Sublingual minoxidil increases fibre diameter in male androgenetic alopecia: a proxy for reversal of hair follicle miniaturization

Abstract Background The histological hallmark of male androgenetic alopecia (MAGA) is the transformation of terminal follicles into miniaturized secondary vellus follicles. As the volume of the dermal papilla determines the size of the hair bulb and hair fibre diameter, any treatment-induced increase in fibre diameter could be used as a proxy for reversal of hair follicle miniaturization. Although clinical trials with minoxidil topical solution in MAGA do not demonstrate increased fibre diameter, vellus-to-terminal reconversion is shown in a humanized mouse model treated with minoxidil. Objectives To investigate whether low-dose sublingual minoxidil (SLM) increases hair fibre diameter in MAGA. Methods Serial tattoo-localized phototrichograms were analysed using hair-to-hair (H2H) matching software in 33 patients with MAGA who participated in a 24-week randomized, double-blinded, placebo-controlled, clinical trial with SLM 0.45 mg once daily. Additional data were obtained from 12 participants who had used a placebo and then rolled into a 24-week, open-label, extension study with either once-daily 1.35 mg or 4.05 mg SLM. TrichoLAB (Warsaw, Masovian, Poland) H2H analysis uniquely identified individual hairs and measured hair fibre diameter at baseline and 24 weeks. Results After 24 weeks, fibre diameter decreased by 2 µm (SD 1) in men receiving placebo. The decrease was most marked in intermediate diameter fibres with a baseline diameter of 40–60 µm. Among men receiving SLM 0.45 mg, 1.35 mg and 4.05 mg, the mean increase in fibre diameter was −2 µm (SD 1 µm), 3 µm (SD 1 µm) and 6 µm (SD 1 µm), respectively. Intermediate-thickness fibres increased the most. H2H matching demonstrated increased diameter in individual fibres. Conclusions The effect of SLM on mean fibre diameter was dose dependent. SLM 1.35 mg and 4.05 mg, but not 0.45 mg, significantly increased mean fibre diameter in MAGA (P < 0.05). The diameter increased most in the intermediate and thickest hairs. This increase in fibre diameter infers reversal of follicle miniaturization in MAGA and is consistent with the observation of vellus-to-terminal reconversion shown in a humanized mouse model treated with minoxidil.