Metabolism of the synthetic progestogen norethynodrel by human ketosteroid reductases of the aldo-keto reductase superfamily

Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women.Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n = 17), estrogen or estrogen plus progestagen (HT, n = 34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT + AT, n = 36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan^® PCR. APOE ?2/?3/?4 genotyping was performed using PCR-RFLP.Total cholesterol (TC), LDL-c and apoB were reduced after each treatment (p < 0.001). Triglycerides, VLDL-c and apoAI were reduced only after atorvastatin (p < 0.05), whereas triglycerides and VLDL-c were increased after HT (p = 0.01). HT women had lower reduction on TC, LDL-c and apoB than AT and HT + AT groups (p < 0.05). APOE mRNA expression was reduced after atorvastatin treatment (p = 0.03). Although LXRA gene expression was not modified by atorvastatin, it was correlated with APOE mRNA before and after treatments. Basal APOE mRNA expression was not influenced by gene polymorphisms, however the reduction on APOE expression was more pronounced in ?3?3 than in ?3?4 carriers.Atorvastatin down-regulates APOE mRNA expression and it is modified by APOE genotypes in PBMC from postmenopausal women.