World J Mens Health.  2019 May;37(2):157-165. 10.5534/wjmh.180029.

Finasteride and Erectile Dysfunction in Patients with Benign Prostatic Hyperplasia or Male Androgenetic Alopecia

• Shin YS
• Karna KK
• Choi BR
• Park JK

• KMID: 2443231
• DOI: http://doi.org/10.5534/wjmh.180029

Abstract

Finasteride is primarily used to treat benign prostatic hyperplasia (BPH) and male androgenetic alopecia (MAA). Five-alpha reductase inhibitors (5α-RIs) could induce male sexual dysfunction due to their effects on testosterone and dihydrotestosterone. There is evidence suggesting that 5α-RIs may independently increase the risk of erectile dysfunction (ED). However, many investigators believe that side effects of 5α-RIs will disappear with continuous treatment. Considerable controversy exists regarding the severity and persistence of side effects of finasteride on ED. The aim of this review was to summarize current research studies on finasteride associated with ED. The search strategy used each term of finasteride and ED against PubMed database to identify related studies. ED data reported from available trials for finasteride were summarized and reviewed. Although there is not enough evidence to prove the relationship between finasteride and ED, most studies in this review found that finasteride for BPH was correlated with ED. However, most studies included in this review revealed that finasteride for MAA was not correlated with ED. On the other hand, some studies reported side effects of finasteride associated with sexual dysfunction, including ED, male infertility, ejaculation problem, and loss of libido, even in MAA patients. Well-designed randomized controlled trials are needed to further determine the mechanism and effects of finasteride on ED. However, physicians should discuss with their patients possible long-term effects of finasteride on sexual function, although we do not have evidence showing that adverse events of sexual dysfunction are absolutely associated with 5α-RIs.

Keyword

Alopecia; Erectile dysfunction; Finasteride; Prostatic hyperplasia

MeSH Terms

Alopecia*
Dihydrotestosterone
Ejaculation
Erectile Dysfunction*
Finasteride*
Hand
Humans
Infertility, Male
Libido
Male
Male*
Oxidoreductases
Prostatic Hyperplasia*
Research Personnel
Testosterone
Dihydrotestosterone
Finasteride
Oxidoreductases
Testosterone

Figure

• 

  Fig. 1 Correlation between finasteride-induced oxidative stess and endoplasmic reticulum stress. ER: endoplasmic reticulum, 5α-RIs: 5-alpha reductase inhibitors, ROS: reactive oxygen species, GRP-78: glucose-regulated protein-78, pIRE1: phosphorylated inositol-requiring transmembrane kinase/endoribonuclease, pJNK: phosphorylated c-jun-N-terminal kinase, Clev.Casp.-3: cleaved caspase-3.

Reference

1. Shin YS, Park JK. Changes in surgical strategy for patients with benign prostatic hyperplasia: 12-year single-center experience. Korean J Urol. 2011; 52:189–193. PMID: 21461283.

2. Shin YS, Zhang LT, Zhao C, Kim YG, Park JK. Twelve-week, prospective, open-label, randomized trial on the effects of an anticholinergic agent or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms. Clin Interv Aging. 2014; 9:1021–1030. PMID: 25031529.

3. Shin YS, Lee JW, Kim MK, Jeong YB, Park SC. Early dutasteride monotherapy in men with detectable serum prostate-specific antigen levels following radical prostatectomy: a prospective trial. Investig Clin Urol. 2017; 58:98–102.

4. Yamana K, Labrie F, Luu-The V. Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride. Horm Mol Biol Clin Investig. 2010; 2:293–299.

5. Severi G, Sinclair R, Hopper JL, English DR, McCredie MR, Boyle P, et al. Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors. Br J Dermatol. 2003; 149:1207–1213. PMID: 14674898.

6. Gan DC, Sinclair RD. Prevalence of male and female pattern hair loss in Maryborough. J Investig Dermatol Symp Proc. 2005; 10:184–189.

7. Traish AM. 5α-reductases in human physiology: an unfolding story. Endocr Pract. 2012; 18:965–975. PMID: 23246684.

8. Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med. 2011; 8:872–884. PMID: 21176115.

9. Baldinotti F, Majore S, Fogli A, Marrocco G, Ghirri P, Vuerich M, et al. Molecular characterization of 6 unrelated Italian patients with 5alpha-reductase type 2 deficiency. J Androl. 2008; 29:20–28. PMID: 17609295.

10. MacLaughlin DT, Donahoe PK. Sex determination and differentiation. N Engl J Med. 2004; 350:367–378. PMID: 14736929.

11. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010; 362:1192–1202. PMID: 20357281.

12. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003; 349:215–224. PMID: 12824459.

13. Amory JK, Wang C, Swerdloff RS, Anawalt BD, Matsumoto AM, Bremner WJ, et al. The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab. 2007; 92:1659–1665. PMID: 17299062.

14. Traish AM, Toselli P, Jeong SJ, Kim NN. Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency. J Androl. 2005; 26:242–248. PMID: 15713830.

15. Zhang MG, Wang XJ, Shen ZJ, Gao PJ. Long-term oral administration of 5α-reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats. Urology. 2013; 82:743.e9–743.e15.

16. Roehrborn CG, Lee M, Meehan A, Waldstreicher J. PLESS Study Group. Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia. Urology. 2003; 62:894–899. PMID: 14624915.

17. Hong SK, Min GE, Ha SB, Doo SH, Kang MY, Park HJ, et al. Effect of the dual 5alpha-reductase inhibitor, dutasteride, on serum testosterone and body mass index in men with benign prostatic hyperplasia. BJU Int. 2010; 105:970–974. PMID: 19793378.

18. Gur S, Kadowitz PJ, Hellstrom WJ. Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin Drug Saf. 2013; 12:81–90. PMID: 23173718.

19. Traish AM. Negative impact of testosterone deficiency and 5α-reductase inhibitors therapy on metabolic and sexual function in men. Adv Exp Med Biol. 2017; 1043:473–526. PMID: 29224108.

20. Melcangi RC, Magnaghi V, Martini L. Steroid metabolism and effects in central and peripheral glial cells. J Neurobiol. 1999; 40:471–483. PMID: 10453050.

21. Melcangi RC, Riva MA, Fumagalli F, Magnaghi V, Racagni G, Martini L. Effect of progesterone, testosterone and their 5 alpha-reduced metabolites on GFAP gene expression in type 1 astrocytes. Brain Res. 1996; 711:10–15. PMID: 8680851.

22. Merck Co. Propecia prescribing information. Whitehouse Station (NJ): Merck Co.;2013.

23. Irwig MS, Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med. 2011; 8:1747–1753. PMID: 21418145.

24. Nguyen HMT, Gabrielson AT, Hellstrom WJG. Erectile dysfunction in young men-a review of the prevalence and risk factors. Sex Med Rev. 2017; 5:508–520. PMID: 28642047.

25. Soni KK, Shin YS, Choi BR, Karna KK, Kim HK, Lee SW, et al. Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway. Drug Des Devel Ther. 2017; 11:2969–2979.

26. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000; 404:787–790. PMID: 10783895.

27. Bivalacqua TJ, Kendirci M, Champion HC, Hellstrom WJ, Andersson KE, Hedlund P. Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1alpha. BJU Int. 2007; 99:1488–1494. PMID: 17355372.

28. Cheng YS, Cong XD, Dai DZ, Zhang Y, Dai Y. Argirein alleviates corpus cavernosum dysfunction by suppressing proinflammatory factors p66Shc and ER stress chaperone Bip in diabetic rats. J Pharm Pharmacol. 2013; 65:94–101. PMID: 23215692.

29. Corona G, Tirabassi G, Santi D, Maseroli E, Gacci M, Dicuio M, et al. Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis. Andrology. 2017; 5:671–678. PMID: 28453908.

30. Liu L, Zhao S, Li F, Li E, Kang R, Luo L, et al. Effect of 5α-reductase inhibitors on sexual function: a meta-analysis and systematic review of randomized controlled trials. J Sex Med. 2016; 13:1297–1310. PMID: 27475241.

31. Hagberg KW, Divan HA, Persson R, Nickel JC, Jick SS. Risk of erectile dysfunction associated with use of 5-α reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink. BMJ. 2016; 354:i4823. PMID: 27659058.

32. 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 Investig. 2015; 23:85–96.

33. Fwu CW, Eggers PW, Kirkali Z, McVary KT, Burrows PK, Kusek JW. Change in sexual function in men with lower urinary tract symptoms/benign prostatic hyperplasia associated with long-term treatment with doxazosin, finasteride and combined therapy. J Urol. 2014; 191:1828–1834. PMID: 24342143.

34. Zhang MG, Wu W, Zhang CM, Wang XJ, Gao PJ, Lu YL, et al. Effects of oral finasteride on erectile function in a rat model. J Sex Med. 2012; 9:1328–1336. PMID: 22375859.

35. Chiriacò 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; 4:245–250. PMID: 26763726.

36. Narasimhalu CR. Randomized questionnaire based case-control research study on evaluation of sexual function in indian patients taking oral finasteride for androgenetic alopecia. Dermatol Ther (Heidelb). 2015; 5:231–234. PMID: 26438381.

37. 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; 4:1708–1712. PMID: 17655657.

38. Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, et al. The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol. 2006; 55:1014–1023. PMID: 17110217.

39. De Almeida Claro J, Kaufmann OG, Alarcon G, Aguiar W, Nadozza A Jr, Ortiz V, et al. Could a rural lifestyle decrease the prevalence of erectile dysfunction? BJU Int. 2007; 99:127–129. PMID: 17034491.

40. Montorsi F, Adaikan G, Becher E, Giuliano F, Khoury S, Lue TF, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med. 2010; 7:3572–3588. PMID: 21040491.

41. DeLay KJ, Haney N, Hellstrom WJ. Modifying risk factors in the management of erectile dysfunction: a review. World J Mens Health. 2016; 34:89–100. PMID: 27574592.

42. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA. 1993; 270:83–90. PMID: 8510302.

43. Lewis RW, Fugl-Meyer KS, Corona G, Hayes RD, Laumann EO, Moreira ED Jr, et al. Definitions/epidemiology/risk factors for sexual dysfunction. J Sex Med. 2010; 7:1598–1607. PMID: 20388160.

44. Salonia A, Capogrosso P, Clementi MC, Castagna G, Damiano R, Montorsi F. Is erectile dysfunction a reliable indicator of general health status in men? Arab J Urol. 2013; 11:203–211. PMID: 26558083.

45. Khanzada U, Khan SA, Hussain M, Adel H, Masood K, Adil SO, et al. Evaluation of the causes of erectile dysfunction in patients undergoing penile doppler ultrasonography in Pakistan. World J Mens Health. 2017; 35:22–27. PMID: 28459144.

46. Corona G, Lee DM, Forti G, O'Connor DB, Maggi M, O'Neill TW, et al. Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med. 2010; 7:1362–1380. PMID: 19929914.

47. Adegun PT, Areo PO, Solomon A, Dada SA, Adebayo PB. Erectile dysfunction in men with and without lower urinary tract symptoms in Nigeria. World J Mens Health. 2017; 35:107–114. PMID: 28868819.

48. Seftel AD, de la Rosette J, Birt J, Porter V, Zarotsky V, Viktrup L. Coexisting lower urinary tract symptoms and erectile dysfunction: a systematic review of epidemiological data. Int J Clin Pract. 2013; 67:32–45. PMID: 23082930.

49. Won JE, Chu JY, Choi HC, Chen Y, Park HJ, Dueñas HJ. Safety and effectiveness of once-daily tadalafil (5 mg) therapy in Korean men with benign prostatic hyperplasia/lower urinary tract symptoms in a real-world clinical setting: results from a post-marketing surveillance study. World J Mens Health. 2018; 36:161–170. PMID: 28879692.

50. Kardasevic A, Milicevic S. The correlation between prostate volume in patients with benign prostatic hyperplasia in relation to erectile dysfunction. Med Arch. 2016; 70:449–452. PMID: 28210019.

51. Choi BR, Kim HK, Park JK. Penile erection induced by scoparone from artemisia capillaris through the nitric oxide-cyclic guanosine monophosphate signaling pathway. World J Mens Health. 2017; 35:196–204. PMID: 29164835.

52. O'Leary MP. LUTS, ED, QOL: alphabet soup or real concerns to aging men? Urology. 2000; 56(5 Suppl 1):7–11. PMID: 11074196.

53. Singh MK, Avram M. Persistent sexual dysfunction and depression in finasteride users for male pattern hair loss: a serious concern or red herring? J Clin Aesthet Dermatol. 2014; 7:51–55. PMID: 25584139.

54. 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; 9:222–228. PMID: 24928450.

55. Irwig MS. Persistent sexual and nonsexual adverse effects of finasteride in younger men. Sex Med Rev. 2014; 2:24–35. PMID: 27784541.

56. Irwig MS. Decreased alcohol consumption among former male users of finasteride with persistent sexual side effects: a preliminary report. Alcohol Clin Exp Res. 2013; 37:1823–1826. PMID: 23763349.

57. Traish AM, Mulgaonkar A, Giordano N. The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression. Korean J Urol. 2014; 55:367–379. PMID: 24955220.

58. 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:e100237. PMID: 24959691.