Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
Department of Paediatrics in Bytom, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
Pharmacol Rep. 2019 Jun;71(3):417-421. doi: 10.1016/j.pharep.2019.01.014. Epub 2019 Jan 31.
Individuals with non-classic congenital adrenal hyperplasia (NC-CAH) often show evidence of hyperandrogenism, including premature pubarche, accelerated linear growth velocity, short final height, hirsutism, acne, alopecia, impaired ovulation, menstrual dysfunction and subfertility. Although statins were found to reduce elevated levels of androgens in subjects with this disorder, no previous study has investigated whether 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors affect cardiometabolic risk factors in patients with NC-CAH.
We studied 12 women with NC-CAH, 6 of whom because of coexisting hypercholesterolemia received atorvastatin (20-40 mg daily). Circulating levels of lipids, glucose homeostasis markers, plasma levels of androgens, 17-hydroxyprogesterone, high-sensitivity C-reactive protein (hsCRP), uric acid, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR) were determined at the beginning of the study and 12 weeks later.
Beyond affecting plasma lipids, atorvastatin reduced circulating levels of testosterone, dehydroepiandrosterone sulphate, androstenedione and 17-hydroxyprogesterone, and decreased free androgen index. Moreover, atorvastatin caused a decrease in plasma levels/urinary loss of uric acid, hsCRP, homocysteine and UACR, and insignificantly increased circulating levels of 25-hydroxyvitamin D. The drug produced no effect on plasma fibrinogen. The effect of atorvastatin on hsCRP, uric acid, homocysteine, 25-hydroxyvitamin D and UACR correlated with the magnitude of reduction in 17-hydroxyprogesterone and androgens.
Our results suggest that statin therapy reduces cardiometabolic risk in women with NC-CAH.
非经典型先天性肾上腺皮质增生症（NC-CAH）患者常表现出雄激素过多的迹象，包括性早熟、加速线性生长速度、最终身高矮小、多毛症、痤疮、脱发、排卵障碍、月经功能障碍和不孕。尽管已经发现他汀类药物可以降低该疾病患者升高的雄激素水平，但之前没有研究调查过 3-羟基-3-甲基戊二酰基辅酶 A 还原酶抑制剂是否会影响 NC-CAH 患者的心血管代谢危险因素。
我们研究了 12 名 NC-CAH 女性，其中 6 名因合并高胆固醇血症接受阿托伐他汀（每日 20-40mg）治疗。在研究开始时和 12 周后，测定了血脂、葡萄糖稳态标志物、雄激素、17-羟孕酮、高敏 C 反应蛋白（hsCRP）、尿酸、纤维蛋白原、同型半胱氨酸和 25-羟维生素 D 的血浆水平，以及尿白蛋白与肌酐比值（UACR）。
除了影响血浆脂质外，阿托伐他汀还降低了循环中的睾酮、硫酸脱氢表雄酮、雄烯二酮和 17-羟孕酮水平，并降低了游离雄激素指数。此外，阿托伐他汀降低了血浆尿酸、hsCRP、同型半胱氨酸和 UACR 的水平/尿丢失，并使循环中的 25-羟维生素 D 水平轻微升高。该药物对血浆纤维蛋白原没有影响。阿托伐他汀对 hsCRP、尿酸、同型半胱氨酸、25-羟维生素 D 和 UACR 的作用与 17-羟孕酮和雄激素降低的幅度相关。
我们的研究结果表明，他汀类药物治疗可降低 NC-CAH 女性的心血管代谢风险。
