The Role of Testosterone in Amplifying the Effect of a Phosphodiesterase Type 5 Inhibitor After Pelvic Irradiation |
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| Affiliation: | 1. Department of Urology, St. Vincent''s Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea;2. Department of Urology, Yeouido St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea;1. Institute for the Study of Urological Diseases, Thessaloniki, Greece;2. Department of Urology, Hacettepe University Hospital, Ankara, Turkey;3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy;4. Department of Urology, Zealand University Hospital, Roskilde, Denmark;5. Men''s Health Clinic, Amstelland Hospital, Amsterdam, The Netherlands;6. Endocrinology Unit, Medical Department, Azienda USL, Maggiore-Bellaria Hospital, Bologna, Italy;7. Institute for Sex Counseling and Sexual Sciences, Zurich, Switzerland;1. Urology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria, Madrid, Spain;2. Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel;3. Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Catanzaro, Italy;4. Department of Urology, Biruni University School of Medicine, Istambul, Turkey;5. The Christie NHS Foundation Trust, Manchester, UK;6. Andrology Department, University College, London, UK;7. Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, CA, USA;8. Flare-Health, Amstelveen, The Netherlands;9. Endocrinology Unit, Medical Department, Azienda USL, Maggiore-Bellaria Hospital, Bologna, Italy;10. Urology Department, Hospital Universitario HM Montepríncipe, Madrid, Spain;1. Department of Obstetrics and Gynaecology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany;2. Department of Medical Statistics and Biomathematics, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany;1. Department of Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands;2. Department of Neuropsychiatry, Al-Mattaria Teaching Hospital, Cairo, Egypt;3. Mutmaena Medical Psychiatric Center, Riyadh, Saudi Arabia;4. Department of Work and Social Psychology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands;1. Escola de Psicologia e Ciências da Vida, Universidade Lusófona de Humanidades e Tecnologias, Lisboa, Portugal;2. HEI-Lab: Digital Human-Environment and Interactions Lab, Universidade Lusófona de Humanidades e Tecnologias, Lisboa, Portugal;3. CICPSI, Faculdade de Psicologia, Universidade de Lisboa, Lisboa, Portugal;4. CPUP, Faculdade de Psicologia e Ciências da Educação, Universidade de Porto, Porto, Portugal |
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| Abstract: | BackgroundAfter radiotherapy, the risk of hypogonadism increases, and the incidence of erectile dysfunction increases with time.AimWe investigated the effect of testosterone and a phosphodiesterase type 5 inhibitor (PDE5I) on erectile tissue after radiotherapy.Methods12 male Wistar rats were assigned to each of 5 groups (group C: control; group R: radiation; group RPT: radiation, testosterone, and a PDE5I; group RP: radiation and a PDE5I; and group RT: radiation and testosterone). A 12.5 Gy/fraction dose was administered to the rectum in groups R, RPT, RP, and RT. Udenafil (20 mg/kg) was administered daily via nasogastric tubes in group RPT and group RP for 4 weeks starting 1 day after radiotherapy. Testosterone enanthate (25 mg/kg, IM) was administered immediately after radiotherapy in group RT and group RPT. 6 rats from each group were used to evaluate endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and NOX2, and cavernosal pressure was evaluated in the other 6 rats in each group.OutcomeTestosterone enhanced the effect of PDE5I on penile tissue after radiotherapy by amplifying the nitric oxide synthase activity.ResultseNOS mRNA expression increased in response to either testosterone replacement or PDE5I administration after radiotherapy. nNOS mRNA expression did not significantly increase in response to testosterone replacement, but testosterone significantly enhanced the effect of PDE5I on nNOS mRNA expression. Testosterone significantly amplified the effect of PDE5I on both eNOS and nNOS protein expression. Both testosterone and PDE5I reduced NOX2 protein expression. The intracavernosal pressure during electrical stimulation showed that testosterone alone did not significantly enhance erectile function.Clinical TranslationClinicians should consider both hypoxic tissue damage and hypogonadism during and after radiation, and the combination of testosterone and PDE5I could be more beneficial for preserving erectile tissue than either individual treatment.Strengths & LimitationsThis study describes the role of testosterone in amplifying the effect of a PDE5I on pelvic radiotherapy-induced hypogonadism. However, we did not show the time-dependent effects of testosterone and PDE5I.ConclusionsDespite the fact that the intracavernosal pressure during electrical stimulation did not significantly increase with testosterone replacement after radiotherapy, important changes in nitric oxide synthase activity and superoxide regulation might have amplifying effects on erectile tissue. Therefore, we recommend that physicians monitor testosterone levels and should not hesitate to combine testosterone and PDE5I in cases of radiation-induced hypogonadism if testosterone replacement is not contraindicated.Lee DS, Sohn DW. The Role of Testosterone in Amplifying the Effect of a Phosphodiesterase Type 5 Inhibitor After Pelvic Irradiation. J Sex Med 2020;17:1268–1279. |
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| Keywords: | Radiotherapy Testosterone Phosphodiesterase Type 5 Inhibitors NO Superoxide Erectile Dysfunction |
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