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

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.

[1]  B. Okopień,et al.  The effect of atorvastatin and atorvastatin-ezetimibe combination therapy on androgen production in hyperandrogenic women with elevated cholesterol levels. , 2014, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[2]  B. Okopień,et al.  The effect of metformin on androgen production in diabetic women with non-classic congenital adrenal hyperplasia. , 2014, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[3]  B. Walker,et al.  Treatment and health outcomes in adults with congenital adrenal hyperplasia , 2014, Nature Reviews Endocrinology.

[4]  R. Auchus,et al.  Approach to the patient: the adult with congenital adrenal hyperplasia. , 2013, The Journal of clinical endocrinology and metabolism.

[5]  B. Okopień,et al.  The Effect of Simvastatin Treatment on Plasma Steroid Levels in Females with Non-classic Congenital Adrenal Hyperplasia , 2013, Experimental and Clinical Endocrinology & Diabetes (Barth).

[6]  D. Rachoń Differential Diagnosis of Hyperandrogenism in Women with Polycystic Ovary Syndrome , 2012, Experimental and Clinical Endocrinology & Diabetes (Barth).

[7]  A. Duleba,et al.  Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. , 2011, The Journal of clinical endocrinology and metabolism.

[8]  A. Kunselman,et al.  Effects of atorvastatin on vascular function, inflammation, and androgens in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial. , 2011, Fertility and sterility.

[9]  F. Ghaffarpasand,et al.  Effects of metformin plus simvastatin on polycystic ovary syndrome: a prospective, randomized, double-blind, placebo-controlled study. , 2010, Fertility and sterility.

[10]  Yasuo Ohashi,et al.  Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials , 2010, The Lancet.

[11]  C. Tack,et al.  Unfavourable trends in cardiovascular and metabolic risk in paediatric and adult patients with congenital adrenal hyperplasia? , 2009, Clinical endocrinology.

[12]  A. Duleba,et al.  Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. , 2009, The Journal of clinical endocrinology and metabolism.

[13]  G. Guyatt,et al.  The effects of metformin on endogenous androgens and SHBG in women: a systematic review and meta‐analysis , 2009, Clinical endocrinology.

[14]  J. Dungan The Effect of Atorvastatin in Patients with Polycystic Ovary Syndrome: A Randomized Double-Blind Placebo-Controlled Study , 2009 .

[15]  P. Libby,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. , 2008, The New England journal of medicine.

[16]  A. Sacerdote,et al.  Metformin-responsive classic salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a case report. , 2008, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[17]  P. Kodaman,et al.  HMG-CoA reductase inhibitors: do they have potential in the treatment of polycystic ovary syndrome? , 2008, Drugs.

[18]  W. Miller Steroidogenic enzymes. , 2008, Endocrine development.

[19]  S. Subramanian,et al.  Immunosuppressive agents: effects on glucose and lipid metabolism. , 2007, Endocrinology and metabolism clinics of North America.

[20]  J. Dziura,et al.  Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial. , 2007, The Journal of clinical endocrinology and metabolism.

[21]  G. Bachmann,et al.  Female androgen insufficiency. , 2006, Obstetrics and gynecology clinics of North America.

[22]  J. Dupont,et al.  Metformin-Induced Stimulation of Adenosine 5′ Monophosphate-Activated Protein Kinase (PRKA) Impairs Progesterone Secretion in Rat Granulosa Cells1 , 2006, Biology of reproduction.

[23]  B. Okopień,et al.  Update on the management of polycystic ovary syndrome. , 2006, Pharmacological reports : PR.

[24]  F. Keleştimur Non-classic congenital adrenal hyperplasia. , 2006, Pediatric endocrinology reviews : PER.

[25]  A. Duleba,et al.  Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis. , 2004, Fertility and sterility.

[26]  R. Azziz,et al.  21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender. , 2003, Seminars in reproductive medicine.

[27]  G. De Pergola,et al.  Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome , 2002, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[28]  E. Diamanti-Kandarakis,et al.  Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. , 1998, European journal of endocrinology.

[29]  M. Krečmerová,et al.  Lipases as Tools in the Synthesis of Prodrugs from Racemic 9-(2,3-Dihydroxypropyl)adenine , 2012, Molecules.

[30]  R. Krauss,et al.  The metabolic impact of oral contraceptives. , 1992, American journal of obstetrics and gynecology.