Women's Health Trials

HERS I and HERS II Trial:

 HERS was a randomized, double blinded, placebo-controlled trial published in 1998 looking at secondary prevention of coronary heart disease (CHD) with estrogen + progesterone hormone therapy (HT)  There were no significant differences found in the treatment vs. placebo groups after 4.1 years  HERS II was published in 2002 and was a subsequent unblinded follow-up of the HERS subjects looking at long-term outcomes for 2.7 more years  HERS II confirmed the findings from HERS that continuous estrogen + progesterone therapy did NOT decrease risk of CHD.

Women's Health Initiative (WHI):

 The WHI was a randomized controlled trial testing primary prevention of CHD with the use of HT  It consisted of two arms: Estrogen alone arm and Estrogen/progesterone combined arm (E+P arm)  The combined E+P vs. placebo arm was stopped early (in 2002) because increased risk of breast cancer (26%), CHD (29%), stroke (41%), and venous thromboembolism (113%) in the treatment group.  Estrogen alone vs. placebo arm also stopped early (in 2004) because it found increased stroke in the treatment group (RR 1.39, 95% CI 1.10-1.77)) and no benefit for primary prevention of CHD.  Thus, conclusion from WHI trial is that hormone therapy (HT) is not effective for prevention of coronary heart disease.

More about the HERS and WHI studies can be found in the powerpoint lecture in the Menopause module.

Women's Health Study:

 A 2005 study of aspirin 100 mg every other day for primary prevention of coronary artery disease and cerebrovascular disease.  Found that aspirin had no effect on risk of MI (RR 1.02, 95% CI 0.84-1.25) or death from cardiovascular causes (RR 0.95, 95% CI 0.74-1.22).  In a subgroup analysis of women >=65, it reduced risk of MI.  Did reduce risk of ischemic CVA (RR 0.76, 95% CI 0.63-0.93).

References: Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998;280:605-618.

Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA. 2002;288:49-57.

Grady D, Applegate W, Bush T, Furberg C, Riggs B, Hulley SB. Heart and estrogen/progestin replacement study (HERS) design, methods, and baseline characteristics. Controlled Clinical Trials. 1998;19:314-335.

The Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the women's health initiative randomized controlled trial. JAMA. 2004;291:1701-1712.

Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart disease: the women's health initiative. Arch Intern Med. 2006;166:357-365.

Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA. 2002;288:321-333.

Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523-34.

Ridker PM, Cook NR, Lee I, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352:1293-304.