The new conundrum: do estrogens have any cardiovascular benefits?
Abstract: Clearly, a new era has begun, with increasing numbers of the scientific/medical community asking whether estrogens have any cardiovascular benefits. Doubts have arisen from two randomized prospective trials. The Heart and Estrogen/progestin Replacement Study (women who were generally beyond 65 years of age with preexisting coronary heart disease) found no benefit in reducing coronary events by a combination of estrogens and a progestin. Later, the Estrogen Replacement Atherosclerosis Trial reported that no benefit could be shown for either conjugated equine estrogens only or the combined therapy group for women with preexisting coronary artery stenosis. There are lessons to be taken from monkey models about the new conundrum. Estrogens have beneficial effects in the early stages of atherogenesis, but have little or no beneficial effects in the final stages of plaque complications, instability and coronary heart disease events. Using the monkey model, we have addressed the question of when "primary prevention" should begin. We examined the effect of contraceptive steroid treatment of stressed animals at high risk to progressing atherosclerosis due to their estrogen deficiency and subsequently examined the effect of estrogen replacement therapy or no estrogen replacement therapy following surgical menopause. The most robust inhibition of atherosclerosis progression was found in those animals given contraceptive steroids premenopausally and subsequently estrogen replacement postmenopausally. The notion of starting contraceptive therapy during the perimenopausal period to be followed immediately with estrogen replacement postmenopausally is likely to be the most favorable approach to the inhibition of atherosclerosis progression.
Publication Date: 2002-05-07 PubMed ID: 11991432
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
- Review
Summary
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The research article investigates whether estrogens provide any cardiovascular benefits, considering recent doubts brought about by the results of two trials. The researchers used a monkey model to study the effects of estrogens at various stages of coronary disease and the impact of contraceptive steroid and estrogen replacement therapy for the prevention of atherosclerosis progression.
Context and Background
- The authors explore the subject against a backdrop of uncertainty within the scientific and medical community. They reference two randomized trials that found no cardiovascular benefit from a combination of estrogens and progestin in women with preexisting coronary heart disease or from conjugated equine estrogens. These trials sparked doubts regarding the commonly held belief that estrogens offer cardiovascular benefits.
Key Findings from the Monkey Model
- The researchers used a monkey model to better understand the degree and context of estrogens’ benefits. It was observed that estrogens have beneficial effects in the early stages of the development of atherosclerosis. However, these benefits seem to diminish or disappear in the final stages of plaque complications and coronary heart disease.
Effect of Contraceptive Steroid Treatment and Estrogen Replacement Therapy
- Further to their identification of the early atherogenesis stage as critical for the beneficial intervention of estrogens, the researchers examined the effects of contraceptive steroid treatment on animals at high risk of progressing atherosclerosis due to their estrogen deficiency. They also evaluated the effects of estrogen replacement therapy, or its absence, after inducing menopause surgically.
- They found that the most significant inhibition of atherosclerosis progression occurred in animals that received contraceptive steroids before menopause and estrogen replacement after menopause.
Implications of the Research
- The findings from this study propose a new approach in the search for cardiovascular benefits. The authors suggest that the initiation of contraceptive therapy during the perimenopausal period, followed immediately by estrogen replacement after menopause, is likely to present the most effective method to inhibit atherosclerosis progression.
Cite This Article
APA
Clarkson TB.
(2002).
The new conundrum: do estrogens have any cardiovascular benefits?
Int J Fertil Womens Med, 47(2), 61-68.
Publication
Researcher Affiliations
- Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
MeSH Terms
- Animals
- Coronary Artery Disease / diet therapy
- Coronary Artery Disease / pathology
- Coronary Artery Disease / prevention & control
- Disease Progression
- Estrogen Replacement Therapy
- Estrogens, Conjugated (USP) / administration & dosage
- Estrogens, Conjugated (USP) / therapeutic use
- Female
- Humans
- Macaca fascicularis
- Menopause / physiology
- Ovariectomy
- Postmenopause / physiology
- Primary Prevention
- Randomized Controlled Trials as Topic
- Risk Factors
- Time Factors
Grant Funding
- P01-HL45666 / NHLBI NIH HHS
Citations
This article has been cited 9 times.- Kristensen SG, Andersen CY. Cryopreservation of Ovarian Tissue: Opportunities Beyond Fertility Preservation and a Positive View Into the Future.. Front Endocrinol (Lausanne) 2018;9:347.
- Tenkorang MA, Snyder B, Cunningham RL. Sex-related differences in oxidative stress and neurodegeneration.. Steroids 2018 May;133:21-27.
- Rubinow DR, Johnson SL, Schmidt PJ, Girdler S, Gaynes B. EFFICACY OF ESTRADIOL IN PERIMENOPAUSAL DEPRESSION: SO MUCH PROMISE AND SO FEW ANSWERS.. Depress Anxiety 2015 Aug;32(8):539-49.
- Yousefzadeh G, Mahdavi-Jafari F, Shokoohi M, Najafipour H, Haghdoost AA, Modares-Nejad V. Modulation of coronary artery disease risk factors by menopausal status: A population based study among Iranian women (KERCADRStudy).. ARYA Atheroscler 2013 Nov;9(6):332-6.
- Eyster KM, Appt S, Chalpe A, Mark-Kappeler CJ, Register TC, Clarkson TB. Effects of estradiol on transcriptional profiles in atherosclerotic iliac arteries in ovariectomized cynomolgus macaques.. Menopause 2014 Feb;21(2):143-52.
- Clarkson TB, Ethun KF, Chen H, Golden D, Floyd E, Appt SE. Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.. Menopause 2013 Mar;20(3):274-81.
- Eyster KM, Appt SE, Mark-Kappeler CJ, Chalpe A, Register TC, Clarkson TB. Gene expression signatures differ with extent of atherosclerosis in monkey iliac artery.. Menopause 2011 Oct;18(10):1087-95.
- van der Mooren MJ, Kenemans P. Postmenopausal hormone therapy: impact on menopause-related symptoms, chronic disease and quality of life.. Drugs 2004;64(8):821-36.
- Hodis HN, Mack WJ, Lobo R. What is the cardioprotective role of hormone replacement therapy?. Curr Atheroscler Rep 2003 Jan;5(1):56-66.
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