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Published on: August 13, 2019
The metabolic basis for the effects of HRT on coronary heart disease
1Reader and Consultant Metabolic Physician, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. j.stevenson@imperial.ac.uk
Insights
Hormone replacement therapy (HRT) may offer cardiovascular benefits, but early harm from high doses can negate advantages. Tailoring HRT regimens, especially dose, by age could unlock coronary benefits for older women.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Pharmacology
Background:
- Hormone replacement therapy (HRT) exerts significant effects on the cardiovascular system via metabolic and direct arterial mechanisms.
- Observational studies suggest coronary heart disease (CHD) benefits from HRT, contrasting with randomized clinical trials (RCTs).
Purpose of the Study:
- To reconcile the discrepancy between observational and RCT findings on HRT and cardiovascular outcomes.
- To explore the potential for age-appropriate HRT dosing to achieve cardiovascular benefits.
Main Methods:
- Analysis of discrepancies between observational studies and RCTs regarding HRT and CHD.
- Hypothesizing mechanisms for early harm and later benefit of HRT based on age and dose.
Main Results:
- RCTs may show no benefit due to early harm from high initial HRT doses, particularly in older women, potentially increasing thrombogenesis and adverse vascular remodeling.
- Observational studies, often including younger women, may avoid this early harm with the same doses, showing apparent benefits.
- Potential later benefits include improved lipid profiles, glucose metabolism, and reduced atherogenesis through estrogen's actions.
Conclusions:
- The apparent lack of cardiovascular benefit in RCTs might stem from inappropriate initial HRT dosing for age, causing transient harm.
- Optimized HRT regimens, focusing on age-specific dosing, could potentially yield coronary benefits in older women.
- Further research is crucial to validate age-tailored HRT strategies before dismissing its cardiovascular benefits entirely.
Abstract:
Hormone replacement therapy has profound effects on the cardiovascular system, through metabolic effects as well as direct effects on arterial function. Observational studies showing coronary heart disease benefit have appeared superficially to be at odds with the outcomes from randomized clinical trials, but the lack of benefit from the latter appears to arise from early harm caused by hormone replacement therapy that outweighs any later benefit. The early harm could arise from starting doses of such therapies that are inappropriately high for the women's age, and could therefore cause transient increases in thrombogenesis and adverse vascular remodeling. Later benefit could result from estrogen action on metabolic risk factors, such as lipids, glucose, and insulin metabolism, as well as direct arterial effects reducing atherogenesis. In contrast, this is avoided in observational studies because the women are 15 yr younger and those same starting doses of hormone replacement therapy are appropriate for their age. It is therefore possible that more appropriate hormone replacement therapy regimens, particular in terms of dose, could be devised to effect coronary benefit in older age groups. This concept needs to be tested as a priority before hormone replacement therapies are rejected as being of no cardiovascular benefit.
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