% of patients did not regularly dye their hair (57.1%). We highlight that this percentage varied greatly by gender: all women dyed their hair regularly, while 72.7% of men did not.

After 6 months of treatment, the examiners identified no modification in graying (64.3% to 71.4% of the absence of improvement). All agreed that 6 patients had no progress (42.9%), and two agreed that five had no change in graying whatsoever (35.7%). Therefore, 78.6% had no clinical improvement for at least two examiners. On self-evaluation, 6 patients (42.9%) reported extensive improvement and five (35.7%) only partial. No statistical significance (p < 0.05) was found among the selected characteristics and graying levels after stratification by progress observed by all or two examiners.

Previous studies established that part of the hair graying process is due to the reduction in melanogenic-active melanocytes in the hair bulb of anagen hair follicles and the increase in oxidative stress in the bulb [1-3]. While follicular melanocyte stem cells can self-renew during hair cycles, the eventual loss of melanocyte stem cells is thought to cause hair graying [5, 6].

The melanogenic process is reduced by lower enzyme activity – tyrosinase and tyrosine-related protein-1 – and a defective melanocyte-keratinocyte interaction, thus affecting the transfer of melanosomes to the surrounding keratinocytes [1, 3]. Consequently, the number of pigments in hair drops until the hair becomes gray and then white. PT-20 apparently acts simultaneously by its genetic modulation, melanogenesis stimulation, and decrease in oxidative stress [4].

Thus, hair graying in young patients could supposedly be reversed, especially for those recently turned gray by melanocyte insult. However, our results did not support this hypothesis. Moreover, differences between patients’ and examiners’ perceptions may be related to patients’ expectations for positive results. Limitations of our study must be noted as the small sample size and the short endpoint for reevaluation.

People’s desire to avoid hair graying has triggered efforts to create products to reverse this process. Despite PT-20’s theoretical effects, our data did not endorse its efficacy. As far as we know, this study is the first prospective case series assessing an α-melanocyte-stimulating hormone analog for hair repigmentation. Further studies are required to confirm our findings.

Statement of Ethics

The study complies with the internationally accepted standards for research practice and reporting. Subjects have given their written informed consent to publish photos and details of the case. Ethical approval was not required for this study as per national guidelines.

Conflict of Interest Statement

The authors declare no conflicts of interest.

Funding Sources

No funding was received for this manuscript.

Authors Contribution

Daniel Fernandes Melo conceived the study, wrote the manuscript, and approved the final version to be published. Sandra Tagliolatto, Ana Cecília Studart, and Bruna Fanton Gallo collected data, wrote the manuscript, and approved the final version to be published. Carla Jorge Machado analyzed and interpreted data, wrote the manuscript, and approved the final version to be published. Simone Carolina Frattini prepared the draft, reviewed the text, and approved the final version to be published. Flávia Weffort and Rita Fernanda Cortez de Almeida conceived the study, critically reviewed the text, and approved the final version to be published.

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