Progesterone abolishes estrogen and/or atorvastatin endothelium dependent vasodilatory effects.
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-beta estradiol 2mg/day (E) (n=17); E + norethisterone acetate 1mg/day (P) (n=18); Atorvastatin 10mg/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.
Faludi
André Arpad
AA
Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. afaludi@uol.com.br
Aldrighi
José Mendes
JM
Bertolami
Marcelo Chiara
MC
Saleh
Mohamed H
MH
Silva
Renata Alves
RA
Nakamura
Yara
Y
Pereira
Isabela R O
IR
Abdalla
Dulcineia Saes Parra
DS
Ramires
José Antonio Franchini
JA
Sousa
Jose Eduardo M R
JE
D000368:Aged; D000069059:Atorvastatin; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists; D004967:Estrogens / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008875:Middle Aged; D009640:Norethindrone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D004965:Estrogen Antagonists; D004967:Estrogens; D006538:Heptanoic Acids; D011758:Pyrroles; D011374:Progesterone; D004958:Estradiol; D000069059:Atorvastatin; D009640:Norethindrone