Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine? Fisiopatologia Medica, Room 37, Viale Policlinico 155, 00161 Rome Italy.
Therapeutic Advances in Urology 10/2009; 1(4):179-97. DOI: 10.1177/1756287209344992
Source: PubMed

ABSTRACT Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone (e.g. nitric oxide; NO), cell adhesion (e.g. endothelins, interleukins), and the homeostasis of clotting and fibrinolysis (e.g. plasminogen inhibitors, von Willebrand factor). The degeneration of endothelial integrity promotes adverse events (AEs) leading to increased atherogenesis and to the development of vascular systemic and penile end-organ disease. Testosterone (T) is an important player in the regulation of vascular tone through non-genomic actions exerted via blockade of extracellular-calcium entry or activation of potassium channels; also, adequate T concentrations are paramount for the regulation of phosphodiesterase type-5 (PDE5) expression and finally, for the actions exerted by hydrogen sulphide, a gas involved in the alternative pathway controlling vasodilator responses in penile tissue. It is known that an age-related decline of serum T is reported in approximately 20 to 30% of men whereas T deficiency is reported in up to 50% of men with metabolic syndrome or diabetes. A number of laboratory and human studies have shown the combination of T and other treatments for erectile dysfunction (ED), such as PDE5 inhibitors, to be more beneficial in patients with ED and hypogonadism, who fail monotherapy for sexual disturbances.The aim of this review is to show evidence on the role of T and PDE5 inhibitors, alone or in combination, as potential boosters of endothelial function in internal medicine diseases associated with reduced T or NO bioavailability, i.e. metabolic syndrome, obesity, diabetes, coronary artery disease, hyperhomocysteinemia, that share common risk factors with ED. Furthermore, the possibility of such a strategy to prevent endothelial dysfunction in men at increased cardiovascular risk is discussed.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Testosterone is the principal androgen in the human male. The decline of testosterone with aging was recognized to be associated with a number of symptoms and signs that reduce the quality of life and that may even have severe, debilitating consequences. Clinically, late-onset hypogonadism (LOH) is diagnosed by use of biochemical and clinical measures. Despite published guidelines and recommendations, however, uncertainty surrounds the profile of clinical symptoms as well as the biochemical threshold of diagnosis. Clinicians should be aware of these shortcomings while adhering to the guidelines. Current treatment methods are centered on restoring testosterone to mid to lower levels of young men with natural testosterone replacements. Although recent studies have highlighted possible additional benefits involving improvement of systemic disorders, the goal of treatment is to improve sexual function, while observing for adverse effects in the prostate. Overall, the problem of LOH in debilitating the quality of life and well-being is real, and by following proper guidelines with attentiveness to the results of treatment trials, testosterone replacement therapy presents a safe and effective treatment option.
    Korean journal of urology 11/2011; 52(11):725-35.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Phosphodiesterase type 5 inhibitors (PDE5-i) are used for the oral treatment of erectile dysfunction (ED). Since the launch of sildenafil more than 15 years ago, new molecules have become available. At present, in addition to tadalafil and vardenafil, there are three other drugs, udenafil, avanafil and mirodenafil, marketed in some countries which appear to be promising. Areas covered: The clinical pharmacological differences in dosage and side effects of all PDE5-i are evaluated. Expert opinion: All PDE5-i are equally effective and safe for the treatment of ED. On-demand use of any PDE5-i is also safe for patients with comorbid conditions. Tadalafil seems to be the preferred drug by patients and physicians, probably due to its peculiar pharmacological profile that makes sexual intercourse more spontaneous for the patients. Preliminary data suggest that the use of vardenafil may also be beneficial in cases of ED associated with premature ejaculation. Daily treatment is another option in men with ED and documented vascular or prostate disease. In geriatric or in difficult-to-treat populations, the evaluation of testosterone plasma levels will help to predict the efficacy of any PDE5-i. Remarkably, when such drugs are withdrawn for any reason, ED most often continues to occur because of the presence of an underlying disease.
    Expert Opinion on Pharmacotherapy 05/2013; · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of testosterone in erectile dysfunction (ED) is increasingly recognized. It is suggested that assessment of testosterone deficiency in men with ED and symptoms of hypogonadism, prior to first-line treatment, may be a useful tool for improving therapy. In this prospective, observational, and longitudinal study, we investigated the effects of vardenafil treatment as adjunctive therapy to testosterone undecanoate in hypogonadal ED patients who failed to respond to testosterone treatment alone. One hundred twenty-nine testosterone deficient (serum total testosterone ≤3.4 ng/mL) patients aged 56 ± 3.9 years received intramuscular injections of long-acting parenteral testosterone undecanoate at 3-month intervals for 8 months mean follow-up. Scores on the International Index of Erectile Function Questionnaire-five items (IIEF-5) and partner survey scores were compared at baseline and posttreatment with testosterone therapy alone or in combination with vardenafil. Patient baseline demographics and concomitant disease were correlated with patients' IIEF-5 scores. Seventy one (58.2%) responded well to monotherapy within 3 months. Nonresponders had lower testosterone levels and higher rates of concomitant diseases and smoking. Thirty-four of the 51 nonresponders accepted the addition of 20 mg vardenafil on demand. Efficacy assessments were measured by the IIEF-erectile function domain (IIEF-EF, questions 1-5 plus 15, 30 points) and partner self-designed survey at baseline after 4-6 weeks and at study end point. Thirty out of 34 patients responded well to this combination. IIEF-EF Sexual Health Inventory for Men score improved from 12 to 24 (P < 0.0001), and partner survey showed significantly higher satisfaction (P < 0.001). These patients reported spontaneous or nocturnal and morning erections or tumescence. No changes in adverse effects were recorded. These data suggest that combination therapy of testosterone and vardenafil is safe and effective in treating hypogonadal ED patients who failed to respond to testosterone monotherapy. Yassin D-J, Yassin AA, and Hammerer PG. Combined testosterone and vardenafil treatment for restoring erectile function in hypogonadal patients who failed to respond to testosterone therapy alone. J Sex Med **;**:**-**.
    Journal of Sexual Medicine 11/2013; · 3.51 Impact Factor


Available from
Jun 5, 2014