A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Am Heart J. 2010 Jun;159(6):987.e1-7. doi: 10.1016/j.ahj.2010.03.024.

Abstract

Background: Compared with men, women have more evidence of myocardial ischemia with no obstructive coronary artery disease. Although low endogenous estrogen levels are associated with endothelial dysfunction, the role of low-dose hormone therapy has not been fully evaluated. We postulate that a 12-week duration of low-dose hormone replacement therapy is associated with myocardial ischemia and endothelial dysfunction.

Methods and results: Using a multicenter, randomized, placebo-controlled design, subjects were randomized to receive either 1 mg norethindrone/10 microg ethinyl estradiol or placebo for 12 weeks. Chest pain and menopausal symptoms, cardiac magnetic resonance spectroscopy, brachial artery reactivity, exercise stress testing, and psychosocial questionnaires were evaluated at baseline and exit. Recruitment was closed prematurely because of failure to recruit after publication of the Women's Health Initiative hormone trial. Of the 35 women who completed the study, there was less frequent chest pain in the treatment group compared with the placebo group (P = .02) at exit. Women taking 1 mg norethindrone/10 microg ethinyl estradiol also had significantly fewer hot flashes/night sweats (P = .003), less avoidance of intimacy (P = .05), and borderline differences in sexual desire and vaginal dryness (P = .06). There were no differences in magnetic resonance spectroscopy, brachial artery reactivity, compliance, or reported adverse events between the groups.

Conclusions: These data suggest that low-dose hormone therapy improved chest pain symptoms, menopausal symptoms, and quality of life, but did not improve ischemia or endothelial dysfunction. Given that it was not possible to enroll the prespecified sample size, these results should not be considered definitive.

Trial registration: ClinicalTrials.gov NCT00600106.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Dose-Response Relationship, Drug
  • Estrogens / administration & dosage
  • Ethinyl Estradiol / administration & dosage*
  • Exercise Test
  • Female
  • Hormone Replacement Therapy / methods*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Middle Aged
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / drug therapy*
  • Norethindrone / administration & dosage*
  • Postmenopause*
  • Quality of Life
  • Surveys and Questionnaires
  • Syndrome
  • Treatment Outcome

Substances

  • Estrogens
  • Ethinyl Estradiol
  • Norethindrone

Associated data

  • ClinicalTrials.gov/NCT00600106