Topical 5% minoxidil versus combined erbium YAG laser and topical 5% minoxidil in androgenetic alopecia: A randomized controlled trial

Androgenetic alopecia (AGA) is the most common type of hair loss in men, and several treatment options have been proposed for it. Fractional ablative erbium YAG laser can promote hair growth through trans‐epidermal drug delivery and the thermal stimulation of hair follicles; this study therefore aims to evaluate minoxidil alone and in combination with fractional ablative erbium YAG laser in male patients with AGA.

areas and progresses over time. 1 The onset of AGA at a young age and its progression can have a negative impact on the quality of life of young people and cause depression. 4erefore, several treatment options have been proposed for male AGA. 2,55][6][7] After converting to its active form, minoxidil sulfate affects the vascular smooth muscle receptors and thus stimulates microcirculation near the hair follicles by inducing arteriolar vasodilation and prolonging the anagen phase of hair, which results in the growth of miniaturized follicles. 4,5,8The need for its long-term use, low efficacy, and adverse side effects, however, have limited the use of minoxidil sulfate. 2,4,5,9In addition, there is no single treatment for all people, and depending on the condition, a combination of treatments will often yield the best response. 5ser therapy is known as a relatively new treatment and a lowrisk and effective alternative in AGA conditions where the use of minoxidil and finasteride and hair transplantation are not possible. 10fferent lasers are used in the treatment of hair loss.One of the most well-known types of laser therapy used for hair loss is lowlevel laser therapy (LLLT) with the wavelength of 650-900 nm, which was approved by the FDA in 2007.It seems that LLLT increases the production of adenosine triphosphate, reduces inflammation, and increases blood flow in the treated area, leading to an increase in the number and thickness of the hair follicles. 1,8High-energy medical lasers can lead to tissue regeneration through photothermal effects.
[11] Erbium YAG is a common laser in dermatology.The ablative fractional erbium YAG 2940-nm laser offers good effectiveness and a short recovery time by stimulating photoablation and photochemical tissue reaction in the form of a mixture of small intact parts and parts affected by the laser. 10,12rious studies have shown the effectiveness of different laser types in the treatment of AGA, especially when combined with other treatments. 1,2,4,10,11This study was designed to evaluate the efficacy of combined fractional ablative erbium YAG laser with topical 5% minoxidil versus minoxidil alone in male patients with AGA.

| Study design
This randomized, parallel-group trial was conducted on 30 male patients with moderate to severe AGA who were referred to medical centers affiliated with Isfahan University of Medical Sciences from May 2020 to May 2022.

| Patients
The inclusion criteria for this study were as follows: The sample size was calculated as 15 per group.

| Randomization
The randomization sequence was performed as the following: patients who were referred on Saturdays, Mondays, and Wednesdays were allocated to the intervention group to receive minoxidil and erbium YAG laser, and patients who were referred on Sundays, Tuesdays, and Thursdays were allocated to the control group to receive only minoxidil.
The control group was treated with 1 mL of topical 5% minoxidil solution twice daily.
Minoxidil treatment of both intervention and control groups continued for 6 months.

| Assessments
The demographic information of all the patients was recorded.
Disease severity was evaluated according to the Hamilton-Norwood scale before beginning the treatment.Safety and adverse effects were also assessed at each follow-up visit.
The treatment results were evaluated by three methods, including photography, dermoscopy, and patient satisfaction assessment before the start of the treatment and again at the end of the 6month treatment period.
The photographs were taken in four vertex views with the middle, temporal, and frontal patterns.Two dermatologists blinded to the group allocations performed the assessment using a 7-point scale for grading the patients' photographs.Dermoscopy was performed (Fotofinder, Bad Birnbach, Germany) from three separate areas of the scalp, and three points with distances of 12, 16, and 24 cm from the glabella were measured and marked on each area, and the dermoscopic photographs were taken from the center of these points.The dermoscopy results were assessed similarly to the photographs using a 7-point grading scale 13 : Relatively decreased = −2.

| Patient satisfaction
The patients' satisfaction with the results of the treatment was eval- Significant improvement = +3.

| Statistical analysis
GraphPad prism version 9 was used to perform the statistical analysis.Data are presented as mean ± SD.For the statistical analysis, the chi-square test, Student's t-test, Mann-Whitney's U-test, and Spearman's correlation test were run with p < 0.05 as statistically significant.

| RE SULTS
Overall, 30 patients were included in this study with a mean age of 33.7 ± 8 years and a mean disease duration of 12.4 ± 8 years (Figure 1).The two groups were comparable in their demographic and clinical characteristics, including age, disease history, grade of hair loss, and disease duration (Table 1).
Patients in both groups showed a good response to the treatment and achieved statistically significant improvement as evaluated by parameters including patient satisfaction, photography score, and dermoscopy results (Table 2; Figure 2).The correlation test showed a negative correlation between disease duration and response to treatment, and the patients with a lower Hamilton-Norwood scale score and shorter duration of disease showed better responses to the treatment in both groups (p < 0.001).
The dermoscopic evaluation showed a significant difference between the groups after 6 months (Figure 3), and the group receiving a combination treatment of laser and minoxidil obtained a higher in both groups.Another patient experienced erythema and contact dermatitis; therefore, the treatment was suspended for him and his dermatitis was treated with antihistamine and corticosteroids (desloratadine 5 mg daily, hydroxyzine 10 mg at bedtime, and prednisolone 15 mg in the morning for 3 days, followed by 10 mg for another 3 days); afterwards, the brand of minoxidil was changed for him and we resumed the treatment.Two other patients had mild burning sensation, which improved without any specific interventions.There were, however, no statistically significant differences between the two groups in terms of the number of cases that experienced adverse effects (p-value > 0.05).

| DISCUSS ION
AGA covers up to 80% of males by the age of 80, 14 and based on its prevalence, different treatments have been proposed to stop the progression of hair loss and stimulate the regrowth of hair. 15actional lasers can stimulate hair regrowth by two routes, including trauma-stimulated wound healing, 16 and enhancing dermal drug delivery. 17is randomized controlled trial evaluated the effects of ablative fractional erbium YAG 2940-nm as one of the treatments suggested by other studies; however, no human clinical trials could be found on this subject. 18udies have shown that alopecia begins at the age of 30 years, 19 which was similar to the age reported in our study.In our study, both groups experienced a significant improvement in hair loss, which is consistent with the results of other studies on the effects of minoxidil, 20,21 and fractional ER-YAG laser on AGA. 22Patients with a lower Hamilton-Norwood scale score and a shorter duration of disease showed better response to the treatment, which could be due to perifollicular fibrosis or the destruction of the affected follicles in patients with a longer disease duration. 23e patients in the laser treatment group achieved better outcomes based on their dermoscopy score, which could be due to the regulation of β-catenin and Wnt 10b pathways and the promotion of hair cycle transition from the telogen to anagen phase by fractional 2940-nm erbium YAG laser. 22Moreover, laser treatment can enhance the dermal delivery of minoxidil. 8,24The 1550nm fractional erbium-glass laser was used in a human clinical trial and had favorable outcomes in combination with minoxidil. 2In the present study, however, we chose ablative fractional erbium YAG 2940 over 1550-nm fractional erbium-glass laser because of the lack of adequate human, randomized, controlled trials to confirm the efficacy of this laser in humans, and also due to the differences in the outcomes achieved with the two lasers for skin rejuvenation.
Using ablative fractional erbium YAG 2940-nm laser proved more effective and had long-lasting effects. 12Azimova et al. conducted a 3-month study on erbium YAG 2940-nm with vitamin therapy, microelements, and angioprotectors.They reported an increase in hair growth in the anagen stage, 25 and our results are also consistent with those of the mentioned study.It should be noted that the cited study did not compare fractional erbium YAG 2940-nm with standard treatments, while our study did make this comparison.
In terms of permanent adverse effects, the patients in neither group experienced any permanent or serious adverse effects, and all of the adverse effects, including itchiness, scaling, and erythema, were tolerable, which is consistent with the literature.

| CON CLUS ION
There was a satisfactory improvement in the hair conditions of both groups due to the mechanisms of action of the interventions.
Nevertheless, the combination of ablative fractional erbium YAG 2940-nm laser with minoxidil was associated with a slightly better outcome, which suggests that lasers can potentiate the effect of minoxidil.

| S TU DY LI M ITATI O N
Small sample size and lack of objective assessments, such as hair density and thickness measurement, are the main limitations of this study.

AUTH O R CO NTR I B UTI O N S
Fatemeh Mokhtari was responsible for conceptualization and study design.Zahra Zavare was responsible for patient management and drafting the manuscript.Fariba Iraji was responsible for laser treatment consult and data arrangement.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.

E TH I C S S TATEM ENT
This study was registered at the Iranian Registry of Clinical Trials

R E FE R E N C E S
(1) AGA patient with moderate to severe scalp involvement based on the Norwood scale; (2) age over 20 years; and (3) patients' consent to participate in the study.Any patient who met the following criteria was excluded from the study: (1) Suffering from other types of alopecia (such as alopecia areata, telogen effluvium, anagen effluvium, and scarring alopecias); (2) having psoriasis or lichen planus; (3) serious systemic disease; (4) photosensitivity; and (5) history of hair transplantation.

F I G U R E 3 F I G U R E 4
Dermoscopic evaluation of the patients; (A1) the patients in topical minoxidil groups before the treatment and (A2) after the treatment; (B1) the patients in Er YAG laser with topical minoxidil groups before the treatment and (B2) after the treatment.Differences between the groups in photography and dermoscopy scores.ns (not significant), ** (p = 0.0001).
with the code IRCT20210404050847N1 and approved by the Ethics Committee of Isfahan University of Medical Sciences with the reference number IR.MUI.MED.REC.1399.1191.