Impairment of sperm characteristics unrelated to hormonal alterations in rats treated with cimetidine
Keywords:Cimetidine, Sperm characteristics, Male fertility hormones
Background: Cimetidine has been reported to possess clinically significant anti androgen activity at high dosage. This study was therefore designed to investigate the effect of medium and high dosages of cimetidine on fertility parameters including hormonal components in male wistar albino rats.
Methods: Eighteen male wistar albino rats were used, and were randomly separated into three groups of 6 rats each. Group one served as control and was gavaged 5ml of distilled water, group II (medium dose) received 475 mg/kg and group III (high dose) received 950 mg/kg of cimetidine respectively twice daily for 21 days. On the 22nd day blood samples were obtained by cardiac puncture; blood serum was obtained for hormonal assay and the testes were harvested for sperm analysis.
Results: FSH level was significantly higher in the medium dose group when compared to the control group. Sperm motility was significantly lower in both medium dose and high dose group when compared to the control group. Percentage sperm concentration was significantly lower in both medium dose and high dose group, this decrease was not dose dependent. Percentage normal sperm morphology was significantly lower in both medium dose and high dose group. Normal sperm morphology was significantly lower in high dose group when compared to medium dose group.
Conclusions: This result is suggestive of a deleterious effect of cimetidine on sperm characteristics with minimal impact on the hormonal component.
Luiz R. Franca, Marcelo C. Leal, Esteia Sasso-cerri, Anitton Vasconcelos, Luciano Debeljuk, Lonnie D. Russell. Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells. Biol Reprod. 2000 Nov;63(5):1403-12.
GlaxoSmithKline. Tagamet, 2009. Available at: https://www.gsk.com.au/resources.ashx/prescriptionmedicinesproductschilddataproinfo/1460/FileName/38A752DE5597F251F19E3B4A0F58AE3D/Tagamet_Tablets_Injection_PI.pdf.
Silverman Richard A. Cimetidine. In: Silverman Richard A, eds. The Organic Chemistry of Drug Design and Drug Action. 2nd ed. Amsterdam: Elsevier Academics Press; 2004: 159.
Amelar RD, Dubin I, Walsh PC. Male fertility. In: Amelar RD, Dubin I, Walsh PC, eds. A Book. 1st ed. Philadelphia: WB Saunders Company; 1977: 258.
Abdulrazzak AA, Bakr SS. Role of mycoplasma in male infertility. Esthern Mediterr Health J. 2000;6(1):149.
Mosher WD. W. F. fecundity and infertility in the United States: incidence and trends. J Tertil Steril. 1991;58:192-3.
Rajmil O, Fernández M, Rojas-Cruz C, Sevilla C, Musquera M, Ruiz-Castañe E. Azoospermia should not be given as the result of vasectomy (in Spanish; Castilian). Arch Esp Urol. 2007;60(1):55-8.
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum. Reprod Update. 2010;16(3):231-45. Licht RS, Handel L, Sigman M. Site of semen collection and its effect on semen analysis parameters. Fertil Steril. 2008;89(2):395-7.
Wang C, Lai CL, Lam KC, Yeung KK. Effect of cimetidine on gonodal function in man. Br J Clin Pharmacol. 1982;13(6):791-4.
Van Thiel DH, Guvaler JS, Smith WI Jr, Paul G. Hypothalamic pituitary gonadal dysfunction in men using cimetidine. New Engl J Med. 1979;300:1012-5.
Bohnet HG, Greiwe M, Hanker JP, Araguna C, Scheider HPG. Effect of cimetidine on prolactin, LH and sex steroid secretion in male and female volunteers. Acta Endocrinol (kbh). 1978;88:428-34.
Paulsen CA, Enzmann GD, Leonard JM, Rogers J. Effect of cimetidine on reproductive function in men. Clin Res. 1981;29:26A.
Rosen SW, Weintraub DB. Monotropic increase in serum FSH correlated with low sperm count in young men wiyh idiopathic oligospermia and aspermia. J Clin Endocrinol Metab. 1971;32:410-6.
Leonard JM, Leach RB, Couture M, Paulsen CA. Plasma and urinary follicle-stimulating hormone in oligospermia. J Clin Endocrinol Metab. 1972;34:209-14.
De Krestser D, Burger HG, Hudson B. The relationship between germinal cells and serum FSH in males with infertility. J Clin Endocrinol Metab. 1974;35:392-401.
Boulpaep EL, Boron WF. FSH. In: Boulpaep EL, Boron WF, eds. Medical Physiology: a Cellular and Molecular Approach. 2nd ed. St. Louis, Mo: Elsevier Saunders; 2005: 1125.
Fowler PA, Sorsa-Leslie T, Harris W, Mason HD. Ovarian gonadotrophin surge-attenuating factor (GnSAF): where are we after 20 years of research? Reproduction. 2003;126(6):689-99.
Santen RJ, Bardin CW. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest. 1973;52:2617-28.
Basu SC. Prolactin. In: Basu SC, eds. Male Reproductive Dysfunction. 2nd ed. New Delhi: JP Medical Ltd; 2011: 223.
Hair WM, Gubbay O, Jabbour HN, Lincoln GA. Prolactin receptor expression in human testis and accessory tissues: localization and function. Mol Hum Reprod. 2002;8(7):606-11.
Nelson RJ. The mechanism of action of cimetidine on prolactin secretion. In: Nelson RJ, eds. An Introduction to Behavioral Endocrinology. 3rd ed. Sunderland, MA: Sinauer Associates; 2005.
Melmed S, Jameson JL. Disorders of the Anterior pituitary and hypothalamus. In Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, et al., eds. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill Medical Publishing Division; 2005: 333.
Winters S, Banks J, Loriaux D. Cimetidine is anti-androgen in the rat. Gastroenterology. 1979;76:504-9.
Van Anders SM, Hamilton LD, Schmidt N, Watson NV. Associations between testosterone secretion and sexual activity in women. Horm Behav. 2007;51(4):477-82.
Mehta PH, Jones AC, Josephs RA. The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat. J Pers Soc Psychol. 2008;94(6):1078-93.
Babe KS, Serafin WE. Histamine, bradykinin, and other antagonists. In: Hardman JG, Molinoff PB, eds. Goodman & Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. New York: McGraw Hill; 1997: 585.