心血管疾患の発症予防を目的とした新しいホルモン補充療法の開発(<特集>第57回学術講演会シンポジウム: ホルモン補充療法-その基礎と臨床-)

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Observational studies have reported that postmenopausal estrogen replacement therapy (ERT) significantly reduced mortality from coronary heart disease (CHD). In fact, ERT has beneficial effects on plasma lipids, endothelial function, low-density lipoprotein (LDL) oxidation, and hemostatic factors. However, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative (WHI) demonstrated that estrogen and progestin therapy increased the risk of CHD. Thus, hormone therapy has adverse effects as well as favorable effects on the risk of CHD. Oral estrogen-induced increase in plasma triglycerides decrease the size of LDL particles that are more susceptible to oxidative modification. Oral estrogen increases vascular inflammatory markers such as C-reactive protein, interleukin-6, and serum amyloid A protein. In addition, it increases plasma matrix metalloproteinase (MMP) that degrades collagen and elastin and predispose it to rupture with thrombus formation, but reduced their inhibitors such as tissue inhibitor of MMP (TIMP). Medroxyprogesterone acetate (MPA) combined with estrogen decreases plasma high-density lipoprotein (HDL) cholesterol and inhibits endothelial function. In contrast, transdermal estrogen administration decreases plasma triglyceride and produces larger LDL particles that are resistant to oxidation, and favorably affects vascular inflammatory and reverses oral estrogen-induced imbalance between MMP and TIMP. Similarly, low dosage oral ERT does not affects adversely on plasma triglycerides or LDL particle size and vascular inflammatory markers or MMP/TIMP. Since androgenic properties of MPA may act adversely on endothelial function and HDL cholesterol, micronized progestin which has less androgenic effect may not attenuate the favorable effects of estrogen on these parameters. Studies are needed to investigate whether low dosage or transdermal ERT and concurrent use of natural progesterone are effective for the risk of CHD in healthy postmenopausal women and women with established coronary disease.
2005-12-01

心血管疾患の発症予防を目的とした新しいホルモン補充療法の開発(<特集>第57回学術講演会シンポジウム: ホルモン補充療法-その基礎と臨床-)

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