5α-Reductase inhibitors (5α-RIs) such as finasteride and dutasteride have proven useful in clinical management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and also in treatment of androgenetic alopecia (AGA). However, these drugs have serious and, in some patients, persistent or irreversible sexual side effects. These agents interfere with the biosynthesis and metabolism of neurosteroids and may adversely affect mood, stress, and anxiety and potentiate the onset of depression. Data from preclinical and clinical studies have provided substantial evidence that these agents cause loss or reduction of libido, increase the risk of erectile dysfunction and ejaculatory dysfunction, and may contribute to the onset of depression. It is imperative that clinicians give serious considerations to these adverse effects and their impact on patients’ health and engage their patients in an open and honest discussion regarding the potential harm of these agents prior to prescribing them.
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Traish AM. 5α-reductases in human physiology: an unfolding story. Endocr Pract. 2012;18(6):965–75.
Imperato-McGinley J, Zhu YS. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol. 2002;198:51–9.
Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, et al. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010;142:203–17.
Stiles AR, Russell DW. SRD5A3: a surprising role in glycosylation. Cell. 2010;142:196–8.
Morava E, Wevers RA, Cantagrel V, Hoefsloot LH, Al-Gazali L, Schoots J, et al. A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain. 2010;133:3210–20.
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(3):872–84.
Russell DW, Wilson JD. Steroid 5α-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25–61.
Poletti A, Coscarella A, Negri-Cesi P, Colciago A, Celotti F, Martini L. 5α-reductase isozymes in the central nervous system. Steroids. 1998;63:246–51.
Thigpen AE, Silver RI, Guileyardo JM, Casey ML, McConnel JD, Russel DW. Tissue distribution and ontogeny of steroid 5a-reductase isozyme expression. J Clin Invest. 1993;92:903–10.
Patte-Mensah C, Penning TM, Mensah-Nyagan AG. Anatomical and cellular localization of neuroactive 5α/3α-reduced steroid synthesizing enzymes in the spinal cord. J Comp Neurol. 2004;477:286–99.
Pozzi P, Bendotti C, Simeoni S, Piccioni F, Guerini V, Marron TU, et al. Androgen 5-alpha-reductase type 2 is highly expressed and active in rat spinal cord motor neurones. J Neuroendocrinol. 2003;15:882–7.
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;267:19548–54.
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(6):367–79. This study provides highlights of the adverse effects resulting from 5 α-RIs therapy.
Melcangi RC, Poletti A, Cavarretta I, Celotti F, Colciago A, Motta V, et al. The 5a-reductase in the central nervous system: expression and modes of control. J Steroid Biochem Mol Biol. 1998;65:295–9.
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. This study points to the importance of 5α-R in central nervous system physiology.
Melcangi RC, Panzica GC. Allopregnanolone: state of the art. Prog Neurobiol. 2014;113:1–5. This study demonstrates the criticlal role of 5 α-R in progesterone metabolism in the CNS.
Borowicz KK, Piskorska B, Banach M, Czuczwar SJ. Neuroprotective actions of neurosteroids. Front Endocrinol (Lausanne). 2011;2:50.
Cooke PS, Nanjappa MK, Yang Z, Wang KK. Therapeutic effects of progesterone and its metabolites in traumatic brain injury may involve non-classical signaling mechanisms. Front Neurosci. 2013;7:108.
Yawno T, Hirst JJ, Castillo-Melendez M, Walker DW. Role of neurosteroids in regulating cell death and proliferation in the late gestation fetal brain. Neuroscience. 2009;163(3):838–47.
Noorbakhsh F, Baker GB, Power C. Allopregnanolone and neuroinflammation: a focus on multiple sclerosis. Front Cell Neurosci. 2014;8:134.
Noorbakhsh F, Ellestad KK, Maingat F, Warren KG, Han MH, Steinman L, et al. Impaired neurosteroid synthesis in multiple sclerosis. Brain. 2011;134(Pt 9):2703–21.
Wirth MM. Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion. Front Endocrinol (Lausanne). 2011;2:19.
Mellon S, Gong W, Griffin LD. Niemann pick type C disease as a model for defects in neurosteroidogenesis. Endocr Res. 2004;30(4):727–35.
Griffin LD, Gong W, Verot L, Mellon SH. Niemann-pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med. 2004;10(7):704–11.
Schumacher M, Mattern C, Ghoumari A, Oudinet JP, Liere P, Labombarda F, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors. Prog Neurobiol. 2014;113:6–39.
Agis-Balboa RC, Guidotti A, Pinna G. 5α-reductase type I expression is downregulated in the prefrontal cortex/Brodmann’s area 9 (BA9) of depressed patients. Psychopharmacology (Berlin). 2014;231(17):3569–80. This study points to the critical role of 5α-R in depression.
Agís-Balboa RC, Pinna G, Pibiri F, Kadriu B, Costa E, Guidotti A. Down-regulation of neurosteroid biosynthesis in corticolimbic circuits mediates social isolation-induced behavior in mice. Proc Natl Acad Sci U S A. 2007;104(47):18736–41. This study highlights the role of 5 α-R in social behavior and isolation.
Schüle C, Eser D, Baghai TC, Nothdurfter C, Kessler JS, Rupprecht R. Neuroactive steroids in affective disorders: target for novel antidepressant or anxiolytic drugs? Neuroscience. 2011;191:55–77.
Eser D, Baghai TC, Schüle C, Nothdurfter C, Rupprecht R. Neuroactive steroids as endogenous modulators of anxiety. Curr Pharm Des. 2008;14(33):3525–33.
Eser D, Schüle C, Baghai TC, Romeo E, Rupprecht R. Neuroactive steroids in depression and anxiety disorders: clinical studies. Neuroendocrinology. 2006;84(4):244–54.
Eser D, Schüle C, Baghai TC, Romeo E, Uzunov DP, Rupprecht R. Neuroactive steroids and affective disorders. Pharmacol Biochem Behav. 2006;84(4):656–66.
Eser D, Romeo E, Baghai TC, di Michele F, Schüle C, Pasini A, et al. Neuroactive steroids as modulators of depression and anxiety. Neuroscience. 2006;138(3):1041–8.
Eser D, Schüle C, Romeo E, Baghai TC, di Michele F, Pasini A, et al. Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders. Psychopharmacology (Berlin). 2006;186(3):373–87.
Padberg F, di Michele F, Zwanzger P, Romeo E, Bernardi G, Schüle C, et al. Plasma concentrations of neuroactive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Neuropsychopharmacology. 2002;27(5):874–8.
Rupprecht R, di Michele F, Hermann B, Ströhle A, Lancel M, Romeo E, et al. Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology. Brain Res Brain Res Rev. 2001;37(1–3):59–67.
Rupprecht R, Holsboer F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 1999;22(9):410–6.
Dubrovsky B. Neurosteroids, neuroactive steroids, and symptoms of affective disorders. Pharmacol Biochem Behav. 2006;84:644–55.
Windahl SH, Andersson N, Börjesson AE, Swanson C, Svensson J, Movérare-Skrtic S, et al. Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice. PLoS One. 2011;6:e21402.
Frye CA, Walf AA, Rhodes ME, Harney JP. Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase. Brain Res. 2004;1004:116–24.
Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, et al. Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients. J Clin Endocrinol Metab. 2011;96:296–307.
Melcangi RC, Poletti A, Cavarretta I, Celotti F, Colciago A, Magnaghi V, et al. The 5α-reductase in the central nervous system: expression and modes of control. J Steroid Biochem Mol Biol. 1998;65:295–9.
Baulieu EE. Neurosteroids: a novel function of the brain. Psychoneuroendocrinology. 1998;23:963–87.
Barbaccia ML, Roscetti G, Trabucchi M, Purdy RH, Mostallino MC, Concas A, et al. The effects of inhibitors of GABAergic transmission and stress on brain and plasma allopregnanolone concentrations. Br J Pharmacol. 1997;120:1582–8.
Reddy DS, Rogawski MA. Stress-induced deoxycorticosterone-derived neurosteroids modulate GABAA receptor function and seizure susceptibility. J Neurosci. 2002;22:3795–805.
Morrow AL, Suzdak PD, Paul SM. Steroid hormone metabolites potentiate GABA receptor-mediated chloride ion flux with nanomolar potency. Eur J Pharmacol. 1987;142:483–5.
Morrow AL. Recent developments in the significance and therapeutic relevance of neuroactive steroids—introduction to the special issue. Pharmacol Ther. 2007;116:1–6.
Reddy DS. Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog Brain Res. 2010;186:113–37.
Rupprecht R, Holsboer F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 1999;22:410–6.
Stoffel-Wagner B. Neurosteroid biosynthesis in the human brain and its clinical implications. Ann N Y Acad Sci. 2003;1007:64–78.
Stoffel-Wagner B. Neurosteroid metabolism in the human brain. Eur J Endocrinol. 2001;145:669–79.
Römer B, Pfeiffer N, Lewicka S, Ben-Abdallah N, Vogt MA, Deuschle M, et al. Finasteride treatment inhibits adult hippocampal neurogenesis in male mice. Pharmacopsychiatry. 2010;43:174–8.
Saalmann YB, Morgan IG, Calford MB. Neurosteriods involved in regulating inhibition in the inferior colliculus. J Neurophysiol. 2006;96:3064–73.
Upreti R, Hughes KA, Livingstone DE, Gray CD, Minns FC, Macfarlane DP, et al. Andrew R.5α-reductase type 1 modulates insulin sensitivity in men. J Clin Endocrinol Metab. 2014;99(8):E1397–406. This study provides new insights to the role of 5 α-RI in onset of Diabetes.
Traish AM, Guay AT, Zitzmann M. 5α-reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis. Horm Mol Biol Clin Investig. 2014;20(3):73–80. This study emphasizes the role of 5 α-R in metabolism of glucocorticoids.
Livingstone DE, Barat P, Di Rollo EM, Rees GA, Weldin BA, Rog-Zielinska EA, et al. 5α-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents. Diabetes. 2015;64(2):447–58. This study demonstrates a role for 5 α-R activity in gllucocorticoid metablism and prevention of insulin resistance.
Marver D, Edelman IS. Dihydrocortisol: a potential mineralocorticoid. J Steroid Biochem. 1978;9:1.
Andersson S, Berman DM, Jenkins EP, Russell DW. Deletion of 5α-reductase 2 gene in male pseudohermaphroditism. Nature. 1991;354:159–61.
Steers WD. 5α-reductase activity in the prostate. Urology. 2001;58:17–24.
Bartsch G, Rittmaster RS, Klocker H. Dihydrotestosterone and the concept of 5α-reductase inhibition in human benign prostatic hyperplasia. World J Urol. 2002;19:413–25.
Gormley GJ, Stoner E, Brusketwitz RC, Imperato-McGinley J, Walsh P, McConnell JD, et al. The effect of finasteride in men with benign prostatic hyperplasia. J Urol. 1992;167:1102–7.
Lepart ED. Age-related changes in brain and pituitary 5alpha-reductase with finasteride (Proscar) treatment. Neurobiol Aging. 1995;16:647–50.
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.
AUA Practice Guidelines Committee. AUA guidelines on management of benign prostatic hyperplasia. Chapter 1: diagnosis and treatment recommendations. J Urol. 2003;170:530–47.
Marberger MJ. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind placebo-controlled, multicenter study. Urology. 1998;51:677–86.
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.
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.
Debruyne F, Koch G, Boyle P, Da Silva FC, Gillenwater JG, Hamdy FC, et al. Comparison of a phytotherapeutic agent (Permixon) with an α-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1 year randomized international study. Eur Urol. 2002;41:497–507.
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.
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.
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.
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;109:1047–51.
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.
Hart BL. Activation of sexual reflexes of male rats by dihydrotestosterone but not estrogen. Physiol Behav. 1979;23:107–9.
Mantzoros CS, Georgiadis EI, Trichopoulos D. Contribution of dihydrotestosterone to male sexual behaviour. BMJ. 1995;310:1289–91.
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.
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.
Penson DF, Ng C, Rajfer J, Gonzalez-Cadavid NF. Adrenal control of erectile function and nitric oxide synthase in the rat penis. Endocrinology. 1997;138:3925–32.
Garban H, Marquez D, Cai L, Rajfer J, Gonzalez-Cadavid NF. Restoration of normal adult penile erectile response in aged rats by long-term treatment with androgens. Biol Reprod. 1995;53:1365–72.
Park KH, Kim SW, Kim KD, Paick JS. Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int. 1999;83:327–33.
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.
Sachs BD. Placing erection in context: the reflexogenic-psychogenic dichotomy reconsidered. Neurosci Biobehav Rev. 1995;19:211–24.
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.
Oztekin CV, Gur S, Abdulkadir NA, Lokman U, Akdemir AO, Cetinkaya M, 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.
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.
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.e9–743.e15.
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, 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. doi:10.1515/hmbci-2015-0015. This study demonstrates that the sexual adverse side effects of 5 α-RI therapy do not resolve by continued treatment and may cause hypogonadism.
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. doi:10.1001/jamadermatol.2015.36. This study highlights the bias and the inaccuracy of reporting of adverse effects of 5 a-RI in clincial trials and we have to be concerned with claims of safety.
Moore TJ. Finasteride and the uncertainties of establishing harms. JAMA Dermatol. 2015. doi:10.1001/jamadermatol.2015.37. This editorial highlights the harm that can be done when claims of safety are unsubstantiated.
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.
Uygur MC, Gür E, Arik AI, Altuğ U, Erol D. Erectile dysfunction following treatments of benign prostatic hyperplasia: a prospective study. Andrologia. 1998;30(1):5–10.
Edwards JE, Moore RA. Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised 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 years randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian 2 years 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.
Roehrborn CG, Siami P, Barkin J, Damiao 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 years 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. Contemp Clin Trials. 2007;28:770–9.
Kaplan SA, Chung DE, Lee RK, Scofield S, Te AE. A 5 years 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.
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(6):1828–34. This study provides critical information pertaining to continued adverse effects of Finasteride and such adverse events do not resolve with continued treatment, as claimed in other studies.
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.
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(6):843–7.
Romeo E, Ströhle A, Spalletta G, di Michele F, Hermann B, Holsboer F, et al. Effects of antidepressant treatment on neuroactive steroids in major depression. Am J Psychiatry. 1998;155(7):910–3.
Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, et al. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci U S A. 1998;95(6):3239–44.
Ströhle A, Romeo E, Hermann B, Pasini A, Spalletta G, di Michele F, et al. Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Biol Psychiatry. 1999;45(3):274–7.
Rupprecht R, Ströhle A, Hermann B, di Michele F, Spalletta G, Pasini A, et al. Neuroactive steroid concentrations following metyrapone administration in depressed patients and healthy volunteers. Biol Psychiatry. 1998;44(9):912–4.
Finn DA, Beadles-Bohling AS, Beckley EH, Ford MM, Gililland KR, Gorin-Meyer RE, et al. A new look at the 5alpha-reductase inhibitor finasteride. CNS Drug Rev. 2006;12(1):53–76.
Gasior M, Carter RB, Witkin JM. Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders. Trends Pharmacol Sci. 1999;20(3):107–12.
Khisti RT, Chopde CT, Jain SP. Antidepressant-like effect of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice forced swim test. Pharmacol Biochem Behav. 2000;67(1):137–43.
Frye CA, Walf AA. Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats. Pharmacol Biochem Behav. 2004;78(3):531–40.
Le Mellédo JM, Baker G. Role of progesterone and other neuroactive steroids in anxiety disorders. Expert Rev Neurother. 2004;4(5):851–60.
Altomare G, Capella GL. Depression circumstantially related to the administration of finasteride for androgenetic alopecia. J Dermatol. 2002;29(10):665–9.
Irwig MS. Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. 2015;22(3):248–53.
Irwig MS. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry. 2012;73(9):1220–3. doi:10.4088/JCP.12m07887. Epub 2012 Aug 7.
Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A. Finasteride induced depression: a prospective study. BMC Clin Pharmacol. 2006;6:7.
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(10):2598–603.
Caruso D, Abbiati F, Giatti S, Romano S, Fusco L, Cavaletti G, et al. 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;146:74–9.
Steen NE, Methlie P, Lorentzen S, Dieset I, Aas M, Nerhus M, et al. Altered systemic cortisol metabolism in bipolar disorder and schizophrenia spectrum disorders. J Psychiatr Res. 2014;52:57–62.
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(12):51–5.
Tosti A, Pazzaglia M, Soli M, Rossi A, Rebora A, Atzori L, et al. Evaluation of sexual function with an international index of erectile function in subjects taking finasteride for androgenetic alopecia. Arch Dermatol. 2004;140(7):857–8.
Rossi A, Carlesimo M, Pranteda G, Fortuna MC, Maxia C, Scali E, et al. Finasteride for androgenetic alopecia and side effects. Clin Dermatol. 2014;1(4):197–203. ISSN: 2282–4103.
Yim E, Nole KL, Tosti A. 5α-Reductase inhibitors in androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. 2014;21(6):493–8.
Koonce CJ, Frye CA. Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5α-reductase type 1 mutant, mice. Behav Brain Res. 2013;253:232–9.
Galea LA, Wainwright SR, Roes MM, Duarte-Guterman P, Chow C, Hamson DK. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications. J Neuroendocrinol. 2013;25(11):1039–61.
McHenry J, Carrier N, Hull E, Kabbaj M. Sex differences in anxiety and depression: role of testosterone. Front Neuroendocrinol. 2014;35(1):42–57.
Shores MM, Sloan KL, Matsumoto AM, Moceri VM, Felker B, Kivlahan DR. Increased incidence of diagnosed depressive illness in hypogonadal older men. Arch Gen Psychiatry. 2004;61(2):162–7.
Shores MM, Kivlahan DR, Sadak TI, Li EJ, Matsumoto AM. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). J Clin Psychiatry. 2009;70(7):1009–16.
Shores MM, Moceri VM, Sloan KL, Matsumoto AM, Kivlahan DR. Low testosterone levels predict incident depressive illness in older men: effects of age and medical morbidity. J Clin Psychiatry. 2005;66(1):7–14.
Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15(4):289–305. doi:10.1097/01.pra.0000358315.88931.fc.
McIntyre RS, Mancini D, Eisfeld BS, Soczynska JK, Grupp L, Konarski JZ, et al. Calculated bioavailable testosterone levels and depression in middle-aged men. Psychoneuroendocrinology. 2006;31(9):1029–35.
Römer B, Gass P. Finasteride-induced depression: new insights into possible pathomechanisms. J Cosmet Dermatol. 2010;9(4):331–2.
Römer B, Pfeiffer N, Lewicka S, Ben-Abdallah N, Vogt MA, Deuschle M, et al. Finasteride treatment inhibits adult hippocampal neurogenesis in male mice. Pharmacopsychiatry. 2010;43(5):174–8.
Roff CF, Strauss 3rd JF, Goldin E, Jaffe H, Patterson MC, Agritellis GC, et al. The murine Niemann-Pick type C lesion affects testosterone production. Endocrinology. 1993;133(6):2913–23.
Luchetti S, Bossers K, Frajese GV, Swaab DF. Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson’s disease. Brain Pathol. 2010;20(5):945–51.
Lin WL, Hsieh YW, Lin CL, Sung FC, Wu CH, Kao CH. A population-based nested case–control study: the use of 5-alpha-reductase inhibitors and the increased risk of osteoporosis diagnosis in patients with benign prostate hyperplasia. Clin Endocrinol (Oxf). 2015;82(4):503–8.
Chou CH, Lin CL, Lin MC, Sung FC, Kao CH. 5α-Reductase inhibitors increase acute coronary syndrome risk in patients with benign prostate hyperplasia. J Endocrinol Investig. 2015;38(7):799–805.
Naylor JC, Kilts JD, Hulette CM, Steffens DC, Blazer DG, Ervin JF, et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer’s disease compared to cognitively intact control subjects. Biochim Biophys Acta. 2010;1801(8):951–9.
Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A. 2010;107(14):6498–503.
Tsuji Y, Nakayama T, Bono K, Kitamura M, Imafuku I. [Two cases of stroke associated with the use of finasteride, an approved drug for male-pattern hair loss in Japan]. Rinsho Shinkeigaku. 2014;54(5):423–8.
Gillespie CF, Almli LM, Smith AK, Bradley B, Kerley K, Crain DF, et al. Sex dependent influence of a functional polymorphism in steroid 5-α-reductase type 2 (SRD5A2) on post-traumatic stress symptoms. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(3):283–92.
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. doi:10.1002/phar.1612.
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Abdulmaged M. Traish declares no conflict of interest.
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 Male Sexual Dysfunction and Disorders
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Traish, A.M. The Impact of the 5α-Reductase Inhibitors (5α-RIs) on Male Sexual Function and Psychological Well-Being. Curr Sex Health Rep 7, 210–219 (2015). https://doi.org/10.1007/s11930-015-0061-y
- Sexual dysfunction