A Pilot Study to Evaluate Effectiveness of Botulinum Toxin in Treatment of Androgenetic Alopecia in Males

INTRODUCTION

Androgenetic alopecia (AGA) is the most common form of baldness and affects almost 80% men in a lifetime.[12] It has multifactorial etiology resulting from the interaction of genetic and environmental factors. It is characterized by progressive miniaturization of hair follicles. The terminal hairs get converted to intermediate and then vellus hairs; however, the number of hair follicles per unit area remains same.[3] Hair follicle contains enzyme 5α-reductase that converts testosterone to more potent dihydrotestosterone (DHT). This DHT is responsible for miniaturization of hair follicle. Oral finasteride and topical minoxidil are the only FDA-approved treatment for AGA management. Finasteride is a 5α-reductase inhibitor, which prevents the conversion of testosterone to DHT. Oral minoxidil is an antihypertensive and a vasodilator. Topical minoxidil has a complex mechanism of action. It results in the synthesis of prostaglandins and vascular endothelial growth factors in dermal papilla and the opening of potassium channels, resulting in an increase in anagen to telogen ratio.[4] Botulinum toxin has been tried for AGA management once previously.[5] We conducted a pilot study to find out the efficacy of botulinum toxin in AGA management.

MATERIALS AND METHODS

Our study was conducted in Dermatology OPD of the tertiary care center. A total of 10 male patients aged 22–42 years with AGA reporting consecutively meeting inclusion criteria were included in the study. Institutional ethics committee clearance to conduct the study was obtained. Diagnosis of AGA was based on clinical examination and trichoscopy. Inclusion criteria for the study included male patients, Norwood–Hamilton grade II–IV, no treatment taken for last 6 months, consent to be part of study, and ready for regular follow-ups and photographs. Exclusion criteria were any concomitant diagnosis such as alopecia areata, localized infection precluding injection, and any concomitant medicines or comorbidities such as neuromuscular disorders, which preclude use of botulinum toxin or any needle phobia.

Injection

Botulinum toxin A 100 U was diluted in 1 mL normal saline. Insulin syringe of capacity 40 U/mL was used for injection, resulting in a concentration of 2.5 U every mark of insulin syringe. In 30 different sites, 5 U was injected resulting in a total of 150 U. Injections were intramuscular and sites were selected in frontalis, occipitalis, temporalis, and periauricular muscles [Figure 1].

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Figure 1

Sites for injections

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RESULTS

Result was assessed at the end of 24 weeks. Of 10 patients, 8 had good to excellent response on photographic assessment. One patient had poor and one showed fair response to treatment at the end of 24 weeks. As per self-assessment, 7 of 10 patients had good to excellent response. Two patients had fair response and one showed poor response [Table 1, Charts 1 and 2] [Figure 2–6]. No adverse effects were noted during the therapy.

Table 1 Clinical characteristics and improvement at 24 weeks

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Chart 1

Improvement as per photographic assessment at 24 weeks

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Chart 2

Improvement as per patient at 24 weeks

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Figure 2

(A and B) Excellent response seen at 24 weeks

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Figure 3

(A and B) Excellent response seen at 24 weeks

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Figure 4

(A and B) Good response seen at 24 weeks

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Figure 5

(A and B) Fair response seen at 24 weeks

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Figure 6

(A and B) Poor response seen at 24 weeks

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DISCUSSION

The exact pathogenesis of male pattern baldness is not yet known. There are various causative factors implicated in causation of male pattern baldness. Orentreich[6] proposed that minituarization of hair follicles occurs in genetically predisposed androgen-sensitive hair follicle. This androgenetic theory has been the most prevailing theory for male pattern baldness and antiandrogens such as finasteride are successfully used for the management of this condition.[6] Zappacosta[7] described treatment of male pattern baldness in patients receiving minoxidil for hypertension, and suggested topical minoxidil as an effective treatment. Few experimental studies suggested that subcutaneous blood flow in the scalp of a patient with male pattern baldness was greatly reduced as compared to controls. Goldman et al.[8] conducted an experiment in which they measured transcutaneous pO₂ of the scalp in male pattern baldness and to find out whether bald scalp actually has some microvascular insufficiency. They found that resting transcutaneous pO₂ was significantly lower in frontal bald scalp as compared to temporal hair-bearing scalp in patient with male pattern baldness. Transcutaneous pO₂ in frontal bald scalp was also significantly lower as compared to hair-bearing frontal scalp of controls and transcutaneous pO₂ of hair-bearing frontal and temporal scalp in controls were not significantly different.[8] This relative microvascular insufficiency possibly results because frontal and vertex areas are supplied by supratrochlear and supraorbital arteries, which are smaller branches of internal carotid artery, and it overlies galea aponeurotica, which is relatively less vascular as compared to the temporal and occipital areas, which overlie muscles.[9] The androgenetic theory states that minituarization of hair follicle results from the action of DHT. Hair follicles contain 5α-reductase enzyme that is responsible for peripheral conversion of testosterone to more active DHT. There is an increased accumulation of DHT in the affected follicle and disturbed DHT to estradiol ratio due to relative microvascular insufficiency, which leads to minituarization of hair follicle.[10]

Injection of botulinum toxin relaxes the muscle, which reduces pressure on the musculocutaneous and perforating vasculature, thereby potentially increasing the blood supply and transcutaneous pO₂. This increased blood flow can also lead to washing out of accumulated DHT, thereby reducing the signal for minituarization of hair follicle. We found that botulinum toxin is an effective therapy for AGA management in our pilot study; however, larger studies and controlled trial to compare it with existing FDA-approved modalities need to be conducted. Transcutaneous pO₂ and blood supply before and after botulinum injection, if conducted, will also provide some insight into the pathogenesis of this common disease and mechanism of action of botulinum toxin in AGA management.