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All these areas have shown PDE5 activity and are potential target of PDE5i action. Prostate smooth muscle relaxation, detrusor muscle overactivity, and contraction of prostate tissue can be inhibited through cGMP increase achieved by either NO donors or PDE5Is. Additionally, PDE5i (including tadalafil, sildenafil, or the NO donor sodium nitroprusside) have been shown to attenuate α-adrenergic-induced contraction of isolated human prostate tissue. Thus cGMP may contribute to the regulation of prostatic smooth muscle cell contraction.

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However, improvements in erectile function were not as pronounced in this population as in ED patients without diabetes in other studies. These studies have shown the efficacy of combined therapy with PDE5i and α-adrenergic antagonists in patients with LUTS. From these results, doxazosin is more risky in association with tadalafil, compared to tamsulosin and alfuzosin