2001 Fiscal Year Final Research Report Summary
Hormone replacement therapy and prevention of coronary heart disease in postomenopausal women.
| Project/Area Number |
12671607
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Kochi Medical School |
|---|
Principal Investigator |
WAKATSUKI Akihiko Kochi Medical School, Associate professor, 医学部・附属病院, 助教授 (90191717)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | Postmenopausal Women / estrogen / medroxyprogesterone / LDL particle diameter / LDL oxidation / endothelial function |
|---|
| Research Abstract |
1. Although estrogen replacement therapy (ERT) has anti-atherogenic effects, ERT-induced increase in plasma triglyceride (TG) may reduce the size of low-density lipoprotein (LDL). We outlined the mechanism of the estrogen-induced decrease in LDL particle size as follows. Estrogen enhances hepatic TG production. Estrogen-induced hypertriglyceridemia enhances lipid transfer reactions, resulting in TG-rich and cholesterol ester-poor LDL particles. Subsequent hydrolysis of the enriched TG content by lipolytic enzymes may increase the formation of LDL particles that are smaller than normal. In addition, we evaluated whether estrogen-induced small LDL particles are atherogenic. In subjects with substantial estrogen-induced plasma TG increases, estrogen significantly reduced the diameter of LDL particles, and significantly increased the LDL oxidation. In contrast, estrogen significantly reduced the LDL oxidation and caused no significant change in LDL particle diameter in subjects whose plasm
… More
a TG concentration was unchanged with estrogen therapy. Because estrogen-induced plasma TG increases may produce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a TG increase. Thus, we clarified that estrogen-induced small LDL particles are atherogenic.
2. Endothelial function which is closely related with development of atherosclerosis, has been reported to decrease after menopause, but increase by ERT. We evaluated the effect of medroxyprogesterone acetate (MPA) on endothelial function in postmenopausal women receiving estrogen. Endothelium-dependent vasodilation was elevated by estrogen alone, but addition of MPA (2.5 mg, 5.0 mg) reversed this beneficial effect of estrogen in a concentration dependent manner. Addition of MPA at 2.5 mg the standard dose used for continuous combined therapy, already attenuates estrogen-induced enhancement of endothelium-dependent vasodilation. Accordingly, concurrent MPA administration may offset favorable effects of estrogen on endothelial function in postmenopausal women. Less
|
