Abstract
Background and Objective
Benign prostatic hyperplasia (BPH) is a common disease found in elderly men and 5α-reductase (5α-R) inhibitors are a commonly used treatment option. 5α-reduced steroids are compounds that play a role in several functions across different organs and systems. In the adult brain, 5α-R accounts for neuroactive steroid production. Whether neuropsychological impairment could be due to dutasteride treatment, a 5α-R inhibitor affecting the production of dihydrotestosterone (DHT), is still unknown. The aim of our study was to investigate neuropsychological features in men receiving dutasteride.
Methods
The Mini Mental State Examination (MMSE), the Clock Drawing Test (CDT), the Frontal Assessment Battery (FAB), the Hamilton Anxiety Rating Scale (HAM-A), the Beck Depression Inventory second edition (BDI-II) and the Short Form-12 (SF-12) questionnaire were administered in order to explore both cognitive impairment and psychological features.
Results
In a sample of BPH patients (n = 40; mean age 71.4 ± 7.4 years), men receiving dutasteride showed no significant differences during the neuropsychological assessment in comparison with an age-matched control group, consisting of BPH men not receiving dutasteride (p < 0.05). No significant associations were recorded between treatment duration and any of the administered tests.
Conclusions
This is the first study investigating the neuropsychological features in dutasteride users. Our preliminary data are consistent with the safety of dutasteride under a mental profile.
Similar content being viewed by others
Change history
26 November 2018
A Correction to this paper has been published: https://doi.org/10.1007/s40261-018-0733-2
References
Egan KB. The Epidemiology of benign prostatic hyperplasia associated with lower urinary tract symptoms: prevalence and incident rates. Urol Clin North Am. 2016;43(3):289–97. https://doi.org/10.1016/j.ucl.2016.04.001.
Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M. An overview on 5α-reductase inhibitors. Steroids. 2010;75(2):109–53.
Cilotti A, Danza G, Serio M. Clinical application of 5alpha-reductase inhibitors. J Endocrinol Invest. 2001;24(3):199–203.
Evans HC, Goa KL. Dutasteride. Drugs Aging. 2003;20(12):905–18.
Saartok T, Dahlberg E, Gustafsson JA. Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin. Endocrinology. 1984;114(6):2100–6.
Tacklind J, Fink HA, Macdonald R, Rutks I, Wilt TJ. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2010;10:CD006015. https://doi.org/10.1002/14651858.cd006015.pub3.
Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS, Dutasteride Alopecia Research Team. 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.
Weinstein BI, Kandalaft N, Ritch R, Camras CB, Morris DJ, Latif SA, Vecsei P, Vittek J, Gordon GG, Southren AL. 5 alpha-dihydrocortisol in human aqueous humor and metabolism of cortisol by human lenses in vitro. Invest Ophthalmol Vis Sci. 1991;32(7):2130–5.
Morris DJ, Souness GW, Saccoccio NA, Harnik M. The effects of infusions of ring-A-reduced derivatives of aldosterone on the antinatriuretic and kaliuretic actions of aldosterone. Steroids. 1989;53(1–2):21–36.
McInnes KJ, Kenyon CJ, Chapman KE, Livingstone DE, Macdonald LJ, Walker BR, Andrew R. 5alpha-reduced glucocorticoids, novel endogenous activators of the glucocorticoid receptor. J Biol Chem. 2004;279(22):22908–12.
Girdler SS, Klatzkin R. Neurosteroids in the context of stress: implications for depressive disorders. Pharmacol Ther. 2007;116(1):125–39.
Castelli MP, Casti A, Casu A, Frau R, Bortolato M, Spiga S, Ennas MG. Regional distribution of 5α-reductase type 2 in the adult rat brain: an immunohistochemical analysis. Psychoneuroendocrinology. 2013;38(2):281–93.
Finn DA, Beadles-Bohling AS, Beckley EH, Ford MM, Gililland KR, Gorin-Meyer RE, Wiren KM. A new look at the 5alpha-reductase inhibitor finasteride. CNS Drug Rev. 2006;12(1):53–76.
Paba S, Frau R, Godar SC, Devoto P, Marrosu F, Bortolato M. Steroid 5α-reductase as a novel therapeutic target for schizophrenia and other neuropsychiatric disorders. Curr Pharm Des. 2011;17(2):151–67.
Anderson SW, Aksan N, Dawson JD, Uc EY, Johnson AM, Rizzo M. Neuropsychological assessment of driving safety risk in older adults with and without neurologic disease. J Clin Exp Neuropsychol. 2012;34(9):895–905.
McGinty HL, Phillips KM, Jim HS, Cessna JM, Asvat Y, Cases MG, Small BJ, Jacobsen PB. Cognitive functioning in men receiving androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Support Care Cancer. 2014;22(8):2271–80.
Permpongkosol S. Iatrogenic disease in the elderly: risk factors, consequences, and prevention. Clin Interv Aging. 2011;6:77–82. https://doi.org/10.2147/CIA.S10252.
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.
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(3):177–98.
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(5):683–91.
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;15(379):109–11.
Pan W, Han S, Kang L, Li S, Du J, Cui H. Effects of dihydrotestosterone on synaptic plasticity of the hippocampus in mild cognitive impairment male SAMP8 mice. Exp Ther Med. 2016;12(3):1455–63.
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;171:229–35.
Mannucci PM, Nobili A, Pasina L, REPOSI Collaborators (REPOSI is the acronym of REgistro POliterapie SIMI, Società Italiana di Medicina Interna). Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register. Intern Emerg Med. 2018. https://doi.org/10.1007/s11739-018-1941-8.
Folstein MF, Folstein SE, McHugh PR. “Mini Mental State” a practical method for grading the cognitive state of patients for the clinicians. J Psychait Res. 1975;12:189–98.
Paganini-Hill A, Clark LJ, Henderson VW, Birge SJ. Clock drawing: analysis in a retirement community. J Am Geriatr Soc. 2001;49:941–7.
Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a frontal assessment battery at bedside. Neurology. 2000;55(11):1621–6.
Catalano A, Martino G, Bellone F, Gaudio A, Lasco C, Langher V, Lasco A, Morabito N. Anxiety levels predict fracture risk in postmenopausal women assessed for osteoporosis. Menopause. 2018;25(10):1110–5.
Beck AT, Steer RA, Brown GK. Manual for the Beck depression inventory–II. San Antonio: Psychological Corporation; 1996.
Ware J Jr, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34(3):220–33.
Melcangi RC, Caruso D, Abbiati F, Giatti S, Calabrese D, Piazza F, Cavaletti G. Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of postfinasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J Sex Med. 2013;10(10):2598–603.
Catalano A, Martino G, Morabito N, Scarcella C, Gaudio A, Basile G, Lasco A. Pain in osteoporosis: from pathophysiology to therapeutic approach. Drugs Aging. 2017;34(10):755–65.
Langher V, Caputo A, Martino G. What happened to the clinical approach to case study in psychological research? A clinical psychological analysis of scientific articles in high impact-factors journals. Mediterr J Clin Psychol. 2017;5:3. https://doi.org/10.1007/s40266-017-0492-4.
Wefel JS, Vardy J, Ahles T, Schagen SB. International cognition and cancer task force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12(7):703–8.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This work received no funding.
Conflicts of interest
Catalano A, Martino G, Bellone F, Papalia M, Lasco C, Basile G, Sardella A, Nicocia G, Morabito N, Lasco A declare that they have no conflicts of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of our institutional research committee and with the 1964 Helsinki declaration and its later amendments. The Ethics Committee of the University Hospital of Messina approved the protocol of this study (approval number: 0007511).
Additional information
The original version of this article was revised. Authors’ names, which previously read: Catalano Antonino, Martino Gabriella, Bellone Federica, Papalia Maria, Lasco Carmen, Basile Giorgio, Sardella Alberto, Nicocia Giacomo, Morabito Nunziata, Lasco Antonino should read: Antonino Catalano, Gabriella Martino, Federica Bellone, Maria Papalia, Carmen Lasco, Giorgio Basile, Alberto Sardella, Giacomo Nicocia, Nunziata Morabito, Antonino Lasco.
Rights and permissions
About this article
Cite this article
Catalano, A., Martino, G., Bellone, F. et al. Neuropsychological Assessment in Elderly Men with Benign Prostatic Hyperplasia Treated with Dutasteride. Clin Drug Investig 39, 97–102 (2019). https://doi.org/10.1007/s40261-018-0720-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40261-018-0720-7