Download PDF
Exp Clin Endocrinol Diabetes 2016; 124(04): 215-219
DOI: 10.1055/s-0035-1569375
Article
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Simvastatin on Plasma Steroid Hormone Levels in Metformin-Treated Women with Non-Classic Congenital Adrenal Hyperplasia

R. Krysiak
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
,
K. Kowalcze
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
,
A. Bednarska-Czerwińska
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
,
B. Okopień
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
› Author Affiliations
Further Information

Publication History

received 29 October 2015
first decision 29 October 2015

accepted 16 December 2015

Publication Date:
29 January 2016 (online)

Also available at
    Permissions and Reprints

Abstract

Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the presence of hyperandrogenism. Recently both simvastatin and metformin were found to reduce plasma steroid hormone levels in this disorder. This study included 8 women with NC-CAH and diabetes or impaired glucose tolerance, as well as 12 matched women with similar glucose metabolism abnormalities but normal adrenal function. Both groups of women, receiving metformin for at least 6 months, were then treated with simvastatin (20 mg daily) for the following 12 weeks. Compared to patients with normal adrenal function, metformin-treated women with NC-CAH showed increased plasma levels of 17-hydroxyprogesterone, total testosterone, free testosterone, androstenedione and DHEA-S. Simvastatin reduced total and LDL cholesterol levels in both patients with NC-CAH and normal adrenal function. Moreover, in the former group of women, statin therapy decreased plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and tended to reduce 17-hydroxyprogesterone. Our results suggest that metformin-statin combination therapy may be useful in the management of symptomatic women with NC-CAH.

Key words

congenital adrenal hyperplasia - metformin - statins - steroid hormones
 

  • References

  • 1 Speiser PW. Non-classic adrenal hyperplasia. Rev Endocr Metab Disord 2009; 10: 77-82
    CrossrefPubMedGoogle Scholar
  • 2 Moran C, Azziz R. 21-hydroxylase-deficient non-classic adrenal hyperplasia: the great pretender. Semin Reprod Med 2003; 21: 295-300
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Witchel SF. Non-classic congenital adrenal hyperplasia. Steroids 2013; 78: 747-750
    CrossrefPubMedGoogle Scholar
  • 4 Kelestimur F. Non-classic congenital adrenal hyperplasia. Pediatr Endocrinol Rev 2006; 3 (Suppl. 03) 451-454
    PubMedGoogle Scholar
  • 5 Rachoń D. Differential diagnosis of hyperandrogenism in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2012; 120: 205-209
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Krysiak R, Okopień B, Gdula-Dymek A et al. Update on the management of polycystic ovary syndrome. Pharmacol Rep 2006; 58: 614-625
    PubMedGoogle Scholar
  • 7 Loverro G, Lorusso F. De Pergola G et al. Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome. Gynecol Endocrinol 2002; 16: 217-224
    CrossrefPubMedGoogle Scholar
  • 8 Diamanti-Kandarakis E, Kouli C, Tsianateli T et al. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol 1998; 138: 269-274
    CrossrefPubMedGoogle Scholar
  • 9 Barba M, Schünemann HJ, Sperati F et al. The effects of metformin on endogenous androgens and SHBG in women: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2009; 70: 661-670
    CrossrefPubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 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
    CrossrefPubMedGoogle Scholar
  • 13 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
    CrossrefPubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 Krysiak R, Okopien B. The effect of atorvastatin and atorvastatin-ezetimibe combination therapy onandrogen production in hyperandrogenic women with elevated cholesterol levels. Exp Clin Endocrinol Diabetes 2014; Oct 28
    PubMedGoogle Scholar
  • 16 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Krysiak R, Okopien B. The effect of metformin on androgen production in diabetic women with non-classic congenital adrenal hyperplasia. Exp Clin Endocrinol Diabetes 2014; 122: 568-571
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Mapas-Dimaya AC, Agdere L, Bahtiyar G et al. Metformin-responsive classic salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a case report. Endocr Pract 2008; 14: 889-891
    CrossrefPubMedGoogle Scholar
  • 19 Kazerooni T, Shojaei-Baghini A. Dehbashi 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
    CrossrefPubMedGoogle Scholar
  • 20 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
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Han TS, Walker BR, Arlt W et al. Treatment and health outcomes in adults with congenital adrenal hyperplasia. Nat Rev Endocrinol 2014; 10: 115-124
    CrossrefPubMedGoogle Scholar
  • 23 Mooij CF, Kroese JM, Claahsen-van der Grinten HL et al. Unfavourable trends in cardiovascular and metabolic risk in paediatric and adult patients with congenital adrenal hyperplasia?. Clin Endocrinol (Oxf) 2010; 73: 137-146
    PubMedGoogle Scholar
  • 24 Subramanian S, Trence DL. Immunosuppressive agents: effects on glucose and lipid metabolism. Endocrinol Metab Clin North Am 2007; 36: 891-905
    CrossrefPubMedGoogle Scholar
  • 25 Krauss RM, Burkman Jr RT. The metabolic impact of oral contraceptives. Am J Obstet Gynecol 1992; 167 (4 Pt 2) 1177-1184
    CrossrefPubMedGoogle Scholar
  • 26 Auchus RJ, Arlt W. Approach to the patient: the adult with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2013; 98: 2645-2655
    CrossrefPubMedGoogle Scholar
  • 27 Tosca L, Solnais P, Ferré P et al. Metformin-induced stimulation of adenosine 5′ monophosphate-activated protein kinase (PRKA) impairs progesterone secretion in rat granulosa cells. Biol Reprod 2006; 75: 342-345
    CrossrefPubMedGoogle Scholar
  • 28 Bachmann G, Oza D. Female androgen insufficiency. Obstet Gynecol Clin North Am 2006; 34: 589-598
    PubMedGoogle Scholar
  • 29 Miller WL. Steroidogenic enzymes. Endocr Dev 2008; 13: 1-18
    PubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 Kodaman PH, Duleba AJ. HMG-CoA reductase inhibitors: do they have potential in the treatment of polycystic ovary syndrome?. Drugs 2008; 68: 1771-1785
    CrossrefPubMedGoogle Scholar