# 5α-Reductase Isoenzymes: From Neurosteroid Biosynthesis to Neuropsychiatric Outcomes

## TL;DR

This review explores how 5α-reductase enzymes affect neurosteroid production and mental health, highlighting risks of psychiatric side effects from their inhibition.

## Contribution

The paper systematically reviews the role of 5α-R isoenzymes in neurosteroidogenesis and their link to psychiatric outcomes.

## Key findings

- SRD5A1 contributes to allopregnanolone synthesis in the central nervous system.
- 5α-R inhibition may increase vulnerability to anxiety, depression, and suicidality.
- Post-finasteride syndrome highlights persistent psychiatric and sexual adverse effects in some patients.

## Abstract

5a-reductase (5a-R) isozymes are essential for androgen metabolism and neurosteroid biosynthesis, linking endocrinology and neuropsychiatry. This systematic review, conducted in accordance with PRISMA 2020 guidelines, aimed to synthesize current evidence on the tissue distribution of SRD5A1, SRD5A2, and SRD5A3 and their implications in mental health. A systematic search of the PubMed, Scopus, and Web of Science databases up to February 2025 identified 257 articles, of which 83 met the inclusion criteria. SRD5A1 is broadly expressed in the liver, skin, and central nervous system, contributing to allopregnanolone synthesis; SRD5A2 is mainly restricted to androgen-dependent tissues, playing a key role in prostate development and alopecia; and SRD5A3 is associated with glycosylation processes and oncogenesis. Converging evidence suggests that impaired neurosteroidogenesis due to 5α-R inhibition may underlie vulnerability to anxiety, depression, and suicidality. While earlier epidemiological findings were heterogeneous, recent pharmacovigilance data have strengthened the evidence supporting this association. Pharmacovigilance and clinical reports show that a subset of patients treated with finasteride or dutasteride may experience persistent psychiatric and sexual adverse effects, known as post-finasteride syndrome. The current findings underscore the need for careful patient counseling, systematic monitoring, and further translational studies integrating genetics, neuroendocrine markers, and standardized psychiatric outcomes to identify individuals at risk and advance personalized medicine in this field.