Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

IJIR publishes special/guest-edited issues and topical collections. The peer review process for articles included in topical collections/special issues is the same as the peer review process of the journal in general. Additionally, if the Guest Editors author an article in their topical collection/special issue, they will not handle the peer review process.​

Are finasteride-related penile curvature/Peyronie’s disease Adverse Event Reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases

International Journal of Impotence Research (2022)Cite this article

Subjects

Abstract

A limited number of studies have described patients on finasteride showing findings which were consistent with Peyronie’s disease (PD). We aimed to detect a pharmacovigilance signal of possible association between finasteride and PD-related clinical features. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the ten drugs which were associated the most with the adverse drug reactions (ADRs) recorded as “penile curvature” and/or “Peyronie’s disease”. A similar analysis, including the same drugs, was carried out for the EMA (European Medicines Agency) EudraVigilance (EV) database. Descriptive data have been analyzed, and Proportional Reporting Ratios (PRRs) have been computed against the other nine drugs of the database. Overall, 860 reports of “penile curvature” and/or “Peyronie’s disease”, were identified in the FAERS database, 214 of which (24.9%) were associated with finasteride. Most reports (56.9%) were submitted by healthcare professionals. Where a treatment-indication was stated, the vast majority of reports (176/210; 83.8%) were associated with androgenetic alopecia. The outcome of most ADRs was “serious” (82.2%), with 96 ADRs resulting in levels of permanent disability. For 97/214 individual cases, penile curvature/PD reports were not part of a syndromic cluster suggestive of post-finasteride syndrome (PFS). The PRR resulted 6.6 (95% CI: 5.6–7.8) and 11.8 (95% CI: 9.08–15.33), respectively, in the FAERS and in the EV databases. Notwithstanding the related limitations and biasing factors of pharmacovigilance studies based on spontaneous reporting, the PRR values here identified should be interpreted as strong signals of disproportionality. These findings, per se, are however not useful to confirm any causal association. Clinical studies are needed to investigate on the possible role for finasteride in causing PD-related clinical features, an hypothesis which remains highly speculative due to the very questionable quality of present data.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Number of finasteride-related “penile curvature” and/or “Peyronie’s disease” reports throughout the years in relation with finasteride-related estimated levels of prescription in U.S.

References

  1. Hussein AA, Alwaal A, Lue TF. All about Peyronie’s disease. Asian J Urol. 2015;2:70–8. https://doi.org/10.1016/j.ajur.2015.04.019.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Nelson CJ, Mulhall JP. Psychological impact of Peyronie’s disease: a review. J Sex Med. 2013;10:653–60. https://doi.org/10.1111/j.1743-6109.2012.02999.x.

    Article  PubMed  Google Scholar 

  3. Sharma KL, Alom M, Trost L. The etiology of Peyronie’s disease: pathogenesis and genetic contributions. Sex Med Rev. 2020;8:314–23. https://doi.org/10.1016/j.sxmr.2019.06.004.

    Article  PubMed  Google Scholar 

  4. Aditya I, Grober ED, Krakowsky Y. Peyronie’s disease and testosterone deficiency: Is there a link? World J Urol. 2019;37:1035–41. https://doi.org/10.1007/s00345-019-02723-9.

    Article  CAS  PubMed  Google Scholar 

  5. Ventimiglia E, Capogrosso P, Colicchia M, Boeri L, Serino A, La Croce G, et al. Peyronie’s disease and autoimmunity—a real-life clinical study and comprehensive review. J Sex Med. 2015. https://doi.org/10.1111/jsm.12825.

  6. Mulhall JP, Matsushita K, Nelson CJ. Testosterone levels are not associated with magnitude of deformity in men with Peyronie’s disease. J Sex Med. 2019. https://doi.org/10.1016/j.jsxm.2019.05.021.

  7. Candela L, Boeri L, Capogrosso P, Oreggia D, Cazzaniga W, Pozzi E, et al. Serum testosterone levels are not associated with the severity of penile curvature in men with Peyronie’s disease—findings from a cross-sectional study. Int J Impot Res. 2020. https://doi.org/10.1038/s41443-020-0340-7.

  8. Sobel V, Zhu YS, Imperato-McGinley J. Fetal hormones and sexual differentiation. Obstet Gynecol Clin North Am. 2004;31:837–56. https://doi.org/10.1016/j.ogc.2004.08.005.

    Article  PubMed  Google Scholar 

  9. Shen ZJ, Zhou XL, Lu YL, Chen ZD. Effect of androgen deprivation on penile ultrastructure. Asian J Androl. 2003;5:33–6.

  10. Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology. 1999. https://doi.org/10.1210/endo.140.4.6655.

  11. Ganzer CA, Jacobs AR, Iqbal F. Persistent sexual, emotional, and cognitive impairment post-finasteride: a survey of men reporting symptoms. Am J Mens Health. 2015;9:222–8. https://doi.org/10.1177/1557988314538445.

    Article  PubMed  Google Scholar 

  12. Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertil Steril. 2020;113:21–50. https://doi.org/10.1016/j.fertnstert.2019.11.030.

    Article  CAS  PubMed  Google Scholar 

  13. Garreton AS, Valzacchi GR, Layus O. Post-finasteride syndrome: about 2 cases and review of the literature. Andrology. 2016;5. https://doi.org/10.4172/2472-1212.1000170.

  14. Montastruc JL, Sommet A, Bagheri H, Lapeyre-Mestre M. Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database. Br J Clin Pharmacol. 2011. https://doi.org/10.1111/j.1365-2125.2011.04037.x.

  15. Schifano F, Chiappini S, Corkery JM, Guirguis A. An insight into Z-drug abuse and dependence: an examination of reports to the European Medicines Agency Database of suspected adverse drug reactions. Int J Neuropsychopharmacol. 2019. https://doi.org/10.1093/ijnp/pyz007.

  16. Kumar A. The newly available FAERS public dashboard: implications for health care professionals. Hosp Pharm. 2019;54:75–7. https://doi.org/10.1177/0018578718795271.

    Article  PubMed  Google Scholar 

  17. EMA. Guideline on good pharmacovigilance practices (GVP) Annex I—Definitions (Rev 4). Heads Med Agencies; 2017.

  18. Schifano N, Chiappini S, Castiglione F, Salonia A, Schifano F. Is medicinal ketamine associated with urinary dysfunction issues? Assessment of both the European Medicines Agency (EMA) and the UK Yellow Card Scheme pharmacovigilance database-related reports. Low Urin Tract Symptoms. 2021;13:230–7. https://doi.org/10.1111/luts.12355.

  19. Chiappini S, Schifano F. A decade of gabapentinoid misuse: an analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ database. CNS Drugs. 2016;30:647–54. https://doi.org/10.1007/s40263-016-0359-y.

    Article  PubMed  Google Scholar 

  20. European Medicines Agency. Guideline on the use of statistical signal detection methods in the EudraVigilance data analysis system. 2008.

  21. Grundmark B, Holmberg L, Garmo H, Zethelius B. Reducing the noise in signal detection of adverse drug reactions by standardizing the background: a pilot study on analyses of proportional reporting ratios-by-therapeutic area. Eur J Clin Pharmacol. 2014. https://doi.org/10.1007/s00228-014-1658-1.

  22. Agency for Healthcare Research and Quality. Medical Expenditure Panel Survey, MEPS Data Files, Documentation, and Codebooks. n.d. https://meps.ahrq.gov/mepsweb/data_stats/download_data_files.jsp.

  23. WHO. The WHO Programme for International Drug Monitoring. 2015.

  24. Felicetti P, Trotta F, Bonetto C, Santuccio C, Brauchli Pernus Y, Burgner D, et al. Spontaneous reports of vasculitis as an adverse event following immunization: a descriptive analysis across three international databases. Vaccine. 2016. https://doi.org/10.1016/j.vaccine.2015.09.027.

  25. Hoffman KB, Demakas AR, Dimbil M, Tatonetti NP, Erdman CB. Stimulated reporting: the impact of US Food and Drug Administration-Issued Alerts on the Adverse Event Reporting System (FAERS). Drug Saf. 2014;37:971–80. https://doi.org/10.1007/s40264-014-0225-0.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Rezende HD, Dias MFRG, Trüeb RM. A comment on the post-finasteride syndrome. Int J Trichology. 2018. https://doi.org/10.4103/ijt.ijt_61_18.

  27. Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, et al. Androgenetic alopecia: a review. Endocrine. 2017;57:9–17. https://doi.org/10.1007/s12020-017-1280-y.

    Article  CAS  PubMed  Google Scholar 

  28. Bhatti HA, Basra MKA, Patel GK. Hair restoration approaches for early onset male androgenetic alopecia. J Cosmet Dermatol. 2013;12:223–31. https://doi.org/10.1111/jocd.12047.

    Article  PubMed  Google Scholar 

  29. Baas WR, Butcher MJ, Lwin A, Holland B, Herberts M, Clemons J, et al. A review of the FAERS data on 5-Alpha Reductase inhibitors: implications for postfinasteride syndrome. Urology. 2018;120:143–9. https://doi.org/10.1016/j.urology.2018.06.022.

    Article  PubMed  Google Scholar 

  30. Brenner S, Matz H. Improvement in androgenetic alopecia in 53-76-year-old men using oral finasteride. Int J Dermatol. 1999;38:928–30. https://doi.org/10.1046/j.1365-4362.1999.00804.x.

    Article  CAS  PubMed  Google Scholar 

  31. Walsh TJ, Hotaling JM, Lue TF, Smith JF. How curved is too curved? the severity of penile deformity may predict sexual disability among men with Peyronie’s disease. Int J Impot Res. 2013;25:109–12. https://doi.org/10.1038/ijir.2012.48.

    Article  CAS  PubMed  Google Scholar 

  32. Irwig MS. Persistent sexual side effects of finasteride: could they be permanent? J Sex Med. 2012;9:2927–32. https://doi.org/10.1111/j.1743-6109.2012.02846.x.

    Article  PubMed  Google Scholar 

  33. Gray SL, Semla TP. Post-finasteride syndrome. BMJ. 2019;366:9–10. https://doi.org/10.1136/bmj.l5047.

    Article  Google Scholar 

  34. Wessells H, Roy J, Bannow J, Grayhack J, Matsumoto AM, Tenover L, et al. Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia. Urology. 2003;61:579–84. https://doi.org/10.1016/S0090-4295(02)02401-9.

    Article  PubMed  Google Scholar 

  35. Ellis JA, Stebbing M, Harrap SB. Polymorphism of the androgen receptor gene is associated with male pattern baldness. J Invest Dermatol. 2001. https://doi.org/10.1046/j.1523-1747.2001.01261.x.

  36. Cauci S, Chiriacò G, Cecchin E, Toffoli G, Xodo S, Stinco G, et al. Androgen receptor (AR) gene (CAG)n and (GGN)n length polymorphisms and symptoms in young males with long-lasting adverse effects after finasteride use against androgenic alopecia. Sex Med. 2017;5:e61–71. https://doi.org/10.1016/j.esxm.2016.11.001.

    Article  PubMed  Google Scholar 

  37. Chew KK, Stuckey BGA, Earle CM, Dhaliwal SS, Keogh EJ, Porst H. Penile fibrosis in intracavernosal prostaglandin E1 injection therapy for erectile dysfunction. Int J Impot Res. 1997. https://doi.org/10.1038/sj.ijir.3900296.

  38. European Medicines Agency. Xiapex product information form. 2020. https://www.ema.europa.eu/en/documents/product-information/xiapex-epar-product-information.

Download references

Author information

Authors and Affiliations

  1. Università Vita-Salute San Raffaele, Milan, Italy

    Nicolò Schifano, Giuseppe Fallara, Francesco Montorsi & Andrea Salonia

  2. Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

    Nicolò Schifano, Luca Boeri, Giuseppe Fallara, Francesco Montorsi & Andrea Salonia

  3. ASST Sette Laghi—Circolo e Fondazione Macchi Hospital, Varese, Italy

    Paolo Capogrosso & Federico Deho’

  4. Department of Urology, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    Luca Boeri

  5. Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK

    Stefania Chiappini & Fabrizio Schifano

  6. Institute of Andrology, Department of Urology, University College London Hospitals NHS Trust, London, UK

    Matthew Rewhorn, Omer Onur Cakir, Fabio Castiglione, Hussain M. Alnajjar & Asif Muneer

  7. Division of Surgery and Interventional Science, UCL, London, UK

    Matthew Rewhorn, Omer Onur Cakir, Fabio Castiglione, Hussain M. Alnajjar & Asif Muneer

  8. King’s College Hospital NHS Foundation Trust, London, UK

    Omer Onur Cakir & Hannah Harvey

Authors
  1. Nicolò Schifano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paolo Capogrosso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luca Boeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Fallara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefania Chiappini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthew Rewhorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Omer Onur Cakir
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hannah Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fabio Castiglione
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hussain M. Alnajjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Asif Muneer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Federico Deho’
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fabrizio Schifano
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Francesco Montorsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Andrea Salonia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception of the work: NS and FS; Data collection: NS, GF, SC, MR, OOC and HH; Data analysis and interpretation: NS, PC, LB, FC, HMA, AM, FD, FM, FS and AS; Drafting the article: NS, SC and FS; Critical revision of the article: PC, LB, GF, SC, MR, OOC, HH, FC, HMA, AM, FD, FS, FM and AS; Final approval of the version to be published: NS, PC, LB, GF, SC, MR, OOC, HH, FC, HMA, AM, FD, FS, FM and AS.

Corresponding author

Correspondence to Andrea Salonia.

Ethics declarations

Competing interests

FS is a member of the EMA Advisory board (Psychiatry). No further conflicts of interest are here declared.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schifano, N., Capogrosso, P., Boeri, L. et al. Are finasteride-related penile curvature/Peyronie’s disease Adverse Event Reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases. Int J Impot Res (2022). https://doi.org/10.1038/s41443-022-00568-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41443-022-00568-2

This article is cited by

Search

Advanced search

Quick links