Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial.

Abstract

BACKGROUND:

Whether menopausal hormone therapy (MHT) protects against cardiovascular disease (CVD) remains unclear.

OBJECTIVE:

To assess atherosclerosis progression and CVD risk factors after MHT initiated in early menopause.

DESIGN:

Randomized, controlled trial. (ClinicalTrials.gov: NCT00154180).

SETTING:

Nine U.S. academic centers.

PARTICIPANTS:

Healthy menopausal women aged 42 to 58 years between 6 and 36 months from last menses without prior CVD events who had a coronary artery calcium (CAC) score less than 50 Agatston units and had not received estrogen or lipid-lowering therapy for at least 90 days.

INTERVENTION:

Oral conjugated equine estrogens (o-CEE), 0.45 mg/d, or transdermal 17β-estradiol (t-E2), 50 mcg/d, each with 200 mg of oral progesterone for 12 days per month, or placebo for 48 months.

MEASUREMENTS:

Primary end point was annual change in carotid artery intima-media thickness (CIMT). Secondary end points included changes in markers of CVD risk.

RESULTS:

Of 727 randomly assigned women, 89.3% had at least 1 follow-up CIMT and 79.8% had CIMT at 48 months. Mean CIMT increases of 0.007 mm/y were similar across groups. The percentages of participants in whom CAC score increased did not differ significantly across groups. No changes in blood pressure were observed with o-CEE or t-E2. Low- and high-density lipoprotein cholesterol levels improved and levels of C-reactive protein and sex hormone-binding globulin but not interleukin-6 increased with o-CEE. Insulin resistance decreased with t-E2. Serious adverse events did not differ by treatment.

LIMITATION:

Power to compare clinical events was insufficient.

CONCLUSION:

Four years of early MHT did not affect progression of atherosclerosis despite improving some markers of CVD risk.

PRIMARY FUNDING SOURCE:

Aurora Foundation.

• Authors: S Mitchell Harman, Dennis M Black, Frederick Naftolin, Eliot A Brinton, Matthew J Budoff, Marcelle I Cedars, Paul N Hopkins, Rogerio A Lobo, JoAnn E Manson, George R Merriam, Virginia M Miller, Genevieve Neal-Perry, Nanette Santoro, Hugh S Taylor, Eric Vittinghoff, Mingzhu Yan, Howard N Hodis
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 161 Issue 4 Pg. 249-60 (Aug 19 2014) ISSN: 1539-3704 [Electronic] United States
• PMID: 25069991 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Estrogens, Conjugated (USP)
• Lipids
• Sex Hormone-Binding Globulin
• Progesterone
• Estradiol
• C-Reactive Protein

Topics

• Administration, Cutaneous
• Administration, Oral
• Adult
• C-Reactive Protein (metabolism)
• Carotid Intima-Media Thickness
• Coronary Artery Disease (diagnostic imaging, prevention & control)
• Disease Progression
• Double-Blind Method
• Estradiol (adverse effects, therapeutic use)
• Estrogen Replacement Therapy (adverse effects)
• Estrogens (blood)
• Estrogens, Conjugated (USP) (adverse effects, therapeutic use)
• Female
• Humans
• Insulin Resistance
• Lipids (blood)
• Middle Aged
• Postmenopause (drug effects, physiology)
• Progesterone (therapeutic use)
• Radiography
• Risk Factors
• Sex Hormone-Binding Globulin (metabolism)