Abstract
Phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to have cognitive-enhancing effects in animal models and in our previous pilot study. To investigate the efficacy of daily low-dose treatment with a PDE5 inhibitor on cognitive function, depression and somatization in patients with erectile dysfunction (ED), 8-week, double-blind, placebo-controlled study enrolled 60 male patients with ED for ≥3 months without cognitive impairment. Forty-nine patients completed the study. Patients were randomized to receive either daily low-dose udenafil 50 mg or placebo for 2 months. The International Index of Erectile Function-5 (IIEF-5), the Korean version of the Mini-Mental State Examination (K-MMSE) for general cognitive function and the Seoul Neuropsychological Screening Battery for comprehensive neuropsychological examination, the Physical Health Questionnaire-9 (PHQ-9) for depression and the Physical Health Questionnaire-15 (PHQ-15) for somatization were administered at baseline and at 2 months. The change in the mean IIEF-5 was significantly higher in the udenafil group than the placebo group (6.08±4.72 vs 2.20±3.50, P=0.008). The changes in the PHQ-9 and PHQ-15 were −2.04±3.14 and −2.17±2.87 in the udenafil group, and 1.20±1.63 and 0.56±2.48 in the placebo group (both, P<0.001). The changes in the K-MMSE and Digit Span Forward were 1.25±1.26 and 0.92±1.02 in the udenafil group, and −0.52±1.19 and −0.24±1.13 in the placebo group (both, P<0.001). However, there were no differences in the other neuropsychological tests. Daily dosing with a PDE5 inhibitor seems to improve cognitive function, depression and somatization, as well as erectile function, in patients with ED.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Stehlik J, Movsesian MA . Combined use of PDE5 inhibitors and nitrates in the treatment of pulmonary arterial hypertension in patients with heart failure. J Card Fail 2009; 15: 31–34.
Giannitsas K, Mitropoulos D, Konstantinopoulos A, Athanasopoulos A, Perimenis P . Phosphodiesterase-5 inhibitors in the treatment of lower urinary tract symptoms and benign prostatic hyperplasia. Expert Opin Pharmacother 2008; 9: 1687–1693.
Bednar MM . The role of sildenafil in the treatment of stroke. Curr Opin Investig Drugs 2008; 9: 754–759.
Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M et al. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 2002; 33: 2675–2680.
Rodefer JS, Saland SK, Eckrich SJ . Selective phosphodiesterase inhibitors improve performance on the ED/ID cognitive task in rats. Neuropharmacology 2012; 62: 1182–1190.
Cuadrado-Tejedor M, Hervias I, Ricobaraza A, Puerta E, Pérez-Roldán JM, García-Barroso C et al. Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer’s disease. Br J Pharmacol 2011; 164: 2029–2041.
Schmidt CJ . Phosphodiesterase inhibitors as potential cognition enhancing agents. Curr Top Med Chem 2010; 10: 222–230.
Shim YS, Pae CU, Kim SW, Kim HW, Kim JC, Koh JS . Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: a pilot study. Int J Impot Res 2011; 23: 109–114.
Prickaerts J, van Staveren WC, Sik A, Markerink-van Ittersum M, Niewöhner U, van der Staay FJ et al. Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat. Neuroscience 2002; 113: 351–361.
Prickaerts J, de Vente J, Honig W, Steinbusch HW, Blokland A . cGMP, but not cAMP, in rat hippocampus is involved in early stages of object memory consolidation. Eur J Pharmacol 2002; 436: 83–87.
Yamada K, Hiramatsu M, Noda Y, Mamiya T, Murai M, Kameyama T et al. Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice. Neuroscience 1996; 74: 365–374.
Araujo AB, Durante R, Feldman HA, Goldstein I, McKinlay JB . The relationship between depressive symptoms and male erectile dysfunction: cross-sectional results from the Massachusetts Male Aging Study. Psychosom Med 1998; 60: 458–465.
Rosen RC, Marin H . Prevalence of antidepressant-associated erectile dysfunction. J Clin Psychiatry 2003; 64: 5–10.
Rosen R, Shabsigh R, Berber M, Assalian P, Menza M, Rodriguez-Vela L . Efficacy and tolerability of vardenafil in men with mild depression and erectile dysfunction: the depression-related improvement with vardenafil for erectile response study. Am J Psychiatry 2006; 163: 79–87.
NIH Consensus Conference. NIH consensus development panel on impotence. JAMA 1993; 270: 83–90.
Rhoden EL, Telöken C, Sogari PR, Vargas Souto CA . The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. Int J Impot Res 2002; 14: 245–250.
Kroenke K, Spitzer RL, Williams JB . The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16: 606–613.
Kroenke K, Spitzer RL, Williams JB . The PHQ-15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med 2002; 64: 258–266.
Interian A, Allen LA, Gara MA, Escobar JI, Diaz-Martinez AM . Somatic complaints in primary care: further examining the validity of the Patient Health Questionnaire (PHQ-15). Psychosomatics 2006; 47: 392–398.
Han C, Jo SA, Jo I, Kim E, Park MH, Kang Y . An adaptation of the Korean mini-mental state examination (K-MMSE) in elderly Koreans: demographic influence and population-based norms (the AGE study). Arch Gerontol Geriatr 2008; 47: 302–310.
Kang YW, Na DL . Seoul Neuropsychological Screening Battery. Human Brain Research & Consulting Co: Incheon, 2003.
Hogervorst E, Combrinck M, Lapuerta P, Rue J, Swales K, Budge M . The Hopkins Verbal Learning Test and screening for dementia. Dement Geriatr Cogn Disord 2002; 13: 13–20.
Zhang ZG, Chopp M . Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 2009; 8: 491–500.
Cocchiarella A . Partial motor restoration upon administration of sildenafil: a case study. Dev Neurorehabil 2012; 15: 39–43.
Ding G, Jiang Q, Li L, Zhang L, Zhang Z, Lu M et al. Longitudinal magnetic resonance imaging of sildenafil treatment of embolic stroke in aged rats. Stroke 2011; 42: 3537–3541.
Kruuse C, Hansen AE, Larsson HB, Lauritzen M, Rostrup E . Cerebral haemodynamic response or excitability is not affected by sildenafil. J Cereb Blood Flow Metab 2009; 29: 830–839.
Brenner S . Sildenafil increases cerebrovascular reactivity: a transcranial Doppler study. Neurology 2006; 66: 1455–1456.
Lorberboym M, Mena I, Wainstein J, Boaz M, Lampl Y . The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors. Acta Neurol Scand 2010; 121: 370–376.
Hatzichristou D, Cuzin B, Martin-Morales A, Buvat J, Porst H, Laferriere N . Vardenafil improves satisfaction rates, depressive symptomatology, and self-confidence in a broad population of men with erectile dysfunction. J Sex Med 2005; 2: 109–116.
Christensen H, Griffiths K, Mackinnon A, Jacomb P . A quantitative review of cognitive deficits in depression and Alzheimer-type dementia. J Int Neuropsychol Soc 1997; 3: 631–651.
Althof SE, Berner MM, Goldstein I, Claes HI, Cappelleri JC, Bushmakin AG et al. Interrelationship of sildenafil treatment effects on the physiological and psychosocial aspects of erectile dysfunction of mixed or organic etiology. J Sex Med 2010; 7: 3170–3178.
Goff DC, Cather C, Freudenreich O, Henderson DC, Evins AE, Culhane MA et al. A placebo-controlled study of sildenafil effects on cognition in schizophrenia. Psychopharmacology (Berl) 2009; 202: 411–417.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Shim, Y., Pae, CU., Cho, K. et al. Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition, depression, somatization and erectile function in patients with erectile dysfunction: a double-blind, placebo-controlled study. Int J Impot Res 26, 76–80 (2014). https://doi.org/10.1038/ijir.2013.38
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijir.2013.38
Keywords
This article is cited by
-
Phosphodiesterase inhibitors in psychiatric disorders
Psychopharmacology (2023)
-
Tadalafil improves erectile dysfunction and quality of life in men with cirrhosis: a randomized double blind placebo controlled trial
Hepatology International (2023)
-
cGMP favors the interaction between APP and BACE1 by inhibiting Rab5 GTPase activity
Scientific Reports (2020)
-
Tadalafil Treatment Improves Inflammation, Cognitive Function, And Mismatch Negativity Of Patients With Low Urinary Tract Symptoms And Erectile Dysfunction
Scientific Reports (2019)
-
Therapeutic targeting of 3′,5′-cyclic nucleotide phosphodiesterases: inhibition and beyond
Nature Reviews Drug Discovery (2019)