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Phosphodiesterase type 5 inhibitors: the day after.

Hatzimouratidis K, Hatzichristou D

2nd Department of Urology, Papageorgiou General Hospital and Center for Sexual and Reproductive Health, Aristotle University of Thessaloniki, Greece.

OBJECTIVE: Review the literature on phosphodiesterase type 5 inhibitors (PDE5-Is), addressing critical issues in their current and future use, assessing unanswered questions, and identifying research needs. METHODS: A MEDLINE search was conducted on PDE5-Is, with emphasis on clinical trials and experience, for interpretation and analysis of their present and future role. RESULTS: Although approximately 40 million patients with erectile dysfunction have been treated successfully worldwide with the three available PDE5-Is, inappropriate instructions, lack of follow-up, and lack of patient-centered care models are the main reasons for "non-response," leading to drop-out rates of >50%. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5-Is. Preservation of corporal smooth muscle with chronic administration of PDE5-Is has been reported and substantial evidence indicates that these drugs have beneficial effects on endothelium and cardiovascular function; sildenafil has been approved for the treatment of idiopathic pulmonary hypertension. Improvement of lower urinary tract symptoms in men with benign prostatic hyperplasia after PDE5-I administration has been also suggested. CONCLUSIONS: The data indicate the necessity for (1) exploration of the pharmacologic characteristics of the three PDE5-Is; (2) research on their pharmacologic differences because some actions seems to be drug-specific; (3) development of alternative management strategies, such as chronic, low, everyday doses of PDE5-Is, if the monthly cost is affordable; and (4) clinical trials on use of PDE5-Is to treat other chronic conditions. The door for innovative therapeutic approaches will open, specifically for cross-risk factor treatment with PDE5-Is or their use in combination treatments or new multimodal pills that take advantage of drugs that exert pleiotropic vascular actions.

Published 4 December 2006 in Eur Urol, 51(1): 75-88; discussion 89.
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