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Treatment of androgenetic alopecia (AGA) with concurrent electrodynamic microneedling and 5% minoxidil may further stimulate hair growth. To evaluate the efficacy of microneedling combined with 5% minoxidil in Chinese male AGA patients and to explore the underlying mechanisms. Seventy-one male volunteers with AGA completed the entire trial and follow-up. The first group (n = 23) received only 5% minoxidil twice daily for 24 weeks; the second group (n = 23) received only microneedle therapy every 3 weeks for eight treatments; and the third group (n = 25) received the combination treatment for a total of 24 weeks. Changes in hair density and diameter were evaluated before and after treatment every 3 weeks, and patients were followed up at 6 months after the final treatment. In the combination group, a PCR array was used to detect the expression of molecules in the Wnt/β-catenin pathway within the hair loss sites on top of the head before and after treatment and within the scalp tissues from non-hair loss sites on top of the head. The tissues were obtained by punches in the most severe area of hair loss on top of the head and in the adjacent normal hair area without hair loss. Real-time quantitative PCR and western blotting were used to further examine changes in the differentially expressed molecules identified by PCR array (FZD3) and in molecules in the Wnt/β-catenin signaling pathway closely related to hair growth (β-catenin and LEF-1). Compared to single minoxidil or single microneedle treatment, the combination therapy showed superior therapeutic effects clinically, with further upregulation of FZD3, β-catenin, and LEF-1 expression levels at both mRNA and protein levels in the treated areas. Microneedling combined with 5% minoxidil can improve AGA, and the underlying mechanism may involve activation of the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]