Oral androgen development has been hampered by the rapid metabolism of orally administered testosterone (T) and low bioavailibility. The addition of the 5alpha-reductase inhibitor dutasteride (D) to oral T in oil dramatically improves concentrations of serum T. In this study we evaluate the absorption of oral T+D, comparing nanomilled T (NmT+D) vs T dissolved in oil (Capmul; CpT+D), as nanomilling might offer a simpler, more practical means of oral T administration, given the limited solubility of T in oil. Twelve healthy men were administered leuprolide on Day -14 to suppress endogenous T biosynthesis and were pretreated with D to block 5alpha-reductase. Once hypogonadal, subjects were sequentially administered 200- and 400-mg doses of CpT+D and NmT+D in the fasted and fed states. Serum T and dihydrotestosterone (DHT) were measured: before dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each dose. Two weeks after leuprolide administration, T levels were below the normal range. A 400-mg dose of either formulation of oral T+D increased mean serum T above the lower limit of the normal range for 8-10 hours. Food had a minimal effect on the pharmacokinetic parameters of the NmT+D formulation but decreased the maximum observed concentration after dosing (C(max)) for CpT+D. Serum DHT remained below the normal range throughout the study period with both formulations. No significant changes in liver function tests or other adverse events were observed. A 400-mg dose of either oral T+D formulation normalized serum T for 8-10 hours and suppressed DHT. NmT allows for tablet formulation, and its pharmacokinetics were not affected by food, demonstrating the feasibility of oral nanomilled T as a promising and practical twice-daily therapy for the treatment of male hypogonadism.