Hormone Replacement Therapy – HRT and Cancer

Female Hormone Replacement Therapy (HRT) refers to commercially manufactured prescription pills, patches and creams containing estrogens and/or progestins to be used to replace the menopausal woman’s decline in those hormones. HRT has been used for decades to relieve bothersome symptoms associated with menopause such as hot flashes and vaginal dryness. Even as the effectiveness of HRT was clear, many researchers and patients throughout the years have wondered about the effects of hormones on the risks of cancers, particularly cancers of the female reproductive organs, because of a possible sensitivity to hormones in those cancers. Generally, the prevailing thought until recent years had been that the overall risk of cancer as a result of HRT was very small. Women were reassured that unless they had certain personal risk factors, the available data did not support the idea of increased risk of cancers from HRT.

Results from a very large and thorough study, the Women’s Health Initiative, along with other recent studies, have challenged the safety of HRT. It does appear that the incidence of three types of female cancers was increased in women who took HRT. Endometrial, ovarian and breast cancer risk appear to be increased by various types of HRT. The risk of colon cancer was found to be decreased in women who were taking HRT. Each cancer and its study results are discussed below.

Breast Cancer and HRT

Results from the Women’s Health Initiative showed that the use of an estrogen/progesterone (combination) HRT increased the chances of developing breast cancer by 25%. This means that a woman taking HRT over the course of the study had a 25% greater chance of developing breast cancer. This translates to 8 additional cases of breast cancer per 10,000 women per year in the group taking combination HRT.

The breast cancer that was found in the women who were taking HRT was generally more advanced at the time of detection. The study also found that mammograms, used to detect cancerous or precancerous changes in the breast, were more likely to be abnormal in the group of women that were prescribed HRT. Two additional studies have been done to investigate whether or not the type of HRT (combination versus sequential) seemed to make any difference in the increase in breast cancers seen in women who were taking HRT. The risk of breast cancer begins to decrease soon after discontinuation of HRT and the risk mirrors that of the general population within 5 years of stopping the drug.

Endometrial Cancer and HRT

The endometrium is the lining of the uterus. Endometrial cancer refers to cancer of the lining of the uterus. Estrogen only HRT has been clearly shown to increase the risk of endometrial cancer. This risk is decreased shortly after the discontinuation of HRT treatment. Even the prolonged use of vaginal creams or rings containing estrogen only may lead to increased estrogen levels in the body and may potentially increase the risk of endometrial cancer. One study also suggests that long-term combination HRT using both progestins and estrogen, may also increase the risk of endometrial cancer. The Women’s Health Initiative study did not find an increased risk of endometrial cancer in the women that used combination HRT as compared to those who took placebo. However, the women taking HRT had a greatly increased chance of uterine bleeding, one of the main signs of uterine cancer, and therefore were required to undertake diagnostic studies for further investigation. So, despite the lowered risk of endometrial cancer, women who were taking HRT required frequent checks to be sure that they had not developed the cancer.

Ovarian Cancer

Ovarian cancer is a rare, often aggressive cancer of the ovaries. The ovaries are the organs that store the eggs that will be fertilized to become a fetus and that produce the hormones in a woman’s body. The Women’s Health Initiative study found that combined HRT taken continuously slightly increases the risk of ovarian cancer. Another recent study showed that estrogen only HRT, taken for more than 10 years, raised the risk of ovarian cancer. In that study, they did not find an increased risk of ovarian cancer in women using combination (progestin/estrogen) HRT.

Colon Cancer

The Women’s Health Initiative study found that combination HRT reduced the risk of colorectal cancer by 40%. This translates to 6 fewer cases of colorectal cancer per 10,000 women per year in the group of women taking combination HRT. However, the colorectal cancers that were diagnosed in the women taking HRT were diagnosed at an advanced stage compared to the women who were taking placebo. Estrogen-only HRT seemed to have no effect on the risk of colorectal cancer.

A Role for Testosterone?

In a study released in September of 2004, taking testosterone along with combination HRT seemed to reduce the risk of breast cancer in women taking HRT. Further studies were said to be needed to confirm these early studies. Testosterone may also be implicated in reducing other forms of cancer in women taking HRT.


The risk for cancer is a very complicated and needs to be personalized for each woman. An individual’s cancer risk is most probably an interplay of genetics, environment and lifestyle. It is important that the perimenopausal or menopausal woman be aware of her risks for various types of cancer and how initiating HRT might contribute to her risk.

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