Effect of very low LDL cholesterol levels on the steroid metabolome

Background Recommended cholesterol levels are continuously being lowered according to clinical guidelines for cardiovascular prevention. Cholesterol is an essential substrate for steroidogenesis in the adrenal glands. Methods To evaluate steroid hormone production associated with intensive hypolipidemic therapy, we measured steroid levels at baseline and following a Synacthen (1–24 ACTH) stimulation test in 36 patients with persistently very low Low-density lipoprotein cholesterol (LDL-C) levels (< 1 mmol/L, < 38.7 mg/dL). Results All patients demonstrated a sufficient cortisol response to stimulation, which excluded partial or complete adrenal insufficiency. We observed correlations between various steroids and LDL-C, High-density lipoprotein cholesterol (HDL-C), and Triglyceride (TG) levels. Conclusions These results confirm the safety of intense hypolipidemic therapy even in patients with very low LDL cholesterol levels. Changes in TG, HDL-C and very low LDL-C cholesterol levels are associated with alterations in adrenal and gonadal steroidogenesis.