Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats

Background: Because androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late. Aim: To investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in t...

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Main Authors: Tomoya Kataoka, PhD, Yuji Hotta, PhD, Yuka Yamamoto, Ayako Fukamoto, Madoka Takeuchi, Yasuhiro Maeda, PhD, Kazunori Kimura, PhD
Format: Article
Language:English
Published: Oxford University Press 2021-08-01
Series:Sexual Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2050116121000283
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author Tomoya Kataoka, PhD
Yuji Hotta, PhD
Yuka Yamamoto
Ayako Fukamoto
Madoka Takeuchi
Yasuhiro Maeda, PhD
Kazunori Kimura, PhD
author_facet Tomoya Kataoka, PhD
Yuji Hotta, PhD
Yuka Yamamoto
Ayako Fukamoto
Madoka Takeuchi
Yasuhiro Maeda, PhD
Kazunori Kimura, PhD
author_sort Tomoya Kataoka, PhD
collection DOAJ
description Background: Because androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late. Aim: To investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in the corpus cavernosum. Methods: Rats were subjected to ART for 4 (Late-ART [4w]) or 8 (Late-ART [8w]) weeks. In either case, rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone (3 mg/kg/day; Cast+T), and sham (Sham). Cast + T rats received daily subcutaneous doses of testosterone starting 4 weeks after castration for 4 or 8 weeks whereas Sham and Cast rats received only the vehicle. Outcomes: Erectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve, corporal veno-occlusive function using dynamic infusion cavernosometry, and histology using Masson's trichrome staining. Results: No increase in the ICP was observed in Cast+T rats in the Late-ART (4w) group (0.47 ± 0.02, P > .05), whereas, in Cast+T rats in the Late-ART (8w) group, there was a significant increase in the ICP/MAP ratio (0.60 ± 0.02, P < .05), drop rate, and smooth muscle/collagen ratio. Clinical Translation: The present study provides scientific evidence for the effect of late ART on erectile function. Strengths and Limitations: This study provides insights into the influence of late ART on erectile function through improvements in the structure of corpus cavernosum. The major limitation of this study is the difference in the time required for healing between the humans and rats, which might have a bearing on the translational relevenace of the results. Conclusions: Late ART could improve erectile function. However, as improvement requires a considerable time period, it is necessary to persist with therapy patiently for optimal results.Kataoka T, Hotta Y, Yamamoto Y, et al. Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats. Sex Med 2021;XX:XX–XXX.
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spelling doaj.art-f2fb49fb742d4640a739ed7a69e9df762023-09-03T02:51:29ZengOxford University PressSexual Medicine2050-11612021-08-0194100348Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated RatsTomoya Kataoka, PhD0Yuji Hotta, PhD1Yuka Yamamoto2Ayako Fukamoto3Madoka Takeuchi4Yasuhiro Maeda, PhD5Kazunori Kimura, PhD6Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, JapanDepartment of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan; Department of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan; Corresponding Author: Kazunori Kimura, PhD, Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Tel: +81-52-858-7404; fax: +81-52-858-7402.Background: Because androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late. Aim: To investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in the corpus cavernosum. Methods: Rats were subjected to ART for 4 (Late-ART [4w]) or 8 (Late-ART [8w]) weeks. In either case, rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone (3 mg/kg/day; Cast+T), and sham (Sham). Cast + T rats received daily subcutaneous doses of testosterone starting 4 weeks after castration for 4 or 8 weeks whereas Sham and Cast rats received only the vehicle. Outcomes: Erectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve, corporal veno-occlusive function using dynamic infusion cavernosometry, and histology using Masson's trichrome staining. Results: No increase in the ICP was observed in Cast+T rats in the Late-ART (4w) group (0.47 ± 0.02, P > .05), whereas, in Cast+T rats in the Late-ART (8w) group, there was a significant increase in the ICP/MAP ratio (0.60 ± 0.02, P < .05), drop rate, and smooth muscle/collagen ratio. Clinical Translation: The present study provides scientific evidence for the effect of late ART on erectile function. Strengths and Limitations: This study provides insights into the influence of late ART on erectile function through improvements in the structure of corpus cavernosum. The major limitation of this study is the difference in the time required for healing between the humans and rats, which might have a bearing on the translational relevenace of the results. Conclusions: Late ART could improve erectile function. However, as improvement requires a considerable time period, it is necessary to persist with therapy patiently for optimal results.Kataoka T, Hotta Y, Yamamoto Y, et al. Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats. Sex Med 2021;XX:XX–XXX.http://www.sciencedirect.com/science/article/pii/S2050116121000283TestosteroneErectile dysfunctionCorporal veno-occlusive functionHistological change
spellingShingle Tomoya Kataoka, PhD
Yuji Hotta, PhD
Yuka Yamamoto
Ayako Fukamoto
Madoka Takeuchi
Yasuhiro Maeda, PhD
Kazunori Kimura, PhD
Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats
Sexual Medicine
Testosterone
Erectile dysfunction
Corporal veno-occlusive function
Histological change
title Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats
title_full Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats
title_fullStr Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats
title_full_unstemmed Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats
title_short Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats
title_sort effect of late androgen replacement therapy on erectile function through structural changes in castrated rats
topic Testosterone
Erectile dysfunction
Corporal veno-occlusive function
Histological change
url http://www.sciencedirect.com/science/article/pii/S2050116121000283
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