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Daily dosing with a phosphodiesterase type 5 (PDE5) inhibitor improves cognitive function, depression, and somatization in patients with erectile dysfunction, according to a pilot study performed by researchers in South Korea. In this double-blind trial, 60 men with erectile dysfunction for >3 months (and no evidence of cognitive impairment) were randomized to receive either daily low-dose udenafil or placebo for 2 months.

Along with a significant improvement in mean International Index of Erectile Function-5 score in the udenafil group compared with the placebo group (6.08 vs 2.20), improvements were also reported in scores for the Korean version of the Mini-Mental State Examination for general cognitive function (1.25 vs 0.52) and the Forward Digit-Span Task for attention and working memory (0.92 vs 0.24), as well as the Physical Health Questionnaire-9 for depression (2.04 vs 1.2) and the Physical Health Questionnaire-15 for somatization (2.17 vs 0.56).

The authors propose three possible mechanisms by which udenafil could improve general cognition and depression in men with erectile dysfunction. Firstly, PDE5 inhibitors could enhance memory and learning by increasing long-term potentiation mediated by the glutamate NO-cGMP intracellular pathway, as cGMP-activated protein kinase is thought to mediate memory consolidation.

Secondly, as cGMP is a known vasodilator, the cognitive effects of PDE inhibition could be explained by enhanced cerebrovascular function owing to increased delivery of glucose and oxygen to the brain. Finally, improved erections might alleviate performance anxiety and boost self-confidence, with potential benefits to mood, cognition, and general health.

A combination of these three proposed mechanisms is probably responsible. “Functional imaging studies should help us to understand the specific accountability of each proposed mechanism,” says Chi-Un Pae, a member of the research team. “Future studies should include patients with cognitive decline and psychiatric comorbidity.”