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. 2025 Mar 31;15(1):10962.
doi: 10.1038/s41598-025-95583-w.

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

Jinhyun Kim  1   2   3 , Suk-Yong Jang  2   4 , Eun-Cheol Park  5   6   7
Affiliations

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

Jinhyun Kim et al. Sci Rep. .

Abstract

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.

Keywords: 5α-Reductase inhibitors; Mortality; Nested case-control; cause-specific.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures were performed in accordance with the relevant guidelines and regulations of the Declaration of Helsinki. The Institutional Review Board (IRB) of Severance Hospital in Seoul, Republic of Korea (IRB No: [4-2024-0367]) approved the study. The IRB, recognizing the sole academic nature of the investigators’ database access and the absence of personally identifiable information utilization, exempted the need for obtaining written informed consent. Competing interests: The authors declare no competing interests. Data sharing statement: The Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC) is a public open-access database. It is based on the health insurance claims data of all Koreans, and the sample cohort is available for public purposes and scientific research. The sample cohort data are available after approval for use by the National Health Insurance Service ( https://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do ).

Figures

Fig. 1
Fig. 1
Flowchart of the selection process of participants in the nested case-control study. (a) The Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC) database is a longitudinal cohort comprising 1,024,340 participants, equivalent to 2.2% of the Korean population, spanning from January 1, 2002 to December 31, 2019. This database encompasses various sociodemographic variables, health insurance classifications, mortality records, medical checkup results, diagnostic information, and prescribed medications. (b) Participants who died following a diagnosis of benign prostatic hyperplasia or androgenic alopecia. (c) Age (± 1 year), sex (male or female), date of the first depression diagnosis (± 30 days), and follow-up duration. Abbreviations: BPH, benign prostate hyperplasia; AGA, androgenic alopecia, 5-ARI, 5-alpha reductase inhibitor.
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