Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads.
Plasma lipoproteins are a major source of cholesterol for steroid hormone synthesis. 3-Hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors, which reduce both intracellular cholesterol synthesis and serum cholesterol levels, thus have a potential negative impact on steroidogenesis. In this study, we evaluated basal and maximally stimulated adrenocortical and testicular steroidogenesis in 24 hypercholesterolemic male subjects during 6-36 months of statin treatment. One group was evaluated before treatment and after 6 months of treatment. A second group, which received long term treatment, was evaluated after 24-36 months and then 2 months after treatment had been discontinued. Fourteen subjects were given simvastatin, and 12 were given pravastatin, both at the maximum therapeutic dosage of 40 mg/day. During statin therapy, serum cholesterol was lowered by about 30%. Basal serum and urinary cortisol levels as well as serum cortisol response to ACTH were not influenced by statin therapy. Basal serum testosterone and its response to hCG were also unchanged by statin treatment. In addition, steroid hormone urinary metabolites were strikingly similar when patients were given HMG-CoA reductase inhibitors and when they were not. These results indicate that maximum therapeutic doses of statins have no negative impact on adrenocortical and testicular steroidogenesis even when these glands are maximally stimulated.
Travia
D
D
Cattedra di Malattie del Metabolismo, University of Verona, Italy.
Tosi
F
F
Negri
C
C
Faccini
G
G
Moghetti
P
P
Muggeo
M
M
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000009:adverse effects; D019821:Simvastatin; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000324:Adrenocorticotropic Hormone; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin