Depression risk of 5-alpha reductase inhibitors: A systematic review and meta-analysis with a focus on comparator groups
Bibliographic record
Abstract
ABSTRACT Objective To investigate the association of 5-ARI use with depression, specifically focusing on explanations for the heterogeneity in results. Design Systematic review and meta-analysis Data Sources A systematic search from Scopus, Embase, and MEDLINE was performed from databased inception to January 2025. Eligibility criteria for study selection Peer-reviewed empirical studies that reported on measurements of record depression associated with 5-ARIs usage were included. Studies with insufficient data and non-English publications were excluded. Data synthesis Study characteristics and relative risk estimates were extracted from each article. Estimates were pooled using random-effects meta-analysis. Studies were further stratified by control groups and type of 5-ARI usage to investigate heterogeneity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Results Five longitudinal studies (n= 2,517,859 patients, effect size = 8), across a wide range of populations (US, UK, Cananda, South Korea) and time-period (1992 – 2018) were included. 5-ARI use was associated with a 31% increased risk of depression (HR 1.31, 95% CI 0.98–1.76), with high heterogeneity (I² = 95.5%, τ 2 = 0.0984, P < 0.0001). When stratified by comparator type, studies using non-drug controls reported significantly elevated risk (HR 1.61, 95% CI 1.20–2.16, I² = 94.4%, τ 2 = 0.0635, P < 0.0001), while those using alpha-blocker comparators showed decreased risk (HR 0.89, 95% CI 0.86–0.92, I² = 0%, τ 2 = 0, P = 0.9711). The choice of comparator group explained the most heterogeneity across studies while the type of 5-ARIs showed similar results (Finasteride HR 1.38, 95% CI 0.51–3.72, I² = 97.4%, τ 2 = 0.1541, P < 0.0001; Dutasteride HR 1.45, 95% CI 0.51–4.10, I² = 96%, τ 2 = 0.1688, P < 0.0001). Conclusions Our findings underscore the importance of comparator selection in pharmacoepidemiologic research and suggest that prior concerns about 5-ARIs may be overstated in studies that use inappropriate control groups. Systematic review registration PROSPERO CRD42024620917
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.027 | 0.055 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.026 | 0.059 |
| Bibliometrics | 0.008 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".