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Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences.
Emanuela A Greco1, Giovanni Spera, Antonio Aversa
1Department of Medical Pathophysiology, University of Rome La Sapienza, 00161 Rome, Italy.
Testosterone supplementation may improve erectile dysfunction (ED) treatment outcomes, especially for hypogonadal men. Screening for low testosterone is crucial for optimizing therapy with phosphodiesterase type 5 inhibitors (PDE5-Is).
Area of Science:
- Andrology
- Urology
- Molecular Endocrinology
Background:
- Erectile dysfunction (ED) and declining testosterone levels are common with aging and conditions involving endothelial damage.
- Androgen deficiency and endothelial dysfunction are linked to ED pathogenesis.
Purpose of the Study:
- To review the molecular mechanisms of androgen action on its receptor and phosphodiesterase type 5 (PDE5) expression.
- To examine testosterone's regulation of PDE5 in cavernous tissue and its clinical implications for treating ED refractory to PDE5 inhibitors (PDE5-Is).
Main Methods:
- An extensive literature search of MEDLINE from January 2003 to May 2006 was conducted.
- Relevant basic and clinical studies on combination therapies for ED were reviewed.
Main Results:
- Testosterone therapy shows superiority over placebo for ED in hypogonadal men, despite methodologic limitations in some trials.
- The efficacy of PDE5 inhibitors (PDE5-Is) may depend on testosterone's regulation of PDE5 expression and can be enhanced by testosterone supplementation.
Conclusions:
- Screening all men with ED for hypogonadism is necessary to identify candidates for testosterone treatment.
- Identifying optimal testosterone thresholds can improve the management of PDE5-Is failure and minimize side effects.
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