What women with breast cancer should know about estrogens

TheConversation: One of every eight women in the United States will develop invasive breast cancer over her lifetime. Eighty percent of those cancers are fueled in part by estrogens. One treatment for women whose breast cancer is fueled by estrogen – or what is often called estrogen receptor (ER)-positive breast cancer – is for them to take drugs that block estrogens. But estrogens have benefits that should be considered. This particularly affects postmenopausal women who have gone through the trauma of surgery for invasive breast cancer. They are typically faced with a very difficult decision. Should they take estrogen blockers or not? Is the treatment worth it, balancing the risk of recurrence of the cancer with potential quality-of-life issues?


When prescribing a particular drug for postmenopausal, ER-positive, breast cancer survivors, physicians often consider the effects of estrogen blockers on bone and the uterus.
However, they also need to consider the effects on other aspects of women’s health. Estrogens also have many positive effects on mental health, cognitive function, libido and protection of the brain, possibly even slowing the onset of Alzheimer’s disease.
I am a neuroendocrinologist, and I have studied the effects of hormones, including estrogens, on the brain, behavior and mental health for over 40 years. Not only is the fact that “estrogen” is actually a class of hormones not well understood, but so are the many positive functions of estrogens. As with any health treatment, the potential negative effects should be weighed against the potential positive effects.

There is no hormone called estrogen

First, a primer on what exactly “estrogen” is. There is actually no hormone called “estrogen.” Estrogens are a class of hormones. There are three different forms of estrogens in the body: estradiol, estriol and estrone. Although they are all pretty similar in function, they vary in potency. Estrogens found in plants, like soy, are also sometimes simply called “estrogen,” although their effects may differ from those of the estrogens produced in the body.
Estradiol is the dominant estrogen circulating prior to menopause. It is produced mainly in the ovaries. In most cases, this is the most potent form of estrogen. During pregnancy, the dominant form is estriol, produced by the placenta. And during menopause, when the levels of estradiol decrease, the dominant estrogen is estrone, produced in fat tissue.
The ovaries stop producing estrogens during menopause, resulting in lower levels of estrogens in the body. Yet other organs, including fat and the brain, continue to produce them. There are still estrogens doing whatever they were doing before, but because their levels are lower, they are not doing their work as effectively.
One class of estrogen blockers that is often prescribed for women with estrogen receptor-positive breast cancer does its job by blocking estrogens from getting to the receptors of the cells in the body, including cancer cells. The body still produces estrogens, but their effects are blocked in some cells.
A second class, called aromatase inhibitors, blocks the production of estrogens. Both types of estrogen blocker act in the brain as well as the breast, ovaries, vagina and many other parts of the body.
Since these drugs block the effects of estrogens, we should expect that, besides blocking the negative effects of estrogens on the breast cancer, they will block the positive effects on the brain and on mental health.
Unfortunately, many experiments directly assessing the effects of these drugs in breast cancer survivors are missing essential controls. It would not be ethical to give one group of women with a high risk of recurrence of breast cancer a placebo.
However, although much more research on the effects of anti-estrogens in postmenopausal women with breast cancer is needed, by considering what we know about the effects of estrogens from animal studies, all that we know about the effects of estrogens in women without breast cancer and what we know from some studies about the effects of anti-estrogens in breast cancer survivors, we can conclude that anti-estrogens are likely to compromise quality of life in some women.

What are the positive effects of estrogens?

The many positive functions of estrogens and their effects on health are often underestimated.
Estrogens are responsible for the development of reproductive tissues and female secondary sexual characteristics (like breasts) at puberty. They also maintain bone density and decrease the risk of osteoporosis, which can result in brittle bones that break easily. But the role estrogens play in women’s health goes far beyond reproductive health and bone density.
Some of the most profound effects of estrogens are in the brain. For instance, hot flashes, which many women experience while going through menopause, are due to the loss of estrogens acting on brain areas involved in temperature regulation.

Estrogen may have a protective role in the brain. Brain image via www.shutterstock.com.

They can also influence cognitive function – how we think, particularly verbal memory and fluency, which is the memory of words and how we express ourselves in language. And around the time of menopause in many women, they are believed to have an anti-depressive effect.
Sleep disturbances during menopause are believed to be caused by absence of the estrogens acting on sleep centers in the brain. The decreased actions of estrogens on the brain during menopause may also influence sexual desire.
And finally, estrogens may be protective in the brain. This has been demonstrated in nonhuman primates. In women, estrogens may decrease the incidence of Alzheimer’s disease if hormone replacement begins soon after menopause.
After menopause, the level of estrogens drops to low amounts. Appreciable amounts are still produced in fat tissue. We now believe that the brain also produces some estrogens as well, a topic that is being studied right now.

Weighing the pros and cons of estrogen blockers

Should women with estrogen receptor-positive breast cancer take inhibitors of estrogens? The decision of whether or not to use estrogen blockers is a complex one that each woman must make in consultation with her oncologist.
The potential negative effects of these blockers on the brain and quality of life should be weighed against the potential positive effects on recurrence of the cancer. The answer to this will depend on the absolute risk of recurrence of the cancer.
In making a decision about a treatment that could impact quality of life, it would be most helpful to speak with an oncologist who is fully aware of the potential negative, as well as positive, effects of these drugs.