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

Ann Intern Med. 2014 Aug 19;161(4):249-60. doi: 10.7326/M14-0353.


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. ( 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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

Associated data