Progesterone abolishes estrogen and/or atorvastatin endothelium dependent vasodilatory effects

Atherosclerosis. 2004 Nov;177(1):89-96. doi: 10.1016/j.atherosclerosis.2004.05.030.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Atorvastatin
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Estradiol / pharmacology*
  • Estrogen Antagonists
  • Estrogens / pharmacology*
  • Heptanoic Acids / antagonists & inhibitors
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / physiopathology*
  • Hypertension / blood
  • Hypertension / physiopathology*
  • Middle Aged
  • Norethindrone / antagonists & inhibitors
  • Norethindrone / pharmacology*
  • Progesterone / pharmacology*
  • Pyrroles / antagonists & inhibitors
  • Pyrroles / pharmacology*
  • Vasodilation / drug effects*

Substances

  • Estrogen Antagonists
  • Estrogens
  • Heptanoic Acids
  • Pyrroles
  • Progesterone
  • Estradiol
  • Atorvastatin
  • Norethindrone