ENDOTHELIAL FUNCTION
Vascular effects of estrogen in type II diabetic postmenopausal women
Kwang Kon Koh, MD, PhD, FACC*,*,
Moon Ho Kang, MD, PhD ,
Dong Kyu Jin, MD, PhD*,
Seon-Kyu Lee, MD ,
Jeong Yeal Ahn, MD, PhD ,
Hee Young Hwang, MD,
Seong Hee Yang, MD||,
Dae Sung Kim, MD, PhD¶,
Tae Hoon Ahn, MD, PhD* and
Eak Kyun Shin, MD, PhD*
* Department of Cardiology, Inchon, South Korea
Endocrinology and Metabolism, Inchon, South Korea
Clinical Pathology, Inchon, South Korea
Radiology, Inchon, South Korea
|| Menopause Clinic, Inchon, South Korea
¶ Preventive Medicine (Biostatistics), Gachon Medical School, Incheon, South Korea
Manuscript received January 5, 2001;
revised manuscript received June 11, 2001,
accepted July 11, 2001.
* Reprint requests and correspondence: Dr. Kwang Kon Koh, Director, Vascular Medicine and Atherosclerosis Unit, Division of Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-Dong, Namdong-Gu, Incheon, North Korea 405-760
kwangk{at}ghil.com
OBJECTIVES
We assessed the effects of estrogen on vascular dilatory and other homeostatic functions potentially affected by nitric oxide (NO)-potentiating properties in type II diabetic postmenopausal women.
BACKGROUND
There is a higher cardiovascular risk in diabetic women than in nondiabetic women. This would suggest that women with diabetes do not have the cardioprotection associated with estrogen.
METHODS
We administered placebo or conjugated equine estrogen, 0.625 mg/day for 8 weeks, to 20 type II diabetic postmenopausal women in a randomized, double-blinded, placebo-controlled, cross-over design.
RESULTS
Compared with placebo, estrogen tended to lower low-density lipoprotein (LDL) cholesterol levels by 15 ± 23% (p = 0.007) and increase high-density lipoprotein (HDL) cholesterol levels by 8 ± 16% (p = 0.034). Thus, the ratio of LDL to HDL cholesterol levels significantly decreased with estrogen, by 20 ± 24%, as compared with placebo (p = 0.001). Compared with placebo, estrogen tended to increase triglyceride levels by 16 ± 48% and lower glycosylated hemoglobin levels by 3 ± 13% (p = 0.295 and p = 0.199, respectively). However, estrogen did not significantly improve the percent flow-mediated dilatory response to hyperemia (17 ± 75% vs. placebo; p = 0.501). The statistical power to accept our observation was 81.5%. Compared with placebo, estrogen did not significantly change E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 or matrix metalloproteinase-9 levels. Compared with placebo, estrogen tended to decrease tissue factor antigen and increase tissue factor activity levels by 7 ± 46% and 5 ± 34%, respectively (p = 0.321 and p = 0.117, respectively) and lower plasminogen activator inhibitor-1 levels by 16 ± 31% (p = 0.043).
CONCLUSIONS
The effects of estrogen on endothelial, vascular dilatory and other homeostatic functions were less apparent in type II diabetic postmenopausal women, despite the beneficial effects of estrogen on lipoprotein levels.
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Abbreviations and Acronyms
| | CAD | = coronary artery disease | | CEE | = conjugated equine estrogen | | CI | = confidence interval | | ELISA | = enzyme-linked immunosorbent assay | | HERS | = Heart and Estrogen/progestin Replacement Study | | HDL | = high-density lipoprotein | | ICAM-1 | = intercellular adhesion molecule-1 | | LDL | = low-density lipoprotein | | MCP-1 | = monocyte chemoattractant protein-1 | | MMP-9 | = matrix metalloproteinase-9 | | mRNA | = messenger ribonucleic acid | | NO | = nitric oxide | | PAI-1 | = plasminogen activator inhibitor-1 | | TF | = tissue factor | | VCAM-1 | = vascular cell adhesion molecule-1 |
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