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.
Key words
glucocorticoids - cholesterol - statin
