{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:37:22Z","timestamp":1785411442349,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UID\/06397\/2025I"],"award-info":[{"award-number":["UID\/06397\/2025I"]}]},{"award":["UID\/06397\/2025I"],"award-info":[{"award-number":["UID\/06397\/2025I"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: 5\u03b1-Reductase inhibitors (5ARIs) are commonly used to treat and prevent androgenic alopecia and benign prostatic hyperplasia. Despite their well-established effectiveness, they are associated with adverse drug reactions (ADRs), highlighting the need for continuous safety assessment. This study aimed to analyze the ADRs associated with finasteride and dutasteride, both as monotherapy and in combination therapy. Methods: A retrospective analysis of ADRs associated with finasteride and dutasteride reported to EudraVigilance between 1 January 2005 and 27 March 2023 was performed. A total of 7777 reports were selected, and various variables were examined, including the temporal evolution of ADR reports, reporter profile, and the age group of the affected population. ADRs were categorized based on their seriousness and outcome, with particular focus on the most common reactions and their alignment with the Summary of Product Characteristics (SmPC). Results: The most affected age group, excluding the \u201cNot Specified\u201d category, was \u201c18\u201364 years.\u201d Overall, finasteride was the most reported. The majority of reported ADRs were classified as \u201cSerious,\u201d with a predominant outcome of \u201cPersists without recovery,\u201d and a significant proportion of these ADRs were not listed in the respective 5ARI SmPCs. Among the ADRs classified as \u201cSerious,\u201d the most frequently reported seriousness criterion was \u201cClinically important\u201d. Conclusions: The results emphasize how crucial it is to continuously monitor these drugs in order to prevent and mitigate ADRs, ensure population safety, and promote public health. Additionally, more research is required to determine whether the ADRs not included in the SmPC could be new warning signs.<\/jats:p>","DOI":"10.3390\/ph19060939","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Risks Associated with 5\u03b1-Reductase Inhibitor Use: Analysis of Adverse Drug Reactions Reported to EudraVigilance"],"prefix":"10.3390","volume":"19","author":[{"given":"Ricardo","family":"Alves","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-5108","authenticated-orcid":false,"given":"Samuel","family":"Silvestre","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Chemistry, Faculty of Sciences, University of Beira Interior, 6201-001 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5225-6222","authenticated-orcid":false,"given":"Cristina","family":"Monteiro","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"UFBI-Pharmacovigilance Unit of Beira Interior, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, September 03). What Is Pharmacovigilance?. Available online: https:\/\/www.who.int\/teams\/regulation-prequalification\/regulation-and-safety\/pharmacovigilance."},{"key":"ref_2","unstructured":"Pharmaceutical Order (2024, September 04). How Does a New Medicine Appear on the Market?. Available online: https:\/\/www.ordemfarmaceuticos.pt\/pt\/artigos\/como-surge-um-novo-medicamento-no-mercado\/."},{"key":"ref_3","unstructured":"EuroGCT (2024, September 03). What Does the Process of Conducting Clinical Trials Consist of?. Available online: https:\/\/www.eurogct.org\/pt-pt\/em-que-consiste-o-processo-de-realizacao-de-ensaios-clinicos."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3810\/pgm.2011.09.2475","article-title":"Key concepts of clinical trials: A narrative review","volume":"123","author":"Umscheid","year":"2011","journal-title":"Postgrad. Med."},{"key":"ref_5","unstructured":"European Medicines Agency (2024, September 08). EudraVigilance. Available online: https:\/\/www.ema.europa.eu\/en\/glossary-terms\/eudravigilance."},{"key":"ref_6","unstructured":"European Medicines Agency (2024, September 08). EudraVigilance. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-development\/pharmacovigilance-research-development\/eudravigilance."},{"key":"ref_7","unstructured":"Salisbury, B.H., Leslie, S.W., and Tadi, P. (2024, August 15). 5 Alpha-Reductase Inhibitor. Definitions 8 June 2020, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK555930\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.21037\/tau-22-690","article-title":"5-alpha reductase inhibitors use in prostatic disease and beyond","volume":"12","author":"Chislett","year":"2023","journal-title":"Transl. Androl. Urol."},{"key":"ref_9","first-page":"56","article-title":"Adverse effects and safety of 5-alpha reductase inhibitors (finasteride, dutasteride): A systematic review","volume":"9","author":"Hirshburg","year":"2016","journal-title":"J. Clin. Aesthetic Dermatol."},{"key":"ref_10","unstructured":"Prostate Institute (2024, September 15). 12 Frequently Asked Questions About the Digital Rectal Exam. Available online: https:\/\/www.institutodaprostata.com\/pt\/blog\/12-perguntas-frequentes-sobre-o-toque-rectal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2147\/CIA.S192435","article-title":"The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia","volume":"14","author":"Zhou","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"ref_12","unstructured":"Zito, P.M., Bistas, K.G., Patel, P., and Syed, K. (2024, September 09). Finasteride, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK513329\/."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fertig, R.M., Gamret, A.C., Darwin, E., and Gaudi, S. (2017). Sexual side effects of 5-\u03b1-reductase inhibitors finasteride and dutasteride: A comprehensive review. Dermatol. Online J., 23.","DOI":"10.5070\/D32311037240"},{"key":"ref_14","unstructured":"(2024, September 15). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/finasteride-dutasteride-containing-medicinal-products."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25nr15862","DOI":"10.4088\/JCP.25nr15862","article-title":"Failing Public Health Again? Analytical Review of Depression and Suicidality from Finasteride","volume":"86","author":"Brezis","year":"2025","journal-title":"J. Clin. Psychiatry"},{"key":"ref_16","unstructured":"European Commission (2023). The Impact of Demographic Change in Europe, European Commission. Available online: https:\/\/commission.europa.eu\/strategy-and-policy\/priorities-2019-2024\/new-push-european-democracy\/impact-demographic-change-europe_en."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kurczewska-Michalak, M., Lewek, P., Jankowska-Pola\u0144ska, B., Giardini, A., Granata, N., Maffoni, M., Costa, E., Mid\u00e3o, L., and Kardas, P. (2021). Polypharmacy Management in the Older Adults: A Scoping Review of Available Interventions. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.734045"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.jamda.2009.03.018","article-title":"Polypharmacy in the Elderly: A Multicenter Study","volume":"10","author":"Barak","year":"2009","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0895-4356(02)00411-0","article-title":"Use of medications and polypharmacy are increasing among the elderly","volume":"55","author":"Linjakumpu","year":"2002","journal-title":"J. Clin. Epidemiol."},{"key":"ref_20","unstructured":"EMA (2024). Implementation of the Pharmacovigilance Legislation, EMA. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/pharmacovigilance-overview\/legal-framework-pharmacovigilance\/implementation-pharmacovigilance-legislation."},{"key":"ref_21","unstructured":"European Parliament and Council of the European Union (2024, September 22). Regulation (EU) No 1235\/2010 of 15 December 2010 Amending, as Regards Pharmacovigilance of Medicinal Products for Human Use, Regulation (EC) No 726\/2004. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:32010R1235."},{"key":"ref_22","unstructured":"European Medicines Agency (2024, September 22). Did You Know? You Can Report Side Effects Yourself. Available online: www.adrreports.eu."},{"key":"ref_23","unstructured":"European Commission Strengthening Pharmacovigilance to Reduce Adverse Effects of Medicines, European Commission. Available online: https:\/\/health.ec.europa.eu\/medicinal-products\/pharmacovigilance_en."},{"key":"ref_24","unstructured":"World Health Organization Medication Without Harm\u2014WHO Global Patient Safety Challenge, WHO. Available online: https:\/\/www.who.int\/initiatives\/medication-without-harm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s40264-018-0647-1","article-title":"EudraVigilance Medicines Safety Database: Publicly Accessible Data for Research and Public Health Protection","volume":"41","author":"Postigo","year":"2018","journal-title":"Drug Saf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E455","DOI":"10.1503\/cmaj.109-4488","article-title":"Propecia lawsuits: The lasting effects of delayed drug warnings","volume":"185","author":"Collier","year":"2013","journal-title":"CMAJ"},{"key":"ref_27","unstructured":"European Medicines Agency (2024, September 22). Change Management for the EudraVigilance System. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-development\/pharmacovigilance-research-development\/eudravigilance\/change-management-eudravigilance-system."},{"key":"ref_28","unstructured":"European Medicines Agency (2024, September 22). Data Qualility. Available online: https:\/\/www.adrreports.eu\/pt\/data_quality.html."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s40264-023-01302-7","article-title":"Factors Associated with Underreporting of Adverse Drug Reactions by Health Care Professionals","volume":"46","author":"Costa","year":"2023","journal-title":"Drug Saf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1590\/S0080-623420140000400023","article-title":"Causes for the underreporting of adverse drug events by health professionals","volume":"48","author":"Varallo","year":"2014","journal-title":"Rev. Esc. Enferm."},{"key":"ref_31","first-page":"e219","article-title":"Spontaneous reporting of adverse reactions associated with the COVID-19 vaccine in health care professionals","volume":"8","author":"Pinho","year":"2023","journal-title":"RISE Health Res. J."},{"key":"ref_32","unstructured":"European Parliament and Council of the European Union (2024, September 22). Directive 2010\/84\/EU of the European Parliament and of the Council of 15 December 2010 Amending Directive 2001\/83\/EC as Regards Pharmacovigilance. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:32010L0084."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s40290-022-00422-2","article-title":"An Industry Survey on Managing the Pharmacovigilance System Master File in a Global Environment: The Need for a Pragmatic Approach","volume":"36","author":"Lavery","year":"2022","journal-title":"Pharm. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/bcp.13098","article-title":"The value of patient reporting to the pharmacovigilance system: A systematic review","volume":"83","author":"Cavaco","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/pds.3687","article-title":"Adverse drug reaction reports of patients and healthcare professionals-differences in reported information","volume":"24","author":"Rolfes","year":"2015","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_36","unstructured":"Eurostat (2024, September 23). Ageing Europe\u2014Statistics on Population Developments. Available online: https:\/\/ec.europa.eu\/eurostat\/statistics-explained\/SEPDF\/cache\/80393.pdf."},{"key":"ref_37","unstructured":"European Medicines Agency (2024, September 22). Detailed Guide Regarding the EudraVigilance Data Management Activities by the European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/other\/detailed-guide-regarding-eudravigilance-data-management-activities-european-medicines-agency_en.pdf."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Antoniou, T., Macdonald, E.M., Yao, Z., Gomes, T., Tadrous, M., Ho, J.M.W., Mamdani, M.M., Juurlink, D.N., and Canadian Drug Safety and Effectiveness Research Network (2018). A population-based study of the risk of osteoporosis and fracture with dutasteride and finasteride. BMC Musculoskelet. Disord., 19.","DOI":"10.1186\/s12891-018-2076-9"},{"key":"ref_39","first-page":"12","article-title":"Adverse Sexual Effects of Treatment with Finasteride or Dutasteride for Male Androgenetic Alopecia","volume":"99","author":"Lee","year":"2019","journal-title":"Acta Derm. Venereol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4103\/0378-6323.188652","article-title":"Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia","volume":"83","author":"Shanshanwal","year":"2017","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1440-0960.2012.00909.x","article-title":"Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia","volume":"54","author":"Boyapati","year":"2013","journal-title":"Australas. J. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2165\/00002018-200932010-00002","article-title":"Determinants of under-reporting of adverse drug reactions: A systematic review","volume":"32","author":"Herdeiro","year":"2009","journal-title":"Drug Saf."},{"key":"ref_43","first-page":"222","article-title":"Pharmacovigilance in Portugal: Activity of the Central Pharmacovigilance Unit","volume":"28","author":"Mendes","year":"2015","journal-title":"Acta Med. Port."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1111\/j.1743-6109.2012.02846.x","article-title":"Persistent Sexual Side Effects of Finasteride: Could They Be Permanent?","volume":"9","author":"Irwig","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Estill, M.C., Ford, A., Omeira, R., and Rodman, M. (2023). Finasteride and Dutasteride for the Treatment of Male Androgenetic Alopecia: A Review of Efficacy and Reproductive Adverse Effects. Georget. Med. Rev., 7.","DOI":"10.52504\/001c.88531"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.abd.2020.02.001","article-title":"Post-finasteride syndrome","volume":"95","author":"Pereira","year":"2020","journal-title":"An. Bras. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1080\/17425255.2025.2503848","article-title":"Pharmacokinetic and pharmacodynamic alterations in older people: What we know so far","volume":"21","author":"Mangoni","year":"2025","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/MOU.0000000000000497","article-title":"Effects of 5-alpha reductase inhibitors: New insights on benefits and harms","volume":"28","author":"Lee","year":"2018","journal-title":"Curr. Opin. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"323","DOI":"10.5534\/wjmh.200012","article-title":"Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It\u2019s Time to Sound the Alarm","volume":"38","author":"Traish","year":"2020","journal-title":"World J. Mens Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9619388","DOI":"10.1155\/2023\/9619388","article-title":"Comorbidity of Anxiety and Hypertension: Common Risk Factors and Potential Mechanisms","volume":"2023","author":"Qiu","year":"2023","journal-title":"Int. J. Hypertens."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/hr.2013.124","article-title":"Effects of salt status and blockade of mineralocorticoid receptors on aldosterone-induced cardiac injury","volume":"37","author":"Hattori","year":"2014","journal-title":"Hypertens. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1159\/000450617","article-title":"Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome","volume":"2","author":"Fertig","year":"2017","journal-title":"Ski. Appendage Disord"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.2522\/ptj.20130597","article-title":"Chronic stress, cortisol dysfunction, and pain: A psychoneuroendocrine rationale for stress management in pain rehabilitation","volume":"94","author":"Hannibal","year":"2014","journal-title":"Phys. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.52965\/001c.37533","article-title":"Male Sexual Dysfunction","volume":"10","author":"Anderson","year":"2022","journal-title":"Health Psychol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1001\/jamadermatol.2020.3385","article-title":"Investigation of Suicidality and Psychological Adverse Events in Patients Treated with Finasteride","volume":"157","author":"Nguyen","year":"2021","journal-title":"JAMA Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/phar.1612","article-title":"Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study","volume":"35","author":"Ali","year":"2015","journal-title":"Pharmacotherapy"},{"key":"ref_57","unstructured":"European Medicines Agency (EMA) (2024, October 04). PRAC Starts Safety Review of Medicines Containing Finasteride and Dutasteride Due to Risk of Suicidal Ideation and Behaviour. Available online: https:\/\/www.ema.europa.eu\/en\/news\/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-30-september-3-october-2024."},{"key":"ref_58","unstructured":"European Medicines Agency (EMA) (2024, April 21). European Database of Suspected Adverse Drug Reaction Reports. Available online: https:\/\/www.adrreports.eu\/pt\/index.html."},{"key":"ref_59","unstructured":"European Medicines Agency (2024, October 08). Signal Management. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/post-authorisation\/pharmacovigilance-post-authorisation\/signal-management."},{"key":"ref_60","unstructured":"European Medicines Agency (EMA) (2024, April 21). Guideline on Good Pharmacovigilance Practices (GVP): Module VI\u2014Collection, Management and Submission of Reports of Suspected Adverse Reactions to Medicinal Products (Rev. 2), 2017. Available online: https:\/\/www.infarmed.pt\/web\/infarmed\/perguntas-frequentes-area-transversal\/medicamentos_uso_humano\/farmacovigilancia."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/939\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:59:38Z","timestamp":1781744378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ph19060939"],"URL":"https:\/\/doi.org\/10.3390\/ph19060939","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]}}}