Combination therapy for erectile dysfunction: an update review

Abstract

The introduction of oral phosphodiesterase-5 inhibitors (PDE5Is) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5Is are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE5I monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE5I therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE5I plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management. 1 Current projections indicate an increase in the prevalence of ED due to aging as well as the continued abundance of comorbidities such as coronary artery disease, hypertension and diabetes in industrialized nations. Over 320 million people in Westernized nations will be affected by 2025, more than double the prevalence seen 15 years ago, indicating a growing need to reevaluate ED therapeutic strategies.2 Over the past four decades, the treatment of ED has evolved rapidly and is still changing with new discovery. Before the 1970s, psychotherapy was the primary means of treatment and undoubtedly was limited in its success. During the 1970s, penile prostheses combined with psychotherapy remained popular but relatively inaccessible. The 1980s was dominated by intracavernous injection (ICI) and followed by intraurethral therapy in the mid-1990s. Despite this transition towards non-surgical management, available treatment modalities were not patient-friendly. The introduction of oral phosphodiesterase-5 inhibitors (PDE5Is) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5Is are currently first-line monotherapy.

Efficacy of Low Density Linear Shockwave Treatment in Severe Arteriogenic Erectile Dysfunction Patients

“…Although application of vasoactive agents and penile prosthesis implantation are recommended as secondary and tertiary treatment options in irresponsive patients, patients are generally not interested in these treatments (5). Thus, treatment methods which may be tolerated easily by non-invasive patients are required.…”

PDE-5 inhibitors in monotherapy versus combination therapy in a sample of 1200 patients with erectile dysfunction

“…The key to the success of this association is the use of two different cavernous ways: PDE5 inhibitors indirectly relax body' s smooth muscle by inhibiting the metabolism of cyclic guanosine monophosphate, for which nitric oxide is required; PG-E1 directly relaxes trabecular smooth muscle tissue through E-prostanoid receptors, which leads to an increase of cyclic adenosine monophosphate. Therefore, the use in combination of these two drugs theoretically allows a therapeutic synergy to activate two different but inter-related ways (10,41). In our series, patients did not report suffering severe adverse effects with this combination, and in particular no higher incidence of priapism compared to monotherapy group.…”

“…In our series, patients did not report suffering severe adverse effects with this combination, and in particular no higher incidence of priapism compared to monotherapy group. There is no scientific evidence of previous use of PG-E1 and TES in combination therapy (10). In one study with 120 men who had not responded to sildenafil or intraurethral alprostadil monotherapy, it is assessed what happens when both are combined.…”

“…It is estimated that over 320 million men will suffer from ED in Western countries, which means more than twice the observed prevalence 15 years ago. This invites us to reassess the therapeutic strategy of this pathology (9,10). The main objective of the treatment strategy for patients with ED is to determine the aetiology of the disease, to treat it whenever possible and not to treat only the symptoms.…”

“…Sildenafil, tadalafil and vardenafil can be nowadays considered equally effective and safe, therefore it is postulated that patients should have the opportunity of trying the three drugs and then select the one that best suits their sexual habits and is most effective (24). Some authors have studied the pharmacological combination value in ED, especially in those cases refractory to conventional treatment (10,25). In patients with testosterone deficiency, normalization of serum testosterone may improve the response to PDE5i: Shabsigh et al (26) studied the administration of testosterone gel and sildenafil 100 mgr versus sildenafil 100mgr in a double-blind (27) assessed administration of patches of testosterone 5 mgr and sildenafil 100 mgr versus sildenafil 100 mgr in monotherapy.…”