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.

Predicting drug–drug interactions through drug structural similarities and interaction networks incorporating pharmacokinetics and pharmacodynamics knowledge

“…Dehydroepiandrosterone sulfate is the metabolite of a steroid hormone, dehydroepiandrosterone. There is a recent report that simvastatin influenced the steroid hormone level in plasma in female patients who had non-classic congenital adrenal hyperplasm and were taking metformin [35]. Overall, five out of the top ten predicted drugs were supported by reports in the literature and databases.…”

The effect of atorvastatin on sexual function and depressive symptoms in young women with elevated cholesterol levels — a pilot study

“…The results of both a meta-analysis by Schooling et al [12] and one By our research group [13] indicate that statins may decrease plasma testosterone levels in men, probably because of their inhibitory action on production of the substrate for the local synthesis of androgens in adrenal cortex and gonads [14]. A decrease in testosterone, dehydroepiandrosterone sulphate (DHEA-S), and androstenedione was also found in women with elevated androgen levels as a consequence of either polycystic ovary syndrome [15][16][17][18] or non-classic congenital adrenal hyperplasia [19,20]. Low testosterone was found to be negatively associated with libido, arousal, and masturbation frequency, while low DHEA-S is associated with desire and masturbation frequency [21].…”

“…It is difficult explain why statins improved orgasmic reaction. This effect cannot be explained by treatment-induced changes in serum androgen levels, because in numerous studies HMG-CoA reductase inhibitors were found to reduce circulating levels of testosterone and DHEA-S, irrespective of the underlying disorder [15][16][17][18][19][20]. Therefore, much more convincing is its association with pleiotropic effects of statins, affecting blood flow to the structures involved in sexual activities.…”

Vitamin D and Insulin Resistance in Polycystic Ovarian Syndrome and Congenital Adrenal Hyperplasia-a Commentary and Natural Expansion

“…Although he took atorvastatin and the similar drug, simvastatin, was reported to ameliorate non-classic 21-hydroxylase deficiency in hypercholesterolemic women, he was taking the same dose of atorvastatin long before hospitalization, so it is unlikely that it played any further role in reducing serum 17OHP. Krysiak et al attributed the benefit of simvastatin in 4 women with non-classic 21-hydroxylase deficiency to lowering of serum insulin levels-a typical effect of interventions that reduce IR [50]. The mildly diabetogenic effect of statins is due more to reduced insulin secretion via beta cell dysfunction and apoptosis than to increased IR [51].…”