Synergetic effect of testosterone and phophodiesterase-5 inhibitors in hypogonadal men with erectile dysfunction: A systematic review

Abstract

Testosterone deficiency seems to impair the clinical response to phophodiesterase-5 (PDE-5) inhibitors in patients with erectile dysfunction (ED). In hypogonadal men, testosterone repletion was associated with enhanced sexual function in patients who failed initial treatment with sildenafil or tadalafil. We conducted a systematic review of studies that evaluated combination therapy of testosterone and PDE-5 inhibitors in patients with ED and low, low-normal testosterone levels who failed monotherapy. The studies we examine are heterogeneous with several methodological drawbacks and that, overall, the addition of testosterone to PDE-5 inhibitors might benefit patients with ED associated with testosterone <300 ng/dL (10.4 nmol/L) who failed monotherapy. Further studies, with a randomized placebo-controlled and double blind design, are needed to describe the appropriate target patient group, testosterone cut-off and to define the optimal dose and duration of combination therapy.

Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum

“…57 Combination therapy was shown to be beneficial in hypogonadal men with comorbidities. [58][59][60] Furthermore, a systematic review by Alhathal et al 61 indicated that T treatment in men with low-normal T levels (300 to 400 ng/dL) appeared helpful for patients with ED who did not respond to initial treatment with PDE5 inhibitors alone. In addition, in a previous study, T administration increased sildenafil-induced relaxant response of CC in high fat diet-induced rabbit model of metabolic syndrome.…”

Effect of low androgen status on the expression of adenosine A 2A and A 2B receptors in rat penile corpus cavernosum

“…It can improve erectile function by targeting the NO/cGMP signalling pathway. However, approximately 30% of patients with ED due to low androgen levels failed to achieve satisfactory results after PDE5I treatment (Alhathal, Elshal, & Carrier, ). It indicates that along with the NO/cGMP signalling pathway, there may be other signalling pathways involved in the mechanism of ED caused by androgen deficiency.…”

Current use of phosphodiesterase inhibitors in urology

“…Recently, a multicenter, double-blind, placebocontrolled TADEST study examined 173 patients with low testosterone levels and ED. [26,27] Men who received 1% testosterone along with tadalafil had a significant increase in IIEF scores. [26,27] In addition to restoring sexual function, PDE5 inhibitors have also been shown to enhance the Leydig cell secretory function, increasing sperm function and aiding sperm motility.…”

“…[26,27] Men who received 1% testosterone along with tadalafil had a significant increase in IIEF scores. [26,27] In addition to restoring sexual function, PDE5 inhibitors have also been shown to enhance the Leydig cell secretory function, increasing sperm function and aiding sperm motility. [28] The emerging studies point to the efficacy of combination therapy (testosterone supplementation and PDE5 inhibitor use) over monotherapy in the management of ED, especially in men who have a low testosterone level.…”

“…[26] In a systematic review, Alhathal et al [27] found that in 14 studies, combination therapy of testosterone plus a PDE5 inhibitor (12 testosterone + sildenafil, 2 testosterone + tadalafil) demonstrated an overall efficacy of 34-100% in patients with ED who failed on either drug alone or in patients who had previously experienced suboptimal improvement on monotherapy. Recently, a multicenter, double-blind, placebocontrolled TADEST study examined 173 patients with low testosterone levels and ED.…”