Rabia Latif, Ghulam Mustafa Lodhi, Muhammad Aslam


Background: Calcium ions are vital in many biological processes including hormonal secretion,
mitosis, reproduction, fertility and regulation of gene expression. Thus, calcium antagonists who are
frequently prescribed for the cure of cardiovascular diseases may affect any of these physiological
processes. Methods: This quasi experimental study was done at Army Medical College, Rawalpindi
from October 2007 to March 2008. Thirty male Sprague Dawley rats, purchased from National Institute
of Health, Islamabad were divided into group A (vehicle treated controls) and group B (amlodipine
treated). After receiving drug treatment for 50 days, all the rats were sacrificed. Serum was stored to
measure testosterone by enzyme immunoassay technique. The testes were removed for measuring
absolute testicular weight and gonado-somatic index. Results: Serum testosterone, absolute testicular
weight and gonado-somatic index were found to be significantly reduced in amlodipine treated rats.
Conclusion: These results suggest that long term treatment with amlodipine might be associated with
significant testicular regression and reduction in serum testosterone. Furthermore, since dihydopyridine
antagonists are widely used in hypertension, our data may have some clinical implication in the
management of infertility associated with hypertension.
Keywords: adverse effects, calcium channel blocker, amlodipine, testosterone, testis, gonadosomatic index


Triggle DJ. Calcium channel antagonists: Clinical uses–Past,

present and future. Biochem Pharmacol 2007;74:1–9.

Benoff S. Voltage-dependent calcium channels in mammalian

spermatozoa. Front Biosci 1998;3:1220–40.

Nowak, R. Antihypertension drug may double as male

contraceptive. J NIH Res 1994;6:27–8.

Almaida SA, Teofilo JM, Franci JAA, Brentegani LG,

Carvalho TLL. Antireproductive effects of calcium channel

blocker amlodipine in male rats. Exp Toxicol Pathol


Albers MM, Johnson W, Vivian V, Jackson RD. Chronic use

of the calcium channel blocker nifedipine has no significant

effect on bone metabolism in men. Bone 1991;12:39–42.

Stepien O, Iouzalen L, Herembert T, Zhu DL, Marche P.

Amlodipine and vascular hypertrophy. Int J Cardiol


Tang J, Liu Z, Ren D, Wu C. Effect of amlodipine on the

growth of vascular smooth muscle cells of spontaneously

hypertensive rats. J Tongji Med Univ 1997;17(3):165–7.

Franca LR, Suescun MO, Miranda JR, Giovambattista A,

Perello M, Spinedi E, et al. Testis structure and function in a

nongenetic hyperadipose rat model at prepubertal and adult

ages. Endocrinology 2006;147(3):1556–63.

Weglarz L, Parfiniewicz B, Orchel A, Dzierzewicz Z.

Antiproliferative effects of inositol hexaphosphate and

verapamil on human colon cancer Caco-2 and HT-29 cells.

Acta Pol Pharm. 2006;63:443–5.

Mel'nikova NP, Timoshin SS. Effect of calcium channel

blocker verapamil on DNA synthesis and activity of nucleolar

organizer in cardiomyocytes of newborn albino rats. Bulletin of

Experimental Biology and Medicine, Biophysics and

Biochemistry 1999;127:658–60.

Romeo JH, Dombrowski R, Kwak YS, Fuehrer S, Aron DC.

Hyperprolactinaemia and verapamil: prevalence and potential

association with hypogonadism in men. Clin Endocrinol


Morad F, Elsayed EM, Mahmoud SM. Inhibition of steroid sex

hormones release in rats by two calcium channel blockers.

Pharmacol Res 1997;35:177–80.

Bourguignon JP, Gerard A, Debougnoux G, Rose J,

Franchimont P. Pulsatile release of GnRH from the rat

hypothalamus in vitro: calcium and glucose dependency and

inhibition by superactive GnRH analogs. Endocrinology


Haisenleder DJ, Ferris HA, Shupnik MA. The calcium

component of gonadotropin releasing hormone stimulated

luteinizing hormone subunit gene transcription is mediated by

calcium/calmodulin dependent protein kinase type II.

Endocrinology 2003;144:2409–16.

Simanainen U, McNamara K, Davey RA, Zajac JD,

Handelsman DJ. Severe subfertility in mice with androgen

receptor inactivation in sex accessory organs but not in testis.

Endocrinology 2008; 149:3330–8.

Rehm S, White TE, Zahalka EA, Stanislaus DJ, Boyce RW,

Wier, P.J. Effects of food restriction on testis and accessory sex

glands in maturing rats. Toxicol Pathol 2008;36:687–94.

Faucher CJ, Berger M, Turckheim MD, Jean GVC. Effect of

preweaning under nutrition on testicular development in male

mice. International Journal of Andrology 2008;5:627–35.

Zindy F, Besten WD, Chen B, Rehg JE, Latres E, Barbacid M,

et al. Control of Spermatogenesis in Mice by the Cyclin DDependent Kinase Inhibitors p18Ink4c and p19Ink4d. Mol Cell

Biol 2001;21:3244–55.

Corbier P, Kerdelhue B, Picon R, Roffi J. Changes in testicular

weight and serum gonadotropin and testosterone levels before,

during, and after birth in the perinatal rat. Endocrinology


Weinbauer GF, Behre HM, Fingscheidt U, Nieschlag E.

Human follicle-stimulating hormone exerts a stimulatory effect

on spermatogenesis, testicular size, and serum inhibin levels in

the gonadotropin-releasing hormone antagonist-treated

nonhuman primate (Macaca fascicularis). Endocrinology



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