Acute Statin Administration Reduces Levels of Steroid Hormone Precursors

Abstract

Cholesterol-lowering statin drugs are used by approximately 25% of US adults 45 years of age and older and frequency of use is even higher among the elderly. Cholesterol provides the substrate for steroid hormone synthesis and its intracellular concentrations are tightly regulated. Our aim was to evaluate whether statin use acutely changes the circulating levels of cortisol, other glucocorticoid precursor molecules and their metabolites. Fourteen subjects not taking statins were administered a single oral dose (2 mg) of pitavastatin. Blood samples collected at baseline and 24 h post-treatment were analyzed for plasma cholesterol and steroid hormone profile. A parallel study in mice entailed the administration of atorvastatin (10 mg/kg) via orogastric delivery for three consecutive days. Cholesterol and corticosterone levels were quantified at baseline and at 1-day and 1-week post-treatment. Several precursor molecules in the steroidogenic pathway (corticosterone, cortisone, and 11-deoxycortisol) were significantly decreased 24 h after administration of a single dose of pitavastatin in human study subjects. Their circulating cholesterol concentrations were unchanged. In mice, there were no significant differences in serum cholesterol or corticosterone at 1-day or 1-week post-treatment compared to both pre-treatment baseline levels and control group levels. We conclude that acute dysregulation of the production of certain glucocorticoid precursor molecules was observed after a single treatment with a lipophilic statin drug. This may be of clinical relevance for individuals with underlying or subclinical adrenal insufficiency.

Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

“…The study by Munkboel et al conducted on mouse models has shown that atorvastatin is able to influence steroid homeostasis, resulting in a down-regulation of the StAR protein and the CYP11A1 enzyme, responsible for cleavage of cholesterol chain leading to pregnenolone [ 32 ]. A recent work by London et al on 14 subjects, confirmed that multiple precursors of steroidogenesis decrease significantly 24 h after the first administration of pitavastatin, despite unsignificant plasma variation in cortisol and aldosterone levels [ 33 ]. This concern could be an intriguing topic of future research.…”

Statin treatment is not associated with an increased risk of adrenal insufficiency in real-world setting

“…From a biological and physiological viewpoint, a cumulative dose-effect would rather have been expected. London et al had shown in their study of 14 patients that a single treatment with a lipophilic statin reduced the production of some glucocorticoid precursors (12). This effect could have a clinical impact but it is possible that a compensatory phenomena allow glucocorticoid synthesis to be maintained or regulated.…”

“…By inhibiting cholesterol synthesis, statins could be responsible of a reduction of steroid hormones synthesis and thereby cause adrenal insufficiency (AI). Today, only a few studies concerning a limited number of patients showed contradictory results on steroid hormone synthesis (12)(13)(14).…”

Impaired Cholesterol Metabolism, Neurons, and Neuropsychiatric Disorders

“…In contrast, HMGCR inhibitors, statins, which are cholesterol-lowering drugs, have an impact on the treatment of depression [81]. Statins can decrease cholesterol de novo synthesis and reduce steroid hormone precursors, such as cortisone and corticosterone [82]. In addition, statins are involved in the regulation of serotonin receptor dynamics, leading to the upregulation of serotonin levels in the hippocampus [81].…”