Clinical Drug Investigation

, Volume 37, Issue 6, pp 511–517

Safety Profile of Finasteride: Distribution of Adverse Effects According to Structural and Informational Dichotomies of the Mind/Brain

  • Ion G. Motofei
  • David L. Rowland
  • Mirela Manea
  • Simona R. Georgescu
  • Ioana Păunică
  • Ioanel Sinescu
Current Opinion


Finasteride is currently used extensively for male androgenic alopecia and benign prostatic hyperplasia; however, some adverse effects are severe and even persistent after treatment cessation, the so-called ‘post-finasteride syndrome’. The following most severe adverse effects—sexual dysfunction and depression—often occur together and may potentiate one other, a fact that could explain (at least in part) the magnitude and persistence of finasteride adverse effects. This paper presents the pharmacological action of finasteride and the corresponding adverse effects, the biological base explaining the occurrence, persistence and distribution of these adverse effects, and a possible therapeutic solution for post-finasteride syndrome. The distribution of finasteride adverse effects is presented within a comprehensive and modern neuro-endocrine perspective related to structural and informational dichotomies of the brain. Understanding the variation of finasteride side effects among different populations would be necessary not only to delineate the safety profile of finasteride for different subgroups of men (a subject may or may not be affected by a certain anti-hormonal compound dependent on the individual neuro-endocrine profile), but also as a possible premise for a therapeutic approach of finasteride adverse effects. Such therapeutic approach should include administration of exogenous hormones, which are deficient in men with post-finasteride syndrome, namely dihydrotestosterone (in right-handed men) or progesterone/dihydroprogesterone (in left-handed subjects).


  1. 1.
    Varothai S, Bergfeld WF. Androgenetic alopecia: an evidence-based treatment update. Am J Clin Dermatol. 2014;15:217–30.CrossRefPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Gupta AK, Sharma N, Shukla P. Atypical post-finasteride syndrome: a pharmacological riddle. Indian J Pharmacol. 2016;48:316–7.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. Adverse side effects of 5a-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med. 2011;8:872–84.CrossRefPubMedGoogle Scholar
  5. 5.
    Irwig MS. Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. 2015;22:248–53.CrossRefPubMedGoogle Scholar
  6. 6.
    Manea M, Paunica I, Puiu GM, Manea CM. Finasteride side effects and post-finasteride syndrome in male androgenic alopecia. J Mind Med Sci. 2015;2:142–9.Google Scholar
  7. 7.
    Motofei IG, Rowland DL, Georgescu SR, Tampa M, Baleanu BC, Paunica S. Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia? Exp Dermatol. 2016;25:557–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Motofei IG, Rowland DL, Georgescu SR, Tampa M, Baconi D, Stefanescu E, Baleanu BC, Balalau C, Constantin V, Paunica S. Finasteride adverse effects in subjects with androgenic alopecia: a possible therapeutic approach according to the lateralization process of the brain. J Dermatol Treat. 2016;4:1–3.Google Scholar
  9. 9.
    Yamana K, Labrie F, Luu-The V. Human type 3 5a-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 Invest. 2010;2:293–9.Google Scholar
  10. 10.
    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;146:74–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Dusková M, Hill M, Hanus M, Matousková M, Stárka L. Finasteride treatment and neuroactive steroid formation. Prague Med Rep. 2009;110:222–30.PubMedGoogle Scholar
  12. 12.
    Rowland DL, Motofei IG, Popa F, Constantin VD, Vasilache A, Păunică I, Bălălău C, Păunică PG, Banu P, Păunică S. The postfinasteride syndrome; an overview. J Mind Med Sci. 2016;3:99–107.Google Scholar
  13. 13.
    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(2):245–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Şalvarci A, Istanbulluoğlu O. Secondary infertility due to use of low-dose finasteride. Int Urol Nephrol. 2013;45:83–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Tu HY, Zini A. Finasteride-induced secondary infertility associated with sperm DNA damage. Fertil Steril. 2011;95(2125):e13–4.Google Scholar
  16. 16.
    Paunica S, Giurgiu M, Vasilache A, Paunica I, Motofei IG, Vasilache A, Dumitriu HT, Dumitriu AS. Finasteride adverse effects and post-finasteride syndrome; implications for dentists. J Mind Med Sci. 2016;3:71–9.Google Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    Markham JA. Sex steroids and schizophrenia. Rev Endocr Metab Disord. 2012;13(3):187–207.CrossRefPubMedGoogle Scholar
  19. 19.
    Bejerot S, Eriksson JM. Sexuality and gender role in autism spectrum disorder: a case control study. PLoS One. 2014;9:e87961.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Aiello TP, Whitaker-Azmitia PM. Sexual differentiation and the neuroendocrine hypothesis of autism. Anat Rec (Hoboken). 2011;294:1663–70.CrossRefGoogle Scholar
  21. 21.
    McMahon CG. The etiology and management of premature ejaculation. Nat Clin Pract Urol. 2005;2(9):426–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Soydan H, Ates F, Adayener C, Akyol I, Semiz UB, Malkoc E, Yilmaz O, Basoglu C, Baykal KV. Attention-deficit hyperactivity disorder in patients with premature ejaculation: a pilot study. Int Urol Nephrol. 2013;45:77–81.CrossRefPubMedGoogle Scholar
  23. 23.
    Brockington IF. Menstrual psychosis: a bipolar disorder with a link to the hypothalamus. Curr Psychiatry Rep. 2011;13:193–7.CrossRefPubMedGoogle Scholar
  24. 24.
    McHenry J, Carrier N, Hull E, Kabbaj M. Sex differences in anxiety and depression: role of testosterone. Front Neuroendocrinol. 2014;35(1):42–57.CrossRefPubMedGoogle Scholar
  25. 25.
    Monteagudo PT, Falcão AA, Verreschi IT. The imbalance of sex-hormones related to depressive symptoms in obese men. Aging Male. 2016;19:20–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Motofei IG. A dual physiological character for cerebral mechanisms of sexuality and cognition: common somatic peripheral afferents. BJU Int. 2011;108:1634–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Motofei IG, Rowland DL. The ventral-hypothalamic input route: a common neural network for abstract cognition and sexuality. BJU Int. 2014;113:296–303.CrossRefPubMedGoogle Scholar
  28. 28.
    Atlantis E, Sullivan T. Bidirectional association between depression and sexual dysfunction: a systematic review and meta-analysis. J Sex Med. 2012;9:1497–507.CrossRefPubMedGoogle Scholar
  29. 29.
    Rajkumar RP, Kumaran AK. Depression and anxiety in men with sexual dysfunction: a retrospective study. Compr Psychiatry. 2015;60:114–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Amiaz R, Pope HG Jr, Mahne T, Kelly JF, Brennan BP, Kanayama G, Weiser M, Hudson JI, Seidman SN. Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial. J Sex Marital Ther. 2011;37(4):243–54.CrossRefPubMedGoogle Scholar
  31. 31.
    Al-Harbi M. Prevalence of depression in vitiligo patients. Skinmed. 2013;11:327–30.PubMedGoogle Scholar
  32. 32.
    Smith LL, Hines M. Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES). Psychoneuroendocrinology. 2000;25:497–512.CrossRefPubMedGoogle Scholar
  33. 33.
    Motofei IG, Rowland DL, Popa F, et al. A pilot study on tamoxifen sexual side effects and hand preference in male breast cancer. Arch Sex Behav. 2015;44(6):1589–94.CrossRefPubMedGoogle Scholar
  34. 34.
    Hampson E, Sankar JS. Hand preference in humans is associated with testosterone levels and androgen receptor gene polymorphism. Neuropsychologia. 2012;50:2018–25.CrossRefPubMedGoogle Scholar
  35. 35.
    Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S. Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal. BJU Int. 2011;108:110–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Motofei IG, Rowland DL, Georgescu SR, et al. A pilot study on the sexual side effects of finasteride as related to hand preference for men undergoing treatment of male pattern baldness. BJU Int. 2013;111:E221–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Hu SH, Wei N, Wang QD, Yan LQ, Wei EQ, Zhang MM, Hu JB, Huang ML, Zhou WH, Xu Y. Patterns of brain activation during visually evoked sexual arousal differ between homosexual and heterosexual men. Am J Neuroradiol. 2008;29:1890–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Berglund H, Lindström P, Savic I. Brain response to putative pheromones in lesbian women. Proc Natl Acad Sci USA. 2006;103:8269–74.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Savic I, Berglund H, Lindström P. Brain response to putative pheromones in homosexual men. Proc Natl Acad Sci USA. 2005;102:7356–61.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Savic I, Lindström P. PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects. Proc Natl Acad Sci USA. 2008;105:9403–8.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    LeVay S. A difference in hypothalamic structure between heterosexual and homosexual men. Science. 1991;253:1034–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Fox MD, Zhang D, Snyder AZ, Raichle ME. The global signal and observed anticorrelated resting state brain networks. J Neurophysiol. 2009;101:3270–83.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Fox MD, Corbetta M, Snyder AZ, Vincent JL, Raichle ME. Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proc Natl Acad Sci USA. 2006;103:10046–51.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Huynh HK, Beers C, Willemsen A, Lont E, Laan E, Dierckx R, Jansen M, Sand M, Weijmar Schultz W, Holstege G. High-intensity erotic visual stimuli de-activate the primary visual cortex in women. J Sex Med. 2012;9:1579–87.CrossRefPubMedGoogle Scholar
  46. 46.
    Wehrum S, Klucken T, Kagerer S, Walter B, Hermann A, Vaitl D, Stark R. Gender commonalities and differences in the neural processing of visual sexual stimuli. J Sex Med. 2013;10:1328–42.CrossRefPubMedGoogle Scholar
  47. 47.
    Sedda A, Scarpina F. Dorsal and ventral streams across sensory modalities. Neurosci Bull. 2012;28:291–300.CrossRefPubMedGoogle Scholar
  48. 48.
    Pickles JO. Auditory pathways: anatomy and physiology. Handb Clin Neurol. 2015;129:3–25.CrossRefPubMedGoogle Scholar
  49. 49.
    Reed CL, Klatzky RL, Halgren E. What vs. where in touch: an fMRI study. Neuroimage. 2005;25:718–26.CrossRefPubMedGoogle Scholar
  50. 50.
    Valeriani M, Pazzaglia C, Ferraro D, Virdis D, Rotellini S, Le Pera D, Testani E, Minciotti I, Balestri M, Vigevano F, Vollono C. Evidence of different spinal pathways for the warmth evoked potentials. Clin Neurophysiol. 2011;122:2469–74.CrossRefPubMedGoogle Scholar
  51. 51.
    Saur D, Kreher BW, Schnell S, Kümmerer D, Kellmeyer P, Vry MS, Umarova R, Musso M, Glauche V, Abel S, Huber W, Rijntjes M, Hennig J, Weiller C. Ventral and dorsal pathways for language. Proc Natl Acad Sci USA. 2008;105:18035–40.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    van Polanen V, Davare M. Interactions between dorsal and ventral streams for controlling skilled grasp. Neuropsychologia. 2015;79:186–91.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Oliveira-Souza R, Tovar-Moll F. The unbearable lightness of the extrapyramidal system. J Hist Neurosci. 2012;21:280–92.CrossRefPubMedGoogle Scholar
  54. 54.
    Scorolli C, Jacquet PO, Binkofski F, Nicoletti R, Tessari A, Borghi AM. Abstract and concrete phrases processing differentially modulate cortico-spinal excitability. Brain Res. 2012;1488:60–71.CrossRefPubMedGoogle Scholar
  55. 55.
    Motofei IG, Rowland DL, Paunica S, Tampa M, Georgescu SR. Lateralized sexual side effects of Finasteride in subjects with androgenic alopecia. J Invest Dermatol. 2014;134:S69.Google Scholar
  56. 56.
    Georgescu SR, Tampa M, Paunica S, Balalau C, Constantin VD, Paunica PG, Motofei IG. Distribution of post-finasteride syndrome in men with androgenic alopecia. J Invest Dermatol. 2015;135:S40.Google Scholar
  57. 57.
    Motofei IG, Rowland DL. Structural dichotomy of the mind; the role of sexual neuromodulators. J Mind Med Sci. 2016;3:131–40.Google Scholar
  58. 58.
    Motofei IG, Rowland DL. The mind body problem, part three: ascension of sexual function to cerebral level. J Mind Med Sci. 2016;3:1–12.Google Scholar
  59. 59.
    Gannon JR, Walsh TJ. Testosterone and sexual function. Urol Clin North Am. 2016;43:217–22.CrossRefPubMedGoogle Scholar
  60. 60.
    Davis SR. Androgen therapy in women, beyond libido. Climacteric. 2013;16:18–24.CrossRefPubMedGoogle Scholar
  61. 61.
    Wilson JD, Leihy MW, Shaw G, Renfree MB. Androgen physiology: unsolved problems at the millennium. Mol Cell Endocrinol. 2002;198:1–5.CrossRefPubMedGoogle Scholar
  62. 62.
    Tsuruo Y. Topography and function of androgen-metabolizing enzymes in the central nervous system. Anat Sci Int. 2005;80:1–11.CrossRefPubMedGoogle Scholar
  63. 63.
    Tan RS, Cook KR, Reilly WG. High estrogen in men after injectable testosterone therapy: the low T experience. Am J Mens Health. 2015;9:229–34.CrossRefPubMedGoogle Scholar
  64. 64.
    Carani C, Rochira V, Faustini-Fustini M, Balestrieri A, Granata AR. Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency. Clin Endocrinol (Oxf). 1999;51:517–24.CrossRefPubMedGoogle Scholar
  65. 65.
    Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer. 1994;74:74–7.CrossRefPubMedGoogle Scholar
  66. 66.
    Davidson JM, Camargo C, Smith ER, Kwan M. Maintenance of sexual function in a castrated man treated with ovarian steroids. Arch Sex Behav. 1983;12:263–74.CrossRefPubMedGoogle Scholar
  67. 67.
    Shang CY, Yan CG, Lin HY, Tseng WY, Castellanos FX, Gau SS. Differential effects of methylphenidate and atomoxetine on intrinsic brain activity in children with attention deficit hyperactivity disorder. Psychol Med. 2016;46:3173–85.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of PsychiatryCarol Davila UniversityBucharestRomania
  2. 2.Department of PsychologyValparaiso UniversityValparaisoUSA
  3. 3.Department of DermatologyCarol Davila UniversityBucharestRomania
  4. 4.Department of UrologyCarol Davila UniversityBucharestRomania

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