Hormone replacement therapy, hormone levels, and lipoprotein cholesterol concentrations in elderly women

doi:10.1016/S0002-9378(96)70322-8

American Journal of Obstetrics and Gynecology

Volume 174, Issue 3, March 1996, Pages 897-902

https://doi.org/10.1016/S0002-9378(96)70322-8 Get rights and content

Abstract

OBJECTIVE: Our purpose was to assess the relationships of lipid and lipoprotein cholesterol levels to hormone replacement therapy and hormone levels in elderly women. STUDY DESIGN: A sample of 292 postmenopausal women 55 to 99 years old (mean 76 years) was drawn from Leisure World Laguna Hills, California, an upper-middle-class, white independent-living population. We compared 84 women receiving unopposed estrogen replacement therapy and 38 women taking combination hormone replacement therapy with 170 women who had never used hormone replacement therapy. Nonparametric tests for differences in lipid and lipoprotein cholesterol levels among groups and multiple stepwise regression models were used. RESULTS: Estrogen users (with and without progestin) had lower total and low-density lipoprotein cholesterol and higher high-density lipoprotein and high-density lipoprotein subfraction types 2, 2a, and 2b cholesterol levels. High-density lipoprotein type 3 subfractions were lower in combination hormone replacement therapy users but higher in unopposed estrogen users relative to nonusers. The conjugated equine estrogen dose was negatively correlated with total (p = 0.0009) and low-density lipoprotein cholesterol (p < 0.0001) levels and positively correlated to high-density lipoprotein cholesterol (p = 0.002) and its subfractions. The medroxyprogesterone acetate dose showed no consistent effect on cholesterol levels. CONCLUSION: The associations found here reaffirm the significant role of estrogen replacement therapy on lipid and lipoprotein cholesterol levels and provide no evidence of a reduction in the beneficial effect of estrogen with the addition of a progestational agent to the replacement regimen. (AM J OBSTET GYNECOL 1996;174:897-902.)

Section snippets

MATERIAL AND METHODS

Study subjects were selected from the 13,979 participants in the Leisure World Cohort Study. We began this cohort study in June 1981 when we mailed a detailed health survey to all residents of Leisure World Laguna Hills, an upper middle class retirement community near Los Angeles. The health questionnaire requested, among other data, information on certain prior medical diagnoses, including angina, acute myocardial infarction, hypertension, and diabetes, and menstrual and reproductive history,

RESULTS

Table I describes the characteristics of the study subjects by use of hormone replacement therapy: women who had never used hormone replacement therapy (n = 170), women who were taking unopposed estrogen replacement therapy (n = 84), and women who were taking combination hormone replacement therapy (n = 38). Women who were taking combination hormone replacement therapy were on average younger than the women in the other two groups. Height, weight, exercise, and alcohol consumption did not

COMMENT

Although the women were not randomly assigned to the hormone replacement therapy treatment groups in this study, factors affecting lipid and lipoprotein levels such as weight, exercise, and alcohol consumption were evenly distributed among the groups. Age and smoking status have also been shown to affect lipoprotein cholesterol levels and were controlled for in this study.

Although these are cross-sectional data and direct causal relations cannot be inferred from them, the results show the

Acknowledgements

We thank Mary Beck and Beverly Ducey for their assistance with data collection and Laura Holl and Charlotte Brown for lipid and lipoprotein assays. We are indebted to the residents of Leisure World, Laguna Hills, whose cooperation made this work possible.

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Estrogens stimulate growth, blood flow, and water retention in sexual organs and are also involved in causing breast cancer and endometrial cancer. In the liver, estrogens increase lipoprotein receptors, resulting in a decrease in serum concentrations of low-density lipoprotein cholesterol (Paganini-Hill et al., 1996). On the other hand, estrogens increase the potential for coagulation.
Much is known about estrogen action in experimental animal models and in human physiology.
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Citation Excerpt :
Menopause is associated with an increase in LDLc and a decrease in HDLc levels. Following ET or HT use, plasma LDLc levels decrease, while those of HDLc increase [83,98–101]. It has been generally accepted that these changes in lipids, particularly the LDL:HDL ratio, are the major mechanisms by which estrogens can exert their cardioprotective effects in postmenopausal women on HT [58].
Oral conjugated equine estrogens (CEE) are the most used estrogen formulation for postmenopausal hormone therapy either alone or in combination with a progestin. CEE is most commonly used for the management of early menopausal symptoms such as hot flashes, vaginitis, insomnia, and mood disturbances. Additionally, if used at the start of the menopausal phase (age 50–59 years), CEE prevents osteoporosis and may in some women reduce the risk of cardiovascular disease (CVD) and Alzheimer's disease (AD). There appears to be a common mechanism through which estrogens can protect against CVD and AD.
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Selective combinations of ring B unsaturated estrogens have the potential of being developed as novel therapeutic agents for the prevention of cardiovascular disease and Alzheimer's disease in both aging women and men.
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^☆: From the Department of Preventive Medicine, University of Southern California School of Medicine,^aand the Lawrence Berkeley National Laboratory, Department of Molecular and Nuclear Medicine, University of California, Berkeley.^b

^☆☆: Supported by grant No. CA32197 from the National Cancer Institute, grants No. HL18574 and No. HL33577 from the National Heart, Lung, and Blood Institute of the National Institutes of Health, and grants from the Wright Foundation and Wyeth-Ayerst Laboratories. Conducted in part at the Lawrence Berkeley National Laboratory through the U.S. Department of Energy under contract No. DE-AC03-76F00098.

^★: Reprint requests: Annlia Paganini-Hill, PhD, University of Southern California School of Medicine, 1721 Griffin Ave #200, Los Angeles, CA 90031.

^★★: 0002-9378/96 $5.00 + 0 6/1/68221

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Hormone replacement therapy, hormone levels, and lipoprotein cholesterol concentrations in elderly women☆,☆☆,★,★★

Abstract

Section snippets

MATERIAL AND METHODS

RESULTS

COMMENT

Acknowledgements

Prev Med

Methods Enzymol

Steroids

AM J OBSTET GYNECOL

Maturitas

Atherosclerosis

Maturitas

Maturitas

J Lipid Res

Correlates of postmenopausal estrogen use and trends through the 1980s in two southeastern New England communities

Am J Epidemiol

Estrogen replacement therapy and cognitive function in older women

JAMA

Effects of pharmacologic agents used during menopause: impact on lipids and lipoproteins