Combination of atorvastatin and fenofibrate altered androgenic activities of male rats

  • Kawa F. Dizaye Department of Pharmacology, College of Medicine, Hawler Medical University, Erbil, Iraq.
  • Sundus Rashad Ahmed Department of Pharmacology, College of Medicine, Hawler Medical University, Erbil, Iraq.
Keywords: Atorvastatin, Fenofibrate, Sperm parameters, Androgens activities, Sexual hormones

Abstract

Background and objective: Many drugs and chemical substances may induce sexual dysfunction and have a negative impact on male fertility. Lipid-lowering agents like statins and fibrates are usually recommended for cardiovascular diseases prevention. However, the combination of atorvastatin and fenofibrate is the subject of questions concerning their effect on androgenic activities in this study. This study was designed to evaluate the efficacy and toxicity of atorvastatin, fenofibrate, and their combination on sperm parameters, sexual hormones, and histopathology of the testis.

Methods: Twenty-four male rats were divided into four groups, each of six. The first group served as a control. The second, third, and fourth groups received atorvastatin, fenofibrate, and their combination, respectively. After 28 days, blood samples were collected for hormones and other parameters evaluations. Testis and epididymis were taken for histopathology studies and sperm parameters assessments.

Results: Fenofibrate showed a significant reduction in sperm viability and serum levels of luteinizing and estradiol hormones. The combination of both drugs significantly reduced the sperm count and viability in normal male rats. Both atorvastatin and its combination mildly changed the histological structures of the testis, reduced number of spermatozoa, and arrested spermatogenesis.

Conclusion: The findings from this prospective study suggested that there was no harmful effect of atorvastatin usage on conventional sperm parameters and sexual hormones.  Fenofibrate usage was not adversely associated with sperm parameters other than sperm viability. The combination of atorvastatin and fenofibrate significantly reduced the sperm count and viability. No deleterious effects of the drugs were seen on the testosterone, which was the essential hormone for all stages of spermatogenesis, sperm production, maturation, and transport.

References

Conaglen HM, Conaglen JV. Drug-induced sexual dysfunction in men and women. Australian prescriber 2013; 36(2):42–5.

Jung I, Gurzu S, Turdean S. Iatrogenic Pathology of the Male Genital System. Textbook of Iatrogenic Pathology. Bentham ebooks; 2017. P. 167–76.

Drobnis EZ, Nangia AK. Male reproductive functions disrupted by pharmacological agents. In: Impacts of Medications on Male Fertility. Adv Exp Med Biol 2017; 1034:13–24.

Schill WB, Comhaire FH, Hargreave TB. Andrology for the clinician. Berlin: Springer Science & Business Media; 2006. P. 76.

Kraemer WJ, Rogol AD. The encyclopaedia of sports medicine: An IOC medical commission publication, the endocrine system in sports and exercise. Hoboken, USA: John Wiley & Sons 2008; 11:86.

Antonopoulos A, Margaritis M, Lee R, Channon K, Antoniades C. Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des 2012; 18(11):1519–30.

Gotto AM, Moon JE. Recent clinical studies of the effects of lipid-modifying therapies. The Am J Cardio 2012; 110(1):15A–26.

Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner J 2010; 10(1):16–21.

Graveline D. Cholesterol-lowering injectables: more harm than good? Journal of American Physicians and Surgeons 2015; 20(4):119–22.

Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A. Antioxidant supplements and semen parameters: An evidence based review. Int J Reprod Biomed 2016; 14(12):729–36.

Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. BMC Medicine 2013; 11(1):57.

Pons-Rejraji H, Brugnon F, Sion B, Maqdasy S, Gouby G, Pereira B, et al. Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial. Reprod Biol Endocrinol 2014; 12(1):65.

Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 2005; 45(10):1649–53.

Amulya K, Gayathri K, Sowjanya G, Priyanka R, Ramesh G, Babu PS. A comparative study on atorvastatin plus fenofibratefor its safety and effectiveness in hyperlipidemic patients in as tertiary care teaching hospital. World J Pharm Res 2017; 6(10):1311–9.

Atanasovska E, Pavlovska K, Jakjovski K, Gjorgjievska K, Zendelovska D, Petrushevska M, et al. Differential effects of peroxisome proliferator-activator receptor (PPAR) alpha and gamma agonists on body weight and adipose depots in fructose Fed Wistarrats. Journal of Morphological Sciences 2018; 1(1):62–72.

Rang HP, Dale MM, Ritte JM, Flower RJ, Henderson G. Atherosclerosis and lipoprotein metabolism. In: Rang HP, Dale MM (Editors), Rang and Dale’s Pharmacology.8thed. Edinburgh: Elsevier Churchill Livingstone; 2016. P. 290.

Dizaye K, Jarjees H. Effects of Omega-3 on lipid profile and haematological parameters in hyperlipidemic rats. Middle East Journal of Internal Medicine 2014; 7(3):34–40.

Dizaye KF, Chalaby LA. Hypolipidemic efficacy of TrigonellaFoenum seeds in comparison with Rosuvastatin and Fenofibrateinhyperlipidemic rats. Middle East Journal of Family Medicine 2015; 13(6):30–8.

Galhotra P, Prabhakar P, Meghwani H, Mohammed SA, Banerjee SK, Seth S, et al. Beneficial effects of fenofibratein pulmonary hypertension in rats. Mol Cell Biochem 2018; 449(1-2):185–94.

Nagahama H, Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Namioka T, Namioka A, et al. Preservation of interhemispheric cortical connections through corpus callosum following intravenous infusion of mesenchymal stem cells in a rat model of cerebral infarction. Brain Res 2018; 1695:37–44.

Shabanian S, Farahbod F, Rafieian M, Ganji F, Adib A. The effects of Vitamin C on sperm quality parameters in laboratory rats following long- term exposure to cyclophosphamide. J Adv Pharm Technol Res 2017; 8(2):73–9.

Yucra S, Gasco M, Rubio J, Nieto J, Gonzales GF. Effect of different fractions from hydroalcoholic extract of Black Maca (Lepidiummeyenii) on testicular function in adult male rats. Fertil Steril 2008; 89(5):1461–7.

Ellenburg J, Drwiega J, Posey A, Goldberg M, Gordetsky J, Kolettis P. MP19-18 The use of formalin as a fixative for testicular biopsies. J Urol 2018; 199(4):250–1.

Tarantino N, Santoro F, De Gennaro L, Correale M, Guastafierro F, Gaglione A, et al. Fenofibrate/simvastatin fixed-dose combination in the treatment of mixed dyslipidemia: safety, efficacy, and place in therapy. Vasc Health Risk Manag 2017; 13:29–41.

Keihani S, Martin C, Craig JR, Zhang C, Presson AP, Myers JB, et al. Semen parameters are unaffected by statin use in men evaluated for infertility. Andrologia 2018; 50(5):e12995.

Monsalve FA, Pyarasani RD, Delgado- Lopez F, Moore-Carrasco R. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators of Inflammation2013; 2013:1–18.

Semet M, Paci M, Saïas-Magnan J, Metzler-Guillemain C, Boissier R, Lejeune H, et al. The impact of drugs on male fertility: a review. Andrology 2017; 5(4):640–63.

Delashoub M, Ziaee M, Khorrami A, Banan-Khojasteh SM. Comparison of the Effects of Clofibrate and Silafibrate on sperm parameters quality and sex hormones in male rats. Urol J 2018; 15(2):38–43.

Schlatt S, Ehmcke J. Regulation of spermatogenesis: an evolutionary biologist's perspective. In Seminarsin cell & developmental biology. Academic Press 2014; 29:2–16.

Sookoian S, Pirola CJ. Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol: WJG 2015; 21(3):711–25.

Jose J. Statins and its hepatic effects: newer data, implications, and changing recommendations. J Pharm Bioallied Sci 2016; 8(1):23–8.

Tsimihodimos V, Miltiadous G, Daskalopoulou SS, Mikhailidis DP, Elisaf MS. Fenofibrate: metabolic and pleiotropic effects. Curr Vasc Pharmacol 2005; 3(1):87–98.

Yamagishi SI, Matsui T, Nakamura K. Atorvastatin and diabetic vascular complications. Curr Pharm Des 2006;12(12):1549–54.

Aguirre L, Hijona E, Macarulla MT, Gracia A, Larrechi I, Bujanda L, et al. Several statins increase body and liver fat accumulation in a model of metabolic syndrome. J Physiol Pharmacol 2013; 64(3):281–8.

Yoon M. PPAR in obesity: sex difference and estrogen involvement. PPAR research 2010; 2010.

Littarru GP, Langsjoen P. Coenzyme Q 10 and statins: biochemical and clinical implications. Mitochondrion 2007; 7:168–74.

Published
2019-08-06
How to Cite
Dizaye, K., & Ahmed, S. (2019). Combination of atorvastatin and fenofibrate altered androgenic activities of male rats. Zanco Journal of Medical Sciences (Zanco J Med Sci), 23(2), 273-282. https://doi.org/10.15218/zjms.2019.034
Section
Original Articles