Estrogen and cancer
As with many medical therapies, the adage that “yesterday’s dogma is today’s pariah” may seem to apply to estrogen. In December 2001, the government’s National Toxicology Program (NTP) added estrogen to the list of known human carcinogens. Estrogen is commonly prescribed to women in many forms, including formulations for post-menopausal hormone replacement and the birth control pill.
The association between estrogen use and cancer, particularly endometrial cancer (cancer of the uterine lining) and less so for breast cancer, has been known for several years, however. In fact, the most commonly prescribed form of estrogen used in hormone replacement therapy, so-called “conjugated estrogens” was already listed as a human carcinogen by the NTP over 5 years ago. The addition of “steroidal estrogen” to the carcinogen list includes the natural form of the most common human estrogen, estradiol.
Physicians have known about the association of estrogen with endometrial and breast cancer for some time, although this information is not always discussed with patients before prescribing. One of the objectives of adding steroidal estrogen to the NTP’s list of human carcinogens was to promote discussions between physicians and their patients regarding the risks and benefits of estrogen therapy.
A difficult 2 years for hormone therapy…
Last January, researchers from the National Cancer Institute reported studies showing higher rates of breast cancer in women taking a combination of oral estrogen and progestin compared to estrogen alone. Traditionally, progestins have been prescribed in combination with estrogen to reduce the risk of endometrial cancer; unfortunately, it seems that in trying to protect against endometrial cancer, it seems the risk of breast cancer may be increased.
Recent studies also cast a shadow of doubt on the commonly held conception that estrogen was protective of the heart and cardiovascular system in women after menopause. This belief sprung from the known rise in heart and cardiovascular disease in women once they reached menopause. Estrogen itself was also proven to have protective effects on the circulation in the laboratory, as well as in animal models. Human studies, however, failed to support the protective effect of oral hormone replacement therapy on the cardiovascular system. In fact, results from the highly publicized HERS trial, reported in August of 1998 actually showed a trend toward higher rates of cardiovascular disease in postmenopausal women taking oral hormone replacement therapy in the first year of therapy.
Benefits of Estrogen and Hormone Replacement Therapy (HRT)…
Although the list of benefits of estrogen and hormone replacement may be shrinking, some important benefits remain:HRT is known to alleviate many of the typical symptoms of menopause such as hot flashes, night sweats, sleep disturbance, vaginal dryness, and thinning of the skin;
- HRT may improve additional menopausal symptoms in some women such as mood swings, irritability, memory impairment, and sex drive or libido;
- HRT is known to preserve and maintain bone density and prevent fractures in post-menopausal women, and can actually increase bone density in many women;
- HRT may have a beneficial effect in protecting women from Alzheimer’s disease; ongoing studies will provide additional information about this potential benefit in the next few years;
- HRT may be associated with lower rates of certain cancers, such as colon cancer, for example – results of ongoing studies will help clarify this, as well.
All Estrogens Are Not Created Equally…
To make matters more confusing, all estrogens are not created equally. Most of the studies on estrogen therapy have been conducted using oral (conjugated) estrogens. All oral forms of estrogen must be processed by the liver before they can enter the bloodstream. The liver traps over 90% of the hormones, allowing less than 10% only to reach the bloodstream. Meanwhile, the estrogen trapped by the liver results in many of the complications and side effects related to the use of oral hormone replacement. This effect on the liver may be responsible for many of the detrimental effects of estrogen and HRT such as:
- Blood clots - oral estrogen can raise the level of fibrinogen, which is our chief clotting factor - produced by the liver.
- Gallbladder disease - women taking oral estrogens have 2 to 2 1/2 times the rate of gallstones and gallbladder surgery than women not taking estrogen.
- High blood pressure - the liver has to process many of the hormones that regulate our blood pressure.
- Elevation of triglyceride levels - the liver is where triglycerides are manufactured and processed from the diet.
- Weight gain - estrogen may impair the liver's ability to process carbohydrates, aggravating or contributing to insulin resistance and weight gain. Estrogen is also thought to increase appetite.
- Migraine
- Benign liver tumors
Also, more recently developed natural forms of estrogen may have fewer of these effects than traditional forms of conjugated estrogens, often obtained from the urine of pregnant horses.
Most recently, hormone patches (containing either natural estradiol, or a combination of estradiol and a progestin) continuously deliver a low dose of hormones directly into the bloodstream through the skin. This route of delivery has the advantage of bypassing the liver and reducing the possibility of the side effects noted above. Dosages of estrogen given in this fashion are typically less than 1/10 of the amounts required orally, while providing the same blood levels of estrogen. Research suggests that while oral hormones raise the level of C-reactive protein, estrogen patches do not. This may explain the increased rates of heart attack and stroke, as well as dementia in women taking oral hormones, although this may not be true of estrogen given through the skin. More studies are needed.
Studies have also shown that hormones given through the skin in this fashion still have the same beneficial effects on bone density as oral hormone replacement. Research in progress may help answer the question of whether these hormone patches may be better than oral hormone pills in protecting the cardiovascular system. It is suspected, but not proven, however, that estrogen given through the skin will be no safer than oral hormones in regard to the risk of uterine and breast cancer.
Making Sense Out of Confusion...
It’s easy to understand how most of us would be tremendously confused by all of the conflicting information about estrogen and hormone replacement therapy. If the experts can’t even agree, how are women expected to make informed decisions about taking estrogen or not? Here are our thoughts and suggestions to help make sense out of confusion:
Each woman needs to be evaluated individually. Studies that show either increased or decreased risk for large groups of women do not apply to an individual. Each woman needs to review the risks and benefits that apply to her with her physician. This requires and individual approach that assesses each woman for the potential risks and benefits of HRT. This means that before considering taking estrogen or HRT, each woman should have a comprehensive evaluation including:
- Bone density measurement;
- Comprehensive cardiovascular risk assessment
- Comprehensive personal assessment of breast and endometrial cancer risk
- Review of family history and personal risk factors for Alzheimer’s disease, colon cancer, risk of clotting, hypertension, gallbladder disease, breast and uterine cancer risk
- Symptom review to identify symptom severity and potential for improvement with estrogen or HRT
Estrogen and HRT should be given for a specific reason. It’s no longer valid to recommend estrogen or HRT “because it’s good for women” or “it will keep you younger” – neither is true. Instead, estrogen and HRT should be given for a specific indication that is identified during a woman’s individual, personal evaluation. When indicated, choose the safest form of estrogen or HRT:
- Choose the safest route of administration: Transdermal, or “through-the-skin” forms of estrogen, as with the estrogen patches, bypass the liver as the estrogen enters the circulation, and are not as likely to cause side effects related to the liver’s accumulation of hormones, such as the risk of clotting, gallbladder disease, high blood pressure, rising triglycerides, migraine and weight gain.
- Use lower dosages of estrogen. Several studies show beneficial effects of estrogen even at lower dosages than conventionally prescribed. Use the lowest dosage of estrogen needed to alleviate symptoms or address your personal reason for using estrogen
Periodic monitoring is crucial. When HRT is given for a specific reason, it’s important to be monitored periodically in order to prove that the HRT is having the desired effect. For example, if bone density is the main issue, it’s important to monitor bone density annually to assess the effect of HRT. Also, once bone density is improved and in the safe range, it may be safest to taper and discontinue hormone use, while continuing to monitor the bone density. It’s also important, of course, for all women taking estrogen or HRT to have annual gynecologic checkups including mammograms, breast exams, PAP smears, and perhaps uterine sonograms.
We also recommend the following blood tests in women taking HRT:
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Ceonex, Inc.