Effects of 5-Alpha reductase inhibitors on erectile function, sexual desire and ejaculation

Expert Opinion on Drug Safety

Volumn 12, Issue 1, 2013, Pages 81-90

  Gur, Serap ^a,b   Kadowitz, Philip J ^a   Hellstrom, Wayne Jg ^a  

^a TULANE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b ANKARA UNIVERSITY   (Turkey)

Author keywords

5 Alpha reductase enzyme; Benign prostatic hyperplasia; Dutasteride; Finasteride; Hair loss; Human erectile function

Indexed keywords

ANDROSTANOLONE; DEOXYCORTICOSTERONE; DUTASTERIDE; FINASTERIDE; PROGESTERONE; PROSTATE SPECIFIC ANTIGEN; SEX HORMONE; STEROID 5ALPHA REDUCTASE; STEROID 5ALPHA REDUCTASE INHIBITOR;

ALOPECIA; ASTROCYTE; BRAIN FUNCTION; CLINICAL TRIAL (TOPIC); DRUG EFFECT; EJACULATION; EJACULATION DISORDER; ELECTROSTIMULATION; ERECTILE DYSFUNCTION; GLIA CELL; GYNECOMASTIA; HUMAN; HYPOACTIVE SEXUAL DESIRE DISORDER; INTERNATIONAL INDEX OF ERECTILE FUNCTION; INTIMACY; MELANCHOLIA; OLIGODENDROGLIA; ORCHIECTOMY; ORGASM; ORGASM DISORDER; PENIS ERECTION; PHASE 3 CLINICAL TRIAL (TOPIC); PROSTATE HYPERTROPHY; PROSTATE SIZE; PROSTATE VOLUME; QUALITY OF LIFE; REVIEW; RISK ASSESSMENT; SCALP HAIR; SELF ESTEEM; SELF EVALUATION; SEXUAL BEHAVIOR; SEXUAL DYSFUNCTION; SEXUAL FUNCTION; TREATMENT DURATION; WELLBEING;

5-ALPHA REDUCTASE INHIBITORS; ANIMALS; AZASTEROIDS; EJACULATION; ERECTILE DYSFUNCTION; FINASTERIDE; HUMANS; MALE; PENILE ERECTION; PREVALENCE; PROSTATIC HYPERPLASIA; QUALITY OF LIFE; RISK ASSESSMENT; RISK FACTORS; SEXUAL BEHAVIOR; SEXUAL DYSFUNCTION, PHYSIOLOGICAL; TREATMENT OUTCOME;

EID: 84871488147     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2013.742885     Document Type: Review

References (71)

1. Gur S, Kadowitz PJ, Hellstrom WJ. Guide to drug therapy for lower urinary tract symptoms in patients with benign prostatic obstruction : implications for sexual dysfunction. Drugs 2008;68(2):209-29
2. Gacci M, Eardley I, Giuliano F, et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 2011;60(4):809-25
3. Carbone DJ Jr, Hodges S. Medical therapy for benign prostatic hyperplasia: sexual dysfunction and impact on quality of life. Int J Impot Res 2003;15(4):299-306
4. Irwig MS, Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med 2011;8(6):1747-53
5. Wessells HRoy J, Bannow J, et al. Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia. Urology 2003;61(3):579-84
6. Traish AM, Goldstein I, Kim NN. Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol 2007;52(1):54-70
7. Bonkhoff H, Stein U, Aumuller G, Remberger K, et al. Differential expression of 5 alpha-reductase isoenzymes in the human prostate and prostatic carcinomas. Prostate 1996;29(4):261-7
8. George FW, Johnson L, Wilson JD. The effect of a 5 alpha-reductase inhibitor on androgen physiology in the immature male rat. Endocrinology 1989;125(5):2434-8
9. Imperato-McGinley J, Gautier T, Zirinsky K, et al. Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. J Clin Endocrinol Metab 1992;75(4):1022-6
10. Carson C 3rd, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology 2003;61(4 Suppl 1):2-7
11. Kaufman M, Pinsky L. The dissociation of testosterone-And 5 alpha-dihydrotestosterone-receptor complexes formed within cultured human genital skin fibroblasts. J Steroid Biochem 1983;18(2):121-5
12. Schirar A, Bonnefond C, Meusnier C, Devinoy E, et al. Androgens modulate nitric oxide synthase messenger ribonucleic acid expression in neurons of the major pelvic ganglion in the rat. Endocrinology 1997;138(8):3093-102
13. Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med 2005;2(6):759-70
14. Traish AM. Androgens play a pivotal role in maintaining penile tissue architecture and erection: a review. J Androl 2009;30(4):363-9
15. Gooren LJ, Saad F. Recent insights into androgen action on the anatomical and physiological substrate of penile erection. Asian J Androl 2006;8(1):3-9
16. Erdemir F, Harbin A, Hellstrom WJ. 5-Alpha reductase inhibitors and erectile dysfunction: the connection. J Sex Med 2008;5(12):2917-24
17. Kiyokage E, Toida K, Suzuki-Yamamoto T, Ishimura Ket al. Localization of 5alpha-reductase in the rat main olfactory bulb. J Comp Neurol 2005;493(3):381-95
18. Lephart ED. Age-related changes in brain and pituitary 5 alpha-reductase with finasteride (Proscar) treatment. Neurobiol Aging 1995;16(4):647-50
19. Iehle C, et al. Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue. J Steroid Biochem Mol Biol 1999;68(5-6):189-95
20. Uemura M, et al. Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci 2008;99(1):81-6
21. Andersson S, Russell DW. Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases. Proc Natl Acad Sci USA 1990;87(10):3640-4
22. Labrie F, et al. Structure of human type II 5 alpha-reductase gene. Endocrinology 1992;131(3):1571-3
23. Normington K, Russell DW. Tissue distribution and kinetic characteristics of rat steroid 5 alpha-reductase isozymes. Evidence for distinct physiological functions. J Biol Chem 1992;267(27):19548-54
24. Thigpen AE, Silver RI, Guileyardo JM, et al. Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. J Clin Invest 1993;92(2):903-10
25. Iehle C, Delos S, Guirou O, et al. Human prostatic steroid 5 alpha-reductase isoforms-A comparative study of selective inhibitors. J Steroid Biochem Mol Biol 1995;54(5-6):273-9
26. Thomas LN, Lazier CB, Gupta R, et al. Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer. Prostate 2005;63(3):231-9
27. Godoy A, Kawinski E, Li Y, et al. 5alpha-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression. Prostate 2011;71(10):1033-46
28. Kramer BS, Hagerty KL, Justman S, et al. Use of 5-Alpha-reductase inhibitors for prostate cancer chemoprevention: american Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Clin Oncol 2009;27(9):1502-16
29. Theoret MR, Ning YM, Zhang JJ, et al. The risks and benefits of 5alpha-reductase inhibitors for prostate-cancer prevention. N Engl J Med 2011;365(2):97-9
30. Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003;44(1):82-8
31. Giuliano F. Impact of medical treatments for benign prostatic hyperplasia on sexual function. BJU Int 2006;97(Suppl 2):34-8; discussion 44-5
32. McConnell JD, Bruskewitz R, Walsh P, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med 1998;338(9):557-63
33. Carlin JR, Hoglund P, Eriksson LO, et al. Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans. Drug Metab Dispos 1992;20(2):148-55
34. Tacklind J, Fink HA, Macdonald R, et al. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev 2010(10):CD006015
35. Clark RV, Hermann DJ, Cunningham GRet al. 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
36. Imperato-McGinley J, et al. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974;186(4170):1213-15
37. Geller J. Five-year follow-up of patients with benign prostatic hyperplasia treated with finasteride. Eur Urol 1995;27(4):267-73
38. Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 1998;39(4 Pt 1):578-89
39. Leyden J, Dunlap F, Miller Bet al. Finasteride in the treatment of men with frontal male pattern hair loss. J Am Acad Dermatol 1999;40(6 Pt 1):930-7
40. McClellan KJ, Markham A. Finasteride: a review of its use in male pattern hair loss. Drugs 1999;57(1):111-26
41. Lowe FC, McConnell JD, Hudson PB, et al. Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia. Urology 2003;61(4):791-6
42. Mondaini N, Gontero P, Giubilei G, 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
43. Olsen EA, Hordinsky M, Whiting D, 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(6):1014-23
44. Byrnes CA, Morton AS, Liss CL, et al. Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar. Clin Ther 1995;17(5):956-69
45. Nickel JC, Fradet Y, Boake RC, et al. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study. CMAJ 1996;155(9):1251-9
46. Smith AB, Carson CC. Finasteride in the treatment of patients with benign prostatic hyperplasia: a review. Ther Clin Risk Manag 2009;5(3):535-45
47. Castro-Magana M, Angulo M, Fuentes B, et al. Effect of finasteride on human testicular steroidogenesis. J Androl 1996;17(5):516-21
48. Frink M, Hsieh YC, Hu S, et al. Mechanism of salutary effects of finasteride on post-traumatic immune/inflammatory response: upregulation of estradiol synthesis. Ann Surg 2007;246(5):836-43
49. Duborija-Kovacevic N, Jakovljevic V, Sabo A, Tomic Z, et al. Anti-nociceptive and anti-inflammatory properties of 5alpha-reductase inhibitor finasteride in experimental animals. Eur J Drug Metab Pharmacokinet 2008;33(3):181-6
50. Romer B, Gass P. Finasteride-induced depression: new insights into possible pathomechanisms. J Cosmet Dermatol 2010;9(4):331-2
51. Duskova M, Hill M, Hanus M, et al. Finasteride treatment and neuroactive steroid formation. Prague Med Rep 2009;110(3):222-30
52. Aggarwal S, Thareja S, Verma A, et al. An overview on 5alpha-reductase inhibitors. Steroids 2010;75(2):109-53
53. O'Leary MP, Roehrborn C, Andriole G, et al. Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride, the novel dual 5alpha-reductase inhibitor. BJU Int 2003;92(3):262-6
54. Debruyne F, Barkin Jvan Erps P, et al. Efficacy and safety of long-term treatment with the dual 5 alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur Urol 2004;46(4):488-94; discussion 495
55. Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of a dual inhibitor of 5-Alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002;60(3):434-41
56. Marihart S, Harik M, Djavan B. Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase. Rev Urol 2005;7(4):203-10
57. Marberger M, Roehrborn CG, Marks LS, et al. Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia. J Clin Endocrinol Metab 2006;91(4):1323-8
58. Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010;362(13):1192-202
59. Whiting DA, Olsen EA, Savin R, et al. Efficacy and tolerability of finasteride 1 mg in men aged 41 to 60 years with male pattern hair loss. Eur J Dermatol 2003;13(2):150-60
60. Marberger MJ. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group. Urology 1998;51(5):677-86
61. McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349(25):2387-98
62. Lugg JA, Rajfer J, Gonzalez-Cadavid NF. Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology 1995;136(4):1495-501
63. Bradshaw WG, Baum MJ, Awh CC. Attenuation by a 5 alpha-reductase inhibitor of the activational effect of testosterone propionate on penile erections in castrated male rats. Endocrinology 1981;109(4):1047-51
64. Pinsky MR, Gur S, Tracey AJ, et al. The effects of chronic 5-Alpha-reductase inhibitor (dutasteride) treatment on rat erectile function. J Sex Med 2011;8(11):3066-74
65. Goldstein I. An old problem with a new cause-5 alpha reductase inhibitors and persistent sexual dysfunction. J Sex Med 2011;8(7):1829-31 . This short article represents future perspectives of persistent sexual dysfunction induced by 5ARIs.
66. Seftel A, Rosen R, Kuritzky L. Physician perceptions of sexual dysfunction related to benign prostatic hyperplasia (BPH) symptoms and sexual side effects related to BPH medications. Int J Impot Res 2007;19(4):386-92
67. Naslund MJ, Miner M. A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clin Ther 2007;29(1):17-25
68. Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996;335(8):533-9
69. Kirby RS, Roehrborn C, Boyle P, et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003;61(1):119-26
70. Hudson PB, Boake R, Trachtenberg J, et al. Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group. Urology 1999;53(4):690-5
71. Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. 1992. J Urol 2002; 167(2 Pt 2):1102-7; discussio