Postmenopausal hormones have been used by many women to relieve menopausal symptoms and to reduce the risk of certain chronic diseases, most often heart disease and osteoporosis. There is now a great deal of evidence that postmenopausal hormone therapy should not be used to prevent chronic disease.

There are two main types of postmenopausal hormone therapy used today: estrogen alone and estrogen plus progestin. Since estrogen alone raises the risk of uterine cancer, it is typically used only by women who no longer have a uterus (those who have had a hysterectomy). Estrogen plus progestin is the therapy used most often by women who still have a uterus.

Estrogen Plus Progestin

Estrogen plus progestin increases the risk of both developing and dying from breast cancer [90-99]. When women take these hormones, their risk of having an abnormal mammogram appears to increase within the first year of use, and their risk of developing breast cancer starts to rise within the first five years of use [97,98]. For each year that a woman takes estrogen plus progestin, her risk goes up slightly [95].

While small yearly increases in risk may seem like nothing to worry about, they can add up over time and become a concern. For example, data from a large prospective study suggest that women who use estrogen plus progestin for five or more years, and are still taking it, have a greater than two-fold increase in breast cancer risk [97]. When women stop using these hormones, their risk of breast cancer starts to decline almost right away and returns to that of someone who has never used hormones in about five to 10 years [91,96]. These patterns of risk have been studied most extensively for one specific type and dose of estrogen plus progestin (Prempro). However, there are no data that show other doses or formulations (including those with natural progesterone) are any safer in terms of breast cancer risk [97,100-103].

In addition to their effect on breast cancer, postmenopausal hormones also have a small but significant negative impact on other aspects of women's health. Results from the Women's Health Initiative (a large randomized clinical trial) showed that after five years of use, estrogen plus progestin does more overall harm to women than good [96]. While using the therapy for this period of time lowers the risk of colon cancer [104] and osteoporosis [105], these benefits are outweighed by a higher risk of breast cancer [104], ovarian cancer [106], heart disease [107], stroke [108] and pulmonary embolism (blood clots in the lungs) [107]. Even short-term use of only one to two years can lead to increases in the rate of heart disease and blood clotting problems [107]. Figure 2.2 below shows the absolute and relative risks for a number of these conditions.

In addition to the findings related to chronic diseases, the data also show that hormone use does little to increase women's quality of life in their postmenopausal years, even in those who had hot flashes. These results call into question one of the main reasons many women choose to take hormones—to simply feel better [109,110]. Moreover, the Women's Health Initiative data also show that taking estrogen plus progestin can increase a woman's risk of developing dementia, a problem that earlier studies suggested might be decreased by hormone use [113-115].

Estrogen Alone

Although observational studies suggested that estrogen alone raised the risk of breast cancer about 30 percent [90-95,97], the Women's Health Initiative trial showed no increased risk of breast cancer with estrogen alone compared to placebo with an average follow-up of 7.1 years [114]. However, results from Nurses Health Study have left open the question of the safety of longer-term estrogen alone. Similar to the Women's Health Initiative, the Nurses Health Study found no increased risk of breast cancer among women who used estrogen alone for less than 10 years. However, there was a significant increase in risk of breast cancer after 20 years of use [115]. Researchers continue to follow the women in this study to better understand exactly how estrogen might affect cancer risk.

Beyond breast cancer, estrogen alone may also influence women's health in many ways. Studies show that it can lower the risk of osteoporosis and possibly colon cancer, but raise the risk of stroke, dementia and ovarian cancer; and in women who still have a uterus, uterine cancer [41,91,116,117]. In terms of heart disease, the data have taken a surprising turn. Although a number of cohort studies have suggested that estrogen can lower the risk of heart disease, findings from the Women's Health Initiative recently showed that estrogen use for up to seven years had virtually no impact on risk [118]. As with the breast cancer results from this study, these results on heart disease differ greatly from those of previous studies, and so researchers will continue to study the issue.

Recommendations for Postmenopausal Hormone Use

In deciding whether or not to take postmenopausal hormones, women should discuss the risks and benefits of these drugs with their health care providers. In general, postmenopausal hormones should not be taken to prevent chronic disease; this is especially true with estrogen plus progestin. The risks simply outweigh the benefits, and there are many safer ways for women to prevent disease and improve their health. For example, women who use postmenopausal hormones to reduce the risk of osteoporosis may choose bisphosphonates as a safer option. For short-term relief of menopausal symptoms, postmenopausal hormones are approved therapies, but the Food and Drug Administration (FDA) recommends that they be used only at the lowest doses for the shortest possible time necessary to have a benefit [119].

Working through these issues with your health care provider is key to helping you decide if, and for how long, you want to use postmenopausal hormones. If you decide to take hormones, you should take them for as brief a time as possible.

Updated 09/12/08

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