Observing the clinical efficacy of combined serum microneedle therapy for moderate to severe androgenetic alopecia in scalp repair

Abstract

Objective

In this study, the safety and efficacy of scalp repair serum microneedles combined with oral drug administration and topical medication were investigated for the treatment of moderate to severe androgenetic alopecia.

Methods

Twenty patients, consisting of 4 males and 16 females, who sought treatment for moderate to severe androgenetic alopecia at our hair medicine research center alopecia specialty clinic between August and December 2022 were randomly selected for the study. Male patients underwent oral administration of finasteride topical application of 5% minoxidil, and biweekly scalp repair serum microneedle therapy. Female patients were administered spironolactone or Diane‐35 orally and applied 2% minoxidil topically, paired with biweekly scalp repair serum microneedle therapy sessions. After seven treatments, the scalp repair serum microneedle was discontinued, but oral administration and topical applications were continued, followed by a 1‐month follow‐up. Using a hair dermoscopy, hair follicles in a fixed region on the top of the head were manually counted per unit area to evaluate the hair restoration status of the patients quantitatively.

Results

All 20 patients completed 3 months of combined therapy and a 1‐month follow‐up. On average, the patients experienced an increase of 42.6 hairs, with an efficiency rate of 100%. Significant differences were observed in hair count between any two of the first seven treatments (p < 0.001). A significant negative correlation was discovered between the initial pre‐treatment hair count and the total improvement of hair (p < 0.001), indicating that the greater the degree of hair loss before treatment, the more pronounced the improvement.

Conclusion

Scalp repair serum microneedle combined therapy in moderate to severe androgenetic alopecia significantly reduces the number of microneedle treatments required, enhances treatment efficacy, and improves therapeutic outcomes.

Abbreviations

• AGA
• androgenetic alopecia
• BASP
• BAsic and SPecific
• DHT
• dihydrotestosterone

INTRODUCTION

Androgenetic alopecia (AGA), clinically the most prevalent form of hair loss disease, primarily manifests as reduced hair density on both sides of the forehead, gradually thinning hair extending to the crown of the head, a receding hairline, and an M-shaped frontal hairline. For the treatment of AGA, numerous options are currently available, including oral administration of finasteride, ethinylestradiol, cyproterone, spironolactone, topical application of minoxidil, phototherapy, microneedle, and hair transplantation, among others. Microneedling is a minimally invasive technique that can enhance the transdermal absorption of drugs, induce collagen production, angiogenesis, and the production of various growth factors in the treated area. This study aims to evaluate the efficacy and safety of scalp repair serum microneedle combined therapy for moderate to severe androgenetic alopecia.

MATERIALS AND METHODS

Clinical data

General information

The selected 20 patients were from the alopecia specialty clinic at our hair medicine research center between August and December 2022. There were 4 males and 16 females, aged between 28 and 46 years, with an average age of 36.95 years. The duration of the treatment was 3 months, with a 1-month follow-up period. Based on the BASP classification, 15 patients were categorized as moderate and 5 patients as severe, all of whom displayed typical clinical manifestations.

Inclusion criteria

Inclusion criteria were (1) clear diagnosis of AGA and categorized as moderate or above according to the BASP classification; (2) absence of local use of hair growth medications or other local treatments 1 month before the initial diagnosis; and (3) absence of systemic use of drugs with hair growth promotion or anti-androgenic effects 2 months before the initial diagnosis.

Exclusion criteria

Exclusion criteria were (1) pregnant or lactating women; (2) history of heart, liver, or kidney dysfunction, hypertension, tumors, neurological or mental disorders; (3) other types of hair loss, such as alopecia areata, autoimmune alopecia, or hair loss caused by drugs or other factors; (4) scalp hair atrophy resulting in a loss of hair growth function; (5) individuals who had received minoxidil or other drugs that may affect hair growth within the previous 6 months; and (6) poor medication adherence or inability to tolerate drug treatment.

Methods

Treatment methods

Male patients were administered finasteride (Baidaying, specification: 1 mg, dosage: 1 mg/d) orally, topically applied 5% minoxidil (Manson, specification: 5% concentration, dosage: 1 mL each time, bid), and underwent scalp repair serum microneedle therapy (Dermaheal Hair Filler cocktail) every 2 weeks. Female patients were administered spironolactone (spironolactone tablets, specification: 20 mg/tablet, dosage: 1 tablet/time, three times a day) or ethinylestradiol cyproterone tablets (Diane-35, specification: each tablet contains 2 mg of cyproterone acetate and 0.035 mg of ethinylestradiol, dosage: 1 tablet/day, taken continuously for 21 days) orally, topically applied 2% minoxidil (Dafeixin, specification: 2% concentration, dosage: 1 mL each time, bid), and underwent scalp repair serum microneedle therapy (Dermaheal Hair Filler cocktail) biweekly. Each session lasted 15 to 20 min and was administered every 2 weeks for a total of seven sessions. Following these sessions, microneedle therapy was discontinued, but local and oral medications were continued for 1 month, followed by observation.

Observation period

Continuous observation was carried out for 12 weeks. During the treatment period, the efficacy and adverse reactions of patients were evaluated every 2 weeks. After discontinuing microneedle treatment for 1 month, the efficacy and adverse reactions were evaluated again, with eight follow-up evaluations.

Efficacy evaluation

Objective evaluation indicators were employed by utilizing a hair dermoscopy to manually count the number of hairs per unit area on a fixed region at the top of the patient's balding area. This quantitative analysis was used to evaluate the recovery of the patient's hair (image capture: multispectral dermoscopy image processing workstation; brand: CBS; manufacturer: Bose View Electron Enterprise Co., Ltd.). To ensure the uniqueness of the counting standard, a designated individual conducted this task. N represents the number of hairs, with the number of hairs being recorded as N_n at the time of the n-th treatment and the follow-up result 1 month after discontinuing microneedle treatment being recorded as N8. T represents the improvement amount of each treatment, and T_n = N_n+1-N_n represents the improvement amount of the n-th treatment.

Statistical analysis

Data entry and organization were conducted using SPSS 25.0 software. One-way repeated measures ANOVA, one-way ANOVA, Spearman's correlation analysis, and the independent samples t-test were employed as statistical methods. A p-value of less than 0.05 was considered statistically significant.

RESULTS

General information

A total of 20 patients, 4 males and 16 females, aged between 28 and 46 years, with an average age of 36.95 years, were selected. All 20 patients underwent seven treatments every 2 weeks and were followed up 1 month after the treatment ended. Table  displays the severity of the condition of the 20 patients in accordance with the BASP classification.

TABLE 1 Statistics on the condition of 20 patients with hair loss.

	Moderate	Severe	Total
Number of cases	15	5	20
Percentage (%)	75.0	25.0	100.0

Partial results of the patients’ treatment are shown in Figures  and .

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Efficacy

Overall efficacy assessment

All 20 patients completed seven treatments. Figure  depicts the average number of hairs before each treatment.

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A one-way repeated measures ANOVA with Greenhouse-Geisser correction was conducted on the average number of hairs. The result indicates that there is a statistically significant difference in the number of hairs between the groups (p < 0.001, partial Eta squared = 0.872). A Bonferroni correction was applied for pairwise comparison of the hair counts at different treatment times. There is a significant difference in the number of hairs between any two treatments from N1 to N7 (p < 0.001). The Bonferroni correction for pairwise comparison revealed no significant difference between N7 and N8 after applying (p > 0.05).

Comparison of improvement in each treatment

T represents the improvement of each treatment, and T_n = N_n+1-N_n represents the improvement of the n-th treatment; the values of T are recorded in Table .

TABLE 2 Improvement after each treatment.

		95% confidence interval of the mean
	Mean	Lower limit	Upper limit
T1	9.45	6.35	12.55
T2	7.35	5.53	9.17
T3	6.40	4.60	8.20
T4	6.65	4.76	8.54
T5	5.20	3.92	6.48
T6	6.90	4.18	9.62
T7	0.65	-2.31	3.61

As shown in Figure , a one-way ANOVA was conducted on T, and there was a significant difference between the improvement of each treatment (p < 0.001). T7 represents the improvement after stopping the scalp repair serum microneedle treatment and maintaining only oral and topical treatments. A one-way ANOVA was conducted on T1 to T7, and the results of the S-N-K post hoc test revealed a significant difference between T7 and T1 through T6 (p < 0.05).

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Relationship between the initial pre-treatment hair count N1 and total improvement

A correlation test was conducted between the initial pre-treatment hair count N1 and total improvement, and a significant negative correlation (p < 0.001) was discovered. In other words, the worse the baseline situation, the better the total improvement. Four patients with an initial hair count of 40−60, 60−80, 80−100, and 100−120 were arbitrarily selected. Figure  depicts the changes in the number of hairs that accompanied the treatment.

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Adverse reactions

During the treatment and follow-up periods, no obvious adverse reactions were observed in patients. No patients experienced allergies or other side effects from the treatment. Pain and desquamation in the microneedle treatment area constituted the majority of the discomfort symptoms observed during the treatment process. The pain subsided on its own within a few hours of the treatment, and no patients discontinued the treatment due to intolerable pain. The desquamation could be enhanced by using scalp care products or washing the hair with warm water.

DISCUSSION

AGA is a hair loss disorder mediated by androgens. It is the most prevalent type of hair loss, affecting up to 53% of men and 30% of women. Circulating androgens, such as dihydrotestosterone, enter hair follicles through the capillaries of the dermal papilla and bind to the androgen receptor within the papilla cells. This activates the DKK pathway, which inhibits Wnt, Stat3, and Shh, thereby suppressing hair growth and causing progressive miniaturization of the hair papilla. This results in a transformation of terminal hair into vellus hair and a decrease in the number of hairs in the growth phase. AGA can trigger both physiological and psychological effects, underscoring the need for more effective methods of early diagnosis and treatment. Medication is indispensable in hair loss treatment. First-line drugs primarily include, among others, minoxidil, finasteride, and ethinylestradiol cyproterone.

A microneedle is a minimally invasive device that has been extensively used in various scar treatments, transdermal delivery, and the treatment of AGA and alopecia areata. In hair regrowth treatments, densely arranged fine needles physically puncture the scalp, causing temporary, water-filled cavities. This enhances the transdermal absorption of large molecules and/or hydrophilic molecules by creating micrometer-sized delivery channels. The potential mechanisms of microneedle therapy for hair loss include the following: (1) inducing the overexpression of hair growth-related genes such as Wnt3a, Wnt10b, VEGF, and so on, thereby regulating the hair growth cycle, stimulating the dermal papilla, and promoting hair growth; (2) disrupting the integrity of the scalp skin barrier, causing the formation and expansion of neoangiogenesis, and the migration of keratinocytes, thereby promoting the growth of new hair; (3) inducing mechanical changes in the keratin barrier, forming micrometer-level channels in the skin, and delivering various effective ingredients, including protein molecules and plant extracts, improving the efficiency of drug delivery. In addition, the risk of scalp infection is reduced because these channels can close spontaneously. Numerous studies have demonstrated the efficacy and safety of microneedle therapy. The majority of clinical trial results indicate that the efficacy of microneedles combined with a 5% minoxidil solution is significantly better than using microneedles or minoxidil alone, and a 0.6 mm microneedle depth is superior to a 1.2 mm microneedle depth. In addition, microneedle treatment can avoid the first-pass effect, increase drug concentrations at the target sites, reduce the frequency of administration, and improve patient compliance.

The hair restoration serum—Dermaheal Hair Filler Cocktail, has passed the mandatory safety assessments required by the United States CTFA, including four tests (acute toxicity, sensitivity, skin irritation, and eye irritation) and all optional toxicity tests (genotoxicity, reproductive toxicity, and penetration test). The serum peptides can bind to numerous growth factor receptors and produce similar effects to those of growth factors. This stimulates hair growth, and angiogenesis, and extends the hair growth period. The serum utilizes high-penetration sustained-release technology, which enhances the metabolic duration of biomimetic peptides in the body, effectively prolonging the active period of the serum's ingredients. In this study, we quantitatively evaluated hair restoration in patients by counting the number of hairs in a fixed area on the top of the head. The results revealed that the average increase in hair count for the 20 patients was 42.6 strands, with an efficiency rate of 100%. The results of the one-way repeated measures ANOVA for N1–N7 were significant, revealing significant differences in all pairwise comparisons, indicating that scalp repair serum microneedle combined therapy had a positive therapeutic effect on moderate to severe androgenetic alopecia. Compared with previous studies, the combined treatment interval in this study was 2 weeks. This interval showcased outstanding efficacy, suggesting that the hair restoration serum significantly improved treatment efficiency and enhanced patient compliance. Improvement measures (T) were analyzed using one-way ANOVA, revealing significant differences between treatment improvements. The increase in hair count after the first (T1) and second treatments (T2) was higher compared to subsequent treatments. One month after discontinuing the hair restoration serum microneedle treatment, there was no significant change in the patients’ hair count, and the improvement in hair count at T7 was significantly lower than at T1–T6. This indicates that the efficacy of the hair restoration serum microneedle treatment is significantly superior to the combination of simple oral administration and topical medication. The observation interval at T7 was 1 month, which suggests that the interval for hair restoration serum microneedle treatment should not exceed 4 weeks. In prior studies, the effect of gender on the effectiveness of AGA treatment remained controversial. In this study, male patients exhibited a notably higher hair count at N8 compared to female patients. Nevertheless, given the limited sample size, it is imperative to expand the sample size to validate this finding conclusively.

Compared with platelet-rich plasma combined with minoxidil in the treatment of androgenic alopecia, scalp repair serum microneedle combined with minoxidil in the treatment of moderate to severe androgenic alopecia shows a better therapeutic effect for moderate to severe patients, which also has the following advantages: (1) simple operation, avoiding infection and other risks in the preparation of blood products; (2) reduce the cost and reduce the economic burden of patients; and (3) avoid side effects such as pain and allergy.

CONCLUSION

The results of this study demonstrated that the combined hair restoration serum microneedle therapy can significantly enhance the treatment efficacy for moderate to severe androgenetic alopecia, reducing the number of traditional microneedle treatments required to achieve significant results.

ACKNOWLEDGMENTS

AThis study was funded by the 2022 Capital Health Development Scientific Research Project (Grant Number: 2022-2Z-2076). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. All participants signed a document of informed consent

ETHIC STATEMENT

This study was conducted with approval from the Ethics Committee of Beijing Jishuitan Hospital (Approval No. K2023-326). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.

CONFLICT OF INTEREST STATEMENT

The authors declare that they have no competing interests.

DATA AVAILABILITY STATEMENT

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

Zhang Z, Li W, Chang D, et al. A combination therapy for androgenic alopecia based on quercetin and zinc/copper dual‐doped mesoporous silica nanocomposite microneedle patch. Bioact Mater. 2022;24:81‐95. doi: [DOI: https://dx.doi.org/10.1016/j.bioactmat.2022.12.007]