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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Progesterone abolishes estrogen and/or atorvastatin endothelium dependent vasodilatory effects
André Arpad Faludi1, José Mendes Aldrighi, Marcelo Chiara Bertolami
1Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. afaludi@uol.com.br
Insights
Atorvastatin effectively lowered cholesterol, while estradiol increased HDL cholesterol in post-menopausal women. Combining these drugs improved vascular function, but adding norethisterone negated these benefits.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacology
Background:
- Post-menopausal women with hypercholesterolemia and arterial hypertension face increased cardiovascular risk.
- Hormone replacement therapy and statins are common treatments, but their combined effects on lipid profiles and vascular function require further investigation.
Purpose of the Study:
- To evaluate the individual and combined effects of estradiol, norethisterone, and atorvastatin on lipid profiles and vascular reactivity.
- To determine the impact of hormone therapy and statin use on endothelial function in post-menopausal women.
Main Methods:
- A double-blind, randomized, placebo-controlled study involving 94 post-menopausal women (aged 50-65) with hypercholesterolemia and hypertension.
- Participants received dietary counseling followed by 12 weeks of drug therapy: estradiol (E), E + norethisterone (P), atorvastatin (A), E + A, or E + P + A.
- Lipid profiles (TC, LDL-c, HDL-c) and endothelial function (flow-mediated vasodilatation via brachial artery ultrasound) were assessed.
Main Results:
- Atorvastatin significantly reduced total cholesterol (TC) and LDL-cholesterol (LDL-c). Estradiol increased HDL-cholesterol (HDL-c).
- Combined therapy (E + A) showed significant improvements in TC and LDL-c reduction, and HDL-c increase.
- Endothelial function improved with atorvastatin, estradiol, or their combination, but this benefit was abolished by the addition of norethisterone.
Conclusions:
- Atorvastatin demonstrated superior lipid-lowering effects (TC, LDL-c), while estradiol positively impacted HDL-c.
- The addition of norethisterone negated the beneficial effects of both atorvastatin and estradiol on lipid profiles and endothelial function.
- Combined therapy of atorvastatin and estradiol improved endothelial function, highlighting a potential synergistic cardiovascular benefit when progesterone derivatives are excluded.
Unlabelled:
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.
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