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HRT and Alzheimer’s Disease/Dementia

Alzheimer's disease is a degenerative brain disease that leads to confusion and memory loss as well as restlessness, problems with perception, speech trouble, trouble moving, and paranoia. Currently, there is no cure for Alzheimer's disease. However, some small studies suggest that estrogen or various combinations of HRT may delay the development of Alzheimer's.

Past studies suggest that women who take HRT have a reduced risk for Alzheimer's disease. In one study, elderly women were followed for five years. Among the women who did not take estrogen, 16% developed Alzheimer's disease compared to only 1.7% who did take estrogen. In another study, women who suffered only moderate memory problems from Alzheimer's disease improved their memory while on HRT.(3)

However, in 2003, results from the Women's Health Initiative Memory Study showed that estrogen plus progestin doubled the risk for developing dementia in post-menopausal women age 65 and older. Dementia is defined as a decline in mental ability in which the patient can no longer function independently on a day-to-day basis. The risk increased for all types of dementia, including Alzheimer's disease.

HRT and Diabetes

Patients with Type II (adult onset) diabetes are resistant to the action of insulin (a hormone released by the pancreas in response to high levels of sugar in the body). Past studies suggest that HRT may improve the body's response to insulin. Rather than making the body's blood sugar level go up, HRT may improve blood sugar metabolism.

Negative Effects of HRT

Side effects of hormone replacement therapy (HRT) vary from individual to individual but may include:

• bloating
• nausea
• breast tenderness (typically during the first three to four months of treatment)
• vaginal bleeding
• fluid retention
• weight gain
• depression
• possible increase in migraine headaches

Since estrogen has been linked to an increased risk of endometrial cancer (cancer of the lining of the uterus), there is a concern that HRT may increase the risk of a recurrence of endometrial cancer in women who have a history of the cancer. Physicians typically prescribe progestin with estrogen to counteract the risk of endometrial cancer.

There are also conflicting studies that show that HRT may increase the risk of blood clots in the veins. Generally, patients who have suffered from phlebitis (the inflammation of a vein, often along with the formation of a blood clot) from either the veins close to the skin (inflammation of varicose veins) or in the deep veins of the leg are not at greater risk of blood clotting. However, if previous blood clotting was associated with estrogen use or a "high-estrogen" state (i.e., pregnancy), it is likely that HRT may cause increased blood clotting.

HRT and Breast Cancer

The link between HRT and breast cancer remains controversial. Some studies have shown the risk of breast cancer to be minimal among women who use HRT while other studies have shown a more significant risk. Although studies have been inconsistent, there appears to be an emerging consensus that HRT may increase the risk for breast cancer.

Recently, women have been overwhelmed with reports that HRT may increase the risk for breast cancer. One particular study of 46,355 women in the Breast Cancer Detection Demonstration Project, a national breast cancer screening program, found nearly a 9% increase in breast cancer risk among women who used combined HRT (estrogen and progestin) each year. However, Dr. Judith Reichman, a professor at the University of California, Los Angeles who spoke at the Congress on Women's Health and Gender-Based Medicine meeting in June 2000, said that the results of the Breast Cancer Detection Demonstration Project are often misinterpreted. Some women may incorrectly assume that a 9% increase in breast cancer risk each year would mean that in 10 years, a woman's risk of breast cancer would be 90%. In reality, the researchers noted a 9% per year incidence of breast cancer among women who took HRT for a long period (typically over five years).

Other studies have shown that HRT can also increase the risk of breast cancer. Most notably, the Women's Health Initiative recently found that postmenopausal women taking estrogen with progestin have an increased risk of breast cancer as well as heart attack, stroke, and blood clots. The results of the Women's Health Initiative are discussed later in this article.

Nevertheless, other studies present a different point of view. In a study published in a March 1999 issue of the medical journal Cancer, 9,494 women with benign (non-cancerous) breast diseases (such as fibroadenoma) who took HRT were found to be at the same risk of developing breast cancer as women with benign breast diseases who did not take HRT. Lead researcher David Page, MD of Vanderbilt University, said that women need to know that the risk of breast cancer for low-dose ERT (HRT with estrogen alone) is minimal, and that there are many benefits to HRT. Dr. Page emphasized that the decision to use HRT or not should be an informed one and not one made out of fear.

The type of estrogen prescribed may have some biologic significance. For instance, ethinyl estradiol is more potent than traditionally used conjugated estrogens and has been associated with a 20% greater breast cancer risk that increases with the length of exposure. In addition, estrogen that is injected into the body (through a vein) rather than taken orally in pill form has been shown to be four times as likely to increase breast cancer risk, according to recent studies.(3)

HRT and Ovarian Cancer

Some research suggests that long-term use of HRT (10 years or more) increases the risk of ovarian cancer. In a study of more than 200,000 women, researchers from the American Cancer Society found that using estrogen replacement therapy (estrogen without progestin) for 10 or more years increases the risk of death from ovarian cancer. While the chances of developing ovarian cancer doubles with prolonged estrogen use, the risk still appears to be small-approximately 2% over a lifetime. However, the study did not include data from women who used combination hormone replacement therapy (estrogen and progestin), which is the most common regimen prescribed today.

While researchers are not certain why estrogen therapy increases the risk of ovarian cancer, they do know that estrogen causes ovarian cells to produce at faster than normal rates. One theory is that the more times a cell divides, the higher the chances that it will result in an abnormal gene copy. If the abnormal copy controls cell growth, this could result in uncontrolled (cancerous) growth.

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