A clinical study on the efficacy of minoxidil liniment in treating female pattern hair loss

Purpose: To investigate the clinical effect of low and high-dose minoxidil liniment in treating female pattern hair loss. Methods: A total of 280 female pattern hair loss patients admitted to the dermatology clinic of Lujiang County People's Hospital of Anhui Province, China from October 2020 to October 2021 were randomly divided into control and study groups comprising 140 patients in each group. Ludwig staging in the two groups included 35 cases of Type I, 80 cases of Type II, and 25 cases of Type III in control group; 40 cases of Type I, 74 cases of Type II, and 26 cases of Type III in study group. Control group was treated with 1 mL (7 sprays) of 2 % minoxidil liniment, twice daily for 6 months. Study group was treated with 1 mL (7 sprays) of 5 % minoxidil liniment. Efficacy of low and high-dose minoxidil liniment was determined according to the area and degree of hair loss before and after treatment, and the incidence of adverse responses was recorded. Results: After treatment for 3 months, the effective rates of control and study groups were 34.3 and 41.4 %, respectively. Effective rates of control and study groups were 57.1 and 72.9 % respectively after 6 months of treatment. There was no significant difference in effective rates after 3 and 6 months of treatment (p > 0.05). Conclusion: Both 2 and 5 % minoxidil liniments demonstrate clinical efficacy in female pattern hair loss in a dose-dependent manner.


INTRODUCTION
Female pattern hair loss (FPHL) is characterized by diffuse alopecia without a scar.The root cause of FPHL is still unknown but it has been linked to gradually shrinking hair follicles and reduced hair numbers.The distribution of hair loss sites is regular, and most hair loss occurs in central, frontal and parietal scalp regions, also with genetic susceptibility [1].
Minoxidil is the only topical medication approved by the FDA for the treatment of androgenetic alopecia (AGA).It is believed to stimulate hair follicle growth, improve blood circulation to hair follicles, and promote hair growth [2].However, the precise mechanism of minoxidil in treating the alopecia area is currently unclear.It is speculated that the opening of potassium ion channels prevents calcium ions from entering the cells, shortening the resting phase and allowing hair follicles to enter the growth phase.This speculation is difficult to prove, and there is no clear evidence and studies to show the relationship between hair follicles and adenosine triphosphate (ATP) [3].Indeed, there is evidence suggesting that minoxidil prolongs hair follicle growth and increases the size of hair follicles.In in vitro studies of various skins and hair follicle cells, minoxidil promotes the production of vascular endothelial growth factor, thereby increasing blood vessels around hair follicles for better hair nourishment, all of which may be related to hair growth [4].Minoxidil also promotes angiogenesis around hair follicles, speeding up blood flow.Recent studies have presented that minoxidil also increases the production of prostaglandin E2 by stimulating prostaglandin lactone-oxide synthase 1, thus promoting hair growth [5].
Side effects of minoxidil include pruritus, dermatitis, hirsutism, desquamation, headache, palpitation, chest pain, abdominal swelling, dizziness, etc. Since, its approval, no study has reported the efficacy and safety of 2 and 5 % minoxidil liniment in female pattern alopecia.This research investigated the efficacy and safety of 2 and 5 % minoxidil liniment in treating female pattern hair loss.

Diagnostic criteria
According to the Chinese Guidelines for Diagnosis and Remedy of Androgenic alopecia [6], all enrolled patients were consistent with FPHL.

Inclusion criteria
Patients who met the diagnostic criteria were in good mental condition, could see the doctor on time, had high medical adherence, and had voluntary consent to participate in the study.

Exclusion criteria
Pregnancy or lactation, abnormal blood pressure, cardiac insufficiency, have received hair loss therapy or used hair loss products within the last 6 months, and have known allergy to the drugs used.

Clinical efficacy evaluation
Patients in both groups were photographed, and effectiveness of treatment (E) was assessed based on changes in the area and severity of hair loss in the top and anterior parietal regions before and after treatment using Eq 1. Ludwig staging method was adopted, and the criteria for efficacy are as follows: -3 = obvious reduction; -2 = moderate reduction; -1 = slight reduction; 0 = no change; +1 = slight improvement; +2 = moderate improvement; +3 = obvious improvement, with higher scores indicating better outcomes.E = (apparent cases + effective cases)/total cases …………... (1)

Adverse reaction indices
Adverse reactions such as scalp itching, hair loss, hirsutism or contact dermatitis after the use of minoxidil liniment were investigated [7].

Statistical analysis
Clinical results were all processed using statistical packages for social sciences (SPSS 21.0 software) and measurement data were expressed as (mean ± SD).Inter-group analysis was done using a t-test and analysis of variance (ANOVA).Comparison of counts was done with chi-square test and p < 0.05 was considered significant.

Clinical efficacy after 3 months of remedy
There was no significant difference in patients' data (Table 1).Comparative analysis of 3 months efficacy revealed that after 3 months of treatment, there was no statistical significance in effective rate (p > 0.05) (Table 2).

Clinical efficacy after 6 months of remedy
After 6 months of treatment, the effective rate of study group was significantly higher compared to control group (p < 0.01) (Table 3, Figure 1).

Efficacy of Ludwig Type I patients
After 3 and 6 months of treatment, there was no statistical significance in the effective rate (p > 0.05) (Table 4).

Efficacy of Ludwig Type II patients
After 3 and 6 months of treatment, there was no statistical significance in the effective rate (p > 0.05) (Table 5).

Efficacy of Ludwig Type III patients
After 3 months of treatment, there was a significant difference in effective rate (p < 0.05).After 6 months of treatment, the effective rate of study group was significantly higher compared to control group (p < 0.01) (Table 6).

Incidence of adverse responses
There were no serious adverse reactions recorded.Furthermore, the incidence of adverse reactions was not statistically significant in two groups (p > 0.05).

DISCUSSION
A total of 50 % of women in the world are affected by female pattern hair loss (FPHL), while the incidence rate among Chinese women is 6 %, which is lower than that of Western countries [8].Female pattern hair loss may be associated with genetic, hormonal, and psychological factors, but overall, androgens are considered the primary cause.Androgens such as androstenedione serve as the primary source of androgens in women.Susceptible hair follicles in the hair loss area contain specific 5αreductase which catalyzes the conversion of androstenedione into Dihydrotestosterone (DHT) [9].
Treatment of FPHL involves the use of topical drugs, oral drugs, microneedles, low-dose laser therapy, autologous fat transfer, platelet-rich plasma, and hair transplantation [10].
Spironolactone is a commonly used oral medication that functions by reducing the secretion of testosterone from the adrenal gland and antagonizing the binding of dihydrotestosterone (DHT) to androgen receptors.However, as spironolactone is an inefficient diuretic, blood potassium concentration should be closely monitored [11].
In this study, the effective rate of 5 % minoxidil significantly improved compared to 2 % after treatment for 6 months in Ludwig type III.In a similar study by Lucky et al [12], a 5 % topical minoxidil solution exhibited greater efficacy compared to 2 % over a 48-week treatment period for FPHL.Furthermore, there was no statistical significance in adverse reactions in both groups, however, incidences were higher with 5 % minoxidil solution.Minoxidil is indeed used clinically as a blood pressure medication.It stimulates sympathetic nerves and affect calcium channels.Although there is no clinical evidence, some minoxidil solution may be absorbed into the scalp skin tissue.This absorption could potentially lead to side effects such as tachycardia, water sodium retention, and postural hypotension.Therefore, in clinical use, attention should be paid to patients' blood pressure and cardiac function [13] as a possible adverse effect.
In this study, both 2 and 5 % minoxidil solutions were found to be effective for all levels of FPHL (female pattern hair loss) patients.Specifically, for Ludwig Type III patients with FPHL, there was a significant difference in response rate after 6 months of treatment compared to other Ludwigtype patients.This suggests that the efficacy of minoxidil in treating FPHL may be related to the stage of hair loss at the time of use.

Limitations of the study
Although minoxidil is already approved for clinical use, this post-clinical investigation would still require a longer treatment duration to establish the effect of long term use as well as mechanism of noticeable adverse effects since such treatment is usually applied over long duration of years by affected patients.

CONCLUSION
Minoxidil solutions are clinically efficacious in treating female pattern hair loss (FPHL).However, the clinical efficacy of 5 % is superior to 2 % minoxidil solution.Additionally, the 5 % minoxidil solution appears to be more efficacious in treating severe cases of FPHL.

DECLARATIONS current
study are available from the corresponding author on reasonable request.

Use of Artificial Intelligence/Large Language Models
None provided.

Use of Research Reporting Tools
None provided.

Open Access
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

Table 3 :
Clinical efficacy after 6 months of treatment (N = 140) Figure 1: Comparison of clinical efficacy

Table 4 :
Efficacy of Ludwig Type I patients

Table 7 :
Comparison of incidence of adverse reactions (N = 140)