Special Offers

Medical Information

Arthritis Center

Allergy Center

Kid's Health

Cancer Center

GI Center

HIV/AIDS Center

Drugs

Medical Dictionary

Health News

Interactive Education

Simulators

PhotoRounds

Medical Databases

MEDLINE

CancerLit

AIDSLine

Healthcare Employment

About Us

Privacy Policy

Terms of Services

Our Company

Contact Us

Hormone Replacement Therapy

To combat the symptoms associated with falling estrogen levels, doctors have turned to hormone replacement therapy (HRT). HRT is the administration of the female hormones estrogen and progesterone. Estrogen replacement therapy (ERT) refers to administration of estrogen alone. The hormones are usually given in pill form, though sometimes skin patches and vaginal creams (just estrogen) are used. ERT is thought to help prevent the devastating effects of heart disease and osteoporosis, conditions that are often difficult and expensive to treat once they appear. The cardiovascular effects of progesterone, however, are still unknown. Hormone treatment for menopause is still quite controversial. Its long-term safety and efficacy remain matters of great concern. There is not enough existing data for physicians to suggest that HRT is the right choice for all women. Several large studies are currently attempting to resolve the questions, though it will take several more years to reach any definitive answers.

In the 1940's when estrogen was first offered to menopausal women, it was given alone and in high doses. Today, after 50 years of trial and error, it is well known that estrogen stimulates growth of the inner lining of the uterus (endometrium) that sheds during menstruation. This growth may continue uncontrollably, resulting in cancer. Today, doctors typically prescribe a lower dose of estrogen. However, few doctors still prescribe estrogen alone to women who have a uterus. Most now prefer to add a synthetic form of progesterone called progestin to counteract estrogen's dangerous effect on the uterus. Progestin reduces the risk of cancer by causing monthly shedding of the endometrium. The obvious drawback to this approach is that menopausal women resume monthly bleeding. Once menopause arrives, most women enjoy the freedom of life without a period. Many are reluctant to begin their cycles again. In addition, there are other unpleasant side effects of progestin which often discourage women from continuing HRT. These include breast tenderness, bloating, abdominal cramping, anxiety, irritability, and depression.

The good news is that researchers are evaluating different schedules of low-dose estrogen and progestin to completely eliminate monthly bleeding. Currently most women receive what is called cyclic HRT. They may take estrogen continually and progestin for the first 12 days of each month. The use of a continuous combined dose, where estrogen and smaller amounts of progestin are taken every day, is also being studied. In theory, this use of progestin stems endometrial growth so no bleeding will occur. Unfortunately, it may take 6 months or more until bleeding finally stops. In many cases, monthly bleeding has been replaced by more bothersome irregular bleeding patterns. Obviously, further research is needed to evaluate and perfect this treatment. Various types of progestins in different dosages, preparations, and schedules are being studied in hopes of reducing its other unpleasant side effects while retaining the known advantages of estrogen.

Estrogen and Your Bones

HRT and ERT are successful methods of combatting osteoporosis. As previously discussed, estrogen halts bone loss but cannot necessarily rebuild bone. Long-term estrogen use (10 or more years) may be required to prevent postmenopausal bone loss. Why estrogen helps protect the skeleton is still unclear. We do know that estrogen helps bones absorb the calcium they need to stay strong. It also helps conserve the calcium stored in the bones by encouraging other cells to use dietary calcium more efficiently. For instance, muscles require calcium to contract. If there is not enough calcium circulating in the blood for muscles to use, calcium is "borrowed" from the bone. Calcium is also needed for blood clotting, sending nerve impulses, and secreting various hormones. Prolonged borrowing from bone calcium for these processes speeds bone loss. That's why it's important to consume adequate amounts of calcium in your diet (see "Keeping Healthy").

Estrogen's Effect on Your Heart

The majority of past clinical studies have shown that women who use estrogen substantially reduce their risk of developing and dying from heart disease. One or two studies demonstrate conflicting evidence, but they are far outnumbered by the positive reports. Results from a 1991 study showed that after 15 years of estrogen replacement, risk of death by CVD was reduced by almost 50 percent and overall deaths were reduced by 40 percent. Some researchers credit this reduction to oral estrogen's ability to maintain HDL and LDL at their healthier, premenopausal levels, through its interaction with proteins in the liver. Others believe it is estrogen's direct effect on the blood vessels themselves (through receptors on the vessel walls) which creates this benefit. In the latter case, both oral estrogen and the skin patch would be effective. Studies are underway to determine which mechanism contributes most to a healthy heart.

Many doctors now believe that estrogen replacement benefits women at risk for heart disease (but not those with blood clots--see "Cautions to Estrogen Use"). Risk factors for heart disease include a strong family history of CVD, high blood pressure, obesity, and smoking.

At any time of life, women who smoke are much more likely to develop heart disease or have a stroke than women who do not smoke. But after menopause, a smoker's risk climbs dramatically. Low estrogen levels and smoking are separate risk factors for CVD. When the two are combined, the risk is much higher than either one alone. Smoking also raises your risks for some types of cancer and for chronic lung disease, such as emphysema. Fortunately, quitting smoking--at any age--can cut the risk of disease almost immediately. Studies have shown that when older people quit, they increase their life expectancy. Their risk of heart disease goes down, their lungs function better, and blood circulation improves. So quitting smoking, whether before, during or after menopause, can have a definite impact on both the length and quality of your life.

Many women who have quit smoking say they found support in group counseling sessions. Local chapters of the American Cancer Society and the American Heart Association are good places to start looking for a smoking cessation group. Nicotine gum and nicotine patches prescribed by a doctor may also help.

While we know that estrogen users have a decreased risk of CVD, women with certain preexisting heart conditions are usually advised not to take HRT or ERT. These conditions include blood clots and recent heart attacks. Researchers hope to further investigate nonhormonal methods of preventing heart disease such as weight reduction or control, exercise, smoking cessation, and dietary modification. According to a 5-year study reported in 1988, weight gain (a common occurrence among many menopausal women) significantly raises blood pressure, total and LDL cholesterol, and fat levels. Together, these make up a dangerous recipe for heart disease. Several other studies also noted that having about one drink per day had a protective effect on the heart.

Physicians advise caution in this area, however, as excess alcohol can increase risks for other serious problems.

While cardiovascular benefits associated with oral estrogen are fairly well-known, there is surprisingly little information on the cardiovascular effects of progestin combined with estrogen. Some studies suggest that progestins counteract the favorable effects of estrogen alone, while other studies show no such effect. This remains just one more gray area where questions outnumber reliable answers.

Source: R.L. Young, N.S. Kumar, and J.W. Goldzieher, Management of Menopause When Estrogen Cannot Be Used, Drugs, 40(2):220-230,1990

Cautions to Estrogen Use
Serious risk	Relative risk	Subjective Complaints
Stroke Recent heart attack Breast cancer (current or family history) Uterine cancer Acute liver disease Gall bladder disease Pancreatic disease Recent blood clot Undiagnosed vaginal bleeding	Cigarette smoking Hypertension Benign breast disease Benign uterine disease Endometriosis Pancreatitis Epilepsy Migraine headaches	Nausea Headaches Breakthrough bleeding Depression Fluid retention

Drawbacks of HRT: The Cancer Risk

A major issue surrounding HRT and ERT is the influence of estrogen on breast cancer. Researchers believe that the longer your lifetime exposure to naturally occurring estrogen, the greater your risk of breast cancer. It has not been proven, however, that estrogen administered at menopause has the same effect. There is disagreement on the many trials conducted to date because of wide variations in the populations studied and the doses, timing, and types of estrogen used. A recent analysis of previous studies suggests that low-dose estrogen taken on a short-term basis (10 years or less) does not pose increased risk of breast cancer. Long-term use (more than 10 years) at a high dose may significantly increase the risk. By how much is still a matter of heated debate. At the very most, researchers think long-term use could possibly increase the risk of getting breast cancer by 30 percent. This means that incidence would rise from 10 women per 10,000 each year to 13 women per 10,000 each year. To reach any consensus, however, more women need to be monitored for an extended period of time. The fear of cancer is one of the most common reasons that women are unwilling to use HRT. Interestingly, actual death rates for breast cancer have not risen at all. This may be because estrogen users have more frequent medical visits and obtain more preventive care including yearly mammograms.

While no one can determine who will eventually develop breast cancer, there are certain risk factors you should be aware of when considering HRT. A family history of breast cancer (sister or mother) is probably the most important risk factor of all. You may also be at an increased risk if: you menstruated before age 12; delayed motherhood until later in life; or have a late menopause (after age 50). Also, the older you are, the higher the risk. Most doctors believe that if you are not in a high-risk category for breast or endometrial cancer, the benefits of HRT far outweigh the risks. However, for some women, the side effects of therapy make it impossible to use. This is a personal decision to be made by each woman with help from her doctor.

Other Risks

Physicians usually caution women not to use HRT if they are already at high risk for developing blood clots. Obesity, severe vericose veins, smoking, and a history of blood clots put you in this category. A history of gall bladder disease could also be cause to avoid HRT, as women taking estrogen may have a greater chance of developing gallstones.

Hormonal Therapy
Here is what scientists can say so far about the advantages and disadvantages of hormone replacement therapy (HRT--estrogen and progesterone) and estrogen replacement therapy (ERT--estrogen alone). More research is underway.
Pro	Con
HRT and ERT reduce the risk of osteoporosis. HRT and ERT relieve hot flashes. HRT and ERT reduce the risk of heart disease. HRT and ERT may improve mood and psychological well-being.	ERT increases the risk of cancer of the uterus (endometrial cancer). HRT can have unpleasant side effects, such as bloating or irritability. HRT and ERT may increase risk of breast cancer; long-term use may pose the greatest risk. In women with blood clots, HRT and ERT may be dangerous.