SÍNDROME PÓS-FINASTERIDA E O IMPACTO DOS INIBIDORES DA 5-ALFA REDUTASE NOS EIXOS NEUROENDÓCRINO E METABÓLICO
Resumo
Objetivo: Analisar as evidências científicas recentes sobre os impactos neuroendócrinos e metabólicos associados ao uso crônico de inibidores da 5-alfa redutase, com ênfase na fisiopatologia da Síndrome Pós-Finasterida. Metodologia: Revisão integrativa da literatura realizada nas bases PubMed/MEDLINE e LILACS/BVS, composta por oito estudos de alto impacto publicados entre 2021 e 2026. A estratégia PICO orientou a análise de desfechos clínicos e mecanismos moleculares. Resultados: Evidências de farmacovigilância descrevem a SPF como uma manifestação multissistêmica, na qual se observa a associação entre o uso de 5-ARIs e relatos de disfunção sexual refratária e transtornos do humor em pacientes jovens. A inibição enzimática, particularmente no sistema nervoso central, suprime a síntese de metabólitos ativos como a alopregnanolona, resultando em desregulação GABAérgica e excitotoxicidade. No eixo metabólico, a supressão do hormônio di-hidrotestosterona associa-se à resistência à insulina, esteatose hepática não alcoólica, Diabetes Mellitus tipo 2 e alterações na microbiota intestinal. Identificou-se que polimorfismos no gene SRD5A2 e alterações epigenéticas, como a metilação do DNA do receptor de androgênio sustentam a cronicidade dos sintomas. Conclusão: A síndrome parece ir além de efeitos colaterais transitórios, sugerindo a importância de modelos de medicina personalizada e o fortalecimento de protocolos de consentimento informado para mitigar potenciais riscos biopsicossociais persistentes.
Biografia do Autor
Doutorando em Ciências da Saúde - Faculdade de Ciências Médicas Universidade de Pernambuco.
Graduado em Medicina - Universidade Federal de Jataí.
Graduando em Medicina – UNIFIMES.
Graduada em Medicina (Universidade Severino Sombra) - Atual: Univassouras.
Graduando em Medicina - Universidade de Rio Verde.
Graduado em Medicina - Universidade Cidade de São Paulo.
Graduando em Medicina - Centro Universitário de Pinhais.
Graduado em Medicina pela Universidade Federal do Oeste da Bahia.
Graduada em Medicina - Universidade Federal de Jataí.
Especialista - Fiocruz Mato Grosso do Sul, FIOCRUZ.
Referências
AN, J. et al. Alteration of Gut Microbiota in a Benign Prostatic Hyperplasia Model and Finasteride-Treated Model. International Journal of Molecular Sciences, v. 24, n. 6, p. 5904, 2023. DOI: https://doi.org/10.3390/ijms24065904
BJÖRNEBO, L. et al. Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality. JAMA Oncology, v. 8, n. 7, p. 1019-1026, 2022. DOI: https://doi.org/10.1001/jamaoncol.2022.1501
BOERO, G.; PORCU, P.; MORROW, A. L. Ações pleiotrópicas da alopregnanolona subjacentes aos benefícios terapêuticos em doenças relacionadas ao estresse. Neurobiology of Stress, v. 12, p. 100203, 2020. DOI: https://doi.org/10.1016/j.ynstr.2019.100203
BORGO, F. et al. Alterations in fecal microbiota composition in post-finasteride patients: a pilot study. Journal of Endocrinological Investigation, v. 44, n. 6, p. 1263-1273, 2021. DOI: https://doi.org/10.1007/s40618-020-01424-0
BOUKTIF, S.; KHANDAY, AMUD.; OUNI, A. Modelo preditivo explicável para ideação suicida durante a COVID-19: estudo do discurso nas mídias sociais. Journal of Medical Internet Research, v. 27, e65434, 2025. DOI: https://doi.org/10.2196/65434
CHENG, L. G.; INAY, F.; HWANG, K. Social media and male sexual health: a systematic review. Fertility and Sterility, v. 122, n. 4, e137, 2024. DOI: https://doi.org/10.1016/j.fertnstert.2024.07.508
CHISLETT, B. et al. 5-alpha reductase inhibitors use in prostatic disease and beyond. Translational Andrology and Urology, v. 12, n. 3, p. 487-496, mar. 2023. DOI: https://doi.org/10.21037/tau-22-690
CHOI, G. S. et al. Safety and tolerability of the dual 5-alpha reductase inhibitor dutasteride in the treatment of androgenetic alopecia. Annals of Dermatology, v. 28, p. 444–450, 2016. DOI: https://doi.org/10.5021/ad.2016.28.4.444
DIVICCARO, S. et al. Gut inflammation induced by finasteride withdrawal: therapeutic effect of allopregnanolone in adult male rats. Biomolecules, v. 12, n. 11, p. 1567, 2022. DOI: https://doi.org/10.3390/biom12111567
DIVICCARO, S. et al. Post-finasteride syndrome: An emerging clinical problem. Neurobiology of Stress, v. 12, p. 100209, 2020. DOI: https://doi.org/10.1016/j.ynstr.2019.100209
ESCAMILLA-CRUZ, M. et al. Uso de inibidores da 5-alfa redutase em dermatologia: uma revisão narrativa. Dermatology and Therapy, v. 13, p. 1721–1731, 2023.
EUROPEAN MEDICINES AGENCY (EMA). Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC). EMA, 5-8 maio 2025.
FEDOTCHEVA, T. A.; SHIMANOVSKY, N. L. Neurosteroids progesterone and dehydroepiandrosterone. Pharmaceuticals, v. 18, n. 7, p. 945, 2025. DOI: https://doi.org/10.3390/ph18070945
FERTIG, R. M. et al. Sexual side effects of 5-alpha-reductase inhibitors finasteride and dutasteride: a comprehensive review. Dermatology Online Journal, v. 23, 2017. DOI: https://doi.org/10.5070/D32311037240
GIATTI, S. et al. Analysis of finasteride treatment and its withdrawal in the hypothalamus and hippocampus of rats at the whole-transcriptome level. Journal of Endocrinological Investigation, v. 47, n. 10, p. 2565-2574, 2024. DOI: https://doi.org/10.1007/s40618-024-02345-y
GUPTA, A. K. et al. Use of finasteride: assessment of depression and suicide risk. Journal of Cosmetic Dermatology, 2025. DOI: https://doi.org/10.1111/jocd.70102
HAMILTON, R. J. et al. 5-α Reductase Inhibitors and Prostate Cancer Mortality. JAMA Network Open, v. 7, n. 8, e2430223, ago. 2024. DOI: https://doi.org/10.1001/jamanetworkopen.2024.30223
HARRELL, M. B. et al. An evaluation of the federal adverse event reporting system data on adverse effects of 5-alpha reductase inhibitors. World Journal of Urology, v. 39, p. 1233–1239, 2021. DOI: https://doi.org/10.1007/s00345-020-03314-9
HOWELL, S. et al. Metabolic and Neuroendocrine Consequences of 5α-Reductase Inhibition. Journal of the Endocrine Society, v. 8, n. 3, 2024.
IRWIG, M. S. How routine pharmacovigilance failed to identify persistent sexual side effects of finasteride. Andrology, v. 10, n. 2, p. 207–208, 2022. DOI: https://doi.org/10.1111/andr.13122
LAANANI, M. et al. Risco de suicídio associado à finasterida versus dutasterida em homens tratados para HPB. Scientific Reports, v. 13, p. 5308, 2023.
LAUCK, K. C. et al. Sexual dysfunction with 5-alpha-reductase inhibitor therapy for androgenetic alopecia. Journal of the American Academy of Dermatology, v. 91, n. 1, p. 163-166, 2024. DOI: https://doi.org/10.1016/j.jaad.2024.03.019
LEE, G. H. et al. The Role of ROS, Inflammation, and ER Stress Response in the Finasteride Protective Effect. The World Journal of Men's Health, v. 42, n. 3, p. 600-609, jul. 2024. DOI: https://doi.org/10.5534/wjmh.230122
LEE, S. et al. Adverse sexual effects of treatment with finasteride or dutasteride for male AGA: a systematic review. Acta Dermato-Venereologica, v. 99, n. 1, p. 12-17, 2019.
LEGESSE, D. H. et al. Insights estruturais sobre ações opostas de neuroesteroides nos receptores GABA_A. Nature Communications, v. 14, p. 5091, 2023.
LELIEFELD, H. H. J. et al. The post-finasteride syndrome: possible etiological mechanisms and symptoms. International Journal of Impotence Research, v. 37, n. 3, p. 414-421, 2023. DOI: https://doi.org/10.1038/s41443-023-00759-5
LI, X. et al. Relato de caso: um estudo das características clínicas e variantes genéticas de pacientes com SPF. Translational Andrology and Urology, v. 11, p. 1452–1457, 2022.
LIU, L. P. et al. Factors associated with early-onset androgenetic alopecia: a scoping review. PLoS One, v. 19, n. 3, e0299212, 2024. DOI: https://doi.org/10.1371/journal.pone.0299212
LYON, M. et al. 5α-reductase inhibitors are associated with reduced risk of SARS-CoV-2 infection. The Journal of Urology, v. 207, n. 1, p. 183-189, jan. 2022. DOI: https://doi.org/10.1097/JU.0000000000002180
MAGUIRE, J. L. et al. Neurosteroids: Mechanistic considerations and clinical perspectives. Neuropsychopharmacology, v. 49, p. 73–82, 2024. DOI: https://doi.org/10.1038/s41386-023-01626-z
NGUYEN, D. D. et al. Investigation of suicidality and psychological adverse events in patients treated with finasteride. JAMA Dermatology, v. 157, p. 35–42, 2021. DOI: https://doi.org/10.1001/jamadermatol.2020.3385
PEREIRA, A. F. J. R.; COELHO, T. O. A. Post-finasteride syndrome. Anais Brasileiros de Dermatologia, v. 95, n. 3, p. 271-277, maio/jun. 2020. DOI: https://doi.org/10.1016/j.abd.2020.02.001
RODRIGUEZ-CERDEIRA, C. et al. 5α-Reductase Isoenzymes: From Neurosteroid Biosynthesis to Neuropsychiatric Outcomes. NeuroSci, v. 7, n. 1, p. 20, 2026. DOI: https://doi.org/10.3390/neurosci7010020
RZESZOTEK, S. et al. The Interplay between Finasteride-Induced Androgen Imbalance and Liver Alterations. Biomedicines, v. 10, n. 11, p. 2725, 2022. DOI: https://doi.org/10.3390/biomedicines10112725
SAENGMEARNUPARP, T. et al. The connection of 5-alpha reductase inhibitors to the development of depression. Biomedicine & Pharmacotherapy, v. 143, p. 112100, nov. 2021. DOI: https://doi.org/10.1016/j.biopha.2021.112100
SALISBURY, B. H.; TADI, P. Inibidores da 5α-redutase. In: StatPearls. Treasure Island: StatPearls Publishing, 2025.
SEIDLER, Z. E. et al. Ideação suicida em homens durante a COVID-19. BMC Psychiatry, v. 23, p. 46, 2023.
SUEKSAKIT, K.; THONGBOONKERD, V. Protective effects of finasteride against testosterone-induced calcium oxalate crystallization. Journal of Biological Inorganic Chemistry, v. 24, n. 7, p. 973-983, 2019. DOI: https://doi.org/10.1007/s00775-019-01692-z
THAIBAH, H. A. et al. Suicidality risks associated with finasteride, a 5-alpha reductase inhibitor. Pharmaceuticals, v. 18, n. 7, p. 957, 2025. DOI: https://doi.org/10.3390/ph18070957
TRAISH, A. M. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertility and Sterility, v. 113, n. 1, p. 21-50, 2020. DOI: https://doi.org/10.1016/j.fertnstert.2019.11.030
ULERI, A. et al. Association of 5α-reductase inhibitors with depression and suicide. European Urology Focus, v. 10, n. 5, p. 751-753, 2024. DOI: https://doi.org/10.1016/j.euf.2024.04.009
VASELKIV, J. B. et al. 5-alpha reductase inhibitors and prostate cancer mortality among men with regular access to screening. Cancer Epidemiology, Biomarkers & Prevention, v. 31, n. 7, p. 1460-1465, 2022. DOI: https://doi.org/10.1158/1055-9965.EPI-21-1234
WALTON, N. et al. Influence of neurosteroids on affective tone. Neuroscience & Biobehavioral Reviews, v. 152, 105327, 2023. DOI: https://doi.org/10.1016/j.neubiorev.2023.105327
WEI, L. et al. Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors. BMJ, v. 365, l1204, 2019. DOI: https://doi.org/10.1136/bmj.l1204
WELK, B. et al. Association between suicidality and depression with 5α-reductase inhibitors. JAMA Internal Medicine, v. 177, n. 5, p. 683-691, 2017. DOI: https://doi.org/10.1001/jamainternmed.2017.0089
XIAO, Q. et al. Structure of human steroid 5α-reductase 2 with the antiandrogen drug finasteride. Nature Communications, v. 11, p. 5430, 2020. DOI: https://doi.org/10.1038/s41467-020-19249-z
YANAGISAWA, M. et al. Long-term (10-year) efficacy of finasteride in 523 Japanese men with AGA. Clinical Research and Trials, v. 5, p. 1–5, 2019. DOI: https://doi.org/10.15761/CRT.1000273
ZHONG, X. et al. Multidimensional assessment of adverse events of finasteride. PLoS ONE, v. 20, n. 8, e0309849, 2025. DOI: https://doi.org/10.1371/journal.pone.0309849
