Botulinum toxin therapy for androgenetic alopecia: From mechanistic insights to clinical applications

Androgenetic alopecia (AGA) is a common hair loss disorder that significantly affects patient's quality of life. Botulinum toxin (BoNT) has emerged as a potential treatment; however, its effectiveness and underlying mechanisms remain unclear. This systematic review aimed to synthesize the existing evidence on BoNT for AGA, analyze its mechanisms, evaluate its efficacy, and explore its potential for precision therapy. A PubMed search was conducted for studies published between 2020 and 2025. A total of 25 studies, including 11 clinical trials and 7 reviews, were included. The studies were analyzed for BoNT mechanisms in AGA, treatment regimens, efficacy, outcomes, cost-effectiveness, and safety profiles. Experimental evidence suggests that BoNT reduces transforming growth factor-β in dermal papilla cells, a key pathological pathway in AGA. Other hypothetical mechanisms, such as scalp muscle relaxation improving microcirculation or inhibiting androgen conversion require further validation. In clinical trials, most studies used 30–150 U of BoNT via intramuscular (six studies) or intradermal (three studies) injections, with 1–3 sessions and up to 6 months of follow-up. Early open-label trials reported response rates of 70%–79%, but recent high-quality randomized controlled trials (RCTs) showed no significant improvement in hair density compared to placebo. Combination therapy with finasteride or minoxidil enhanced treatment outcomes, though large-scale evidence is lacking. BoNT was less cost-effective than first-line therapies such as minoxidil, with session costs approximately 37 times higher. Intramuscular injection appeared more effective than intradermal injection, possibly due to scalp muscle relaxation and vascular decompression. BoNT generally had a mild safety profile. Currently, BoNT lacks robust evidence to replace traditional treatments for AGA. Future research should focus on establishing standardized dosing protocols, conducting large-scale, long-term RCTs, and integrating molecular biomarkers to improve understanding and optimize the clinical use of BoNT in AGA management.