Low Doses of 5-ARIs Linked to Higher Suicide Risk, Lower Cardiovascular Mortality: Study Finds

The findings, published in Scientific Reports, stress the need for careful monitoring of patients undergoing treatment with these medications, especially given the increased risk of suicide associated with certain dosage levels.

5α-reductase inhibitors, widely prescribed for benign prostatic hyperplasia and androgenic alopecia, have been associated with a range of health outcomes, raising concerns about their long-term safety. However, the relationship between varying cumulative doses of 5-ARIs and mortality risk remains unclear. To explore this further, Eun-Cheol Park, Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea, and colleagues conducted a nested case-control study aimed at evaluating both absolute and time-averaged cumulative doses of 5-ARIs and their potential association with all-cause and cause-specific mortality in patients diagnosed with BPH or AGA.

For this purpose, the researchers conducted a nested case-control study, enrolling 3,084 cases and 14,630 matched controls. For each patient who died, up to five controls were matched based on age, sex, duration of follow-up, and the date of BPH or AGA diagnosis. To assess exposure, the cumulative 5-ARI dose was calculated using the cumulative defined daily dose (cDDD), capturing both absolute and time-averaged doses over the follow-up period.

The study led to the following findings:

• Patients with cumulative 5-ARI doses of less than 365 cDDDs and between 365–730 cDDDs showed higher mortality rates.
• Those with cumulative doses greater than 5840 cDDDs had a significantly reduced risk of mortality.
• Similar trends were observed with duration-averaged cumulative doses.
• Cause-specific analysis indicated a higher risk of suicide at lower cumulative doses.
• Higher cumulative doses were associated with a lower risk of cardiovascular-related mortality.
• Mortality rates from other specific causes did not show statistically significant differences.

The study revealed a nuanced association between cumulative 5-ARI use and all-cause mortality in patients with benign prostatic hyperplasia and androgenic alopecia, emphasizing the importance of careful patient monitoring. Notably, low cumulative doses of 5-ARIs were linked to a more than twofold increase in the risk of completed suicide compared to non-users, while higher doses were associated with a reduced risk of cardiovascular mortality.

"These findings emphasize the need for clinicians to remain vigilant, particularly during the early stages of treatment or when prescribing lower doses," the researchers noted. They further highlighted the importance of closely monitoring patients for signs of suicidal ideation, depressed mood, or a history of suicide attempts. Additionally, they recommended maintaining a consistent and sufficiently high dosage regimen to help optimize treatment outcomes and minimize potential risks.

Reference:

Kim, J., Jang, S., & Park, E. (2025). Differential association between cumulative dose of 5α-reductase inhibitors and mortality. Scientific Reports, 15(1), 1-11. https://doi.org/10.1038/s41598-025-95583-w