A large study conducted in the UK has reported that early use of menopausal hormone therapy (use before or soon after menopause) may increase breast cancer risk to a greater extent than later use. These results were published in the Journal of the National Cancer Institute. A limitation of this study, however, is that it is an observational study (not a randomized clinical trial), and therefore susceptible to certain types of bias.

For many years, hormone therapy with estrogen (with or without progestin) has provided an effective way for women to manage menopausal symptoms such as hot flashes. 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. Estrogen alone did not increase the risk of breast or lung cancer in the WHI trial, but did increase risk of stroke.

As research into hormone therapy has continued, there has been growing interest in whether the health effects vary by a woman’s age and proximity to the time of menopause. In the WHI study of combined estrogen plus progestin, for example, the risk of heart disease among hormone users appeared to be greater among women who were farther past menopause. The risk of breast cancer among hormone users didn’t clearly vary by time since menopause, although there was a suggestion that earlier hormone use posed a greater risk than later hormone use.

To further explore the timing of menopausal hormone therapy and risk of breast cancer, researchers evaluated information from the UK Million Women Study. Unlike the WHI hormone trials, the Million Women Study is an observational study. In an observational study, scientists do not control the medications that women take. Rather, they observe what happens to women after the women themselves decide whether or not to take a particular medication. A limitation of this type of study is that the women who take a particular medication (such as hormones) are likely to differ from women who do not take the medication; these differences between groups can affect the study results. Researchers attempt to account for differences between groups when they analyze the data, but some differences may be difficult to identify or measure.

The results of the Million Women Study suggest that hormone use that begins close to the time of menopause may increase breast cancer risk to a greater extent than hormone use that begins later:

  • Among current users of estrogen only, women who began hormone use more than five years after menopause did not have a significantly increased risk of breast cancer. In contrast, women who began hormone use within five years of menopause had a 43% increased risk of breast cancer compared with women who had never used menopausal hormones.
  • Among current users of estrogen plus progestin, women who began hormone use more than five years after menopause had a 53% increased risk of breast cancer, and women who began hormone use within five years of menopause had a roughly two-fold increase in breast cancer risk.

The finding that early use of estrogen alone may increase the risk of breast cancer differs from what was observed in the WHI trial of estrogen alone. Questions remain about whether estrogen alone affects breast cancer risk.

For combined estrogen plus progestin, the finding that earlier use may have a greater effect on breast cancer risk than later use is generally consistent with what was observed in the WHI trial, although the WHI trial did not find strong evidence that risk varied by the timing of hormone use.

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Because many factors may influence a woman’s decision about use of hormone therapy to manage menopausal symptoms, women who have questions about the risks and benefits are advised to talk with their healthcare provider.


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.

Toh S, Hernandez-Diaz S, Logan R, Rossouw JE, Hernan MA. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: does the increased risk ever disappear? A randomized trial. Annals of Internal Medicine. 2010;152:211-217.

Chlebowski RT, Anderson GL, Gass M et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. Journal of the American Medical Association. 2010;304:1684-1692.

Beral V, Reeves G, Bull D, and Green J for the Million Women Study Collaborators. Breast cancer risk in relation to the interval between menopause and starting hormone therapy. Journal of the National Cancer Institute. Early online publication January 28, 2011.

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