Phosphodiesterase inhibitors and testicular torsion: A systematic review and meta-analysis of animal studies.

Background: Testicular torsion is a common urological emergency in children and teenagers that, in most cases, requires surgical exploration and detorsion. However, even after a successful intervention, a high number of patients still develop irreversible damage.

Objectives: To investigate whether the administration of phosphodiesterase inhibitors (PDE) in animal models of testicular torsion can reduce damages caused by the ischemia-reperfusion syndrome.

Materials and methods: A systematic search of the Medline, Web of Science, Embase, and Ovid databases for studies up to December 2023 was performed using PRISMA guidelines. A detailed search was conducted using the following key terms: "testicles," "ischemia," "reperfusion," and "phosphodiesterase inhibitors." There was no restriction regarding language or year of publication. We investigated spermatogenesis by the Johnsen's biopsy score (JTBS) and histological damage by the Cosentino's biopsy score (CBS). Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) testicular levels were also analyzed.

Results: Initially, 296 articles were identified. However, only 20 studies met the inclusion criteria. PDE inhibitors improved JTBS (MD = 2.53, CI = 1.94 to 3.13), CBS (MD = -1.11, CI = -1.25 to -0.97) and SOD (SMD = 3.27, CI = 1.59 to 4.95) outcomes. PDE did not improve MDA (SMD = -0.93, CI = -2.19 to 0.34), NO (SMD = -0.54, CI = -1.56 to 0.48), and GPx (SMD = 0.77, CI = -0.38 to 1.92) outcomes. A higher dose of PDE inhibitors only improved CBS outcome.

Discussion and conclusion: This review indicates that the administration of PDE inhibitors in rats ameliorated the outcomes, representing a promising complementary strategy for spermatogenesis recovery following testicular torsion. Our review suggests that JTBS and CBS could be translated into future human studies, validating and extending these findings within the context of human physiopathology, while providing applicability of interventions in real clinical practice.