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Updated: Oct 4, 2026

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Interactive effects of soy protein and estradiol on coronary artery reactivity in atherosclerotic, ovariectomized
J K Williams1, M S Anthony, D M Herrington
1Department of Pathology, Section on Comparative Medicine, The Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
Objective:
Results of recent clinical trials indicate that mammalian estrogens may be less effective in reducing coronary heart disease risk than once thought. This study was designed to determine whether mammalian estrogen's coronary artery dilator benefits could be enhanced by adding soy with phytoestrogens.
Design:
Forty-five atherosclerotic, ovariectomized monkeys were fed one of four diets: (1) atherogenic diet with casein/lactalbumin as source of protein (Casein, n = 12); (2) casein diet with micronized estradiol equivalent to a woman's dose of 1 mg/day (Casein + E2, n = 12); (3) atherogenic diet with soy protein with phytoestrogens (129 mg woman/day equivalent) (Soy, n = 11); and (4) the soy diet plus estradiol (Soy + E2, n = 10).
Methods:
Quantitative angiography and intravascular Doppler were done after 6 months of experimental diet to measure changes in diameter and coronary flow reserve in the circumflex coronary artery in response to intracoronary acetylcholine and nitroglycerin.
Results:
Arteries from the E2 and Soy + E2 groups dilated in response to acetylcholine 5 +/- 3% and 12 +/- 5%, respectively (p < 0.05 vs. Casein). There was an interactive effect of soy and E2 on dilator response to acetylcholine (p < 0.05). Flow reserve was greatest in animals fed casein + E2 and soy + E2 (2.3 +/- 0.3 and 2.6 +/- 0.5, respectively; p < 0.05 vs. Casein). Soy protein alone had no effect on coronary artery reactivity (p > 0.05).
Conclusion:
Soy protein itself does not affect coronary artery dilator responses but interacts with estradiol to promote dilator responses to acetylcholine.
Insights
Soy phytoestrogens enhance estradiol's (E2) benefits for coronary artery dilation. Combining soy and E2 improved artery response to acetylcholine, suggesting a synergistic effect for cardiovascular health.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Nutritional Science
Background:
- Mammalian estrogens' role in coronary heart disease (CHD) risk reduction is debated.
- Recent trials suggest reduced efficacy of estrogens in mitigating CHD.
- Estrogen therapy may have limited benefits for cardiovascular health.
Purpose of the Study:
- To investigate if soy phytoestrogens can enhance the coronary artery dilator benefits of mammalian estrogen.
- To determine the combined effect of soy and estradiol on coronary artery function.
- To assess the potential of soy-phytoestrogen and estradiol synergy for cardiovascular protection.
Main Methods:
- Atherosclerotic, ovariectomized monkeys were assigned to four diets: casein, casein + estradiol (E2), soy protein, or soy + E2.
- Diets were administered for 6 months.
- Coronary artery diameter and flow reserve were measured using quantitative angiography and intravascular Doppler, responding to acetylcholine and nitroglycerin.
Main Results:
- The Soy + E2 group showed a significantly enhanced dilator response to acetylcholine (12 +/- 5%) compared to the Casein group.
- Estradiol alone (E2) also improved dilator response (5 +/- 3%) compared to Casein.
- An interactive effect between soy and E2 was observed on acetylcholine-induced dilation (p < 0.05).
- Coronary flow reserve was highest in the Casein + E2 and Soy + E2 groups.
- Soy protein alone did not significantly impact coronary artery reactivity.
Conclusions:
- Soy protein alone does not influence coronary artery dilator responses.
- Soy phytoestrogens interact with estradiol to significantly promote dilator responses to acetylcholine.
- The combination of soy and estradiol shows potential for enhancing estrogen-mediated cardiovascular benefits.

