Estrogen Types and Their Connection to Breast Cancer

Naturally Occurring, Synthetic, Plant-Based, and Xenoestrogens

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What are the different types of estrogen both naturally occurring and found outside the body?. Credit: BSIP / Contributor / Getty Images

Estrogen is an important hormone controlling changes in a woman's body. Some of these changes are very positive, such as keeping your bones strong but can also lead to the growth of breast cancer. What should you know about the types of natural estrogens produced within a woman's body, synthetic estrogens, plant-based estrogens, and xenoestrogens?

What are Estrogens?

Estrogen is not just one chemical but instead is a group of hormones that are responsible for a woman's development and ability to have children.

Estrogen also helps regulate your menstrual cycle, protects bones from thinning, and keeps cholesterol levels low to protect your heart. While estrogen is a normal and necessary hormone, estrogen can sometimes help turn normal breast tissue into cancers.

Not all estrogens are produced in a woman's body, however, and you may be familiar with synthetic estrogens in birth-control pills and hormone replacement therapy. The list doesn't stop there. There are phytoestrogens which are simply translated into "plant estrogens" as well as xenoestrogens, potent estrogens that may live in everything from plastics to pollution..

Natural Estrogens in the Female Body

The kinds of estrogen in a woman's body differ based on whether she is premenopausal or postmenopausal. There are also different forms of estrogen within your body which are made in different ways.

Pre-Menopausal Estrogens

  • Estrone (E1): Estrone is made in the ovaries before menopause. After menopause, estrone is stored in body fat and muscle cells. Women who have more body fat will still experience hot flashes during menopause, even though their body is storing more estrone than slimmer women. Estrone production goes down during pregnancy, which reduces your lifetime exposure to estrogen. (This is why pregnancy has a protective effect against the development of breast cancer).
  • Estradiol (E2): Like estrone, estradiol is made in the ovaries. During pregnancy, there is less production of estradiol as well.
  • Estriol (E3): Estriol is made by the placenta during pregnancy. This kind of estrogen is produced in the greatest quantities, more than estrone or estradiol, during pregnancy. Estriol production is an indicator of the health of your baby

    Menopausal Estrogens

    As you approach menopause, your ovaries will shrink (atrophy) and production of estrogen and progesterone will fluctuate during that process. It is the lower levels of these hormones that cause hot flashes, irregular periods, night sweats, mood swings and other symptoms. Doctors may treat these symptoms with hormone replacement therapy (HRT) for a short period of time, but prolonged use has been associated with increased risk of breast cancer.

    After menopause, androgens (male hormones) produced by the adrenal glands are converted in the tissues into estrogen. It is this reaction which is targeted in women with postmenopausal estrogen receptor-positive breast cancer. The enzyme (protein) responsible for converting androgens to estrogen is called aromatase. Breast cancer drugs called aromatase inhibitors (such as Aromasin, Arimidex, and Femara) interfere with the actions of this enzyme so that estrogen can no longer be produced.

    Estrogens Produced Outside the Body

    There are three main kinds of estrogen produced outside of your body as well. Some are created by plants, others are in the environment, and the third type includes those which are made synthetically in the lab.

     

    Phytoestrogens 

    Phytoestrogens are plant estrogens found in plants and botanicals. These phytoestrogens can have estrogen-like effects in your body when you inject them. The effect of plant estrogens are much weaker than estrogens produced by your ovaries but can have clinically apparent effects.

    It is confusing talking about phytoestrogens. Knowing estrogen is associated with an increased risk of breast cancer, does this mean you shouldn't eat plants? It helps to understand that plant-based estrogens function somewhat differently than our ovarian hormones. In our bodies, phytoestrogens may have either estrogen-like or anti-estrogen effects depending on the specific tissue.

    It might be easier to explain this by noting how the breast cancer drug tamoxifen works. When women who have had premenopausal estrogen receptor-positive breast cancer, this drug can reduce the risk of recurrence. Tamoxifen binds to estrogen receptors but has estrogen-like effects on some tissues and anti-estrogen effects on others. With breast cells (and breast cancer cells), tamoxifen binds at the estrogen receptor so that estrogen cannot bind. This action prevents estrogen from binding and stimulating the growth of the tumor. In other tissues, however, it can have estrogen-like effects. Due to its pro-estrogen affect on bones, it can actually work to strengthen bones similar to the way in which natural estrogen does.

    Some plants that contain phytoestrogens include soybeans, red clover, beans, cereal brans, and flaxseeds. There are several "natural" dietary supplements that contain phytoestrogens which are used to treat menopausal symptoms. It's important to note that some of these herbal treatments should not be used by women with breast cancer or at an increased risk of developing the disease.

    Xenoestrogens 

    Xenoestrogens are derived from chemicals present in our environment, many of which are petrochemicals. Xenoestrogens are much more potent than the estrogen your body makes, and too much exposure to these environmental estrogen-like compounds may have adverse effects on your health. Xenoestrogens are in a category of compounds referred to as endocrine disrupting agents which are drawing interest and concern in how they affect the human body in growth and development. Bisphenol-A found in some plastics is one example.

    While research is far from complete, there is evidence that some of these compounds may interfere with normal sexual development, reproduction, and may potentially be a risk factor for breast cancer. We use products that contain xenoestrogens daily. They can be found in some plastics, electronics, medicines, foods, soaps, and pesticides. Our environment (water, air, soil and plants) is being polluted by xenoestrogens from manufacturing runoff and the disposal of products containing xenoestrogens.

    Synthetic Estrogens

    Synthetic estrogens are produced by pharmaceutical companies and include the synthetic form of estrogen known as Ethinyl estradiol. Synthetic estrogens, like xenoestrogens, are generally more powerful than natural estrogens. They can be found in common medications such as birth control pills and hormone replacement therapy.

    Prior to 2002, hormone replacement therapy (HRT) was prescribed for a variety of reasons and was generally considered a miracle pill that could slow the aging process. It is very effective in reducing menopausal symptoms such as hot flashes and vaginal dryness, and also appears to help with the mood swings so common during menopause. In addition to control of menopausal symptoms, it was celebrated for its ability to reduce bone thinning, as well as then thought benefits with regard to heart disease risk and Alzheimer's.

    The Women's Health Initiative Study published in 2002 was a shock to women and their physicians alike. The former miracle drug, while still of benefit for menopausal symptoms had no benefit for reducing heart attacks and strokes. And most significant of all it was that HRT actually increased the risk of breast cancer. A confirmation of this finding, the rates of new cases of breast cancer began to decline as larger numbers of women stopped taking HRT.

    Estrogens and Breast Cancer Risk

    Estradiol increases the risk of developing breast cancer in postmenopausal women.

    Oral contraceptives (birth control pills) also contain estrogen, and there are some cautions in using these drugs. For women at risk of breast cancer, birth controls may potentiate risk. Birth control pills are also (but rarely) associated with strokes and blood clots (deep vein thrombosis).

    Lower estrogen levels are associated with a lower risk of developing breast cancer. Having a first child before the age of 30 and having more children is associated with a lower risk (due to the reduced production of estrogens during pregnancy). Of note, however, is that pregnancy is associated with a lower risk of developing breast cancer down the line, but the absolute risk following childbirth is actually higher than women who have not given birth.

    While doctors do not use blood estrogen levels to discover your risk of breast cancer, it's important to recognize the role of these hormones in causing cancer. To maintain healthy estrogen levels, doctors recommend that you take some steps to minimize your risk of developing breast cancer:

    • Maintain a healthy weight
    • Limit your alcohol intake
    • Exercise regularly
    • Avoid post-menopausal hormone therapy if your doctor thinks you're at risk
    • Keep your eyes and ears open to learn more about xenoestrogens. Many of these chemicals are difficult to avoid, but practicing caution until we know more is probably wise. There is much research in progress and we will likely be hearing more in the coming years. Studies such as one looking at Bisphenol-A inducing a particular breast cancer gene expression suggest that the role of xenoestrogens in breast cancer development needs careful scrutiny are likely only the tip of the iceberg.
    • If you are considering taking an herbal preparation taking phytoestrogens, talk to a healthcare professional who has studied these supplements. There are some physicians who have taken an active interest in combining these alternative approaches with conventional medicine who can help you understand the potential risks and benefits.

    Sources:

    Fucic, A., Gamulin, M., Ferencic, Z. et al. Environmental Exposure to Xenoestrogens and Oestrogen Related Cancers: Reproductive System, Breast, Lung, Kidney, Pancreas, and Brain. Environmental Health. 2012. 11Suppl 2):S8.

    Nagaprashantha, L., Adhikari, R., Singhal, J. et al. Translational Opportunities for Broad-Spectrum Natural Phytochemicals and Targeted Agent Combinations in Breast Cancer. International Journal of Cancer. 2017 Oct 4. (Epub ahead of print).

    Fuhrman BJ, Schairer C, Gail MH, et al. "Estrogen metabolism and risk of breast cancer in postmenopausal women". National Cancer Institute. 2012, 326-339. 

     

     

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