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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
HRT and the primary prevention of cardiovascular disease
1National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK. j.stevenson@imperial.ac.uk
Insights
Hormone replacement therapy (HRT) may benefit coronary heart disease (CHD) in postmenopausal women, particularly when initiated earlier with appropriate doses. Older women may also benefit from lower-dose HRT.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Women's Health
Background:
- Observational studies suggest hormone replacement therapy (HRT) benefits coronary heart disease (CHD), but randomized trials show mixed results.
- Estrogen's known beneficial cardiovascular effects on risk factors and arterial function contrast with the uncertainty surrounding HRT's impact on CHD.
- Discrepancies in trial outcomes may stem from varying HRT doses and participant ages, with higher doses and older participants potentially obscuring benefits.
Purpose of the Study:
- To investigate the discrepancies between observational and randomized studies on HRT's effect on CHD.
- To determine the optimal conditions, including age and dosage, for potential HRT benefits in coronary heart disease.
Main Methods:
- Review of observational studies and randomized controlled trials on HRT and CHD.
- Analysis of the impact of different HRT doses and participant ages on study outcomes.
- Consideration of biological mechanisms of estrogen on the cardiovascular system.
Main Results:
- Observational studies, largely featuring younger women starting HRT at menopause, consistently show CHD benefits.
- Randomized trials often used high HRT doses in older women (mid-60s), with older participants showing no benefit and younger ones a trend toward benefit.
- Lower-dose HRT in older women did not demonstrate cardiovascular harm, suggesting dose and timing are critical.
Conclusions:
- HRT's benefit for CHD is plausible, but dependent on appropriate dosing and initiation timing.
- Starting HRT in early postmenopause may yield the greatest CHD benefit.
- Older women might still benefit from HRT, provided a lower, appropriate dose is used, mitigating potential harm from high estrogen levels.
Abstract:
Observational studies have consistently shown a benefit of hormone replacement therapy (HRT) on coronary heart disease (CHD), but some randomised studies have not shown any significant effect. Thus questions still remains as to whether HRT is beneficial for CHD, and in whom this benefit might be achieved. The biological effects of oestrogen on the cardiovascular system have been extensively studied, and beneficial effects on metabolic CHD risk factors, as well as on arterial function and on surrogate clinical markers of CHD, have been demonstrated. Thus it seems implausible that HRT should not benefit CHD in postmenopausal women. Most randomised trials using clinical outcomes have studied just one dose of one HRT regimen, a dose inappropriately high with the average starting age of the participants being in their mid-60s. The observational population studies largely comprise women starting on HRT at appropriate dose around the age of menopause, i.e. early 50s. In fact, it was the older women in the randomised trials that failed to show benefit, whereas there was a trend to benefit in the younger ones for whom the starting dose of HRT was appropriate. Furthermore, a pilot study of lower dose HRT in older women did not show any cardiovascular harm. Inappropriately high doses of oestrogen could cause cardiovascular harm due to transient disturbances in thrombogenesis and vascular remodelling. Whilst the greatest CHD benefit may be seen by starting HRT in the early postmenopause, this does not exclude benefit in older women given appropriate low dose therapy.
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