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document
Determinants of the effect of estrogen on the progression of subclinical atherosclerosis : Estrogen in the Prevention of Atherosclerosis Trial . OBJECTIVE To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness ( IMT ) in postmenopausal women . DESIGN A randomized , double-blind , placebo-controlled , single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein ( LDL ) cholesterol levels of 3.37 mmol/L or greater ( > or = 130 mg/dL ) . Intervention was unopposed micronized 17beta-estradiol versus placebo . Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial . RESULTS Progression of carotid IMT was inversely related to on-trial high-density lipoprotein ( HDL ) cholesterol ( P = 0.04 ) and was directly related to on-trial LDL-cholesterol ( P = 0.005 ) . Compared with placebo , women randomized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level . In contrast , fasting glucose , insulin , and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy , but the changes were not related to carotid IMT progression . On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression , jointly explaining 30 % of the treatment effect of unopposed estrogen on the progression of carotid IMT . CONCLUSION Unopposed 17beta-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol . Although women randomized to estradiol showed improvement in all the markers of carbohydrate metabolism , these factors did not play a significant role in carotid IMT progression .
22796
Intervention_Pharmacological
estrogen
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Intervention_Pharmacological
Estrogen
22798
Intervention_Pharmacological
estrogen therapy
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Intervention_Control
placebo-controlled
22800
Intervention_Pharmacological
unopposed micronized 17beta-estradiol
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Intervention_Control
placebo
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Intervention_Physical
B-mode ultrasonography
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Intervention_Control
placebo
22804
Intervention_Pharmacological
estradiol
22805
Intervention_Pharmacological
estradiol
22806
Intervention_Pharmacological
unopposed estrogen
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Intervention_Pharmacological
Unopposed 17beta-estradiol
22808
Intervention_Pharmacological
estradiol
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Outcome_Physical
subclinical atherosclerosis
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Outcome_Physical
progression of carotid artery intima-media thickness ( IMT )
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Outcome_Physical
carotid artery IMT
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Outcome_Physical
carotid IMT
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Outcome_Physical
high-density lipoprotein ( HDL ) cholesterol
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Outcome_Physical
HDL-cholesterol level
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Outcome_Physical
LDL-cholesterol level .
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Outcome_Physical
fasting glucose
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Outcome_Physical
insulin
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Outcome_Physical
hemoglobin A1C
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Outcome_Physical
HDL-cholesterol
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Outcome_Physical
LDL-cholesterol
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Outcome_Physical
carotid IMT
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Outcome_Physical
carotid IMT
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Outcome_Physical
carotid IMT
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Outcome_Physical
HDL-cholesterol
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Outcome_Physical
LDL-cholesterol
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Outcome_Physical
carotid IMT
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Participant_Condition
postmenopausal
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Participant_Sex
women
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Participant_Sample-size
222
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Participant_Sex
women
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Participant_Age
45 years and older
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Participant_Condition
cardiovascular disease
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Participant_Condition
with low-density lipoprotein ( LDL ) cholesterol levels of 3.37 mmol/L or greater ( > or = 130 mg/dL
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Participant_Condition
postmenopausal
22835
Participant_Sex
women
22836
Participant_Sex
women