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Postmenopausal estrogen use brings both benefits, risks

Longer-term Women’s Health Initiative follow-up of estrogen therapy users finds reduced risk of breast cancer, decreased heart disease in younger women

April 11, 2011
Dr. Andrea LaCroix

“Our results emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status,” wrote Dr. Andrea LaCroix and colleagues.

Photo by Dean Forbes

Strokes and other health problems linked with estrogen pills appear to fade when women quit taking them after menopause, a long-term follow-up study from the landmark Women’s Health Initiative has found. The findings also confirm that concerns about breast cancer and heart attacks are largely unfounded for those who take the hormone for a short period of time to relieve hot flashes and other menopause symptoms.

Longer-term follow-up of postmenopausal women with prior hysterectomy in the WHI who used estrogen-only therapy for about six years and then stopped indicates:

  • Increased risk of stroke seen during the intervention period dissipated
  • Decreased risk of hip fracture was not maintained
  • Decreased risk of breast cancer persisted
  • Decreased risk of heart attack for women in their 50s; increased risk for those in their 70s.

The findings were published April 6 in the Journal of the American Medical Association.

The WHI estrogen-only trial was stopped one year early after an average of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the intervention’s planned end date. Earlier study findings focused on health outcomes occurring during the intervention phase.

The Public Health Sciences Division’s Dr. Andrea LaCroix and colleagues, including PHS statistical analyst Aaron Aragaki, analyzed data on health outcomes after the estrogen-only intervention for an average of almost 11 years of follow-up, through August 2009. The 10,739 U.S. postmenopausal women in the trial, ages 50 to 79 years with prior hysterectomy, took 0.625 mg/d of estrogen or a placebo. Longer-term follow-up continued in 78 percent (7,645) of surviving participants who consented.

HRT pills

Study findings confirm that concerns about breast cancer and heart attacks are largely unfounded for those who take estrogen pills for a short period of time to relieve hot flashes and other menopause symptoms.

Photo by Dean Forbes

Heart disease rates differ by age

While the researchers saw no long-term differences in heart disease overall in estrogen users versus the placebo group, those results differed by age.

“Women in their 50s taking estrogen had 12 fewer heart attacks per 10,000 women over a year’s time and the women in their 70s had 16 extra heart attacks, so the effect of estrogen on heart disease differed significantly by age,” LaCroix said.

The risk of breast cancer was reduced, regardless of age, and hip fracture rates also reduced while on the medication but that changed after women stopped.

“Rates of hip fracture in the treated group started to rise and move toward the rate in the placebo group so that by the end of the follow-up period, the rates were about equivalent,” LaCroix said.

Risk of stroke, blood clots and pulmonary embolism decreased after women stopped taking estrogen but the overall death rate increased, again depending on a women's age. LaCroix said women taking estrogen had fewer deaths in their 50s but an increased number of deaths in their 70s.

 
“Our results emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status,” the authors wrote.

The researchers said the risks and benefits of estrogen use for periods of longer than five to six years couldn’t be inferred from these findings for any age group. Mechanisms underlying the reduced risks of breast cancer in all women, and coronary events in younger but not older women, warrant further study.

The National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services fund WHI.

[Adapted from a JAMA news release]


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