Effects of Testosterone Treatment on Anal Sphincter Damage Repair in Ovariectomized Rats

Overview

Journal Turk J Med Sci

Specialty General Medicine

Date 2023 Jul 21

PMID 37476872

Authors

Irem Senyuva

Duygu Baki Acar

Hasan Huseyin Demirel

Ece Tunc

Affiliations

Soon will be listed here.

Abstract

Background: Fecal incontinence (FI) generally occurs with anal sphincter damage caused by vaginal delivery in women, obvious FI can develop in the postmenopausal stage. This pelvic floor dysfunction has no rational medical therapeutic options. We investigated the effect of testosterone treatment on the anal sphincter structure, serum thiol/disulfide levels, uterine tissue, and body composition in female rats in an experimental menopause-FI model.

Methods: The animal experiments were performed between September and November 2020 at Experimental Animal Application and Research Center, Afyon Kocatepe University, Afyonkarahisar, Turkey. Thirty-two female rats were divided into four groups: sham, saline, 10 mg/kg testosterone undecanoate, 100 mg/kg testosterone undecanoate. Except for the sham group, all the other groups underwent ovariectomy (OVE) to create a menopause model. Two weeks after this procedure, the FI model was created under general anesthesia in all rat groups. At the end of the experiment, the rats were placed under general anesthesia, weighed, and euthanized after recording the data. The anal sphincter region and uterine tissue samples were collected for histopathological examinations, and blood samples were collected for total testosterone and thiol/disulfide homeostasis analyses.

Results: An increase in anal sphincter muscles and connective tissue thickness was observed in the testosterone-administered groups (p = 0.001). No difference was detected between the groups in the total thiol, native thiol, and disulfide balance (p = 0.087, p = 0.604, p = 0.092). The testosterone-treated groups did not have severe uterine epithelial degradation, hyperemia, or increased endometrial thickness (p = 0.186, p = 0.222, p = 0.630). The body weight of all rats increased (p < 0.05), but the omental weight did not increase (p = 0.061).

Discussion: Testosterone treatment increased the anal sphincter muscle and connective tissue thickness without causing any oxidative stress and did not result in a pathological change in the uterine tissue and body fat composition.

References

Gharaibeh B, Chun-Lansinger Y, Hagen T, Ingham S, Wright V, Fu F . Biological approaches to improve skeletal muscle healing after injury and disease. Birth Defects Res C Embryo Today. 2012; 96(1):82-94. PMC: 4360899. DOI: 10.1002/bdrc.21005. View

Filippin L, Moreira A, Marroni N, Xavier R . Nitric oxide and repair of skeletal muscle injury. Nitric Oxide. 2009; 21(3-4):157-63. DOI: 10.1016/j.niox.2009.08.002. View

Joubert Y, Tobin C . Satellite cell proliferation and increase in the number of myonuclei induced by testosterone in the levator ani muscle of the adult female rat. Dev Biol. 1989; 131(2):550-7. DOI: 10.1016/s0012-1606(89)80025-9. View

Ho M, Bhatia N, Bhasin S . Anabolic effects of androgens on muscles of female pelvic floor and lower urinary tract. Curr Opin Obstet Gynecol. 2004; 16(5):405-9. DOI: 10.1097/00001703-200410000-00009. View

Gibson D, Simitsidellis I, Collins F, Saunders P . Androgens, oestrogens and endometrium: a fine balance between perfection and pathology. J Endocrinol. 2020; 246(3):R75-R93. DOI: 10.1530/JOE-20-0106. View

Vegunta S, Kling J, Kapoor E . Androgen Therapy in Women. J Womens Health (Larchmt). 2019; 29(1):57-64. DOI: 10.1089/jwh.2018.7494. View

Erel O, Neselioglu S . A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014; 47(18):326-32. DOI: 10.1016/j.clinbiochem.2014.09.026. View

Woodhouse L, Gupta N, Bhasin M, Singh A, Ross R, Phillips J . Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab. 2004; 89(2):718-26. DOI: 10.1210/jc.2003-031492. View

Tobin C, Joubert Y . Testosterone-induced development of the rat levator ani muscle. Dev Biol. 1991; 146(1):131-8. DOI: 10.1016/0012-1606(91)90453-a. View

10.

Aslan M, Erkanli Senturk G, Akkaya H, Sahin S, Yilmaz B . The effect of oxytocin and Kisspeptin-10 in ovary and uterus of ischemia-reperfusion injured rats. Taiwan J Obstet Gynecol. 2017; 56(4):456-462. DOI: 10.1016/j.tjog.2016.12.018. View

11.

Chainy G, Sahoo D . Hormones and oxidative stress: an overview. Free Radic Res. 2019; 54(1):1-26. DOI: 10.1080/10715762.2019.1702656. View

12.

Sies H . Oxidative stress: from basic research to clinical application. Am J Med. 1991; 91(3C):31S-38S. DOI: 10.1016/0002-9343(91)90281-2. View

13.

Bonilla-Becerra S, de Oliveira M, Calmasini F, Rojas-Moscoso J, Zanesco A, Antunes E . Micturition dysfunction in four-month old ovariectomized rats: Effects of testosterone replacement. Life Sci. 2017; 179:120-129. DOI: 10.1016/j.lfs.2017.05.006. View

14.

Kammerer-Doak D . Assessment of sexual function in women with pelvic floor dysfunction. Int Urogynecol J Pelvic Floor Dysfunct. 2009; 20 Suppl 1:S45-50. DOI: 10.1007/s00192-009-0832-y. View

15.

Schiaffino S, Dyar K, Ciciliot S, Blaauw B, Sandri M . Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 2013; 280(17):4294-314. DOI: 10.1111/febs.12253. View

16.

Joubert Y, Tobin C, Lebart M . Testosterone-induced masculinization of the rat levator ani muscle during puberty. Dev Biol. 1994; 162(1):104-10. DOI: 10.1006/dbio.1994.1070. View

17.

Simitsidellis I, Saunders P, Gibson D . Androgens and endometrium: New insights and new targets. Mol Cell Endocrinol. 2017; 465:48-60. DOI: 10.1016/j.mce.2017.09.022. View

18.

Padero M, Bhasin S, Friedman T . Androgen supplementation in older women: too much hype, not enough data. J Am Geriatr Soc. 2002; 50(6):1131-40. DOI: 10.1046/j.1532-5415.2002.50273.x. View

19.

Raafat A, Hofseth L, Li S, Bennett J, Haslam S . A mouse model to study the effects of hormone replacement therapy on normal mammary gland during menopause: enhanced proliferative response to estrogen in late postmenopausal mice. Endocrinology. 1999; 140(6):2570-80. DOI: 10.1210/endo.140.6.6634. View

20.

Herbst K, Bhasin S . Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care. 2004; 7(3):271-7. DOI: 10.1097/00075197-200405000-00006. View