Menopause and Hormone Use: Questions and Answers

Key Points

  • Menopausal hormone use involves taking either:
    • estrogen alone or
    • estrogen in combination with progesterone or
    • progestin, a synthetic hormone with effects similar to those of progesterone (see Question 2)
  • Estrogen is prescribed to treat some of the problems often associated with menopause. Those include problems such as:
    • hot flashes
    • night sweats
    • sleeplessness
    • vaginal dryness
    Doctors may also recommend hormones to prevent long-term conditions more common in postmenopausal women. For instance, hormones may be used to prevent osteoporosis (see Question 2).
  • A recent large clinical trial showed that the health risks associated with estrogen plus progestin were greater than the benefits (see Questions 4–11).
  • The overall health effects of estrogen alone in postmenopausal women are less clear. The best evidence will come from a large ongoing clinical trial involving women taking estrogen alone, which is expected to end in 2005 (see Questions 4–11).

1. What is menopause?

Menopause is when a woman stops having her periods. It’s actually part of a process. For most women, this process starts in their mid-thirties.

The ovaries produce two sex hormones—estrogen and progesterone. The first one promotes the development of breasts and the uterus. It also controls when an ovary releases an egg. Many aspects of a woman’s physical and emotional health are also controlled by estrogen. Progesterone controls having a period. It also prepares the uterus to receive a fertilized egg. At some point in the mid thirties, the ovaries start to gradually produce less of these two hormones.

It’s typical that a woman has her last period between the ages of 45 and 55. Exactly when varies from woman to woman. When it happens “natural menopause” starts. After a year of no periods, menopause is complete. When both ovaries are removed by surgery, the result is “surgical menopause.” That surgery is called bilateral oophorectomy. No more hormones are produced. And there are no more periods.

A woman may have problems during menopause. For instance, she may have hot flashes or night sweats. She may not sleep well. She may have vaginal dryness. Also, some long-term health problems are more common after menopause. Osteoporosis is one example. Heart disease is another.

After menopause, the adrenal glands and fat cells do produce some estrogen. But the level of the hormone is only about one-tenth of what it was before menopause. And progesterone is nearly absent.

2. What are menopausal hormones and why are they used?

During and after menopause, there are two types of treatment that might be used. The first uses estrogen by itself. It’s called estrogen replacement therapy or ERT. The second one combines estrogen with progesterone. It’s commonly called hormone replacement therapy or HRT. Both treatments can double a woman’s estrogen level. Neither one, though, will raise the level to what it was before menopause.

Doctors may recommend the use of hormones to offset some of the problems that come with menopause:

  • hot flashes
  • night sweats
  • sleeplessness
  • vaginal dryness

They might also be used to prevent long-term problems such as osteoporosis. A 1997 survey showed that nearly half of all U.S. women over the age of 47 used hormones for at least 1 month. One out of every five used them for 5 or more years.1

3. How do scientists know what health outcomes result from hormone use?

Researchers use two types of studies to learn about outcomes: clinical trials and observational studies.

In the first type, some people are given hormones. Others are given placebos. Placebos look like the same pill. They do not, though, contain any drug. The results show the effect the hormones have. In observational studies, researchers compare the health status of women who take hormones to those who don’t. Clinical trials provide the strongest evidence for what hormones do.

4. How do the benefits of hormone use compare with the risks?

A lot of what is known about the risks and benefits of hormone use comes from the Women’s Health Initiative (WHI). The WHI is a large clinical trial of over 16,000 healthy women between the ages of 50 and 79. Half of the women took hormones. The other half took a placebo. In July 2002, part of the trial was stopped early. That’s because the data showed the overall risks of estrogen plus progestin outweighed the benefits.2 Using the combined hormone pill increased the risk of:

  • breast cancer
  • heart disease
  • stroke
  • blood clots

On the other hand, women taking the pill had fewer cases of hip fractures and colon cancer.2

Another part of the WHI looked at the risk of developing dementia. Women 65 and over who took the combined hormones had more risk.3 They also did more poorly on cognitive function tests.4

In women ages 50 through 79 who took the combined drugs there was no change in:

  • general health
  • vitality
  • mental health
  • depressive symptoms
  • sexual satisfaction5

The risks and benefits of estrogen alone are less clear. Results still aren’t available for women in the WHI who took estrogen alone. That study didn’t end until 2005.

5. How does hormone use affect the uterus?

Using estrogen alone increases the risk of endometrial cancer. That’s cancer of the lining of the uterus. When estrogen and progestin are combined, it appears the risk is much less. But it isn’t clear whether it’s higher than it would be if no hormones are used. For instance, some reports show that the risk is nearly the same as for women not using estrogen.6 In those studies, progestin was used for 10 or more days each month.7,8 Another study, though, looked at what happened when the combined drug was used less than 10 days per month. Women who used it were twice as likely to develop endometrial cancer than women who used no hormones. At the same time, women who used the combined drug 10 to 21 days per month were not at increased risk.9

In the WHI trial women taking the combined hormone daily had the same risk as those taking the placebo. Uterine bleeding, though, was a common side effect. Bleeding led to more frequent biopsies and ultrasounds for women taking combined hormones.10

Women who have had their uterus removed and are being treated with hormones are generally given estrogen alone. Women who still have their uterus are given the given combined hormones.

6. What is the connection between hormone replacement and breast cancer?

The WHI showed that using combined estrogen and progestin increased the risk of breast cancer by 26 percent. That meant if you compared 10,000 women treated with HRT to the same number who were not, there would be 8 more cases of breast cancer.2

A more detailed analysis showed that breast cancers were slightly larger in women taking the combined hormones. They were also found at more advanced stages. Plus, in about one out of every four cases, the cancers had spread outside the breast.11 The effect of estrogen alone is still being studied.

Other studies also show an increase in breast cancer risk. In 1997 an analysis of over 90 percent of breast cancer studies showed higher risk of breast cancer for women who used hormones for 5 or more years. Most of the women had used estrogen alone. The women who used combined hormones seemed to have an even higher risk.12 The higher risk was also seen in women who had stopped therapy in the previous 4 years. No higher risk was seen in women who had stopped more than 4 years earlier.

Other studies support the finding that hormone use results in a higher risk of breast cancer. They also support the idea the greatest risk comes from using combined hormones.13,14,15 In one study, current hormone users were more likely to die from breast cancer than women who did not use them. After about 5 years having stopped, the higher risk largely disappeared.13

7. How does hormone use affect the risk of ovarian cancer?

Using estrogen by itself seems to cause a higher risk of ovarian cancer. Using it for 10 years appears to double the risk compared to women who don’t use it.16 Also, using it for 10 may increase the chance of dying from ovarian cancer.17

In the WHI study, combined hormone use also seemed to increase the risk. But the increased risk was not statistically significant when compared to women who did not use hormones. Another study suggested that combined hormone treatment does not increase the risk of ovarian cancer if progestin is used for more than 15 days per month.18 But this study was too small to draw firm conclusions. More research is needed to know exactly what effect hormone use has on the risk of ovarian cancer.

8. How does hormone use relate to heart disease?

WHI found that combined hormone use does not protect the heart. It may, in fact, increase the risk of heart disease. The greatest increased risk occurred in the first year.2 Analysis showed that estrogen plus progestin resulted in a 24-percent increase in the risk of heart disease overall. In the first year, though, there was an 81-percent increased risk.19

In another trial, women with a history of heart disease got no heart benefit from using combined hormones. After more than six years, there was no reduction in the risk of heart attacks. Nor was the risk of deaths from heart disease reduced.20

One study looked at the effects of the use of estrogen alone and combined hormones by women with coronary artery disease. It found that neither treatment had any significant effect on the progression of the disease.21

There have, though been some studies that suggest estrogen alone may protect a woman against coronary heart disease.22 Most of the participants in these studies were healthy women at low risk for developing heart disease.

9. How does hormone use relate to bone health?

Osteoporosis is the loss of bone mass and density. It causes bones to become fragile. That increases the chance of bone fractures. Low levels of estrogen have been linked to osteoporosis in women.

Estrogen alone has been shown to protect against osteoporosis. So has estrogen combined with progestin. The WHI showed that combined hormone use can prevent fractures of the hip, vertebrae, and other bones.2 Analysis of the data found a decreased risk of fracture in all subgroups of women regardless of:

  • age
  • smoking
  • fall and fracture history
  • past use of hormones
  • parental fracture history
  • years since menopause

Using combined hormones also had a consistent positive effect on bone mineral density. Some studies have shown, though, that the benefits on bone health end after short-term hormone use is stopped. Use of estrogen for 3 to 5 years to relieve symptoms of menopause did very little to prevent fractures when women were older.24,25 These studies suggest that women who take estrogen for bone density must keep taking it to get the benefit.

10. What effects does hormone use have on quality of life? And how does it affect cognitive functions such as memory and learning?

Quality of life

Estrogen is used to treat problems that come with menopause. For instance, it’s used to treat hot flashes and night sweats. It’s also used to treat vaginal dryness. Hormones have also been used to improve mood and psychological well-being. These can be problems for women who have hot flashes and sleeplessness during menopause.

The WHI looked at quality of life of women ages 50 through 79 who used combined hormones. It did not find any significant effect of hormone treatment on:

  • general health
  • vitality
  • mental health
  • depressive symptoms
  • sexual satisfaction

It did seem to have a small benefit after 1 year of use in some areas:

  • sleep disturbance
  • physical functioning
  • bodily pain

The effects, though, were too small to be significant. After 3 years, there were no benefits in any quality of life issues.4

WHI results may not be relevant for women with severe menopausal symptoms. Women in the WHI who had menopausal symptoms said they got relief with hormone use. In the study women were randomly assigned to receive either hormones or placebo. As a result, some who felt they needed hormones to treat symptoms may not have taken part. That’s because they may have not been willing to take the chance of not receiving hormones. If they had taken part, there might have been more benefit noted.

Another study looked at combined hormone treatment and quality of life. It found the effect depended on whether or not a woman had menopausal symptoms. Women who had hot flashes had improved mental health. Depressive symptoms also improved. Women who did not have hot flashes, though, received no emotional benefits. And physical functioning—from the ability to dress and bathe to the ability to take part in strenuous sports—was somewhat worse.26

Memory and learning

The WHI Memory Study should combined hormone treatment doubled the risk for dementia in women who were at least 65. The risk increased for all types of dementia, including Alzheimer’s disease.3 A separate study showed that combined hormone treatment affected cognitive function. In the WHI Memory Study, women 65 and older did well on cognitive tests during the study. But the women on combination therapy did not do as well.5

11. Are there other benefits or risks with hormone use?

Colon cancer

In the WHI, combined hormones had a benefit on the risk of colon cancer. Women who took combined hormone had about one third less risk.2 That would mean 6 fewer cases in every ten thousand women taking combined hormones.

Data about the use of estrogen by itself is not yet available.

Blood clots

The WHI showed that women who use combined hormones have two times more risk of blood clots in lungs and legs.2 Other studies have shown similar increased risks of blood clots.27,28,29

Stroke

The WHI showed a 41 percent increase in strokes for women using combined hormones.2 A longer follow up for the same women found a 31-percent increase in stroke. That would be 7 additional cases of stroke for every 10,000 women for each year of treatment.30 Earlier studies have had conflicting results in terms of stroke risk. But two small trials showed no significant effect on stroke for women taking either estrogen alone31 or combined hormone treatment.32

Gallbladder disease

Studies show that women who use combined hormones have more risk for gallbladder disease.28,33,34

12. What are the risks of hormones for women who have a history of cancer?

When estrogen occurs naturally, it promotes normal growth of breast cells. It does the same for cells in the uterus. So there is concern that estrogen use by women who have had cancer may promote more tumor growth. It’s not clear what the effect of taking estrogen after endometrial and breast cancer is.35 There’s been little research on the risks for women who have had endometrial cancer. A few small studies have found no evidence that hormone use has a negative effect on survival. The same is true for recurrence of the disease.36 No large, long-term studies, though, have compared the benefits with the cancer risks.

One study of breast cancer patients involved women who continued hormone use after their diagnosis. Most of them were using estrogen alone. Results showed no increase in recurrence or mortality.37 Another study showed that users of estrogen had lower mortality rates from breast cancer. Most of these patients stopped using estrogen when the cancer was diagnosed. The benefit of prior use, though, lessened over time.38

13. Does it matter how hormones are administered?

Most of what we know come from studies where hormones were given orally in the form of pills. But hormones can be given in other ways:

  • transdermal patches
  • gels
  • vaginal creams and rings

These forms of estrogen are all effective methods for treating symptoms of menopause. That includes hot flashes and vaginal dryness. Progesterone also comes as a pill or gel.

We know the patches have a similar effect on bone health as oral treatment.39,40,41 We don’t know yet what effect the patch and progestin will have on the heart and blood vessels.

How much estrogen enters the blood from vaginal creams and rings depends on the types of hormones and the dose. Generally, the result is a lower level of circulating hormones than there would be with an oral dose. The thin layer of tissue that covers the vagina responds to very small doses of estrogen. Creams with low doses can be used to correct some effects of menopause on the vagina. But vaginal estrogen therapy does not seem to protect against bone loss.39,40

14. Are there any alternatives for women who choose not to take hormones?

Hormones can have short-term benefits. But there are several health concerns related to their use. So many women feel that hormones are not a good choice for them. You should discuss taking hormones with your health care provider. You should also ask what alternatives might be appropriate for you.

There are things you can do to adopt a healthy lifestyle:

  • not smoking
  • getting regular exercise
  • eating a healthy diet

Doing those things helps decrease your risk of bone loss. Calcium and vitamin D supplements can also help prevent osteoporosis.42 Part of the WHI, has been testing the effect of calcium and vitamin D supplements. It’s focused on the effect on hip and other fractures as well as on colon cancer. Other drugs have been shown to prevent bone loss. Examples include:

  • alendronate (Fosamax®)
  • raloxifene (Evista®)
  • risedronate (Actonel®)

These drugs are being used more and more to treat osteoporosis in many women.43 The FDA has recently approved parathyroid hormone (Forteo®) for osteoporosis treatment. Tibolone is being studied in clinical trials to prevent osteoporosis.

Short-term problems related to menopause may go away on their own. Often, they require no treatment at all. But some women seek relief from symptoms with remedies that don’t need a prescription. Examples include:

  • estrogen-containing foods (soy products, whole-grain cereal, seeds, and certain fruits and vegetables)
  • creams with estrogen
  • herbs such as black cohosh
  • vitamin E and vitamin B complexes

The benefits and risks of most of these agents are not known. But they are being studied.42 There are also local therapies for vaginal dryness. The same is true for urinary bladder conditions.

15. What research still needs to be done?

There are questions about the adverse health effects from using estrogen alone. Other questions include:

  • Are different forms of the hormones safer or more effective?
  • Are lower doses safer or more effective?
  • Are there different hormones that would be safer and more effective?
  • How do different ways of taking the hormone affect the safety and how effective it will be?
  • Are there risks and/or benefits that persist after women stop taking hormones?
  • Is it possible to take hormones safely for a short period of time?
  • Are certain subgroups of women at higher or lower risk than the general population?

Research by the WHI is focusing on ways to prevent:

  • heart disease
  • breast cancer
  • colorectal cancer
  • osteoporosis44

Parts of the WHI will evaluate the effect of a diet low in fats and high in fruits, vegetables, and grains. Can such a diet prevent breast cancer? Can it prevent colorectal cancer or heart disease? And can calcium and vitamin D supplements prevent osteoporosis-related fractures?

Several studies to evaluate the association between menopausal hormones and the occurrence of colorectal cancer are currently under way.45 Other research projects are described at various Government web sites.