Estrogens are hormones that are important for sexual and reproductive development, mainly in women. They are also referred to as female sex hormones. The term “estrogen” refers to all of the chemically similar hormones in this group, which are estrone, estradiol (primary in women of reproductive age) and estriol.

Estrogens are natural hormones that are important in sexual development and other body functions. Higher amounts of estrogen in the blood are linked to an increased risk of breast cancer in women after menopause. 

Estrogen Dependent Cancers

Breast cancer

In the Women’s Health Initiative, 8,506 women took combination hormone replacement therapy (estrogen and progestin) and were followed for an average of 5.2 years. The women were evaluated for high risk by the Gail Model and were not found to be at increased risk of developing breast cancer. They had yearly mammograms and breast exams during their follow-up visits. However, after long-term therapy, the women on the combination hormone replacement therapy had a 26% higher incidence of breast cancer than those taking a placebo. The number of in situ (early stage) breast cancers was not affected. This study was stopped early because of the increased number of breast cancers seen in the estrogen-progestin group.

This is consistent with previous studies, which reported an increase in the number of breast cancer cases in women who took the estrogen-progestin combination. However, the Women’s Health Initiative revealed that women (with hysterectomies) who took estrogen alone did not show a significant increase in breast cancer risk. The women who stopped their hormones were followed for breast cancer risk and were found to have decreased risk once they stopped their hormones. This risk reduction was seen after 18 months of being off their hormones.

Endometrial cancer

Endometrial cancer is a type of uterine cancer that involves the lining of the uterus. It is seen in women who take estrogen only and still have a uterus. This is due to estrogen’s effect on this lining, which builds up with prolonged estrogen stimulation. When this occurs, endometrial hyperplasia can result.

This cancer was also monitored in the Women’s Health Initiative. The risk of endometrial cancer was not increased by estrogen-progestin therapy in the study. Tamoxifen, an agent that can reduce the risk of developing breast cancer, can also cause endometrial cancer due to its similar effect on the endometrial lining.

Colorectal cancer

In the Women’s Health Initiative study, there was a 37% decrease in colon cancers in women who had taken hormones compared to women who did not. This was a beneficial effect seen with hormones. The actual mechanism as to how this occurs is not clear.

Ovarian cancer

A study from the Breast Cancer Detection Demonstration Project looked at 329 cases of ovarian cancer to determine whether hormones increase ovarian cancer risk. Results showed that women who took estrogen only were at increased risk of developing ovarian cancer. This risk increased with longer duration of use, especially if taken for 10 or more years. Short-term estrogen-progestin combination therapy did not show an increase in risk.

Hormone replacement therapy and estrogen-dependent cancers have been a controversial issue. The Women’s Health Initiative was a large prospective study trying to answer specific questions about hormones and their effects on the body. The results showed a 26% increase in breast cancers, no effect on endometrial cancer, and a 37% reduction in colon cancers. However, the results have raised additional questions about hormone replacement therapy.

It is important to discuss your risk of developing these cancers with your physician. If you are at increased risk, then long-term hormone replacement therapy may not be the best option for you. Review the risks and benefits of hormone therapy so you can make an informed decision.

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