Testosterone Therapy Can Enhance Erectile Function Response to Sildenafil in Patients with PADAM: A Pilot Study

Abstract

Introduction Recent studies suggest a direct relationship between free testosterone and cavernous vasodilatation. Some men with erectile dysfunction (ED) associated with PADAM (partial androgen deficiency in aging men) might possibly benefit from testosterone undecanoate therapy (TRT). Objectives To determine the efficacy of testosterone undecanoate in facilitating the erectile response and patient satisfaction with sildenafil in men 40–70 years old with PADAM symptoms. Design and Methods Prospective study including 40 patients recruited after a sildenafil therapeutic trial. Total testosterone and sex hormone binding globulin (SHBG) were measured to calculate the free androgen index. Prostate specific antigen (PSA) was measured and repeated 2 months after treatment. A rating score was used for PADAM symptoms, and the 5-point abbreviated version of the International Index of Erectile Function (IIEF-5) to assess erectile function. Men failing to respond to sildenafil were randomized into two groups receiving sildenafil plus continuous TRT (group 1ST), and TRT (group 1T) alone. Men partially responding to sildenafil were randomized into two groups receiving sildenafil plus continuous TRT for 2 months (group 2ST), or sildenafil alone (group 2S). Treatment efficacy was assessed by analysis of between-group differences. Results Groups 1T, 2S, and 2ST showed significant improvement in PADAM scores (P < 0.05, Wilcoxon matched pairs test). Patients receiving both sildenafil plus continuous TRT (groups 1ST and 2ST) showed significant improvement in IIEF-5 scores (P < 0.5, paired t-test). No significant changes in serum levels of PSA were detected (paired t-test). Conclusions We conclude that TRT appears to be beneficial and safe in facilitating the erectile response and patient satisfaction with sildenafil in men with PADAM symptoms. Androgen supplementation should be carried out cautiously with careful monitoring to avoid possible adverse effects.

Does testosterone supplementation increase PDE5-inhibitor responses in difficult-to-treat erectile dysfunction patients?

“…We then demonstrated that in men with ED who failed sildenafil treatment (100 mg dose) and had free T levels falling into the lower quartile of the lower range, T improved clinical response to sildenafil [10]. These findings were then confirmed by other authors' clinical studies, with either sildenafil [11] or tadalafil [12]. These results were recently not confirmed by an elegant controlled study by Spitzer et al [13] who demonstrated that sildenafil plus T was not superior to sildenafil plus placebo in improving erectile function in men with ED and low T levels.…”

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

“…In light of the established historic link of androgens to both facilitating sexual function and vasodilatory function, it is not surprising that the contemporary management of aging men and their sexual health concerns involves frequent use of PDE5 inhibitors and off-label use of androgens [70][71][72][73][74][75][76]. These clinical uses are based in part on the recent explosion of basic science and clinical data concerning androgens and erectile physiology [1,3,[77][78][79][80][81][82][83].…”

“…Failure to respond to a maximum dose of oral PDE5 with maximum erection hardness may be the first sign of androgen insufficiency [70][71][72][73][74][75][76]. This perspective is based on the observation that androgens may directly control the expression and activity of NOS in human corpus cavernosum [91][92][93][94].…”

“…This perspective is based on the observation that androgens may directly control the expression and activity of NOS in human corpus cavernosum [91][92][93][94]. The clinical responsiveness of PDE5 inhibitors appears to be strongly linked to NOS activity in vascular tissues [70][71][72][73][74][75][76].…”

“…In patients with androgen insufficiency, in whom treatment with testosterone supplementation alone failed, combined treatment with a PDE5 inhibitor and testosterone gel improved erectile function [72]. Likewise, aging men with androgen insufficiency who failed first-line oral PDE5 inhibitor treatment and in whom androgens were not contraindicated had improved erectile function and quality of life when treated with a combination of testosterone and PDE5 inhibitors [74][75][76]. These findings provide clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function.…”