Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys.
Abstract: We attempted to determine whether continuous and cyclic medroxyprogesterone acetate modulates the effects of estrogen on dilation of atherosclerotic coronary arteries in surgically postmenopausal female monkeys. Background: Estrogen replacement in postmenopausal women preserves normal dilator responses of atherosclerotic coronary arteries. The effects of progestins on coronary artery reactivity have not been determined. Methods: Repeated quantitative coronary angiography was used to study the effects after 1 month of 1) no hormone replacement (control) or oral administration of 2) continuous conjugated equine estrogens, 3) cyclic high dose medroxyprogesterone acetate (MPA) given on days 16 to 26 of the month, 4) conjugated equine estrogens plus continuous low dose MPA, or 5) conjugated equine estrogens plus cyclic high dose MPA on endothelium-mediated dilation of atherosclerotic coronary arteries in 12 cynomolgus monkeys. Change in diameter of the left circumflex coronary artery was measured in response to intracoronary infusions of acetylcholine (10(-6) mol/liter per min) and nitroglycerin (15 micrograms/min). Results: Coronary arteries constricted during no hormone treatment (-8 +/- 3% [mean +/- SEM]), dilated during conjugated equine estrogen treatment (+3 +/- 1%, p < 0.05 vs. control) and constricted during cyclic MPA treatment (-3 +/- 2%). Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen inhibited acetylcholine responses by 50% (p 0.05). Conclusions: Treatment with conjugated equine estrogens, but not MPA, augmented endothelium-mediated dilation of atherosclerotic coronary arteries. Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen diminished endothelium-mediated dilation.
Publication Date: 1994-12-01 PubMed ID: 7963125DOI: 10.1016/0735-1097(94)90184-8Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This study examined the impact of hormone replacement therapy, specifically continuous and cyclic medroxyprogesterone acetate, on the dilation of atherosclerotic coronary arteries in menopausal monkeys. The results showed that estrogen treatment improved the dilation of these arteries, but this effect was diminished when medroxyprogesterone acetate was also administered.
Research Methods
- The researchers studied the effects of five hormone replacement therapy treatments on the dilation of the atherosclerotic coronary arteries of 12 surgically postmenopausal female cynomolgus monkeys.
- These treatments were no hormone replacement (control), oral administration of continuous conjugated equine estrogens, cyclic high dose medroxyprogesterone acetate (MPA) administered from days 16 to 26 of the month, equine estrogens plus continuous low dose MPA, and equine estrogens plus cyclic high dose MPA.
- Quantitative coronary angiography was used to capture the changes in the diameter of the monkeys’ left circumflex coronary artery in response to intracoronary infusions of both acetylcholine and nitroglycerin.
Research Results
- Arteries constricted during the no hormone treatment, dilated during the conjugated equine estrogen treatment, and constricted again during the cyclic MPA treatment.
- When cyclic or continuous MPA was added to the equine estrogen regimen, it reduced acetylcholine responses by 50%.
- Treatment had no effect on the vascular response to nitroglycerin.
Conclusions
- Treatment with conjugated equine estrogens, but not MPA, increased the dilation of atherosclerotic coronary arteries. This is particularly important for postmenopausal women, as estrogen levels drop after menopause, potentially increasing the risk of coronary artery disease.
- The addition of cyclic or continuous MPA to the equine estrogen regimen decreased this dilation effect, though it did not affect the arterial response to nitroglycerin, a common treatment for angina pectoris. This suggests that while MPA might diminish the benefits of equine estrogen treatment on arterial dilation, it does not impact the arteries’ responsiveness to other treatments.
Cite This Article
APA
Williams JK, Honoré EK, Washburn SA, Clarkson TB.
(1994).
Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys.
J Am Coll Cardiol, 24(7), 1757-1761.
https://doi.org/10.1016/0735-1097(94)90184-8 Publication
Researcher Affiliations
- Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1040.
MeSH Terms
- Animals
- Coronary Angiography
- Coronary Artery Disease / drug therapy
- Coronary Artery Disease / physiopathology
- Coronary Vessels / drug effects
- Coronary Vessels / physiopathology
- Estrogen Replacement Therapy
- Estrogens / pharmacology
- Female
- Macaca fascicularis
- Medroxyprogesterone Acetate / pharmacology
- Vasodilation / drug effects
Grant Funding
- HV53029 / NHLBI NIH HHS
- P01-HL45666 / NHLBI NIH HHS
Citations
This article has been cited 18 times.- Wáng YX, Griffith JF, Deng M, Yeung DK, Yuan J. Rapid increase in marrow fat content and decrease in marrow perfusion in lumbar vertebra following bilateral oophorectomy: an MR imaging-based prospective longitudinal study.. Korean J Radiol 2015 Jan-Feb;16(1):154-9.
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