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Menopause, the cardiovascular risk factor homocysteine, and the effects of treatment
Vincenzo De Leo1, Antonio la Marca, Giuseppe Morgante
1Department of Pediatrics, Obstetrics and Reproductive Medicine, Institute of Obstetrics and Gynecology, University of Siena, Siena 53100, Italy. deleo@unisi.it
Insights
Homocysteine (Hcy) levels, a cardiovascular disease risk factor, are lower in premenopausal women. Hormone therapy and related drugs can reduce Hcy, but their cardiovascular benefits require further investigation.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Nutritional Science
Background:
- Homocysteine (Hcy) is a recognized risk factor for cardiovascular disease (CVD).
- Plasma Hcy levels exhibit a gender difference, being lower in premenopausal women compared to men and postmenopausal women.
- Increased Hcy levels in postmenopausal women are hypothesized to contribute to their elevated CVD risk.
Purpose of the Study:
- To investigate the impact of estrogen replacement therapy (ERT) and related interventions on plasma homocysteine levels.
- To explore the potential cardioprotective effects associated with Hcy reduction.
Main Methods:
- Review of studies examining the effects of hormone therapy, raloxifene, tamoxifen, and folic acid on Hcy levels.
- Analysis of changes in basal and methionine-loaded Hcy levels following therapeutic interventions.
Main Results:
- Estrogen therapy and hormone therapy significantly lower basal and post-methionine loading Hcy levels, with a mean reduction of 10-15% reported after 6 months.
- Raloxifene, tamoxifen, and low-dose folic acid also induce comparable reductions in plasma Hcy levels.
- These reductions are sustained over several months, suggesting potential cardioprotective mechanisms.
Conclusions:
- Hormone therapy and related agents effectively reduce plasma homocysteine levels.
- Despite the positive effect on Hcy, current evidence does not support the use of ERT or hormone replacement therapy (HRT) for primary or secondary CVD prevention.
- Further research is needed to optimize HRT strategies for cardiovascular health while mitigating risks.
Abstract:
Since the identification of homocysteine (Hcy) as a risk factor for cardiovascular disease, it has been the subject of much research. As with other cardiovascular risk factors, a gender difference exists for Hcy. Plasma levels are lower in women of reproductive age than in men and postmenopausal women. This has led to the hypothesis that the increased risk of cardiovascular disease documented in postmenopausal women may be related to the increase in Hcy levels. Factors affecting total plasma levels of Hcy include genetic factors, nutritional factors, and lifestyle. Many studies appear to support the ability of estrogen replacement therapy to significantly lower both basal levels of Hcy and levels following methionine loading. A mean reduction of 10-15% in Hcy levels after 6 months of hormone therapy has been reported. Similarly, raloxifene and tamoxifen and low-dose folic acid administration induce reductions in plasma Hcy levels of the same degree observed for hormone therapy. The reduction occurs after a few months of therapy and is sustained, suggesting the potential for cardioprotective effects. Although there is a positive effect of estrogen therapy and hormone therapy on Hcy levels, recent studies do not recommend the use of estrogen or hormone replacement therapy for the primary or secondary prevention of cardiovascular disease. Further research is therefore needed to identify strategies to maximize the efficacy of hormone replacement therapy, while minimizing the risks.
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