Pamela MANDELA, Isaac CHERUIYOT, Beda OLABU, Martin KAMAU, Kevin ONGETI

Castration induces progressive increase in the carotid intima-medial thickness of the male rat

Objectives: The role of androgens in the development of cardiovascular diseases remains controversial. The current studytherefore aimed to determine the changes in the carotid intima-medial thickness of the male rat in surgically-induced hypogonadism.Methods: Twenty-two Rattus norvegicus male rats aged two months were used. The rats were randomly assigned into baseline (4), experimental (9) and control (9) groups. Hypogonadism was surgically induced in the experimental group by bilateralorchiectomy under local anesthesia. At experiment weeks 3, 6 and 9, three rats from each group (experimental and control) wereeuthanized, their common carotid artery harvested, and routine processing was done for paraffin embedding, sectioning andstaining. The photomicrographs were taken using a digital photomicroscope for morphometric analysis.Results: The mean carotid intima-median thickness was 321.97 μm at baseline. There was a progressive increase in the carotidintima-median thickness by 17.6%, 37% and 67.1% of the baseline values in the castrated group at the end of the third, sixthand ninth week respectively (p

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Liviakis L, Pogue B, Paramsothy P, Bourne A, Gill EA. Carotid intima-media thickness for the practicing lipidologist. J Clin Lipidol 2010;4:24–35.
Kasliwal RR, Bansal M, Desai D, Sharma M. Carotid intima–media thickness: current evidence, practices, and Indian experience. Indian J Endocrinol Metab 2014;18:13–22.
Provost EB, Madhloum N, Panis LI, De Boever P, Nawrot TS. Carotid intima-media thickness, a marker of subclinical atherosclerosis, and particulate air pollution exposure: the meta-analytical evidence. PloS One 2015;10:e0127014.
Holland Z, Ntyintyane L, Gill G, Raal F. Carotid intima–media thickness is a predictor of coronary artery disease in South African black patients. Cardiovasc J Africa 2009;20:237–8.
Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007;115:459–67.
Hurst RT, Ng DW, Kendall C, Khandheria B. Clinical use of carotid intima-media thickness: review of the literature. J Am Soc Echocardiogr 2007;20:907–14.
Peters SA, den Ruijter HM, Grobbee DE, Bots ML. Results from a carotid intima-media thickness trial as a decision tool for launching a large-scale morbidity and mortality trial. Circ Cardiovasc Imaging 2013;6:20–5.
Bots ML. Carotid intima-media thickness as a surrogate marker for cardiovascular disease in intervention studies. Curr Med Res Opin 2006;22:2181–90.
Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H, Christiansen C. Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circ Res 1999;84:813–9.
McGrath KC, McRobb LS, Heather AK. Androgen therapy and atherosclerotic cardiovascular disease. Vasc Health Risk Manag 2008;4:11–21.
Maravelias C, Dona A, Stefanidou M, Spiliopoulou C. Adverse effects of anabolic steroids in athletes. A constant threat. Toxicol Lett 2005;158:167–75.
Luque-Ramírez M, Mendieta-Azcona C, Alvarez-Blasco F, EscobarMorreale HF. Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome. Hum Reprod 2007;22:3197–203.
Allameh Z, Rouholamin S, Adibi A, Mehdipour M, Adeli M. Does carotid intima-media thickness have relationship with polycystic ovary syndrome? Int J Prev Med 2013;4:1266–70.
Kim MS, Dao-Tran A, Davidowitz E, Tseng T, Gilsanz V, RyabetsLienhard A, Nguyen E, Geffner ME. Carotid intima-media thickness is associated with increased androgens in adolescents and young adults with classical congenital adrenal hyperplasia. Horm Res Paediatr 2016;85:242–9.
Haring R, Baumeister SE, Völzke H, Dörr M, Felix SB, Kroemer HK, Nauck M, Wallaschofski H. Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia. Eur J Cardiovasc Prev Rehabil 2011;18:86–96.
Fahed AC, Gholmieh JM, Azar ST. Connecting the lines between hypogonadism and atherosclerosis. Int J Endocrinol 2012;2012: 793953.
Soisson V, Brailly-Tabard S, Empana JP, Féart C, Ryan J, Bertrand M, Guiochon-Mantel A, Scarabin PY. Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men. Atherosclerosis 2012;223:244–9.
Martín-Merino E, Johansson S, Morris T, Garcia Rodríguez LA. Androgen deprivation therapy and the risk of coronary heart disease and heart failure in patients with prostate cancer. Drug Saf 2011;34:1061–77.
Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007;116:2694–701.
Menke A, Guallar E, Rohrmann S, Nelson WG, Rifai N, Kanarek N, Feinleib M, Michos ED, Dobs A, Platz EA. Sex steroid hormone concentrations and risk of death in US men. Am J Epidemiol 2010;171:583–92.
Karakitsos D, Patrianakos AP, De Groot E, Boletis J, Karabinis A, Kyriazis J, Samonis G, Parthenakis FI, Vardas PE, Daphnis E. Androgen deficiency and endothelial dysfunction in men with endstage kidney disease receiving maintenance hemodialysis. Am J Nephrol 2006;26:536–43.
Kumar N, Swamy R, Patil J, Guru A, Aithal A, Shetty P. Presence of arteriovenous communication between left testicular vessels and its clinical significance. Case Rep Vasc Med 2014;2014:160824.
Christe N, Meier CA. Hypotestosteronaemia in the aging male: should we treat it? Swiss Med Wkly 2015;145:w14216.
Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004;109:2074–9.
Farias JM, Tinetti M, Khoury M, Umpierrez GE. Low testosterone concentration and atherosclerotic disease markers in male patients with type 2 diabetes. J Clin Endocrinol Metabol 2014;99:4698–703.
Chan YX, Knuiman MW, Hung J, Divitini ML, Handelsman DJ, Beilby JP, McQuillan B, Yeap BB. Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intimamedia thickness and the presence of carotid plaque in men with and without coronary artery disease. Endocr J 2015;62:777–86.
Gilliver SC, Ashworth JJ, Mills SJ, Hardman MJ, Ashcroft GS. Androgens modulate the inflammatory response during acute wound healing. J Cell Sci 2006;119:722–32.
Shiota M, Song Y, Takeuchi A, Yokomizo A, Kashiwagi E, Kuroiwa K, Tatsugami K, Uchiumi T, Oda Y, Naito S. Antioxidant therapy alleviates oxidative stress by androgen deprivation and prevents conversion from androgen dependent to castration resistant prostate cancer. J Urol 2012;187:707–14.
Patel SD, Waltham M, Wadoodi A, Burnand KG, Smith A. The role of endothelial cells and their progenitors in intimal hyperplasia. Therap Adv Cardiovasc Dis 2010;4:129–41.
Sadasivam K, Nagarajan P, Durai I, Sundari M, Ayyavoo S, Ramamoorthy T. Carotid artery intima-media thickness in young adults with family history of coronary artery disease. J Clin Diagn Res 2015;9:CC01–4.
Ellul J, Talelli P, Terzis G, Chrysanthopoulou A, Gioldasis G, Papapetropoulos T. Is the common carotid artery intima–media thickness associated with functional outcome after acute ischaemic stroke? J Neurol Neurosurg Psychiatry 2004;75:1197–9.
Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SA, Jamrozik K, Flicker L, Hankey GJ. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. J Clin Endocrinol Metab 2009;94:2353–9.
Oskui PM, French WJ, Herring MJ, Mayeda GS, Burstein S, Kloner RA. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. J Am Heart Assoc 2013;2:e000272.
Kalinchenko S, Zemlyanoy A, Gooren LJ. Improvement of the diabetic foot upon testosterone administration to hypogonadal men with peripheral arterial disease. Report of three cases. Cardiovasc Diabetol 2009;8:19.