Low 5-ARI Use Linked to Increased Suicide Risk, Reduced Heart Disease Mortality

Low cumulative 5α-reductase inhibitors (5-ARIs) doses in individuals with benign prostatic hyperplasia (BPH) or androgenic alopecia are linked to an increased suicide risk and a diminished risk of cardiovascular mortality, new findings suggest, highlighting the importance of careful monitoring and consistent dosing.1

These findings were the conclusion of research led by Jinhyun Kim—from the Department of Preventive Medicine at Yonsei University College of Medicine in South Korea—who worked alongside a team of investigators in this analysis. Kim and colleagues highlighted data which they drew from the Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC), which was designed to function as a representative, population-based database in South Korea.2

“Given the limited and inconclusive nature of existing research and the widespread use of 5-ARIs for managing BPH or [androgenic alopecia], the aim of this study was to investigate the dose-dependent association between 5-ARI intake and all-cause or cause-specific mortality among patients with BPH and [androgenic alopecia] by using a large population-based cohort,” Kim and colleagues wrote.1

The investigators looked at data from the NHIS-NSC that had been prospectively gathered between January 2002 - December 2019. A nested case-control design was implemented by the team, with their method particularly suited for assessing rare outcomes, time-dependent variables, and larger-level datasets.

The study would include 92,444 subjects who had each been diagnosed with BPH or androgenetic alopecia. For the purposes of improving their diagnostic precision, the investigative team did not include those who may have been misdiagnosed or received prescriptions through illegitimate channels. Only patients who had either 3 or more outpatient interactions or were hospitalized for BPH or androgenic alopecia were involved in the study population.

The team sought to examine incident cases, so individuals who developed BPH or androgenic alopecia within 2 years of enrollment in the cohort were excluded through during a 2-year washout period. Their analysis was further limited to those diagnosed at age 40 or older, and subjects were excluded if they were enrolled in the Medical Aid Program. Additionally, only participants who had had been given prescriptions for either 5-ARIs or alpha-blockers (ABs) for a minimum of 30 days were considered eligible for study involvement.

Follow-up took place on the date of initial diagnoses of BPH or androgenic alopecia, and they would continue until the earliest of the following occurrences among participants: death, a disqualification from the National Health Insurance (NHI) program, or the conclusion of the study's period of observation in December 2019.

Each of the individuals who passed away during the analysis was matched with up to 5 controls based on their sex, age, duration of follow-up, and the date of diagnosis of BPH or androgenic alopecia. The investigators would quantify participants' cumulative exposure to 5-ARIs through the use of the cumulative defined daily dose (cDDD), both in absolute terms and as a time-averaged metric over the period of follow-up in the study.

There were a total of 3084 cases (deaths) and 14,630 matched controls that the research team was able to evaluate. Overall, the team highlighted higher rates of mortality among subjects who had been given lower cumulative doses of 5-ARIs (<365 cDDDs and 365–730 cDDDs).

Additionally, they concluded that participants shown to have a cumulative dose exceeding 5,840 cDDDs demonstrated a substantially lower risk of mortality. The investigators observed comparable trends when assessing time-averaged cumulative doses.

In their cause-specific mortality assessment, the investigative team's results suggested that there was a rise in suicide rates among subjects with lower cumulative exposure. Conversely, there was a link between higher cumulative dosing and reduced cardiovascular-associated mortality. Other cause-specific mortality outcomes were shown not to have attained statistical significance.

In sum, the team's data point to a nuanced association between long-term 5-ARI utilization and all-cause mortality. These results, therefore, highlight the value of close clinical monitoring, especially with respect to the elevated suicide risk observed in their analysis at lower cumulative exposures.

“In conclusion, this study highlights the complex relationship between 5-ARI dosing and all-cause mortality risk in patients with BPH and [androgenic alopecia] and indicates increased suicide risk and decreased CVD mortality associated with 5-ARI use,”1 they wrote. “Specifically, among patients with BPH or [androgenic alopecia] who received low cumulative doses of 5-ARI, the risk of completed suicide was more than double compared to non-users.”

References

1. Kim, J., Jang, SY. & Park, EC. Differential association between cumulative dose of 5α-reductase inhibitors and mortality. Sci Rep 15, 10962 (2025). https://doi.org/10.1038/s41598-025-95583-w.

2. Lee, J., Lee, J. S., Park, S. H., Shin, S. A. & Kim, K. Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int. J. Epidemiol. 46, e15 https://doi.org/10.1093/ije/dyv319 (2017).