Exp Clin Endocrinol Diabetes 2015; 123(02): 75-79
DOI: 10.1055/s-0034-1394400
Article
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Atorvastatin and Atorvastatin-Ezetimibe Combination Therapy on Androgen Production in Hyperandrogenic Women with Elevated Cholesterol Levels

R. Krysiak
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
,
B. Okopien
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
› Author Affiliations
Further Information

Publication History

received 30 July 2014
first decision 30 September 2014

accepted 08 October 2014

Publication Date:
28 October 2014 (online)

Abstract

Statins decreased serum androgen levels in hyperandrogenemic women with polycystic ovary syndrome. No previous study has investigated whether this effect is dose-dependent and observed in patients simultaneously treated with other hypolipidemic agents. The study included 23 premenopausal women with elevated total testosterone levels coexisting with hypercholesterolemia, unsuccessfully treated for at least 6 months with atorvastatin (20 mg daily). These patients were then treated with either an increased dose of atorvastatin (40 mg daily, n=11) or atorvastatin (20 mg daily) plus ezetimibe (10 mg daily) (n=12). Plasma lipids, glucose homeostasis markers and serum levels of androgens, sex hormone-binding globulin and gonadotropins were assessed at baseline and after 3 months of treatment. Although both treatments decreased plasma levels of total and LDL-cholesterol levels, only high-dose atorvastatin reduced serum levels of total testosterone, free testosterone and androstendione. The effect of high-dose atorvastatin on serum androgen levels did not differ between insulin-resistant and insulin-sensitive subjects. The obtained results suggest that atorvastatin reduces serum androgen levels in a dose-dependent manner and that its administration in a higher dose is associated with a more pronounced effect on serum androgens than combination therapy with low-dose atorvastatin and ezetimibe.

 
  • References

  • 1 Banaszewska B, Pawelczyk L, Spaczynski RZ et al. Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial. J Clin Endocrinol Metab 2007; 92: 456-461
  • 2 Banaszewska B, Pawelczyk L, Spaczynski RZ et al. Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. J Clin Endocrinol Metab 2009; 94: 4938-4945
  • 3 Banaszewska B, Pawelczyk L, Spaczynski RZ et al. Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. J Clin Endocrinol Metab 2011; 96: 3493-3501
  • 4 Sathyapalan T, Kilpatrick ES, Coady AM et al. The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. J Clin Endocrinol Metab 2009; 94: 103-108
  • 5 Kazerooni T, Shojaei-Baghini A, Dehbashi S et al. Effects of metformin plus simvastatin on polycystic ovary syndrome: a prospective, randomized, double-blind, placebo-controlled study. Fertil Steril 2010; 94: 2208-2213
  • 6 Celik O, Acbay O. Effects of metformin plus rosuvastatin on hyperandrogenism in polycystic ovary syndrome patients with hyperlipidemia and impaired glucose tolerance. J Endocrinol Invest 2012; 35: 905-910
  • 7 Krysiak R, Zmuda W, Okopien B. The effect of ezetimibe on androgen production in hypercholesterolemic women with polycystic ovary syndrome. Cardiovasc Ther 2014; 32: 219-223
  • 8 Raja-Khan N, Kunselman AR, Hogeman CS et al. Effects of atorvastatin on vascular function, inflammation, and androgens in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial. Fertil Steril 2011; 95: 1849-1852
  • 9 Schooling CM, Au Yeung SL, Freeman G et al. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. BMC Med 2013; 11: 57
  • 10 Gao L, Zhao FL, Li SC. Statin is a reasonable treatment option for patients with polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Exp Clin Endocrinol Diabetes 2012; 120: 367-375
  • 11 Krysiak R, Okopien B. The effect of simvastatin treatment on plasma steroid levels in females with non-classic congenital adrenal hyperplasia. Exp Clin Endocrinol Diabetes 2013; 121: 643-646
  • 12 Sathyapalan T, Atkin SL. Recent advances in cardiovascular aspects of polycystic ovary syndrome. Eur J Endocrinol 2012; 166: 575-583
  • 13 Wild RA, Carmina E, Diamanti-Kandarakis E et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010; 95: 2038-2049
  • 14 Kim MS, Merke DP. Cardiovascular disease risk in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Semin Reprod Med 2009; 27: 316-321
  • 15 Schaefer JR. Lipid management for the prevention of cardiovascular disease. Curr Pharm Des 2011; 17: 852-860
  • 16 Miller WL. Steroidogenic enzymes. Endocr Dev 2008; 13: 1-18
  • 17 Arem R, Ghusn H, Ellerhorst J et al. Effect of decreased plasma low-density lipoprotein levels on adrenal and testicular function in man. Clin Biochem 1997; 30: 419-424
  • 18 Krysiak R, Okopień B. Chronic adrenal failure and hypergonadotropic hypogonadism in a patient with abetalipoproteinemia. Eur Rev Med Pharmacol Sci 2012; 16 (Suppl. 04) 95-97
  • 19 Bays HE, Neff D, Tomassini JE et al. Ezetimibe: cholesterol lowering and beyond. Expert Rev Cardiovasc Ther 2008; 6: 447-670
  • 20 Krysiak R, Okopien B. The effect of ezetimibe and simvastatin on monocyte cytokine release in patients with isolated hypercholesterolemia. J Cardiovasc Pharmacol 2011; 57: 505-512
  • 21 Krysiak R, Zmuda W, Okopien B. The effect of ezetimibe, administered alone or in combination with simvastatin, on lymphocyte cytokine release in patients with elevated cholesterol levels. J Intern Med 2012; 271: 32-42
  • 22 Krysiak R, Zmuda W, Okopien B. The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia. Fundam Clin Pharmacol 2012; 26: 424-431
  • 23 Kastelein JJ, Akdim F, Stroes ES et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358: 1431-1443
  • 24 Taylor AJ, Villines TC, Stanek EJ et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009; 361: 2113-2122
  • 25 Rossebø AB, Pedersen TR, Boman K et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359: 1343-1356
  • 26 Jasinska M, Owczarek J, Orszulak-Michalak D. Statins: a new insight into their mechanisms of action and consequent pleiotropic effects. Pharmacol Rep 2007; 59: 483-499
  • 27 Izquierdo D, Foyouzi N, Kwintkiewicz J et al. Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis. Fertil Steril 2004; 82 (Suppl. 03) 1193-1197
  • 28 Kodaman PH, Duleba AJ. HMG-CoA reductase inhibitors: do they have potential in the treatment of polycystic ovary syndrome?. Drugs 2008; 68: 1771-1785
  • 29 Ridker PM, Danielson E, Fonseca FAH et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. New Engl J Med 2008; 359: 2195-2207
  • 30 Sattar N, Preiss D, Murray HM et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375: 735-742
  • 31 Krysiak R, Okopien B, Gdula-Dymek A et al. Update on the management of polycystic ovary syndrome. Pharmacol Rep 2006; 58: 614-625