{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:02:55Z","timestamp":1780066975164,"version":"3.54.0"},"reference-count":83,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>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 5\u03b1-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.<\/jats:p>","DOI":"10.3390\/neurosci7010020","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:12:37Z","timestamp":1770048757000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["5\u03b1-Reductase Isoenzymes: From Neurosteroid Biosynthesis to Neuropsychiatric Outcomes"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-0771","authenticated-orcid":false,"given":"Carmen","family":"Rodriguez-Cerdeira","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n Vithas, Grupo Hospitalario Vithas, 28043 Madrid, Spain"},{"name":"Dermatology Department, Grupo Hospitalario (CMQ Concheiro), Manuel Olivi\u00e9 11, 36203 Vigo, Spain"},{"name":"Department of Health Sciences, University of Vigo, Campus of Vigo, As Lagoas, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41467-020-20675-2","article-title":"Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism","volume":"12","author":"Han","year":"2021","journal-title":"Nat. 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