Oxybutynin is superior to placebo in reducing ADT-associated hot flashes

Oxybutynin, a drug often used to treat overactive bladder symptoms, was found to be superior to placebo in reducing hot flashes among men receiving hormone therapy for prostate cancer, according to results from the phase 2 A222001 trial (NCT04600336).¹

“Oxybutynin demonstrated clear and clinically meaningful improvements in both hot flash frequency and quality of life for men undergoing hormone therapy for prostate cancer,” said lead investigator Bradley J. Stish, MD, a radiation oncologist at Mayo Clinic in Rochester, Minnesota, in a news release on the findings.² “These results provide strong support for its use as an effective management option for this challenging and often overlooked [adverse] effect of prostate cancer treatment.”

The randomized, double-blind study enrolled 88 men, and 81 were included in the final analysis. Individuals were eligible for enrollment if they were receiving a stable regimen of androgen deprivation therapy (ADT) and experienced at least 28 hot flashes per week. The average age of participants was 68.5 years.²

The men were randomly assigned to receive oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or a matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash score (determined by multiplying the number of hot flashes by the mean hot flash severity) from baseline to 6 weeks. Secondary outcome measures included the incidence of adverse events (AEs), changes from baseline in Hot Flash Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.¹

At baseline, participants reported an average (SD) of 10.1 (5.6) hot flashes per day, with an average (SD) daily hot flash score of 18.2 (13.5). At 6 weeks, the average reduction in hot flashes per day in the placebo arm was 2.15 vs 4.77 (P = .02) in the 2.5-mg oxybutynin arm and 6.89 (P < .001) in the 5-mg oxybutynin arm. Daily hot flash scores were reduced by an average of 4.85 in the placebo arm vs 9.94 (P = .07) in the 2.5-mg oxybutynin arm and 13.95 (P = .002) in the 5-mg oxybutynin arm.¹

Improvements in hot flashes often occurred during the first week of treatment and were sustained throughout the study. The proportion of participants achieving at least a 50% reduction in hot flash scores was 57% in the 2.5-mg oxybutynin arm and 79% in the 5-mg oxybutynin arm vs 32% in the placebo group.²

From baseline to 6 weeks, HFRDIS scores improved by 14.2 (P = .042) and 20.7 (P < .01) points in the 2.5-mg and 5-mg oxybutynin arms, respectively, compared with 3.1 points in the placebo arm.¹

Treatment with oxybutynin was also well tolerated, and no grade 3 or higher treatment-related AEs were reported. The most common AE was dry mouth.¹

“These results are incredibly encouraging,” Stish said in the news release.² “Men with hot flashes from hormone therapy now have another therapeutic option available to help reduce their symptom burden. Future research will look to further our understanding of hot flash therapy options in this patient population.”

REFERENCES

1. Stish BJ, Mazza GL, Nauseef JT, et al. Alliance A222001: oxybutynin versus placebo for the treatment of hot flashes in patients receiving androgen-deprivation therapy for prostate cancer. J Clin Oncol. Published online January 26, 2026. doi:10.1200/JCO-25-01486

2. Randomized trial finds drug therapy reduces hot flashes during prostate cancer treatment. News release. Alliance for Clinical Trials in Oncology. February 2, 2026. Accessed February 11, 2026. https://www.eurekalert.org/news-releases/1114737