Efficacy and safety of combined oral dutasteride 0.5 mg and minoxidil 2.5 mg versus dutasteride or minoxidil monotherapy in male androgenetic alopecia

Androgenetic alopecia (AGA) is the leading cause of hair loss in men, impacting nearly 80% throughout their lives and frequently associated with significant psychosocial burden. Current FDA-approved therapies, such as topical minoxidil and oral finasteride, face challenges related to adherence, scalp irritation, and concerns about sexual side effects. Dutasteride, a dual type I and II 5α-reductase inhibitor along with low-dose oral minoxidil (LDOM) has recently been recognized as a potential off-label systemic therapy. Although each agent has demonstrated effectiveness on its own, there is limited evidence on their combined application. This double-blind, randomized, three-arm clinical trial enrolled 45 men with mild-to-moderate AGA, who were randomly assigned to receive (1) dutasteride 0.5 mg + minoxidil 2.5 mg, (2) dutasteride 0.5 mg, or (3) minoxidil 2.5 mg daily for 6 months. Efficacy was evaluated using TrichoScan parameters (hair count, hair shaft diameter, terminal hair rate), standardized scalp photography, patient satisfaction, and Investigator Global Assessment (IGA). Safety was evaluated through monitoring for adverse event and conducting laboratory tests. Thirty-nine participants completed the study. At 6 months, adjusted mean hair counts were 181.8 in the combination group, 167.3 in the dutasteride monotherapy group, and 156.0 in the LDOM monotherapy group. However, ANCOVA did not demonstrate a statistically significant overall between-group difference in hair count (P = 0.055), and the difference between combination therapy and LDOM monotherapy was also not statistically significant (mean difference, 25.8 hairs; 95% CI, − 0.16 to 51.90; P = 0.052). Terminal hair rate differed significantly among the treatment groups (P = 0.01), with a higher adjusted mean value in the combination group than in the LDOM monotherapy group (70.3% vs. 63.5%; P = 0.01). Hair shaft diameter increased over time without a statistically significant between-group difference. IGA scores were higher in the combination group than in either monotherapy group (P < 0.001 for both comparisons). Patient satisfaction did not differ significantly among groups (P = 0.107). Two participants discontinued treatment because of adverse events, and no serious adverse events were reported. All three treatment regimens were associated with improvements in hair parameters over the 6-month treatment period. The combination group had numerically higher adjusted mean hair count and terminal hair rate, but the between-group difference in hair count did not reach statistical significance. Statistically significant between-group differences were observed for terminal hair rate and Investigator Global Assessment. Larger, adequately powered studies with longer follow-up are needed to determine whether these findings are reproducible and to further evaluate the comparative efficacy and safety of combination therapy.