OBJECTIVES:To determine the effects of long-term, low-dose difluoromethylornithine (DFMO) on audiometric thresholds and distortion product otoacoustic emission (DPOAE) levels in humans. DESIGN:A prospective, randomized, placebo-controlled phase 2 clinical trial of DFMO in participants with a prior adenomatous colonic polyp. SETTING:Academic tertiary care referral center. PARTICIPANTS:One hundred twenty-three volunteer subjects with colorectal polyps and normal hearing for the frequencies 250 through 2000 Hz. INTERVENTIONS:Subjects were randomized to receive placebo or oral DFMO at daily dosages between 0.075 and 0.4 g/m(2) of body surface area for 12 months. OUTCOME MEASURES:Pure-tone audiometric thresholds for the frequencies 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz and DPOAE levels were measured at baseline and 1, 3, 6, 9, and 12 months after starting treatment with DFMO or placebo and 3 months after cessation of treatment if there was a suggestion of possible changes at the 12-month measurement. RESULTS:At these low dosages, there was little evidence for shifts in auditory pure-tone thresholds, and there were no statistically significant shifts in DPOAE levels. For auditory pure-tone thresholds, there was a subtle, approximately 2- to 3-dB hearing level decrease in hearing sensitivity for the 2 higher DFMO dosages, but only at the 2 lowest frequencies, 250 and 500 Hz. CONCLUSIONS:Administration of low-dose DFMO for 12 months did not produce hearing loss, in contrast to prior studies that used higher dosages.