Testosterone Replacement with 1% Testosterone Gel and Priapism: No Definite Risk Relationship

Abstract

Introduction Although testosterone replacement therapy (TRT) is the preferred treatment for hypogonadism, information for patients using testosterone includes too frequent or prolonged erections as a potential side effect. Aim To assess the frequency and risk of priapism or related adverse events (AEs) in hypogonadal men treated with a 1% testosterone gel. Methods Safety and tolerability data for AndroGel 1% were assessed, including three randomized, controlled clinical trials in varying populations of hypogonadal or near hypogonadal men. Study 1 was a Phase 3 trial of AndroGel 1% 5 g, 7.5 g, or 10 g once daily for 6 months (N = 227). Study 2 was a Phase 2 trial of AndroGel 1% 7.5 g once daily titrated as needed vs. placebo for 26 weeks in men with type 2 diabetes (N = 180). Study 3 was a Phase 4 trial of AndroGel 1% 5 g once daily vs. placebo for 12 weeks in men previously unresponsive to sildenafil 100 mg monotherapy and receiving concomitant sildenafil 100 mg (N = 75). Postmarketing AndroGel pharmacovigilance reporting data from 2001 to 2011 was searched for events coded as priapism. Main Outcome Measures The incidence of priapism and/or related symptoms reported as urogenital or reproductive system AEs. Results In the 283 men exposed to AndroGel 1% over the three trials, mean exposure ranged from 84 days to 149 days. No AEs described as priapism or related symptoms were reported in the three trials. In the postmarketing data, representing 40 million units sold, eight cases described as priapism were reported. Of the six cases with accompanying data, all were judged as possibly related to AndroGel. Conclusions Safety data from the clinical trials for AndroGel 1% did not report any cases of priapism, and its incidence in the postmarketing pharmacovigilance data is extremely low, indicating a minimal risk of inducing priapism.

Advances in the understanding of priapism

“…Ninety four percent of patients reported resolution of priapism while on treatment, and 29% reported no recurrence after discontinuation of treatment (55). On the other hand, hypogonadal men supplemented with topical testosterone do not experience higher rates of priapism (56), suggesting that modulating testosterone may be less beneficial than other molecular targets. While testosterone deficiency and priapism are common in sickle cell disease patients, a cross-sectional study of 50 men with sickle cell disease was not able to demonstrate an association between testosterone deficiency and priapism (57).…”

Molecular Pathophysiology of Priapism: Emerging Targets

“…Several medical case reports have, even recently, documented priapism episodes in association with TRT in hypogonadal males [73–75]. However, these cases of priapism have all occurred with use of intramuscular testosterone esters that result in supra-physiologic levels of testosterone [76]. The sporadic and infrequent occurrence of these cases questions the association of the priapism episodes and TRT.…”

“…The sporadic and infrequent occurrence of these cases questions the association of the priapism episodes and TRT. In fact, Burnett et al reported no association between priapism episodes and TRT in men using AndroGel, a commonly prescribed agent in hypogonadal males [76]. In 283 men investigated in 3 trials, no episode of priapism was reported.…”

“…Although TRT has commonly been thought to precipitate episodes in isolated case reports, recent clinical studies have failed to identify such an association [76, 79]. Additionally, elevated testosterone levels have never been demonstrated in patients with recurrent priapism.…”

How I treat priapism

“…Despite isolated case reports describing TRT as a precipitant of priapism, recent clinical studies have not found an association and elevated testosterone levels have never been demonstrated in RIP. [66][67][68] Given the critical role of androgens in erection physiology, particularly in regulating NOS and PDE5 expression, [69][70][71] and the high prevalence of hypogonadism among SCD patients with priapism, 68 emerging evidence suggests that TRT may be beneficial by restoring NO regulation. 65, 69 Further studies of TRT in priapism are ongoing.…”