IntroductionALRV5XR treatment of androgenetic alopecia (AGA) and telogen effluvium (TE) has early evidence of regenerating a normal scalp hair phenotype in both sexes.DesignWe performed two 24-week double-blinded placebo-controlled comparison trials, one in each sex, on the ALRV5XR treatment effect on hair regeneration, in AGA and TE, in 92 AGA subjects (24 also had TE). Forty-six women (age 24–64 years) and 46 men (age 22–63 years) were randomized 1:1 to either ALRV5XR or placebo regimens (one b.i.d. oral capsule and daily administration of shampoo, conditioner, and follicle serum).EvaluationPrimary outcomes: Absolute and relative changes in terminal hair (TH) density. Secondary outcomes: Response rate, changes in vellus hair (VH) density, TH/VH ratio, hair diameter, growth, and shedding rate.ResultsForty-one women (20 ALRV5XR, 21 placebo) and 36 men (17 ALRV5XR, 19 placebo) completed the trials. TH outcome was evaluable for 18 and 21 women and 11 and 11 men (ALRV5XR, placebo, respectively). Efficacy in women: 30.1 THs/cm2 (p = 0.0002) and 19.7% (p = 0.0016). Efficacy in men: 21.0 THs/cm2 (p = 0.0014) and 16.4% (p = 0.0012). 66.7% of women and 100% of men responded to ALRV5XR. TH/VH ratio for men increased 33.0% (p = 0.0033). Growth rate in women increased by 30.7 μm/24 h (p < 0.0001) and 10.0% (p < 0.0001). There were no adverse events reported.Conclusion and relevanceALRV5XR induced significant regrowth of TH. Accelerating regrowth by reactivation of dormant telogen follicles were the dominant effects in women. Thickening of miniaturized hair and regrowth of dormant telogen follicles contributed equally to the increased TH seen in men (see Graphical Abstract).

BackgroundAndrogenetic alopecia (AGA) affects almost half the population, and several treatments intending to regenerate a normal scalp hair phenotype are used. This is the first study comparing treatment efficacy response and resistance using standardized continuous outcomes.ObjectiveTo systematically compare the relative efficacy of treatments used for terminal hair (TH) regrowth in women and men with AGA.MethodsA systematic literature review was conducted (from inception to August 11, 2021) to identify randomized, Placebo-controlled trials with ≥ 20 patients and reporting changes in TH density after 24 weeks. Efficacy was analyzed by sex at 12 and 24 weeks using Bayesian network meta-analysis (B-NMA) and compared to frequentist and continuous outcomes profiles.ResultsThe search identified 2,314 unique articles. Ninety-eight were included for full-text review, and 17 articles met the inclusion criteria for data extraction and analyses. Eligible treatments included ALRV5XR, Dutasteride 0.5 mg/day, Finasteride 1 mg/day, low-level laser comb treatment (LLLT), Minoxidil 2% and 5%, Nutrafol, and Viviscal. At 24 weeks, the B-NMA regrowth efficacy in TH/cm2 and significance (**) in women were ALRV5XR: 30.09**, LLLT: 16.62**, Minoxidil 2%: 12.13**, Minoxidil 5%: 10.82**, and Nutrafol: 7.32**, and in men; ALRV5XR: 21.03**, LLLT: 18.75**, Dutasteride: 18.37**, Viviscal: 13.23, Minoxidil 5%: 13.13**, Finasteride: 12.38, and Minoxidil 2%: 10.54. Two distinct TH regrowth response profiles were found; Continuous: ALRV5XR regrowth rates were linear in men and accelerated in women; Resistant: after 12 weeks, LLLT, Nutrafol, and Viviscal regrowth rates attenuated while Dutasteride and Finasteride plateaued; Minoxidil 2% and 5% lost some regrowth. There were no statistical differences for the same treatment between women and men. B-NMA provided more accurate, statistically relevant, and conservative results than the frequentist-NMA.ConclusionSome TH regrowth can be expected from most AGA treatments with less variability in women than men. Responses to drug treatments were rapid, showing strong early efficacy followed by the greatest resistance effects from flatlining to loss of regrowth after 12–16 weeks. Finasteride, Minoxidil 2% and Viviscal in men were not statistically different from Placebo. LLLT appeared more efficacious than pharmaceuticals. The natural product formulation ALRV5XR showed better efficacy in all tested parameters without signs of treatment resistance (see Graphical abstract).Systematic review registrationwww.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42021268040, identifier CRD42021268040.