Each month, questions with a common theme will be selected and answered comprehensively by our Steering Committee and Distinguished Faculty members. Previously answered questions will be archived each month for your reference. If you wish to submit a question, click here. To view archived responses, click here.

This Month's Question:

Many patients with erectile dysfunction (ED) have comorbid conditions or severe ED that renders them less responsive to on-demand phosphodiesterase type 5 (PDE5) inhibitor therapy. Which patients might benefit from daily or chronic administration of PDE5 inhibitors?

Response by Culley C. Carson III, MD, Posted 10/16/06:

Some difficult-to-treat patients—those for whom the typical on-demand regimen of PDE5 inhibitors is significantly less efficacious—may benefit from daily or chronic administration of these agents. These subpopulations include patients with ED associated with diabetes and diabetic complications, postradical prostatectomy surgery, severe vasculogenic ED, and hypertension.^1,2 In addition, perhaps because of the likely link between endothelial dysfunction, ED, and cardiovascular (CV) risk factors,³ daily PDE5 inhibitor therapy improves endothelial function in men with increased CV risk.⁴

Studies of nonresponders to on-demand PDE5 therapy found that daily tadalafil was effective and well tolerated.¹ One study using tadalafil comprised patients with predominantly organic, moderate ED² and another included high percentages of patients with diabetes (46%), hypertension (56%), and hyperlipidemia (62%).¹ The improved response with daily administration was thought to be related to improved endothelial function,^1,2 and based on this theory, similar results would be expected with sildenafil and vardenafil. It has also been postulated that daily tadalafil, alone or in combination with behavioral psychosocial therapy, may benefit patients with psychogenic ED related to performance anxiety by removing the mental connection between taking a drug and feeling an expectation to perform sexually.¹

In 2 reports, in men who underwent nerve-sparing radical retropubic prostatectomy, nightly sildenafil was shown to significantly increase the return of spontaneous erections (27% vs 4% taking placebo and 29% vs 5% taking placebo, respectively).^5,6 Similarly, a small cohort of bilateral nerve-sparing radical laparoscopic prostatectomy patients showed that tadalafil, dosed at 20 mg every 3 days, resulted in improved erections at 6 months.⁷

Men with lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia with ED have shown improvement in erectile function with daily administration of tadalafil.⁸ Sildenafil 50 mg daily improved erectile function and may improve LUTS.^9,10

CV benefits may be seen with chronic administration of PDE5 inhibitors. Endothelial function in patients with cardiovascular disease was improved with chronic administration of tadalafil.⁴ Similarly, chronic administration of PDE5 inhibitors has been associated with vasodilation of epicardial coronary arteries, improvement in endothelial function, and inhibition of platelet activation in patients with coronary artery disease¹¹ and may be effective in patients with diabetes,¹² chronic heart failure, or hypertension and in current smokers.^1,2,4

References

1. McMahon C. Efficacy and safety of daily tadalafil in men with erectile dysfunction previously unresponsive to on-demand tadalafil. J Sex Med. 2004;1:292-300.

2. McMahon C. Comparison of efficacy, safety, and tolerability of on-demand tadalafil and daily dosed tadalafil for the treatment of erectile dysfunction. J Sex Med. 2005;2:415-427.

3. Billups KL , Bank AJ, Padma-Nathan H, Katz S, Williams R. Erectile dysfunction is a marker for cardiovascular disease: results of the Minority Health Institute expert advisory panel. J Sex Med. 2005;2:40-52.

4. Rosano GM, Aversa A, Vitale C, Fabbri A, Fini M, Spera G. Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol. 2005;47:214-220.

5. Padma-Nathan H, McCullough A, Forest C. Erectile dysfunction secondary to nerve-sparing radical retropubic prostatectomy: comparative phosphodiesterase-5 inhibitor efficacy for therapy and novel prevention strategies. Curr Urol Rep. 2004;5:467-471.

6. Levine LA, McCullough AR, Padma-Nathan H. Longitudinal randomized placebo-controlled study of the return of nocturnal erections after nerve-sparing radical prostatectomy in men treated with nightly sildenafil citrate [abstract]. J Urol. 2004;171(suppl):231-232. Abstract 875.

7. Carson CC III, Hubbard JS, Wallen E. Erectile dysfunction and treatment of carcinoma of the prostate. Curr Urol Rep. 2005;6:461-469.

8. Roehrborn CG, McVary KT, Kaminetsky JC, et al. The efficacy and safety of tadalafil administered once a day for lower urinary tract symptoms (LUTS) in men with benign prostate hyperplasia (BPH) [abstract]. J Urol. 2006;175:527. Abstract 1636.

9. McVary KT, Swierzewski MJ, Monnig WB, et al. Sildenafil improves erectile function and concomitant lower urinary tract symptoms in men [abstract]. J Urol. 2006;175(suppl 4):298. Abstract 920.

10. Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC. Sildenafil influences lower urinary tract symptoms. BJU Int. 2002;90:836-839.

11. Halcox JPJ, Nour KRA, Zalos G, et al. The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia. J Am Coll Cardiol. 2002;40:1232-1240.

12. Buvat J, van Ahlen H, Schmitt H, Chan M, Kuepfer C, Varanese L. Efficacy and safety of two dosing regimens of tadalafil and patterns of sexual activity in men with diabetes mellitus and erectile dysfunction: scheduled use vs. on-demand regimen evaluation (SURE) study in 14 European countries. J Sex Med. 2006;3:512-520.

13. Hatzimouratidis K, Moysidis K, Bekos A, Tsimtsiou Z, Ioannidis E, Hatzichristou D. Treatment strategy for “non-responders” to tadalafil and vardenafil: a real-life study. Eur Urol. 2006;50:126-133.