Differential association between cumulative dose of 5α-reductase inhibitors and mortality.

The association between various cumulative doses of 5-ARIs and mortality remains unclear. To examine the absolute and time-averaged cumulative doses of 5-ARIs and their association with all-cause and cause-specific mortality among patients with benign prostatic hyperplasia (BPH) or androgenic alopecia (AGA). A nested case-control study was conducted. For each patient who died, up to five controls were matched, based on age, sex, follow-up duration, and date of BPH or AGA diagnosis. The cumulative 5-ARI dose was calculated as the cumulative defined daily dose (cDDD) for the absolute and time-averaged doses over the follow-up period. The study involved 3,084 cases and 14,630 controls. The < 365 cDDDs group and 365-730 cDDDs group had higher mortality rates, whereas the > 5840 cDDDs group had a significantly reduced mortality risk. A similar result was observed for the duration-averaged cumulative doses. Cause-specific analysis revealed higher suicide rates at lower cumulative doses and lower cardiovascular mortality rates at higher cumulative doses. Other cause-specific mortality rates were not statistically significant. The findings revealed a complex relationship between cumulative 5-ARI dosage and all-cause mortality, highlighting the need for careful monitoring of patients using 5-ARIs, particularly concerning the elevated risk of suicide.