The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism

To the Editor: Dihydrotestosterone (DHT) induces transforming growth factor β1 (TGF-β1) in dermal papilla cells (DPCs) to suppress follicular epithelial cell growth. Thus, TGF-β1 is one of the key players in androgenetic alopecia (AGA), and its antagonist may prevent AGA.1Inui S. Itami S. Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla.J Dermatol Sci. 2011; 61: 1-6Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar Botulinum toxin type A (BTX) may inhibit TGF-β1 secretion from DPCs as it does with scar tissue fibroblasts,2Xiao Z. Zhang F. Lin W. Zhang M. Liu Y. Effect of botulinum toxin type A on transforming growth factor β1 in fibroblasts derived from hypertrophic scar: a preliminary report.Aesthet Plast Surg. 2010; 34: 424-427Crossref PubMed Scopus (87) Google Scholar which share the mesenchymal origin. Recently, BTX has been effective for the treatment of AGA.3Freund B.J. Schwartz M. Treatment of male pattern baldness with botulinum toxin: a pilot study.Plast Reconstr Surg. 2010; 126: 246e-248eCrossref PubMed Scopus (37) Google Scholar,4Singh S. Neema S. Vasudevan B. A pilot study to evaluate effectiveness of botulinum toxin in treatment of androgenetic alopecia in males.J Cutan Aesthet Surg. 2017; 10: 163-167Crossref PubMed Scopus (15) Google Scholar Here, we evaluated the efficacy and safety of intradermal injection of BTX (Nabota, Daewoong Pharmaceutical Co, Seoul, Korea) in AGA and its relationship with TGF-β1. Patients with AGA were enrolled according to the basic and specific classification.5Lee W.S. Ro B.I. Hong S.P. et al.A new classification of pattern hair loss that is universal for men and women: basic and specific (BASP) classification.J Am Acad Dermatol. 2007; 57: 37-46Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Patients undergoing treatment with finasteride, minoxidil, or supplements that affect hair growth were excluded. This study was approved by the institutional review board. The participants received intradermal BTX injections every 4 weeks for 24 weeks. A total of 30 units of BTX were injected at 20 different sites on the balding scalp in each treatment session. The expression of TGF-β1 from cultured DPCs under 10-9mol/L DHT was evaluated by reverse transcription polymerase chain reaction analysis. Suppression of DHT-induced TGF-β1 secretion from DPCs by BTX (2.5 U/106 cells) was assessed by immunofluorescence staining. The doses of BTX in the in vitro study were selected on the basis of a previous report investigating the effect of BTX (2.5 U/106 cells) on TGF-β1 secretion from the fibroblasts.2Xiao Z. Zhang F. Lin W. Zhang M. Liu Y. Effect of botulinum toxin type A on transforming growth factor β1 in fibroblasts derived from hypertrophic scar: a preliminary report.Aesthet Plast Surg. 2010; 34: 424-427Crossref PubMed Scopus (87) Google Scholar This study comprised 18 male patients with a mean age of 49.00 ± 6.50 years. In an unblinded phototrichogram image analysis (Lead M Corp, Seoul, Korea), the mean ± standard deviation of hairs per square centimeter at weeks 0, 12, and 24 were 129.61 ± 28.05, 129.11 ± 28.80, and 136.22 ± 33.05, respectively. The number of hairs significantly increased at week 24 (P = .012) but not at week 12 (P = .803). Comparison of the pre- and posttreatment photographs showed significant improvement at week 24 (P = .031) (Fig 1). DHT upregulated the TGF-β1 expression of DPCs in 96 hours, whereas BTX downregulated the TGF-β1 expression in 96 hours (Fig 2). No serious adverse events or changes in laboratory parameters were reported.Fig 2Immunofluorescent assay for TGF-β1 in DPCs. Suppression of DHT (10−9 mol/L)-induced secretion of TGF-β1 from DPCs of balding scalps by treatment with botulinum toxin (2.5 U/106 cells) compared with control scalps. DHT, Dihydrotestosterone; DPC, dermal papilla cell; hr, hour; PBS, phosphate-buffered saline; TGF, transforming growth factor.View Large Image Figure ViewerDownload Hi-res image Download (PPT) DHT-induced synthesis of paracrine mediators (Dkk-1, interleukin 6, TGF-β1) in balding DPCs may play a role in AGA and represent alternative treatment targets.1Inui S. Itami S. Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla.J Dermatol Sci. 2011; 61: 1-6Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar,6Kwack M.H. Ahn J.S. Kim M.K. Kim J.C. Sung Y.K. Dihydrotestosterone-inducible IL-6 inhibits elongation of human hair shafts by suppressing matrix cell proliferation and promotes regression of hair follicles in mice.J Invest Dermatol. 2012; 132: 43-49Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar However, clinical studies targeting these paracrine mediators have not been reported. In our in vitro study, BTX successfully abrogated DHT-induced secretion of TGF-β1 from DPC. Intradermal injection of BTX was effective against AGA by inhibiting TGF-β1 secretion in the hair bulb, which is thought to suppress follicular keratinocyte growth and changes in the hair cycle.1Inui S. Itami S. Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla.J Dermatol Sci. 2011; 61: 1-6Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar Previous studies reported the use of intramuscular BTX injections to treat AGA without elucidating the exact underlying mechanism.3Freund B.J. Schwartz M. Treatment of male pattern baldness with botulinum toxin: a pilot study.Plast Reconstr Surg. 2010; 126: 246e-248eCrossref PubMed Scopus (37) Google Scholar,4Singh S. Neema S. Vasudevan B. A pilot study to evaluate effectiveness of botulinum toxin in treatment of androgenetic alopecia in males.J Cutan Aesthet Surg. 2017; 10: 163-167Crossref PubMed Scopus (15) Google Scholar Considering the diffusion of the injected liquid BTX and scalp anatomy, even the intramuscular injection3Freund B.J. Schwartz M. Treatment of male pattern baldness with botulinum toxin: a pilot study.Plast Reconstr Surg. 2010; 126: 246e-248eCrossref PubMed Scopus (37) Google Scholar,4Singh S. Neema S. Vasudevan B. A pilot study to evaluate effectiveness of botulinum toxin in treatment of androgenetic alopecia in males.J Cutan Aesthet Surg. 2017; 10: 163-167Crossref PubMed Scopus (15) Google Scholar may indirectly inhibit the secretion of TGF-β1 from DPCs in the hair bulb. Advanced AGA or older age may have adversely influenced our treatment outcome. In conclusion, we suggest that intradermal injection of botulinum toxin could be a possible treatment option for AGA by inhibiting TGF-β1 secretion from the hair follicles. However, further research and long-term follow-up are required. Reply to: “The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism”Journal of the American Academy of DermatologyVol. 83Issue 6PreviewTo the Editor: We read with great interest the letter “The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism.”1 This study introduces a new mechanism on how botulinum toxin could influence androgenetic alopecia (AGA) through a downregulation of the synthesis of transforming growth factor-β1, which is usually increased by dihydrotestosterone. Full-Text PDF