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A 12.5\u00a0Gy\/fraction dose was administered to the rectum in groups R, RPT, RP, and RT. Udenafil (20\u00a0mg\/kg) was administered daily via nasogastric tubes in group RPT and group RP for 4\u00a0weeks starting 1\u00a0day after radiotherapy. Testosterone enanthate (25\u00a0mg\/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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcome<\/jats:title>\n                  <jats:p>Testosterone enhanced the effect of PDE5I on penile tissue after radiotherapy by amplifying the nitric oxide synthase activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>eNOS 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Translation<\/jats:title>\n                  <jats:p>Clinicians 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strengths &amp; Limitations<\/jats:title>\n                  <jats:p>This 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Despite 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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2020.04.004","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T21:43:11Z","timestamp":1590615791000},"page":"1268-1279","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Testosterone in Amplifying the Effect of a Phosphodiesterase Type 5 Inhibitor After Pelvic Irradiation"],"prefix":"10.1093","volume":"17","author":[{"given":"Dong Sup","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Urology , , Suwon , South Korea"},{"name":"St. Vincent's Hospital , , Suwon , South Korea"},{"name":"College of Medicine , , Suwon , South Korea"},{"name":"The Catholic University of Korea , , Suwon , South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Wan","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Urology , Seoul , South Korea"},{"name":"Yeouido St. Mary's Hospital , Seoul , South Korea"},{"name":"College of Medicine , Seoul , South Korea"},{"name":"The Catholic University of Korea , Seoul , South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"2023011111122877500_bib1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S1470-2045(11)70097-3","article-title":"Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial","volume":"12","author":"van Gijn","year":"2011","journal-title":"Lancet Oncol"},{"key":"2023011111122877500_bib2","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1002\/(SICI)1097-0142(19961101)78:9<1871::AID-CNCR5>3.0.CO;2-I","article-title":"Pelvic autonomic nerve preservation for patients with rectal carcinoma. 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