Progesterone abolishes estrogen and/or atorvastatin endothelium dependent vasodilatory effects

• Published in: Atherosclerosis Vol. 177; no. 1; pp. 89 - 96
• Main Authors: Faludi, André Arpad, Aldrighi, José Mendes, Bertolami, Marcelo Chiara, Saleh, Mohamed H., Silva, Renata Alves, Nakamura, Yara, Pereira, Isabela R.O., Abdalla, Dulcineia Saes Parra, Ramires, José Antonio Franchini, Sousa, Jose Eduardo M.R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-11-2004; Elsevier
• Subjects: Aged; Atherosclerosis (general aspects, experimental research); Atorvastatin; Atorvastatin Calcium; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Double-Blind Method; Drug Therapy, Combination; Endothelial function; Endothelium, Vascular - drug effects; Estradiol - pharmacology; Estrogen Antagonists; Estrogens - pharmacology; Heptanoic Acids - antagonists & inhibitors; Heptanoic Acids - pharmacology; Hormonal replacement therapy; Humans; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - physiopathology; Hypertension; Hypertension - blood; Hypertension - physiopathology; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Menopause; Middle Aged; Norethindrone - antagonists & inhibitors; Norethindrone - pharmacology; Pharmacology. Drug treatments; Progesterone - pharmacology; Pyrroles - antagonists & inhibitors; Pyrroles - pharmacology; Vasodilation - drug effects; Vasodilator agents. Cerebral vasodilators; Hypertension; Atorvastatin; Hypercholesterolemia; Endothelial function; Menopause; Hormonal replacement therapy; Replacement therapy; Estrogen; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Compounds; Estradiol; Progestagen; Vascular disease; Lipoprotein LDL; Cholesterol HDL; Atherosclerosis; Norethisterone; Dyslipemia; Lipoprotein HDL; Ultrasound; Human; Enzyme; Brachial artery; Enzyme inhibitor; Metabolic diseases; Cholesterol LDL; Statin derivative; Ovarian hormone; Endothelium; Double blind study; Hydroxymethylglutaryl-CoA reductase; Contraceptive; Oxidoreductases; Progesterone; Sex steroid hormone; Antilipemic agent
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2004.05.030

This double blind randomized placebo controlled study assessed the effects of atorvastatin, estradiol and norethisterone, isolated and in combination, on the lipid profile and on vascular reactivity, in post-menopausal women with hypercholesterolemia and arterial hypertension. Ninety-four women aged 50–65 were selected. All have received dietary counseling (4 weeks), placebo (4 weeks), and drug therapy (12 weeks): 17-β estradiol 2mg/day (E) (
n = 17); E + norethisterone acetate 1
mg/day (P) (
n = 18); Atorvastatin 10
mg/day (A) (
n = 20); E + A (
n = 21) and E + P + A (
n = 18). All treatment modalities have significantly reduced total cholesterol (TC) (E = 8.8%, E + P = 10.1%, A = 27.9%, A + E = 29.4% and E + P + A = 35.7%) and LDL-cholesterol (LDL-c) levels (E + P + A = 46.6%, E + A = 45.9%, A = 40.2%, E = 20.3%, and E + P = 12.1%). As concerns HDL-cholesterol (HDL-c), Groups E and E + A had increases of 15.5% and 13.1%, respectively. The addition of a progesterone compound reduced its concentration (Group E + P = −9.1%, and Group E + P + A = −9.5%). By random, approximately half of the patients in each group were designated to the endothelial function evaluation (brachial artery ultrasound). We observed that in Group A (
n = 10), in Group E (
n = 10) and with the association (Group E + A) (
n = 7), there was a significant increase in the flow-mediated vasodilatation as compared to basal measurements. The addition of a progestin has annulled these benefits.
Conclusions: Atorvastatin has promoted more beneficial effects on TC and LDL-c, whereas estradiol was responsible for an increase in HDL-c. The addition of a progesterone derivative abolished these benefits. Atorvastatin, estradiol or both together improved endothelial function, an effect suppressed by the addition of norethisterone.