ED: When a PDE5i Fails

Michael Scally MD

Doctor of Medicine
10+ Year Member
Lee M, Sharifi R. Non-invasive Management Options for Erectile Dysfunction When a Phosphodiesterase Type 5 Inhibitor Fails. Drugs & aging 2018. https://link.springer.com/article/10.1007%2Fs40266-018-0528-4

Phosphodiesterase type 5 inhibitors (PDE5Is) are the drug of choice for medical management of erectile dysfunction (ED). On-demand PDE5Is have an overall efficacy of 60-70% for ED; 30-35% of patients fail to respond to a PDE5I, and 30-50% of non-responders can be salvaged with detailed counseling on proper use and physician follow-up to ensure that the patient has been prescribed an appropriate and full PDE5I clinical trial.

True non-responders may be offered intracavernosal injections of erectogenic drugs, intraurethral alprostadil, or surgical insertion of a penile prosthesis. Such options are not discreet and are associated with more adverse effects than PDE5Is. Thus patients may request additional non-invasive medical management options.

This review describes published literature on patients who failed to respond to an on-demand PDE5I regimen and were treated with a non-invasive PDEI-based regimen, including switching from one PDE5I to another; increasing the dose of PDE5I above the labeled dosage range; using two PDE5Is concurrently; using a daily PDE5I regimen; or combining a PDE5I with a testosterone supplement, alpha-adrenergic antagonist, intraurethral or intracavernosal alprostadil, vacuum erection device, or low-intensity shock wave therapy.

The limitations of published clinical trials do not allow for sufficient evidence to recommend one option over another. Therefore, in PDE5I-refractory patients, the choice of a specific next step should be individualized based on the preference of the patient and his sexual partner, the advantages and disadvantages of the various options, the concurrent medical illnesses and medications of the patient, and the patient's response to treatment.
 

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Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails

INTRODUCTION: On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection.

AIM: To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails.

METHODS: PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy.

MAIN OUTCOME MEASURES: The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD).

RESULTS: Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy.

Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an alpha1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED.

CONCLUSION: For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an alpha1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment.

Munk NE, Knudsen JS, Comerma-Steffensen S, Simonsen U. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019. https://www.sciencedirect.com/science/article/pii/S2050052118301446?via=ihub
 

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or combining a PDE5I with a testosterone supplement

Combination therapy with androgen supplementation and PDE5i appears safe.

Imagine that ... admitting that androgens can be safe! And that they can help ED. These guys risk being disbarred for such heresy.

Thanks for the full copies

True non-responders may be offered intracavernosal injections of erectogenic drugs, intraurethral alprostadil, or surgical insertion of a penile prosthesis. Such options are not discreet and are associated with more adverse effects than PDE5Is. Thus patients may request additional non-invasive medical management options.

Guess if one forgets to deflate their implant it might not be discreet. But then again it is a matter of size.
 

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