Combination therapy of testosterone enanthate and tadalafil on PDE5 inhibitor non-reponders with severe and intermediate testosterone deficiency

Abstract

Several studies have suggested combination therapy with testosterone supplementation in patients not responding to PDE5 inhibitors. Considering the pathophysiological basis for testosterone supplementation, the present study aims to identify whether combination therapy allows persistence of treatment effect after testosterone discontinuation. Furthermore, we evaluated whether the degree of testosterone depletion affects treatment outcome from combination therapy. Hypogonadal patients (<350 ng dl(-1)) with erectile dysfunction who previously did not respond to PDE5 inhibitors were treated with testosterone enanthate injections and daily tadalafil. Patients were stratified into two groups depending on the level of testosterone deficiency, with 250 ng dl(-1) as a reference point. Following testosterone supplementation (12 weeks) and combination therapy (12 weeks), patients with severe testosterone deficiency showed higher IIEF (International Index of Erectile Function) erectile function (EF) domain score (16.47±4.019 vs 12.36±4.051, P=0.001) and more patients responding satisfactorily to treatment by general assessment (57.9 vs 16.0%, P=0.009), despite reaching similar levels of serum total testosterone (602±169 ng dl(-1) vs 698±165 ng dl(-1), P=0.057). Testosterone supplementation was then discontinued and patients were maintained only on daily tadalafil (12 weeks). The severe depletion group maintained higher EF domain scores than baseline (13.06±3.38 vs 7.20±2.24, P=0.0004), despite testosterone levels returning to baseline. The results suggest that combination therapy was more beneficial to patients with severe testosterone depletion, possibly by improving underlying pathophysiology.

Impact of Baseline Total Testosterone Level on Successful Treatment of Sexual Dysfunction in Men Taking Once-Daily Tadalafil 5 mg for Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: An Integrated Analysis of Three Randomized Controlled Trials

“…The findings of this integrated analysis challenge earlier reports that suggest normalizing testosterone levels is essential towards achieving a response to PDE5i therapy in men with low TT levels [14,16–18,20–23]. Our analysis corroborates and extends earlier reports that support that low androgen levels do not compromise PDE5i efficacy [24,32].…”

“…Numerous reports suggest that erectile response to PDE5i is compromised in men with low TT levels [13–19] and that there is an improved response to PDE5i therapy in men with low TT levels following testosterone replacement therapy (TRT) [14,16–23]. However, despite evidence supporting a possible link between low testosterone levels and reduced PDE5i efficacy for ED, a study in testosterone-deficient men not experiencing prior PDE5i failure suggests that TRT may not enhance the efficacy of PDE5i therapy [24].…”

Modifying Risk Factors in the Management of Erectile Dysfunction: A Review

“…The basic science literature has confirmed the necessity of androgens to generate adequate intracavernosal pressures and smooth muscle function to obtain an erection [59]. The literature showing the impact of testosterone replacement therapy (TRT) on erectile function is quite heterogenous (Table 1) [6061626364656667686970717273747576777879808182838485868788899091]. A subset analysis of the Olmstead County Cohort published by Gades et al [92] showed that testosterone has a statistically significant positive correlation with erectile function, even when adjusted for age.…”

The Efficacy of Combination Treatment with Injectable Testosterone Undecanoate and Daily Tadalafil for Erectile Dysfunction with Testosterone Deficiency Syndrome

“…However, few clinical studies have been conducted in humans that evaluate the efficacy of combination therapy with testosterone and chronic PDE5Is. Kim et al [26] demonstrated that the combination of testosterone replacement and chronic PDE5Is was more beneficial to patients with severe testosterone deficiency. The patients received an intramuscular testosterone enanthate injection every 4 weeks for 12 weeks; they received a combination of testosterone enanthate injection and daily tadalafil 5 mg for the next 12 weeks.…”