Published: 2018-03-28

Investigation the effect of propranolol, metoprolol and carvedilol on spermatogenesis in rat testis

Huseyin Eren, Abdullah Sivrikaya, Umit Cobanoglu, Nuri Ihsan Kalyoncu, Ersagun Karaguzel, Murat Topbaş, Ilke Onur Kazaz, Mustafa Ozan Horsanali, Omer Kutlu


Background: Coronary arterial diseases are one of the increasing disease around the worldwide. Because of common using of the beta blockers, we aimed to investigate the effect of different beta-adrenergic receptor blockers on spermatogenesis in male rats.

Methods: Adult male Sprague Dawley rats were obtained. Totally 32 rats homogenized according to their weight and divided into four groups that each one includes eight rats. Three of groups were determined as drug groups and remained groups were determined as a control group. Propranolol 40mg/kg, Metoprolol succinate 60mg/kg, Carvedilol 30mg/kg dosage was given by oral gavage within the saline solution, and the only saline solution was given to control group for 21 days, respectively. After 21 days rats were sacrificed, and testis were extracted. Then, histopathologic evaluation was performed.

Results: There was statistical significance both right and left testis volume of experimental between control and carvedilol groups (p<0.05). There was statistical histopathological significance between control and carvedilol (p<0.05), control and propranolol (p<0.05), metoprolol succinate and propranolol (p<0.05), metoprolol succinate and carvedilol groups (p<0.05), respectively.

Conclusions: Beta-adrenergic receptor blockers have adverse effects on spermatogenesis. Especially propranolol and carvedilol that were non-selective, effects spermatogenesis worse than selective beta blockers such as metoprolol succinate. Extensive use of these drugs may affect spermatogenesis in male, so male patients who have a complaint of infertility should be questioned regarding the use of beta blockers.


Carvedilol, Metoprolol succinate, Propranolol, Spermatogenesis, Testis

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Zhou Y, Xu M, Zhang Y, Guo Y, Zhang Y, He B. Effects of long‐term application of metoprolol and propranolol in a rat model of smoking. Clinical Experimental Pharmacology Physiology. 2014;41(9):708-15.

Moss HB, Procci WR. Sexual dysfunction associated with oral antihypertensive medication: a critical survey of the literature. General hospital psychiatry. 1982;4(2):121-9.

Poloniecki J, Hamilton M. Subjective costs of antihypertensive treatment. Human toxicology. 1985;4(3):287-91.

Croog SH, Levine S, Testa MA, Brown B, Bulpitt CJ, Jenkins CD, et al. The effects of antihypertensive therapy on the quality of life. New Eng J Med. 1986;314(26):1657-64.

Heel R, Brogden R, Speight T, Avery G. Atenolol: A review of its pharmacological properties and therapeutic efficacy in angina pectoris and hypertension. Drugs. 1979;17(6):425-60.

Mann KV, Abbott E, Gray J, Thiebaux H, Belzer Jr E. Sexual dysfunction with beta-blocker therapy: More common than we think? Sexuality and disability. 1982;5(2):67-77.

Martinez D, Barthe D. Histological study of the action of propranolol on the genital tract of the male rat. Acta anatomica. 1980;109(4):346-54.

Liaqat Ali AKN, Liaqat Ali M, Tahir M. Effects of the propranolol on morphology of adult rats testis. Inter J Pathol. 2008;6(1):19-22.

Vidt DG. Contributing factors in resistant hypertension: truly refractory disease is rarely found in a properly conducted workup. Postgraduate Med. 2000;107(5):57-70.

Barron AJ, Zaman N, Cole GD, Wensel R, Okonko DO, Francis DP. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information. Inter J Cardiol. 2013;168(4):3572-9.

Leonetti G, Egan CG. Use of carvedilol in hypertension: an update. Vasc Health Risk Manag. 2012;8:307-22.

Hayashi T, De Velasco MA, Saitou Y, Nose K, Nishioka T, Ishii T, Uemura H. Carvedilol protects tubular epithelial cells from ischemia-reperfusion injury by inhibiting oxidative stress. Inter J Urol. 2010;17(12):989-95.

Yasar A, Erdemir F, Parlaktas BS, Atilgan D, Koseoglu RD, Saylan O, et al. The effect of carvedilol on serum and tissue oxidative stress parameters in partial ureteral obstruction induced rat model. Kaohsiung J Med Sci. 2013;29(1):19-25.

Hayashi T, Saitou Y, Nose K, Nishioka T, Ishii T, Uemura H. Efficacy of carvedilol for ischemia/reperfusion-induced oxidative renal injury in rats. Elsevier. 2008;40(7):2139-41.

Singh D, Chander V, Chopra K. Carvedilol attenuates ischemia-reperfusion‐induced oxidative renal injury in rats. Fundamental clinical Pharmacol. 2004;18(6):627-634.

Creasy DM. Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging. Toxicologic pathology. 1997;25(2):119-31.

Prichard B, Tomlinson B. The additional properties of beta adrenoceptor blocking drugs. J Cardiovas Pharmaco. 1986;8:S1.

Morgan T. Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clinical pharmacokinetics. 1994;26(5):335-46.

McDevitt DG. Pharmacological Characteristics of [beta] Blockers and Their Role in Clinical Practice. J cardiovascular pharmacology. 1986;8:S5.

Bandmann F. Weitere Beobachtungen über die Hodenfunktion nach lumbaler Grenzstrangresektion. Bruns’ Beitr klin Chir. 1950;181:419.

Semczuk M. The Effects of β‐adrenergic Drugs on the Human Sperm Motility in Vitro. I. The Effects of Propranolol and Isoprenaline. Andrologia. 1987;19(S1):256-61.

El-Sayed M, El-Sayed M, Elazab AeS, Hafeiz M, El-Komy A, Hassan E. Effects of some beta-adrenergic blockers on male fertility parameters in rats. DTW Deutsche tierarztliche Wochenschrift. 1998;105(1):10-2.

Hassan AB E-sM, Shkry IM, Mahdy MY. Effect of beta-adrenergic blocker on male rat fertility. Proc VII Annual Conf Egypt Soc Pharmacol Expt Ther. 1981.

Razzak MA. Beta-adrenergic blockade and blood sugar in dogs. J Egypt Med Assoc. 1976;59:65-75.

Alexander NJ. Animal models for research on contraception and fertility: proceedings of a Symposium on Animal Models for Research on Contraception and Fertility held at the National Academy of Sciences, Washington, DC, United States of America, sponsored by the Institute of Laboratory Animal Resources, Assembly of Life Sciences, National Research Council. Harper and Row;1979.

Suzuki H, Tominaga T, Kumagai H, Saruta T. Effects of first-line antihypertensive agents on sexual function and sex hormones. J Hypertension. 1988;6(4):S649-651.