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

Y S Shim; C-U Pae; K J Cho; S W Kim; J C Kim; J S Koh


Int J Impot Res. 2014;26(2):76-80. 

In This Article

Abstract and Introduction


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.


Phosphodiesterase type 5 (PDE5) inhibitors are commonly used to treat erectile dysfunction (ED), but there have been several different attempts to evaluate the additional beneficial effects of PDE5 inhibitors, such as the effects on pulmonary hypertension[1] and benign prostatic hyperplasia.[2] In addition, PDE5 inhibitors are known to be effective for the treatment of strokes[3,4] and cognitive dysfunction.[5–8] These medications readily cross the blood–brain barrier, and sub-chronic administration of sildenafil has been shown to increase cortical cyclic guanosine monophosphate (cGMP) in an animal model.[9] These increased concentrations in the intracellular pathway activate N-methy-D-aspartic acid receptors, which are believed to mediate long-term potentiation and memory consolidation.[10,11] Cyclic nucleotides have critical roles in regulating synaptic plasticity, and consequently, PDE inhibitors are of considerable interest as treatments for cognitive dysfunction.

Sexual disorders are commonly associated with depression. From a recent large cross-sectional and population-based survey study consisting of 1265 males, patients with depressive symptomatology, defined by having a score of ≥16 on the Center for Epidemiological Studies-Depression scale had 1.82-fold higher risk of having moderate to complete ED compared with those without.[12,13] A loss of interest in and withdrawal from all regular and pleasurable activities is often associated with depression; however, the mechanisms underlying the link between depression and ED are complex and not fully understood.[14] ED may contribute to, or be a consequence of, depression.

In our previous pilot study, repeated dosing with udenafil 100 mg seemed to improve cognitive function and somatization, as well as erectile function, in patients with ED.[8] However, our findings were based on a non-randomized design without a placebo control group. Thus, considering the limitations of that study, we conducted this double-blind, placebo-controlled study to better assess whether or not daily dosing with a PDE5 inhibitor improves cognitive function, depression and somatization in addition to erectile function in patients with ED.