Menopausal hormone therapy and coronary heart disease: the roller-coaster history.

In the USA it is estimated that more than one million women become menopausal each year. Coronary heart disease (CHD) is the leading cause of mortality in menopausal woman globally. The majority of perimenopausal to postmenopausal women experience bothersome symptoms including hot flashes, night sweats, mood liability, sleep disturbances, irregular bleeding and sexual dysfunction. While menopausal hormone therapy (HT) effectively treats most of these symptoms, use of HT has become confusing, especially related to CHD risk. Despite years of observational and retrospective studies supporting a CHD benefit and improved survival among HT users, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative (WHI) raised doubts about this long-held premise. The timing hypothesis has since emerged and states that when HT is initiated in younger women, soon after menopause onset, there may be cardiovascular benefit. The following review discusses the roller-coaster history of HT use as it pertains to CHD in postmenopausal women. Studies that highlight HT's CHD benefit are reviewed and provide reassurance that HT utilized in appropriately selected younger postmenopausal women close to the onset of menopause is safe from a cardiovascular perspective, in line with consensus recommendations.

Association between coronary artery vitamin D receptor expression and select systemic risks factors for coronary artery atherosclerosis.

OBJECTIVE: The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. METHODS: Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD3, lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. RESULTS: In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 ± 174.2 pg/ml vs. 349.1 ± 163.2 pg/ml, respectively; p < 0.001; d = 0.79) and at the start of menopause (363.4 ± 117.2 pg/ml; p < 0.001; d = 0.80). Coronary VDR expression was inversely correlated with serum MCP-1 (p = 0.042). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to below the median, VDR expression (p = 0.038). The combination of plasma 25OHD3 and total plasma cholesterol/high-density lipoprotein cholesterol was subsequently broken into low-risk, moderate-risk and high-risk groups; as the risk increased, the VDR quantity decreased (p = 0.04). CAA was not associated with various atherogenic diets. CONCLUSION: Coronary artery VDR expression was inversely correlated with markers of CAA risk and inflammation, including MCP-1, suggesting that systemic and perhaps local inflammation in the artery may be associated with reduced arterial VDR expression.