Kronos Early Estrogen Prevention Study - KEEPS

Description:

The goal of the trial was to evaluate treatment with hormone replacement therapy compared with placebo among recently menopausal women.

Hypothesis:

Hormone replacement therapy will slow progression of carotid atherosclerosis.

Study Design

  • Placebo Controlled
  • Randomized
  • Parallel

Patient Populations:

  • Healthy postmenopausal women (ages 42-58 years) between 6 and 36 months from last menses, without prior cardiovascular disease, and with calcium score <50 Agatson units

    Number of screened applicants: 4,532
    Number of enrollees: 727 patients
    Duration of follow-up: 48 months
    Mean patient age: 53 years
    Percentage female: 100%

Primary Endpoints:

  • Annual change in carotid artery intima-media thickness

Secondary Endpoints:

  • Changes in markers of cardiovascular disease risk

Drug/Procedures Used:

Healthy postmenopausal women were randomized to oral estrogen plus progesterone (n = 230), transdermal estrogen plus progesterone (n = 222), versus placebo (n = 275).

Estrogen was administered as oral conjugated equine estrogen 0.45 mg/d or transdermal 17β-estradiol 50 mcg/day. Oral progesterone was 200 mg/d. Hormones were given 12 days per month.

Principal Findings:

Overall, 727 women were randomized. The mean age was 53 years, 7% were current smokers, mean systolic blood pressure was 118 mm Hg, and mean low-density lipoprotein cholesterol was 111 mg/dl.

In the oral estrogen plus progesterone group, carotid artery intima-media thickness was 0.7268 mm at baseline and 0.7591 mm at year 4 (p = 0.43 compared with placebo).

In the transdermal estrogen plus progesterone group, carotid artery intima-media thickness was 0.7176 mm at baseline and 0.7488 mm at year 4 (p = 0.64 compared with placebo).

Interpretation:

Among recently postmenopausal women, hormone replacement therapy did not slow the progression of atherosclerosis as detected by carotid artery intima-media thickness compared with placebo. In the Women’s Health Initiative, hormone replacement therapy was associated with an increase in adverse cardiovascular events. Routine hormone replacement therapy is not recommended among postmenopausal women.

References:

Harman SM, Black DM, Naftolin F, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med 2014;Jul 29:[Epub ahead of print].

Clinical Topics: Dyslipidemia, Noninvasive Imaging, Vascular Medicine, Lipid Metabolism, Nonstatins, Echocardiography/Ultrasound

Keywords: Progesterone, Atherosclerosis, Estradiol, Cholesterol, LDL, Estrogens, Conjugated (USP), Carotid Intima-Media Thickness, Women's Health, Blood Pressure, Carotid Artery Diseases, Lipoproteins, LDL, Menopause, Estrogens, Hormone Replacement Therapy


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