Purpose of Review
Post-finasteride syndrome (PFS) is a disorder characterized by a set of clinical symptoms experienced during use or after drug discontinuation. This cluster of symptoms encompasses overall sexual dysfunction (SD), erectile dysfunction (ED), loss of libido, depression, suicidal ideation, anxiety, panic attacks, insomnia, and cognitive dysfunction. To date, there is lack of comprehensive understanding of the biochemical and pathophysiological mechanisms responsible for the adverse effects of finasteride. More importantly, there is lack of knowledge and effective clinical tools for treatments of this condition, resulting in outright dismissal of complaints by individuals afflicted with this syndrome. Psychological symptoms and cognitive dysfunction of PFS are far more serious and difficult to treat than sexual dysfunction symptoms and may lead young men to contemplate, attempt, or even commit suicide. Therefore, an urgent need exists to fill the knowledge gap in physiology, pathophysiology, and clinical management of patients with PFS.
Finasteride treatment impairs biosynthesis and function of neurosteroids, which are critical regulators of central (CNS) as well as peripheral nervous system functions and modulate a host of neurotransmitter receptors, such as gamma amino butyric acid receptors. Thus, finasteride-induced neuroendocrine disruption of biosynthesis of critical signaling molecules results in pathophysiological states, which contribute to inhibition of biochemical pathways responsible for a host of physiological functions, ranging from sexual activity, mood, and cognition. In addition, finasteride-induced epigenetic changes in gene expression, including upregulation of androgen receptors (AR), increased histone acetylation, and methylation results in undesirable biological outcomes such as impairment of dopaminergic signaling and modulation of other neurotransmitter receptors, may be the underlying mechanism causing persistent or permanent adverse effects, manifested in anxiety, depression, and suicidal ideation.
The medical community has an obligation not to turn a blind eye on this rare yet debilitating condition in young men. Patients with this condition should not be stereotyped or stigmatized by untrained and unprepared clinicians, due to lack of awareness and knowledge pertaining to this new and rare syndrome. Greater awareness and education is needed among the medical and scientific communities in order to develop better approaches for managing men with PFS. It is paramount that steps are taken to develop better understanding of the underlying mechanisms contributing to the onset and progression of PFS and to promote educational and training programs to increase awareness and improve management of this condition.
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Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25–61.
Baulieu EE. Neurosteroids: a novel function of the brain. Psychoneuroendocrinology. 1998;23:963–87.
Melcangi RC, Giatti S, Garcia-Segura LM. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: sex-specific features. Neurosci Biobehav Rev. 2016;67:25–40.
Melcangi RC, Garcia-Segura LM, Mensah-Nyagan AG. Neuroactive steroids: state of the art and new perspectives. Cell Mol Life Sci. 2008;65:777–97.
Melcangi RC, Garcia-Segura LM. Sex-specific therapeutic strategies based on neuroactive steroids: in search for innovative tools for neuroprotection. Horm Behav. 2010;57:2–11.
Melcangi RC, Panzica G, Garcia-Segura LM. Neuroactive steroids: focus on human brain. Neuroscience. 2011;191:1–5.
Melcangi RC, Giatti S, Pesaresi M, Calabrese D, Mitro N, Caruso D, et al. Role of neuroactive steroids in the peripheral nervous system. Front Endocrinol (Lausanne). 2011;2:104.
Melcangi RC, Caruso D, Levandis G, Abbiati F, Armentero MT, Blandini F. Modifications of neuroactive steroid levels in an experimental model of nigrostriatal degeneration: potential relevance to the pathophysiology of Parkinson’s disease. J Mol Neurosci. 2012;46:177–83.
Melcangi RC, Giatti S, Calabrese D, Pesaresi M, Cermenati G, Mitro N, et al. Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions. Prog Neurobiol. 2014;113:56–69.
Melcangi RC, Panzica GC. Allopregnanolone: state of the art. Prog Neurobiol. 2014;113:1–5.
Melcangi RC, Panzica GC. Neuroactive steroids and the nervous system: further observations on an incomplete tricky puzzle. J Neuroendocrinol. 2013;25:957–63.
Panzica GC, Balthazart J, Frye CA, Garcia-Segura LM, Herbison AE, Mensah-Nyagan AG, et al. Milestones on steroids and the nervous system: 10 years of basic and translational research. J Neuroendocrinol. 2012;24:1–15.
Faller B, Farley D, Nick H. Finasteride: a slow-binding 5 alpha-reductase inhibitor. Biochemistry. 1993;32:5705–10.
•• Bull HG, Garcia-Calvo M, Andersson S, Baginsky WF, Chan HK, Ellsworth DE, et al. Mechanism-based inhibition of human steroid 5α-reductase by finasteride: enzyme-catalyzed formation of NADP-dihydrofinasteride, a potent bi-substrate analog inhibitor. J Am Chem Soc. 1996;118:2359–65. This is a key study on the kinetics of drug-enzyme interactions that explained the near irreversible nature of the enzyme adduct complex formed by binding of finasteride to the enzyme
Morrison JF, Walsh CT. The behavior and significance of slow-binding enzyme inhibitors. Adv Enzymol. 1988;61:201–301.
•• Frankel S. Study of the Food and Drug Administration files on Propecia: dosages, side effects, and recommendations. Arch Dermatol. 1999;135:257–8. This study demonstrated that the enzyme is inhibited at a dose of approximately 0.2 mg of finasteride; therefore, a 1- or 5-mg dose is expected to provide similar effects.
Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y. Saturable binding of finasteride to steroid 5 alpha-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet. 2010;25:208–13.
Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M. Adverse effects of 5α-reductase inhibitors: what do we know, don’t know, and need to know? Rev Endocr Metab Disord. 2015;16:177–98.
Negri-Cesi P, Colciago A, Celotti F, Motta M. Sexual differentiation of the brain: role of testosterone and its active metabolites. J Endocrinol Investig. 2004;27:120–7.
Frye CA. Some rewarding effects of androgens may be mediated by actions of its 5alpha-reduced metabolite 3alpha-androstanediol. Pharmacol Biochem Behav. 2007;86:354–67.
Handa RJ, Kudwa AE, Donner NC, McGivern RF, Brown R. Central 5-alpha reduction of testosterone is required for testosterone’s inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress in adult male rats. Brain Res. 2013;1529:74–82.
Morrow AL. Recent developments in the significance and therapeutic relevance of neuroactive steroids—introduction to the special issue. Pharmacol Ther. 2007;116:1–6.
•• Giatti S, Diviccaro S, Panzica G, Melcangi RC. Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin? Endocrine. 2018; https://doi.org/10.1007/s12020-018-1593-5. This review provides strong evidence to the potential underlying finasteride-induced neuropathological mechanisms contributing to sexual dysfunction
•• Melcangi RC, Santi D, Spezzano R, Grimoldi M, Tabacchi T, Fusco ML, Diviccaro S, Giatti S, Carrà G, Caruso D, Simoni M, Cavaletti G. Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. J Steroid Biochem Mol Biol. 2017 ;171:229–235. This study provides evidence to the potential underlying finasteride-induced reduction in neuroactive steroids and how this may impact psychological and sexual function.
• Caruso D, Abbiati F, Giatti S, Romano S, Fusco L, Cavaletti G, Melcangi RC. Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma. J Steroid Biochem Mol Biol. 2015; 146:74–79. This study provides evidence to the potential underlying finasteride-induced reduction in neuroactive steroids and how this may impact psychological and sexual function.
Melcangi RC, Caruso D, Abbiati F, Giatti S, Calabrese D, Piazza F, et al. Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J Sex Med. 2013;10:2598–603.
• Bechis SK, Otsetov AG, Ge R, Olumi AF. Personalized medicine for management of benign prostatic hyperplasia. J Urol. 2014;192:16–23. This study highlights that approximately 30% of patients with BPH do not express 5alpha reductase type 2 in the prostate.
Niu Y, Ge R, Hu L, Diaz C, Wang Z, Wu CL, et al. Reduced levels of 5α-reductase 2 in adult prostate tissue and implications for BPH therapy. Prostate. 2011;71:1317–24.
Whitelaw NC, Whitelaw E. How lifetimes shape epigenotype within and across generations. Hum Mol Genet. 2006;15:R131–7.
Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007;447:433–40.
Palotas M, Palotas A, Puskas LG, Kitajka K, Pakaski M, Janka Z, et al. Gene expression profile analysis of the rat cortex following treatment with imipramine and citalopram. Int J Neuropsychopharmacol. 2004;7:401–13.
Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9:519–25.
Panzer C, Wise S, Fantini G, Kang D, Munarriz R, Guay A, et al. Impact of oral contraceptives on sex hormone-binding globulin and androgen levels: a retrospective study in women with sexual dysfunction. J Sex Med. 2006;3:104–13.
Maciag D, Simpson KL, Coppinger D, Lu Y, Wang Y, Lin RC, et al. Antidepressant exposure has lasting effects on behavior and serotonin circuitry. Neuropsychopharmacology. 2006;31:47–57.
de Jong TR, Snaphaan LJ, Pattij T, Veening JG, Waldinger MD, Cools AR, et al. Effects of chronic treatment with fluvoxamine and paroxetine during adolescence on serotonin-related behavior in adult male rats. Eur Neuropsychopharmacol. 2006;16:39–48.
Csoka AB, Bahrick A, Mehtonen OP. Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. J Sex Med. 2008;5:227–33.
Pradhan S, Bacolla A, Wells RD, Roberts RJ. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem. 1999;274:33002–10.
• Vottero A, Minari R, Viani I, Tassi F, Bonatti F, Neri TM, et al. Evidence for epigenetic abnormalities of the androgen receptor gene in foreskin from children with hypospadias. J Clin Endocrinol Metab. 2011;96:E1953–62. This study provided evidence that epigenetic changes in the androgen receptor are real in children with hypospadias and suggests that epigenetic changes can play a role as a result of inhibition of DHT formation
Cecchin E, De Mattia E, Mazzon G, Cauci S, Trombetta C, Toffoli G. A pharmacogenetic survey of androgen receptor (CAG)n and (GGN)n polymorphisms in patients experiencing long term side effects after finasteride discontinuation. Int J Biol Markers. 2014;29:e310–6.
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.
Bauman TM, Sehgal PD, Johnson KA, Pier T, Bruskewitz RC, Ricke WA, et al. Finasteride treatment alters tissue specific androgen receptor expression in prostate tissues. Prostate. 2014;74:923–32.
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.
Schug TT, Janesick A, Blumberg B, Heindel JJ. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol. 2011;127:204–15.
Traish A. Effects of endocrine-disrupting chemicals on penile tissue development, histoarchitecture and erectile physiology. In: Bioenvironmental issues affecting men’s reproductive and sexual health. Eds Sikka SC and Hellstrom WJG. Academic Press. 2018 pp 401–416.
Kavlock RJ, Daston GP, Derosa C, Fenner-Crisp P, Gray LE, Kaattari S, et al. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ Health Perspect. 1996;104(Suppl 4):715–40.
MRC institute for Environment and Health. European workshop on the impact of endocrine disrupters on human health and wildlife. Brussels: European Commission; 1997.
Duarte-Guterman P, Langlois VS, Hodgkinson K, Pauli BD, Cooke GM, Wade MG, et al. The aromatase inhibitor fadrozole and the 5α-reductase inhibitor finasteride affect gonadal differentiation and gene expression in the frog Silurana tropicalis. Sex Dev. 2010;3:333–41.
Urbatzka R, Watermann B, Lutz I, Kloas W. Exposure of Xenopus laevis tadpoles to finasteride, an inhibitor of 5-alpha reductase activity, impairs spermatogenesis and alters hypophyseal feedback mechanisms. J Mol Endocrinol. 2009;43:209–19.
Christiansen S, Scholze M, Axelstad M, Boberg J, Kortenkamp A, Hass U. Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat. Int J Androl. 2008;31:241–8.
Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A, et al. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ Health Perspect. 2009;117:1839–46.
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.
Giatti S, Foglio B, Romano S, Pesaresi M, Panzica G, Garcia-Segura LM, et al. Effects of subchronic finasteride treatment and withdrawal on neuroactive steroid levels and their receptors in the male rat brain. Neuroendocrinology. 2016;103:746–57.
Bradshaw WG, Baum MJ, Awh CC. Attenuation by a 5α-reductase inhibitor of the activational effect of testosterone propionate on penile erections in castrated male rats. Endocrinology. 1981;109:1047–51.
Gray GD, Smith ER, Davidson JM. Hormonal regulation of penile erection in castrated male rats. Physiol Behav. 1980;24:463–8.
Hart BL. Effects of testosterone propionate and dihydrotestosterone on penile morphology and sexual reflexes of spinal male rats. Horm Behav. 1973;4:239–46.
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;136:1495–501.
Saksena SK, Lau IF, Chang MC. The inhibition of the conversion of testosterone into 5alpha-dihydrotestosterone in the reproductive organs of the male rat. Steroids. 1976;27:751–7.
Baum MJ. A comparison of the effects of methyltrienolone (R 1881) and 5 alpha-dihydrotestosterone on sexual behavior of castrated male rats. Horm Behav. 1979;13:165–74.
Mantzoros CS, Georgiadis EI, Trichopoulos D. Contribution of dihydrotestosterone to male sexual behaviour. Br Med J. 1995;310:1289–91.
Bialy M, Sachs BD. Androgen implants in medial amygdala briefly maintain noncontact erection in castrated male rats. Horm Behav. 2002;42:345–55.
Manzo J, Cruz MR, Hernandez ME, Pacheco P, Sachs BD. Regulation of noncontact erection in rats by gonadal steroids. Horm Behav. 1999;35:264–70.
Seo SI, Kim SW, Paick JS. The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat. Asian J Androl. 1999;1:169–74.
•• Pinsky MR, Gur S, Tracey AJ, Harbin A, Hellstrom WJ. The effects of chronic 5-alpha-reductase inhibitor (dutasteride) treatment on rat erectile function. J Sex Med. 2011;8:3066–74. This study illustrated that chronic inhibition of 5alpha reductase in the rat penis with dutasteride produced erectile dysfunction
•• Oztekin CV, Gur S, Abdulkadir NA, et al. Incomplete recovery of erectile function in rat after discontinuation of dual 5-alpha reductase inhibitor therapy. J Sex Med. 2012;9:1773–81. This study illustrated that chronic inhibition of 5alpha reductase in the rat penis with dutasteride produced persistent erectile dysfunction which is not reversible by a wash out period
•• Zhang MG, Wang XJ, Shen ZJ, Gao PJ. Long-term oral administration of 5alpha-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):e9–15. This study illustrated that chronic inhibition of 5alpha reductase in the rat penis with finasteride produced erectile dysfunction and loss of smooth muscle and reduction in endothelial nitric oxide synthase expression
Lu YL, Kuang L, Zhu H, Wu H, Wang XF, Pang YP, et al. Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5alpha-reductase inhibitor. Asian J Androl. 2007;9:843–7.
Rogers RS, Graziottin TM, Lin CS, Kan YW, Lue TF. Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res. 2003;15:26–37.
Traish AM, Munarriz R, O’Connell L, Choi S, Kim SW, Kim NN, et al. Effects of medical or surgical castration on erectile function in an animal model. J Androl. 2003;24:381–7.
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;26:242–8.
Kacker R, Morgentaler A, Traish A. Medical hypothesis: loss of the endocrine function of the prostate is important to the pathophysiology of postprostatectomy erectile dysfunction. J Sex Med. 2014;11:1898–902.
Liao S, Liang T, Fang S, Castañeda E, Shao TC. Steroid structure and androgenic activity. Specificities involved in the receptor binding and nuclear retention of various androgens. J Biol Chem. 1973;248:6154–62.
Edwards JE, Moore RA. Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomized trials. BMC Urol. 2002;2:14.
Nickel JC, Fradet Y, Boake RC, Pommerville PJ, Perreault JP, Afridi SK, et al. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECTstudy). PROscar Safety Plus Efficacy Canadian Two-year Study. CMAJ. 1996;155:1251–9.
Tenover JL, Pagano GA, Morton AS, Liss CL, Byrnes CA. Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group. Clin Ther. 1997;19:243–58.
Hudson PB, Boake R, Trachtenberg J, Romas NA, Rosenblatt S, Narayan P, 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;53:690–5.
Bruskewitz R, Girman CJ, Fowler J, Rigby OF, Sullivan M, Bracken RB, et al. Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. PLESS Study Group. Proscar Long-term Efficacy and Safety Study. Urology. 1999;54:670–8.
Wilton L, Pearce G, Edet E, Freemantle S, Stephens MD, Mann RD. The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients. Br J Urol. 1996;78:379–84.
Kaufman KD, Olsen EA, Whiting D. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39:578–89.
Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol. 1998;39:578–89.
Lowe FC, McConnell JD, Hudson PB, Romas NA, Boake R, Lieber M, et al. Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia. Urology. 2003;61:791–6.
Marberger MJ, PROWESS Study Group. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind placebo-controlled, multicenter study. Urology. 1998;51:677–86.
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;89:2179–84.
Belknap SM, Aslam I, Kiguradze T, Temps WH, Yarnold PR, Cashy J, et al. Adverse event reporting in clinical trials of finasteride for androgenic alopecia: a meta-analysis. JAMA Dermatol. 2015;151:600–6.
Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;60:434–41.
Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Morrill B, et al. The effects of Dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol. 2008;179:616–21.
Siami P, Roehrborn CG, Barkin J, Damiao R, Wyczolkowski M, Duggan A, et al. Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart and Tamsulosin) trial rationale and study design. Control Clin Trials. 2007;28:770–9.
Desgrandchamps F, Droupy S, Irani J, Saussine C, Comenducci A. Effect of dutasteride on the symptoms of benign prostatic hyperplasia, and patient quality of life and discomfort, in clinical practice. BJU Int. 2006;98:83–8.
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;66:1052–5.
Uygur MC, Arik AI, Altuğ U, Erol D. Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of gonadal, adrenal, and hypophyseal hormones and its clinical significance: a prospective clinical study. Steroids. 1998;63:208–13.
AUA guidelines on management of benign prostatic hyperplasia. Chapter 1: diagnosis and treatment recommendations. J Urol. 2003;170:530–47.
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;349:215–24.
• 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. This study showed that the sexual adverse effects were not resolved in more than 50% of all patients
McConnell JD, Brusketwitz R, Walsh P, Andriole G, Lieber M, Holtgrewe L, 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. N Engl J Med. 1998;338:557–63.
McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Dixon CM, Kusek JW, 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;349:2387–98.
Kaplan SA, Holtgrewe HL, Bruskewitz R, Saltzman B, Mobley D, Narayan P, et al. Comparison of the efficacy and safety of finasteride in older versus younger men with benign prostatic hyperplasia. Urology. 2001;57(6):1073–7.
• Fwu CW, Eggers PW, Kirkali Z, McVary KT, Burrows PK, Kusek JW. Change in sexual function in men with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) associated with long-term treatment with doxazosin, finasteride, and combined therapy. J Urol. 2014;191:1828–34. This study showed that the sexual adverse effects persist with continued treatment
Fwu C-W, Eggers PW, Kaplan SA, Kirkali Z, Lee JY, Kusek JW. Long-term effects of doxazosin, finasteride and combination therapy on quality of life in men with benign prostatic hyperplasia. J Urol. 2013;190:187–93.
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.
•• 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. HormMol Biol Clin Investig. 2015;23:85–96. This study demonstrated that finasteride-induced sexual adverse effects did not diminish with continued treatment, contrary to previous claims
Amory JK, Anawalt BD, Matsumoto AM, Page ST. The effect of 5α-reductase inhibition with dutasteride and finasteride on bone mineral density, serum lipoproteins, hemoglobin, prostate specific antigen, and sexual functions in healthy young men J Urol 2008;179: 2333–2338.
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;92:1659–65.
Debruyne F, Barkin J, van Erps P, Reis M, Tammela TL, Roehrborn C, 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;46:488–94.
Na Y, Ye Z, Zhang S, Chinese Dutasteride Phase III Trial (ARIA108898) Study Group. Efficacy and safety of dutasteride in Chinese adults with symptomatic benign prostatic hyperplasia: a randomized, double-blind, parallel-group, placebo-controlled study with an open-label extension. Clin Drug Investig. 2012;32:29–39.
Glina S, Roehrborn CG, Esen A, Plekhanov A, Sorsaburu S, Henneges C, et al. Sexual function in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: results of a 6-month, randomized, double-blind, placebo-controlled study of tadalafil co-administered with finasteride. J Sex Med. 2015;12:129–38.
Choi GS, Kim JH, Oh SY, Park JM, Hong JS, Lee YS, et al. Safety and tolerability of the dual 5-alpha reductase inhibitor dutasteride in the treatment of androgenetic alopecia. Ann Dermatol. 2016;28:444–50.
Tsunemi Y, Irisawa R, Yoshiie H, Brotherton B, Ito H, Tsuboi R, et al. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. J Dermatol. 2016;43:1051–8.
Guo M, Heran B, Flannigan R, Kezouh A, Etminan M. Persistent sexual dysfunction with finasteride 1 mg taken for hair loss. Pharmacotherapy. 2016;36:1180–4.
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;362:1192–202.
Gupta AK, Charrette A. The efficacy and safety of 5alpha-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride. J Dermatol Treat. 2014;25:156–61.
Mella JM, Perret MC, Manzotti M, Catalano HN, Guyatt G. Efficacy and safety of finasteride therapy for androgenetic alopecia: a systematic review. Arch Dermatol. 2010;146:1141–50.
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(9):1297–310.
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.
Ganzer CA, Jacobs AR. Emotional consequences of finasteride: fool’s gold. Am J Mens Health 2016.
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; 8:872–884. 9.
Irwig MS. Persistent sexual side effects of finasteride: could they be permanent? J Sex Med. 2012;9:2927–32.
Irwig MS. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry. 2012;73:1220–3.
Irwig MS. Decreased alcohol consumption among former male users of finasteride with persistent sexual side effects: a preliminary report. Alcohol Clin Exp Res. 2013;37:1823–6.
Irwig MS. Androgen levels and semen parameters among former users of finasteride with persistent sexual adverse effects. J Am Med Assoc Dermatol. 2014;150:1361–3.
Irwig MS. Persistent sexual and non-sexual adverse effects of finasteride in younger men. Sex Med Rev. 2014;2:24–35.
Irwig MS. Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. 2015;22:248–53.
•• 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;101:4669–80. This study showed that men with post-finasteride syndrome exhibited abnormal functional MRI
Ali AK, Heran BS, Etminan M. Persistent sexual dysfunction and suicidal ideation in young men treated with low-dose finasteride: a pharmacovigilance study. Pharmacotherapy. 2015;35:687–95.
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;4:245–50.
Butcher M, Baas W, Lwin A, Holland B, Herberts M, Clemons J, et al. Post-finasteride syndrome: real or imagined. J Urol. 2016;195(4S, Supplement):e1139.
Fertig R, Shapiro J, Bergfeld W, Tosti A. Investigation of the plausibility of 5-alpha-reductase inhibitor syndrome. Skin Appendage Disord. 2017;2:3–4.
•• 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;5:671–8. This meta-analysis showed that finasteride contributes to sexual dysfunction
Favilla V, Russo GI, Privitera S, Castelli T, Giardina R, Calogero AE, et al. Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis. Aging Male. 2016 Sep;19(3):175–81.
Golder S, Loke YK, Wright K, Norman G. Reporting of adverse events in published and unpublished studies of health care interventions: a systematic review. PLoS Med. 2016;13:e1002127.
Altomare G, Capella GL. Depression circumstantially related to the administration of finasteride for androgenetic alopecia. J Dermatol. 2002;29:665–9.
Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A. Finasteride induced depression: a prospective study. BMC Clin Pharmacol. 2006;6:7.
Römer B, Gass P. Finasteride-induced depression: new insights into possible pathomechanisms. J Cosmet Dermatol. 2010;9:331–2.
Welk B, McArthur E, Ordon M, Anderson KK, Hayward J, Dixon S. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med. 2017;177:683–91.
Welk B, McArthur E, Ordon M, Dirk J, Dixon S, Garg AX. Risk of rhabdomyolysis from 5-α reductase inhibitors. Pharmacoepidemiol Drug Saf. 2018;27:351–5.
Welk B, McArthur E, Ordon M, Morrow SA, Hayward J, Dixon S. The risk of dementia with the use of 5 alpha reductase inhibitors. J Neurol Sci. 2017;379:109–11.
Propecia Adverse Drug Reactions. VigiAccess Uppsala Monitoring Centre. WHO Collaborating Centre for International Drug Monitoring, accessed August 16, 2017. Available from: http://www.vigiaccess.org/
Gupta NK, McVary KT. Re: Risk of erectile dysfunction associated with use of 5α-reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the clinical practice research datalink. Eur Urol. 2017;72:317–8.
Walf AA, Sumida K, Frye CA. Inhibiting 5alpha-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats. Psychopharmacology. 2006;186:302–11.
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;140:1861–8.
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;52:54–70.
Traish AM, Guay AT. Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med. 2006;3:382–404.
Zhang XH, Filippi S, Morelli A, Vignozzi L, Luconi M, Donati S, et al. Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J Sex Med. 2006;3:253–64.
Peters CA, Walsh PC. The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia. N Engl J Med 1987; 317:599–604.
Zorumski CF, Paul SM, Izumi Y, Covey DF, Mennerick S. Neurosteroids, stress and depression: potential therapeutic opportunities. Neurosci Biobehav Rev. 2013;37:109–22.
Hsieh JT, Chen SC, Yu HJ, Chang HC. Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: implications for chemoprevention of prostate cancer. Prostate. 2011;71:1115–21.
Soggiu A, Piras C, Greco V, Devoto P, Urbani A, Calzetta L, et al. Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens. Psychoneuroendocrinology. 2016;74:387–96.
Frau R, Mosher LJ, Bini V, Pillolla G, Pes R, Saba P, et al. The neurosteroidogenic enzyme 5alpha-reductase modulates the role of D1 dopamine receptors in rat sensorimotor gating. Psychoneuroendocrinology. 2016;63:59–67.
Devoto P, Frau R, Bini V, Pillolla G, Saba P, Flore G, et al. Inhibition of 5α-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation. Psychoneuroendocrinology. 2012;37:1630–45.
Hart BL. Activation of sexual reflexes of male rats by dihydrotestosterone but not estrogen. Physiol Behav. 1979;23:107–9.
Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci. 2005;6:565–75.
Irwig MS, Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med. 2011;8:1747–53.
Conflict of Interest
Abdulmaged M Traish reports personal fees from Johnson and Becker Law firm, 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.
This article is part of the Topical Collection on Medical Comorbidities
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Traish, A.M. The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption. Curr Sex Health Rep 10, 88–103 (2018). https://doi.org/10.1007/s11930-018-0161-6
- 5α-Reductases (5α-R)
- Post-finasteride syndrome (PFS)
- Erectile dysfunction (ED)