Korean J Androl.  2011 Aug;29(2):91-100. 10.5534/kja.2011.29.2.91.

Role of Phosphodiesterase Type 5 Inhibitor on Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms

• Kim SD
• Park JK

• KMID: 2226462
• DOI: http://doi.org/10.5534/kja.2011.29.2.91

Abstract

There is strong evidence from multiple epidemiological studies that benign prostate hyperplasia (BPH) induced lower urinary tract symptoms (LUTS) are correlated with erectile dysfunction (ED). Although a direct causal relationship is not established yet, four pathophysiological mechanisms can explain the relationship. These include alteration in activity of nitric oxide (NO)-cyclic GMP signal pathway, autonomic hyperactivity, increased Rho kinase/Rho A pathway and pelvic atherosclerosis. Androgens have been suggested to have an important role in the maintenance of the functional and structural integrity of the urinary tract. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. Sildenafil is a pioneer of this clinical trial and appears to improve both erectile function and LUTS in subjects with ED. Basically PDE5 I with long half life is an appropriate candidate, therefore tadalafil and undenafil had been used to evaluate both diseases. Placebo-controlled trials of tadalafil showed improvement of LUTS secondary to BPH, but none of the studies showed a significant effect on urodynamic measures. PDE5 Is, such as sildenafil and tadalafil, increase the concentration of cGMP in plasma and smooth muscle, facilitating erection of the penis, relaxation of the bladder neck and prostate and subsequent bladder emptying. And theses PDE5 Is increase cAMP and cGMP levels and are more highly distributed in the prostate than plasma. These findings may help in the assessment of the feasibility of using PDE5 Is to concurrently treat both LUTS and ED.

Keyword

Phosphodiesterase type 5 inhibitor (PDE5 I); Sexual function; erectile dysfunction (ED); Lower urinary tract symptoms (LUTS)

MeSH Terms

Androgens
Atherosclerosis
Carbolines
Cyclic Nucleotide Phosphodiesterases, Type 5
Erectile Dysfunction
Half-Life
Humans
Hyperplasia
Lower Urinary Tract Symptoms
Male
Muscle, Smooth
Neck
Nitric Oxide
Penis
Piperazines
Plasma
Prostate
Purines
Relaxation
Signal Transduction
Sulfones
Urinary Bladder
Urinary Tract
Urodynamics
Sildenafil Citrate
Tadalafil
Androgens
Carbolines
Cyclic Nucleotide Phosphodiesterases, Type 5
Nitric Oxide
Piperazines
Purines
Sulfones

Figure

• 

  Fig. 1. cAMP and cGMP levels in prostate tissue. (A) cAMP and (B) cGMP levels were significantly higher in prostate tissues of groups 2 (udenafil, 200 mg) and 3 (tadalafil, 20 mg) than group 1 (control). ∗p＜0.05, ∗∗p＜0.01.

• 

  Fig. 2. cAMP and cGMP levels in plasma. (A) cAMP and (B) cGMP levels increased significantly 1 h after TURP in the plasma of groups 2 (udenafil, 200 mg) and 3 (tadalafil, 20 mg), but not group 1 (control). ∗p＜0.01.

• 

  Fig. 3. The prostate tissue-to-plasma (T/P) ratio of the phosphodiesterase type 5 inhibitor (PDE5 I) concentration. The ratio was significantly higher in group 2 (udenafil, 200 mg) than in group 3 (tadalafil, 20 mg).

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