Hormone Replacement Therapy

What is hormone replacement therapy?

What are the benefits of HRT?

What are the risks of HRT?

Does the duration of taking HRT affect breast cancer risk?

What kind of research is underway to answer some of these confusing questions?

Why is menopausal hormone replacement therapy used in spite of the cancer risk?

Are there other drug therapies known to relieve the symptoms of menopause?

What about herbal remedies?

Who should not use HRT?

     Also See:

                   Menopause
                   Osteoporosis
                   Calcium intake

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What is hormone replacement therapy?

Hormone Replacement Therapy (HRT) provides women with the female hormones that decrease as they age. When the hormone estrogen is given alone, it is usually referred to as "ERT." When the hormone progestin is combined with estrogen, it is generally called "HRT." Estrogen is a female hormone that brings about changes in other organs in the body. Progesterone is a female hormone that prepares the uterus for a pregnancy each month. During the transition to menopause ("perimenopause") these hormone levels start to fluctuate, causing some uncomfortable symptoms. When the ovaries stop producing estrogen and progesterone, menstrual periods cease and the woman has experienced menopause.

What are the benefits of HRT?

HRT has been used to relieve the short-term symptoms of menopause, such as hot flashes, sweats, and disturbed sleep. It is also believed to be useful in preventing or alleviating an increased rate of bone loss that leads to osteoporosis. In the recent past, HRT also was prescribed to help prevent heart disease, but new evidence shows that heart health should not be a reason to take HRT. New study results now show that HRT does not cut the risk of heart attack and death for women with established heart disease, and it is unclear whether HRT can help prevent the onset of heart disease in healthy postmenopausal women. Preliminary evidence shows that HRT may be helpful in preventing Alzheimer's disease, colon cancer, and macular degeneration (age-related vision loss).

What are the risks of HRT?

Short-term side effects: Some women report side effects from taking HRT, including unusual vaginal discharge and bleeding, headaches, nausea, fluid retention and swollen breasts. Some women think HRT will make them gain weight while taking HRT, but research now shows this is not true. Some women do gain weight during menopause, but it is because their metabolism slows down as they age, and they many not be increasing their amount or level of physical activity. Short-term benefits or side effects should become apparent within weeks or months after treatment begins.

Long-term risks (These will not be readily apparent for each individual woman):
Cancer: There is concern that HRT can increase the risk of some cancers. When estrogen is taken alone, it raises the risk of endometrial cancer (lining of the uterus). Adding progestin with estrogen (HRT) can dramatically reduce this risk. Progestin is added to prevent the overgrowth (or hyperplasia) of cells in the lining of the uterus, so women who still have an intact uterus are generally given this combined therapy.

There are some studies that suggest long term use of HRT (more than 10 years) increases the risk of breast cancer. While there is no definite proof that HRT increases the risk of breast cancer, two new studies that published in the winter of 2000, suggest that combined HRT (estrogen plus progestin) increases the risk of breast cancer more than taking estrogen alone. The National Cancer Institute (NCI) explains that in the first study, the risk for breast cancer among women who had used any form of HRT during the past 4 years was higher than the risk for women who did not use HRT. For women who had taken the combination HRT, however, the risk of breast cancer increased by 8 percent per year; compared to a one- percent increase for women taking estrogen alone. There was no increase in risk among women who had stopped using either type of HRT for 4 years or more. In the second study on HRT, the risk of developing breast cancer increased by 24 percent for every 5 years of use; compared to a 6 percent increase for estrogen-only therapy. Both studies reported that the increased risk of breast cancer associated with either ERT or HRT was higher in thin women. This is an interesting finding, since obesity is a risk factor for breast cancer.

The Hormone Foundation, part of the Endocrine Society and a recognized authority for endocrine-related consumer health information, explains the actual risks described in these studies as:

• A woman taking estrogen replacement therapy (ERT) for less than 2 years for relief of menopausal symptoms has about a 1 in 10,000 chance of developing a breast cancer due to use of this hormone, compared to a 1 in 1200 chance for HRT for the same time period.

• A 50 year old woman has about a 1 in 400 chance of developing a breast cancer that she would not otherwise have developed if she takes estrogen alone for a ten year period, compared to a 1 in 50 chance for HRT.

To make matters more confusing, recent research suggests that HRT might lower the risk of recurrence in breast cancer patients, but increase the risk of a new cancer in the other breast. The decision to take HRT should not be based on a single study, however, but on an overall look at the risk and benefits and how they fit with your personal health profile. It is important to note that these studies are not the last word on HRT and breast cancer risk. There is much more work ahead to clarify these results.

Breast Density: Taking both estrogen and progestin also can affect a woman's breast density. Increased breast density from HRT makes it more difficult for a radiologist to read some mammograms, leading to the need for follow-up mammograms or breast biopsies. Increased density also is a concern because other studies have shown that women age 45 and older whose mammograms show at least 75 percent dense tissue are at increased risk for breast cancer. However, it is not known if increased breast density due to HRT carries the same risk for breast cancer as having naturally dense breasts.

Data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial at NCI indicate that about 25 percent of women who use combined HRT have an increase in breast density on their mammograms, compared to about 8 percent of women taking estrogen alone. One study showed that stopping HRT for about 2 weeks before having a mammogram improved the readability of the mammogram. However, further research is needed to confirm the usefulness of this approach.

Heart Disease: Two studies released in July 2001 confirm a pattern of an early increased heart risk for women with established heart disease who take HRT. The American Heart Association (AHA) recommends that women should not be prescribed HRT for the sole purpose of preventing second heart attacks. Despite the early risk of heart attack and death found in these studies, there is not enough evidence to advise women with heart disease to stay away from HRT altogether. And heart disease patients who have been on hormones for a while and are happy with the therapy can continue taking it. Experts are still waiting for the results of trials looking at HRT and the prevention of heart disease, so for now AHA concludes that there is not enough evidence to recommend HRT for preventing heart disease.

Does the duration of taking HRT affect breast cancer risk?

There is considerable uncertainty about the relationship between a woman's risk of developing breast cancer and the length of time that she receives HRT. Some women take HRT for only a few years, until the worst of their menopausal symptoms have passed, while others take it for a decade or more. Some researchers believe that there is little or no increased risk of breast cancer associated with short-term use (3 years or less) of either HRT with estrogen alone or estrogen combined with progestin, while long-term use (more than10 years) is linked to an increased risk.

The two most recent studies suggest that, with short-term use of HRT, the benefits seem to outweigh the risks, but for long-term use, the benefits must be carefully weighed against the risks.

What kind of research is underway to answer some of these confusing questions?

The Institute of Medicine will be reviewing the medical research on the use of HRT to prevent heart disease, osteoporosis and other problems associated with the aging process, and should release its findings in early 2002. The National Institutes of Health's (NIH) Women's Health Initiative, the largest clinical trial in the U.S., is exploring the association between HRT and the development of breast and colon cancer, heart disease and osteoporosis. Results from this study, available in 2005, should provide us with valuable information on the use of HRT. In the meantime, you should discuss these issues with your health care provider.

Why is menopausal hormone replacement therapy used in spite of the cancer risk?

The known benefits of HRT can improve the quality of life for many women, by reducing uncomfortable hot flashes, night sweats, and vaginal dryness. There also is evidence that HRT helps prevent and treats osteoporosis, and preliminary evidence that it can help prevent other problems associated with age, including Alzheimer's disease, colon cancer and deterioration of eyesight. The addition of progestin to the treatment has dramatically reduced the risk of endometrial cancer. Until the questions about the risk of breast cancer are more fully answered, many women and their health care providers believe the benefits outweigh the risks. However, women considered to be at high risk for breast cancer, or who have other concerns about the risks, might want to use alternative methods to alleviate menopausal symptoms. Family history of breast cancer, early age of the first menstrual period (menarche), late age of child bearing, high fat diet, obesity, increased breast density on mammograms, and certain benign breast lesions increase the underlying risk of developing a breast cancer. These factors need to be considered when deciding to take HRT. A woman also might consider any family history of osteoporosis or heart disease when making a decision about HRT.

Are there other drug therapies known to treat conditions related to menopause?

A class of drugs called SSRIs (such as Prozac and Zoloft) is very effective in treating menopause-related symptoms of depression or mood changes. Vitamin E and Clonidine, a drug typically used for high blood pressure, can alleviate hot flashes. To prevent osteoporosis, bisphosphonates, alendronate, raloxifene and calcitonin are used in women who are at high risk for bone loss. Lastly, a class of cholesterol-lowering drugs called HMG-CoA-reductase inhibitors (statins) are proven to be effective for reducing risk of heart disease and are being explored to prevent osteoporosis. No alternatives to estrogen exist for prevention of Alzheimer's disease, colon cancer, and macular degeneration - diseases for which preliminary evidence suggests HRT is beneficial.

What about herbal remedies?

There are many "herbal" products for sale that claim to help menopausal symptoms. These products are not regulated through the same government system as drugs, so there is little research to back up their claims. In addition, most have to be taken routinely, are not covered by insurance, and can become costly over time. Any herbal remedies for menopause should be thoroughly discussed with your health care provider. You should tell your provider if you are taking any other medications, since some of the herbal products can have harmful interactions with other drugs.

However, there are some products that seem to help some women. Soy and soy products have been used for the alleviation of menopausal symptoms due to their high concentration of phytoestrogens. Phytoestrogens are plant-derived compounds that possess estrogenic activity, and therefore could have some of the same effects as HRT, but their long-term safety has not been adequately studied. There is limited, and sometimes conflicting, research on the safety and effectiveness of many other popular herbal products that claim to help menopause, including ginseng, black cohosh, dong quai, and evening primrose.

Recently, the American College of Obstetricians (ACOG) issued the following guidelines on the most popular "alternative" medicines for menopause:

• Soy and Isoflavones (plant estrogens found in beans, particularly soybeans) - High isoflavone intake (about 50 grams of soy protein per day) may be helpful in the short term (2 years or less) in relieving hot flashes and night sweats. Taken over the long term, it also may have beneficial effects on cholesterol and bones. While safe in dietary amounts, the consumption of extraordinary amounts of soy and isoflavone supplements may interact with estrogen and may be harmful to women with a history of estrogen-dependent breast cancer and possibly to other women as well.

• St. John's wort - May be helpful in the short-term (2 years or less) to treat mild to moderate depression in women (when given in doses of less than 1.2 milligrams a day.) A recent study showed it is not effective in treating severe depression. It also can increase skin sensitivity to the sun and may interfere with prescription antidepressants.

• Black cohosh - May be helpful in the short term (6 months or less) to treat hot flashes and night sweats. It seems to be extremely safe, although studies have been small and brief, none longer than six months.

• Chasteberry (also known as monk's pepper, Indian spice, sage tree hemp, and tree wild pepper) - This may inhibit prolactin, a natural hormone that acts on the breast. It is touted for breast pain and premenstrual syndrome. There are very few studies in menopausal women. A study of women with premenstrual syndrome found they reported improvements in mood, anger, headache, breast fullness, but not bloating and other symptoms.

• Evening primrose - This plant produces seeds rich in gamma-linolenic acid, which some experts believe is the nutritionally perfect fatty acid for humans. Although evening primrose capsules are taken for breast pain, bladder symptoms and menopausal symptoms, there is little or no evidence that they work. The one high quality study of effects on hot flashes found that evening primrose was no better than placebo.

• Dong quai - A study aimed at reducing hot flashes found that dong quai was not better than placebo - although the 4.5-gram dose used in the study was lower than that typically given in Chinese medicine. The herb is potentially toxic. It contains compounds that can thin the blood, causing excessive bleeding, and make the skin more sensitive to sun, possibly increasing skin cancer risk.

• Valerian root - This has traditionally been used as a tranquilizer and sleeping aid. But the U.S. Pharmacopoeia, which sets manufacturing standards for medicines, does not support its use, and there have been reports of heart problems and delirium attributed to sudden withdrawal from valerian.

• Ginseng - Most of the many types of ginseng (including Siberian, Korean, and American, white and red), are promoted for relieving stress and boosting immunity. A study of menopausal women by the leading ginseng manufacturer found the product did not relieve hot flashes but did improve women's sense of well being. Analyses of ginseng products have found a troubling lack of quality control: some contained little or no ginseng, contained large amounts of caffeine, or were tainted by pesticides or lead.

• Wild and Mexican yam - There are no published reports that show wild and Mexican yam cream is effective in helping menopausal symptoms. The hormones in wild and Mexican yam do not have any estrogenic or progestational properties, so they are not expected to help women with these symptoms.

Who should not use HRT?

HRT is often not recommended for women who have any of the following conditions:

• Vaginal bleeding of an unknown cause;

• Suspected breast cancer or history of breast cancer;

• History of endometrial cancer or cancer of the uterus;

• Chronic disease of the liver; or

• History of venous thrombosis (blood clots in the veins or legs, or in the lung). This includes women who have had thrombosis or blood clots during pregnancy or when taking birth control pills. Although the risk of blood clots in women is very low, HRT increases the risk.

from The Office On Women's Health - US Department of Health and Human Services

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