Menopause, the cardiovascular risk factor homocysteine, and the effects of treatment

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.