- Farhad Moradi
- - Department of Biology, Faculty of Science, Azad Islamic University, Nour-Abad Mamasani, Iran
- Akbar Zeraatpishe
- - Department of Biology, Faculty of Science, Azad Islamic University, Jiroft, Iran
- Mehrdad Shariati
- - Department of Biology, Islamic Azad University, Kazeroun, Iran
- Mokhtar Mokhtari
- - Department of Biology, Islamic Azad University, Kazeroun, Iran
Received: 9/17/2008 Accepted: 12/24/2008 - Publisher : Avicenna Research Institute
Introduction: Spironolactone is a diuretic drug with aldosterone-antagonistic properties, used in the treatment of hypertension, congestive heart failure, cirrhosis, kidney disorders, and hirsutism. Some studies have reported decreased libido and menstrual disorders as the side-effects of this medication. The present study was done to investigate the effects of spironolactone on pituitary-gonadal axis hormones.Materials and Methods: Five groups of rats, each including nine adult females and with an average weight of 180 – 200gr, were selected. The control group received no drugs, while the sham group received spironolactone solvent (Normal saline), and the three experimental groups were put on oral spironolactone 25, 50 and 100mg/kg of the total body weight for 14 days. Hormonal measurements, including luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone were performed by radioimmunoassay (RIA) after the test interval.Results: The mean values for FSH (mIU/ml) were 0.11±0.01, 0.14±0.02, 0.38±0.06, 0.16±0.02 and 0.18±0.03 for the three experimental (at 25, 50 and 100mg/kg doses of spironolactone), sham and the control groups, respectively with significant increase in the third experimental group in comparison to the controls. LH concentrations (mIU/ml) were 0.130.01, 0.190.02, 0.140.02, 0.130.02 and 0.120.02 respectively with significant increases at 50mg/kg spironolactone intake. Estrogen concentrations (pg/ml) were 99.921.03, 143.722.5, 139.132.01, 131.932.04 and 125.246.37, whilst progesterone concentrations (pMol/ml) were 100.224.9, 72.615.09, 79.419.7, 62.126.02 and 66.527.6 respectively with no significant changes in the experimental, sham or the control groups. Conclusion: Spironolactone had significant and dose-dependent effects on LH and FSH hormones. However, the medication neither had any negative effects on the concentration or production of sex steroids nor on the function of the gonads. Therefore, its intake does not interfere with hormonal and subsequently gonadal functions.
Keywords: Female fertility, Gonadal axis, Gonadotropin, Pituitary, Sex hormone, Sex steroid, Sexual function, Spironolactone To cite this article:
- Katzung BG. Basic and clinical pharmacology. 10th ed. Toronto: McGraw-Hill; 2006. Chapter 15, Diurtic agents; p. 246-52.
- Katzung BG. Basic and clinical pharmacology. 10th ed. Toronto: McGraw-Hill; 2006. Chapter 39, Adreno-corticosteroids & Adrenocorticalantagonists; p. 650.
- Katzung BG. Basic and clinical pharmacology. 10th ed. Toronto: McGraw-Hill; 2006. Chapter 41, The gonadal hormones & inhibitors; p. 678-80.
- Preston RA, Norris PM, Alonso AB, Ni P, Hanes V, Karara AH. Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide. Menopause. 2007;14(3 Pt 1):408-14. [PubMed]
- Rapkin AJ, Winer SA. Drospirenone: a novel progestin. Expert Opin Pharmacother. 2007;8(7):989-99. Review. [PubMed]
- Hauben M, Reich L, Gerrits CM, Madigan D. Detec-tion of spironolactone-associated hyperkalaemia fol-lowing the Randomized Aldactone Evaluation Study (RALES). Drug Saf. 2007;30(12):1143-9. [PubMed]
- Baumann M, Megens R, Bartholome R, Dolff S, van Zandvoort MA, Smits JF, et al. Prehypertensive renin-angiotensin-aldosterone system blockade in spontan-eously hypertensive rats ameliorates the loss of long-term vascular function. Hypertens Res. 2007;30(9): 853-61. [PubMed]
- Vacher C, Ferrière F, Marmignon MH, Pellegrini E, Saligaut C. Dopamine D2 receptors and secretion of FSH and LH: role of sexual steroids on the pituitary of the female rainbow trout. Gen Comp Endocrinol. 2002; 127(2):198-206. [PubMed]
- Frances JH, Decruz S, William FJ, Serroni N. Prolactin, LH, FSH and TSH responses to a dopamine antagonist Crowly. J Clin Endocrinol Metab. 2003;86 (1):53-58.
- Shevchenko IuL, Vetshev PS, Podzolkov VI, Ippoli-tov LI, Rodionov AV, Polunin GV. [Current aspects of diagnosis and treatment of symptomatic arterial hypertension of adrenal genesis]. Ter Arkh. 2003;75 (4):8-15. Russian. [PubMed]
- Ebeid TA, Eid YZ, El-Abd EA, El-Habbak MM. Effects of catecholamines on ovary morphology, blood concentrations of estradiol-17beta, progesterone, zinc, triglycerides and rate of ovulation in domestic hens. Theriogenology. 2008;69(7):870-6. [PubMed]
- Zouboulis CC, Chen WC, Thornton MJ, Qin K, Rosenfield R. Sexual hormones in human skin. Horm Metab Res. 2007;39(2):85-95. [PubMed]
- De Berardis D, Serroni N, Salerno RM, Ferro FM. Treatment of premenstrual dysphoric disorder (PMDD) with a novel formulation of drospirenone and ethinyl estradiol. Ther Clin Risk Manag. 2007;3(4):585-90. [PubMed]
- Pétra PH, Stanczyk FZ, Namkung PC, Fritz MA, Novy MJ. Direct effect of sex steroid-binding protein (SBP) of plasma on the metabolic clearance rate of testosterone in the rhesus macaque. J Steroid Biochem. 1985;22(6):739-46. [PubMed]
- Knüttgen D, Wappler F. [Anaesthesia for patients with adrenal gland diseases]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2007;42(3):170-8. German. [PubMed]
- Corbould A. Effects of spironolactone on glucose transport and interleukin-6 secretion in adipose cells of women. Horm Metab Res. 2007;39(12):915-8. [PubMed]
- Ganie MA, Khurana ML, Eunice M, Gupta N, Gulati M, Dwivedi SN, et al. Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. J Clin Endocrinol Metab. 2004;89(6):2756-62. [PubMed]
- B?ckstr?m T, Andreen L, Birzniece V, Bj?rn I, Johansson IM, Nordenstam-Haghjo M, et al. The role of hormones and hormonal treatments in premenstrual syndrome. CNS Drugs. 2003;17(5):325-42. [PubMed]
- Wu KM, Farrelly JG. Preclinical development of new drugs that enhance thyroid hormone metabolism and clearance: inadequacy of using rats as an animal model for predicting human risks in an IND and NDA. Am J Ther. 2006;13(2):141-4. Review. [PubMed]
- Buss SJ, Backs J, Kreusser MN, Hardt SE, Maser-Gluth C, Katus HA, et al. Spironolactone preserves cardiac norepinephrine re-uptake in salt- sensitive Dahl rats. Endocrinology. 2006;147(5):252-34. [PubMed]
- Adriaens I, Jacquet P, Cortvrindt R, Janssen K, Smitz J. Melatonin has dose-dependent effects on folliculo-genesis, oocyte maturation capacity and steroidogen-esis. Toxicology. 2006;228(2-3):333-43. [PubMed]
- Watts BA 3rd, George T, Good DW. Aldosterone inhibits apical NHE3 and HCO3- absorption via a nongenomic ERK-dependent pathway in medullary thick ascending limb. Am J Physiol Renal Physiol. 2006;291(5):F1005-13. [PubMed]
- Sabbieti MG, Marchetti L, Menghi G, Yamamoto K, Kikuyama S, Vaudry H, et al. Occurrence of beta-endorphin binding sites in the pituitary of the frog Rana esculenta: effect of beta-endorphin on luteinizing hormone secretion. Gen Comp Endocrinol. 2003;132 (3):391-8. [PubMed]
- Takebayashi K, Matsumoto S, Aso Y, Inukai T. Aldosterone blockade attenuates urinary monocyte chemoattractant protein-1 and oxidative stress in patients with type 2 diabetes complicated by diabetic nephropathy. J Clin Endocrinol Metab. 2006;91(6): 2214-7. [PubMed]
- Swaminathan K, Davies J, George J, Rajendra NS, Morris AD, Struthers AD. Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, gly-caemic control and hormonal profiles. Diabetologia. 2008;51(5):762-8. [PubMed]
- Sainsbury A, Herzog H. Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones. Peptids. 2001;22(3):467-71. [PubMed]
- Karram T, Abbasi A, Keidar S, Golomb E, Hochberg I, Winaver J, et al. The role of mineralocoticoid recap-tors in the circadian activity of the human hypo-thalamus-pituitary- adrenal system: effect of age. Neurobiol Aging. 2000;21(4):585-9.
- Ferreira R, Oliveira JF, Fernandes R, Moraes JF, Goncalves PB. The role of angiotensin II in the early stages of bovine ovulation. Reproduction. 2007;134(5): 713-9. [PubMed]
- Ito O, Omata K, Ito S, Hoagland KM, Roman RJ. Effects of converting enzyme inhibitors on renal P-450 metabolism of arachidonic acid. Am J Physiol Regul Integr Comp Physiol. 2001;280(3):R822-830. [PubMed]
- Fernandez MD, Carter GD, Palmer TN. The interact-tion of canrenone with oestrogen and progesterone receptors in human uterine cytosol. Br J Clin Pharmacol. 1983;15(1):95-101. [PubMed]
- Iranzo A, Santamar?a J, Vilaseca I, de Osaba MJ. Absence of alterations in serum sex hormone levels in idiopathic REM sleep behavior disorder. Sleep. 2007 ;30(6):803-6. [PubMed]