WHI Trial Suggests Possible Reduction in Breast Cancer Risk with Estrogen Alone

Postmenopausal women who take hormone therapy consisting of estrogen alone may have a somewhat reduced risk of breast cancer. These findings—from longer-term follow-up of the Women’s Health Initiative trial of estrogen alone—were published in the Journal of the American Medical Association. It should be noted that this report addressed only estrogen alone; it did not include combined estrogen plus progestin, which has previously been linked with an increased risk of breast cancer.

Menopause—when menstrual cycles end and ovarian hormone production drops dramatically—produces symptoms such as hot flashes and night sweats in up to 80% of women. When these symptoms are severe, they can have a profound effect on a woman’s quality of life and ability to function.

For many years, hormone therapy with estrogen (with or without progestin) has provided an effective way for women to manage menopausal symptoms. Studies over the last several years, however, have raised some concerns about the health effects of hormone therapy. In the Women’s Health Initiative (WHI) clinical trial of estrogen plus progestin, hormone use decreased the risks of fracture and colorectal cancer, but increased the risks of heart disease, breast cancer, stroke, and blood clots. More recent reports suggest that combined hormone therapy may also increase lung cancer mortality.

Initial reports from the WHI study of estrogen alone found that estrogen alone did not appear to increase the risk of breast or lung cancer, but did increase risk of stroke. Because estrogen alone increases the risk of endometrial (uterine) cancer, it is generally only used in women who have had a hysterectomy.

Treatment with hormone therapy was stopped in both of the WHI hormone trials after these early reports, but study participants continue to be followed in order to document longer-term health effects. The current report addressed a range of health outcomes among women who had participated in the study of estrogen alone. Information was available for 7,645 of the original 10,739 women.

  • Overall, risk of breast cancer was 0.27% among women who had been assigned to the estrogen group compared with 0.35% among women who had been assigned to the placebo group.
  • The increased risk of stroke that was observed during estrogen treatment was no longer apparent after treatment stopped.
  • Younger women (those in their 50s) tended to have more favorable health outcomes with estrogen than older women. Among younger women, for example, estrogen alone was linked with a decreased risk of heart attack; no such decrease was observed among older women.

The researchers note that their results “emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status.”

The finding that estrogen alone may decrease the risk of breast cancer was questioned in an accompanying editorial, which noted that this finding is “inconsistent with a longstanding, corroborated body of evidence…”

Women who are considering using hormone therapy to manage menopausal symptoms are advised to discuss the risks and benefits with their physician.

References:

Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321-33

Chlebowski RT, Schwartz AG, Wakelee H et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374:1243-1251.

Anderson GL, Limacher M, Assaf AR et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004; 291:1701-1712.

LaCroix AZ, Chlebowski RT, Manson JE et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305:1305-1314.

Jungheim ES, Colditz GA. Short-term use of unopposed estrogen: a balance of inferred risks and benefits. JAMA. 2011;305:1354-1355.

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