Post-finasteride Syndrome: A Review of Current Literature

Abstract

Purpose of Review

A constellation of persistent adverse effects—collectively termed post-finasteride syndrome (PFS)—after 5α-reductase inhibitor treatment for benign prostatic hyperplasia (BPH) and androgenic alopecia (AGA) has recently been described. The severity of these sexual, physical, neurological, and psychiatric side effects raises important concerns regarding the treatment of these conditions, especially given the prevalence of indications for these medications. Here we review the literature exploring the symptoms, proposed mechanisms, and potential disease modulating factors for PFS.

Recent Findings

While the persistent sexual side effects associated with PFS are well documented, research on the physical, neurological, and psychiatric adverse effects is much less ubiquitous. Though the mechanisms leading to PFS have been proposed, a clear treatment plan for these patients has not been established. In the treatment of BPH and AGA with 5α-reductase inhibitors, the risks of PFS should be considered.

Summary

The occurrence of persistent adverse sexual, physical, neurological, and psychiatric side effects after 5α-reductase inhibitor is well supported by the existing data. While additional studies are needed to better evaluate the role of 5α-reductase inhibitors in the manifestation of the symptoms of PFS, the risks of PFS should be critically evaluated when treating patients with BPH or AGA.

This is a preview of subscription content, log in to check access.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Foundation P-FS. Overview. 2013. http://www.pfsfoundation.org/post-finasteride-syndrome-overview/.

  2. 2.

    Research CfDEa. Approval package for application number NDA 20-788/S-020/S-021/S-023. 2011.

    Google Scholar 

  3. 3.

    Gupta AK, Sharma N, Shukla P. Atypical post-finasteride syndrome: a pharmacological riddle. Indian J Pharmacol. 2016;48(3):316–7. https://doi.org/10.4103/0253-7613.182898.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Reddy GK, Sartor O. Finasteride, a selective 5-alpha-reductase inhibitor, in the prevention and treatment of human prostate cancer. Clin Prostate Cancer. 2004;2(4):206–8. https://doi.org/10.1016/S1540-0352(11)70045-2.

    Article  PubMed  Google Scholar 

  5. 5.

    Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179–84. https://doi.org/10.1210/jc.2003-030330.

    Article  PubMed  CAS  Google Scholar 

  6. 6.

    Kiguradze T, Temps WH, Yarnold PR, Cashy J, Brannigan RE, Nardone B, et al. Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride. PeerJ. 2017;5:e3020. https://doi.org/10.7717/peerj.3020.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 7.

    Bartsch G, Rittmaster R, Klocker H. Dihydrotestosterone and the concept of 5α-reductase inhibition in human benign prostatic hyperplasia. World J Urol. 2002;19(6):413–25. https://doi.org/10.1007/s00345-002-0248-5.

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    Zito PM, Hin N. Finasteride in androgenic alopecia. J Dermatol Nurses’ Assoc. 2017;9(1):43–5. https://doi.org/10.1097/JDN.0000000000000279.

    Article  Google Scholar 

  9. 9.

    Hoffmann R, Happle R. Current understanding of androgenetic alopecia. Part II: clinical aspects and treatment. Eur J Dermatol: EJD. 2000;10(5):410–7.

    PubMed  CAS  Google Scholar 

  10. 10.

    Lu S-H, Chen C-S. Natural history and epidemiology of benign prostatic hyperplasia. Formosan J Surg. 2014;47(6):207–10. https://doi.org/10.1016/j.fjs.2014.10.001.

    Article  Google Scholar 

  11. 11.••

    Basaria S, Jasuja R, Huang G, Wharton W, Pan H, Pencina K, et al. Characteristics of men who report persistent sexual symptoms after finasteride use for hair loss. J Clin Endocrinol Metab. 2016;101(12):4669–80. https://doi.org/10.1210/jc.2016-2726. This study compares PFS patient body composition, fMRI responses, sexual function, mood, cognition, and hormonal levels to those of asymptomatic finasteride users and healthy controls to investigate the pathophysiologic mechanism of PFS

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. 12.•

    Liu L, Zhao S, Li F, Li E, Kang R, Luo L, et al. Effect of 5alpha-reductase inhibitors on sexual function: a meta-analysis and systematic review of randomized controlled trials. J Sex Med. 2016;13(9):1297–310. https://doi.org/10.1016/j.jsxm.2016.07.006. This comprehensive meta-analysis examines changes in sexual function in BPH and AGA patients using 5α-reductase inhibitors

    Article  PubMed  Google Scholar 

  13. 13.

    Irwig MS. Persistent sexual side effects of finasteride: could they be permanent? J Sex Med. 2012;9(11):2927–32. https://doi.org/10.1111/j.1743-6109.2012.02846.x.

    Article  PubMed  Google Scholar 

  14. 14.

    Ganzer CA, Jacobs AR, Persistent Sexual IF. Emotional, and cognitive impairment post-finasteride:a survey of men reporting symptoms. Am J Mens Health. 2015;9(3):222–8. https://doi.org/10.1177/1557988314538445.

    Article  PubMed  Google Scholar 

  15. 15.

    Kaplan SA, Chung DE, Lee RK, Scofield S, Te AE. A 5-year retrospective analysis of 5alpha-reductase inhibitors in men with benign prostatic hyperplasia: finasteride has comparable urinary symptom efficacy and prostate volume reduction, but less sexual side effects and breast complications than dutasteride. Int J Clin Pract. 2012;66(11):1052–5. https://doi.org/10.1111/j.1742-1241.2012.03010.x.

    Article  PubMed  CAS  Google Scholar 

  16. 16.•

    Mervis JS, Borda LJ, Miteva M. “Post-finasteride syndrome”: what to tell our female patients? Br J Dermatol. 2018; https://doi.org/10.1111/bjd.16658. This meta-analysis investigates the sexual side effects in female patients using 5α-reductase inhibitors off-label for hair loss

  17. 17.

    Mondaini N, Gontero P, Giubilei G, Lombardi G, Cai T, Gavazzi A, et al. Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon? J Sex Med. 2007;4(6):1708–12. https://doi.org/10.1111/j.1743-6109.2007.00563.x.

    Article  PubMed  Google Scholar 

  18. 18.

    Traish AM, Haider KS, Doros G, Haider A. Finasteride, not tamsulosin, increases severity of erectile dysfunction and decreases testosterone levels in men with benign prostatic hyperplasia. Horm Mol Biol Clin Invest. 2015;23(3):85–96. https://doi.org/10.1515/hmbci-2015-0015.

    CAS  Article  Google Scholar 

  19. 19.

    Stojanovic N, Ignjatovic I, Djenic N, Bogdanovic D. Adverse effects of pharmacological therapy of benign prostatic hyperplasia on sexual function in men. Srp Arh Celok Lek. 2015;143(5–6):284–9.

    Article  PubMed  Google Scholar 

  20. 20.

    Perez-Mora N, Velasco C, Bermudez F. Oral finasteride presents with sexual-unrelated withdrawal in long-term treated androgenic alopecia in men. Skinmed. 2015;13(3):179–83.

    PubMed  Google Scholar 

  21. 21.•

    Melcangi RC, Santi D, Spezzano R, Grimoldi M, Tabacchi T, Fusco ML, et al. Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. J Steroid Biochem Mol Biol. 2017;171:229–35. https://doi.org/10.1016/j.jsbmb.2017.04.003. This study explores psychiatric and andrological findings in PFS patients and compares their CSF and plasma neurohormonal levels

    Article  PubMed  CAS  Google Scholar 

  22. 22.

    Walf AA, Kaurejo S, Frye CA. Research brief: self-reports of a constellation of persistent antiandrogenic, estrogenic, physical, and psychological effects of finasteride usage among men. Am J Mens Health. 2018;0(0):1557988317750989. https://doi.org/10.1177/1557988317750989.

    Article  Google Scholar 

  23. 23.

    Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. Adverse side effects of 5alpha-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med. 2011;8(3):872–84. https://doi.org/10.1111/j.1743-6109.2010.02157.x.

    Article  PubMed  CAS  Google Scholar 

  24. 24.

    Jacobsen SJ, Cheetham TC, Haque R, Shi JM, Loo RK. Association between 5-alpha reductase inhibition and risk of hip fracture. JAMA. 2008;300(14):1660–4. https://doi.org/10.1001/jama.300.14.1660.

    Article  PubMed  CAS  Google Scholar 

  25. 25.

    Chiriaco G, Cauci S, Mazzon G, Trombetta C. An observational retrospective evaluation of 79 young men with long-term adverse effects after use of finasteride against androgenetic alopecia. Andrology. 2016;4(2):245–50. https://doi.org/10.1111/andr.12147.

    Article  PubMed  CAS  Google Scholar 

  26. 26.

    Di Loreto C, La Marra F, Mazzon G, Belgrano E, Trombetta C, Cauci S. Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia. PLoS One. 2014;9(6):e100237. https://doi.org/10.1371/journal.pone.0100237.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. 27.

    Motofei IG, Rowland DL, Georgescu SR, Tampa M, Paunica S, Constantin VD, et al. Post-finasteride adverse effects in male androgenic alopecia: a case report of vitiligo. Skin Pharmacol Physiol. 2017;30(1):42–5. https://doi.org/10.1159/000455972.

    Article  PubMed  CAS  Google Scholar 

  28. 28.•

    Ganzer CA, Jacobs AR. Emotional consequences of finasteride: fool's gold. Am J Mens Health. 2018;12(1):90–5. https://doi.org/10.1177/1557988316631624. This study examines the psychiatric and family history of PFS patients to determine the effect of pre-treatment factors on the course of PFS

    Article  PubMed  Google Scholar 

  29. 29.

    Aumuller G, Eicheler W, Renneberg H, Adermann K, Vilja P, Forssmann WG. Immunocytochemical evidence for differential subcellular localization of 5 alpha-reductase isoenzymes in human tissues. Acta Anat. 1996;156(4):241–52.

    Article  PubMed  CAS  Google Scholar 

  30. 30.

    Cauci S, Chiriaco 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(1):e61–71. https://doi.org/10.1016/j.esxm.2016.11.001.

    Article  PubMed  Google Scholar 

  31. 31.

    Motofei IG, Rowland DL, Manea M, Georgescu SR, Paunica I, Sinescu I. Safety profile of finasteride: distribution of adverse effects according to structural and informational dichotomies of the mind/brain. Clin Drug Investig. 2017;37(6):511–7. https://doi.org/10.1007/s40261-017-0501-8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mohit Khera.

Ethics declarations

Conflict of Interest

Jeffrey K Than and Katherine Rodriguez declare no conflicts of interest; Mohit Khera reports research support from the Post-Finasteride Foundation and Boston Scientific, and consulting fees from Boston Scientific, Abbvie, Endo, and Coloplast, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Male Sexual Dysfunction and Disorders

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Than, J.K., Rodriguez, K. & Khera, M. Post-finasteride Syndrome: A Review of Current Literature. Curr Sex Health Rep 10, 152–157 (2018). https://doi.org/10.1007/s11930-018-0163-4

Download citation

Keywords

  • Finasteride
  • Post-finasteride syndrome
  • Benign prostatic hyperplasia
  • Androgenic alopecia