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Hormone Therapy for Women: Side Effects, Cancer Risks

Facts you should know about hormone therapy

  • Hormone therapy (HT) refers to either estrogen or combination estrogen/progesterone treatment.
  • Estrogen therapy is the most highly effective prescription medication for treating menopause symptoms and in light of recent research is still safe and effective for many women when used for fewer than five years.
  • Estrogen therapy reduces or eliminates several symptoms of menopause such as hot flashes, disturbed sleep resulting from hot flashes, and vaginal dryness.
  • Other safe and effective non-hormonal medications exist to address a woman's concerns regarding osteoporosis.
  • The use of estrogen therapy without progesterone (progestin), is associated with an increase in the risk of uterine cancer (endometrial cancer, cancer of the lining of the uterus).
  • Treatment with progesterone along with estrogen substantially reduces the risk of uterine cancer (endometrial cancer) so that the risk of developing this cancer is equivalent to that of women not taking estrogen.
  • Users of oral hormone therapy (HT) (in the doses of the Women's Health Initiative) for more than five years are at slightly increased risk of breast cancer, heart disease, and stroke than are nonusers.

The term "hormone therapy" or "HT" is being used to replace the outdated terminology "hormone replacement therapy" or "HRT."

What is menopause?

Menopause is the stage in a woman’s life when menstruation stops and
she can no longer bear children. During menopause, the body produces less of the
hormones, estrogen and progesterone. After
menopause, the lower hormone levels cause the monthly menstrual periods to stop
and gradually eliminate the possibility of
becoming pregnant. These fluctuations in hormone levels can also
cause troublesome symptoms, such as hot flashes (a sudden
sensation of warmth, sometimes associated with flushing, and often followed by
sweating) and sleep
disturbance. Sometimes women experience other symptoms, such as vaginal dryness
and mood changes.

While many women
encounter little or no trouble during menopause, others endure moderate to
severe discomfort.

Does menopause cause bone loss?

The lower estrogen levels of menopause can lead to
progressive bone loss that is especially rapid in the first five years after
menopause. Some bone loss in both men and women is normal as people age. Lack of
estrogen after menopause adds another strain on the bones in addition to the
usual age-related bone loss. When bone loss is severe, a condition called
osteoporosis weakens
bones and renders them susceptible to breaking.

Menopause Symptoms & Signs

Some of the symptoms of menopause can actually begin years before
menstrual periods stop occurring. Doctors generally use the term “perimenopause” to refer
to the time period beginning prior to the menopause (when some of the signs and
symptoms of menopause begin to occur) up through the first year following
menopause. Menopause itself is defined as having had 12 consecutive months
without a menstrual period.

Menopause symptoms begin gradually while the ovaries are still functioning
and a woman is still having menstrual periods. These symptoms can begin as early
as the 4th decade of life (when a woman is in her 30s) and may persist for years
until menopause has occurred. The symptoms occur early because the levels of
hormones produced by the ovaries (estrogen and progesterone) decline
slowly over time, explaining why pregnancy is still possible, but less likely to occur, as a
woman reaches her forties. The severity and duration of symptoms vary widely
among individuals – some women may experience only minimal symptoms for a year
or two, while others may experience at least some of the symptoms for several

While most women will experience a gradual transition to
menopause with a slow onset of symptoms, some women will experience an early (premature)
menopause that may bring on immediate symptoms, depending on the cause of the
ovarian failure. One common cause of immediate symptoms is a “surgical
menopause” following the surgical removal of functioning ovaries.

Menopause symptoms can be perceived as physical problems, emotional
disturbances, or problems associated with sexual functioning.

Read more about the emotional, physical, and sexual symptoms of menopause »

What are estrogen therapy and hormone therapy (HT)?

Estrogen, in pill,
patch, or gel form, is the single most effective therapy for suppressing hot

The term estrogen therapy, or ET, refers to estrogen
administered alone. Because ET alone can cause uterine cancer
(endometrial cancer) (see below), a
progestin is
administered together with estrogen in women who have a uterus (those who have
not undergone a hysterectomy) to eliminate the
increased risk. Thus, the term estrogen/progestin therapy, or EPT, refers to a
combination of estrogen and progestin therapy, as is given to a woman who still
has a uterus. This method of prescribing hormones is also known as combination
hormone therapy.

The term hormone therapy (HT) is a more general term
that is used to refer to either administration of estrogen alone (women who have
had a hysterectomy), or combined estrogen/progestin therapy (women with a uterus).

forms of hormone therapy (HT) that are FDA-approved for therapy of hot flashes are similarly
effective in suppressing hot flashes.

What are the side effects and risks of hormone therapy (HT)?

Women can experience side effects during hormone therapy; these can be divided into more minor side effects, and more serious side effects. The more minor side effects are more common than the serious side effects, and are generally perceived by women as "annoying." These symptoms include:

It is still controversial which of these side effects are due to the estrogen component as compared to the progesterone component. Therefore, if side effects persist for a few months, the doctor will often alter either the progesterone or the estrogen part of the hormone therapy (HT).

Contrary to common belief, recent research has confirmed that women who take commonly prescribed doses of hormone therapy (HT) are no more likely to gain weight than women not taking hormone therapy (HT). This is probably because menopause or aging itself is associated with weight gain, regardless of whether or not a woman takes hormone therapy.

The more serious health concerns for women undergoing hormone therapy (HT) include:

  • Hormone therapy (HT) increases the risk of vein clots in the legs (deep vein thrombosis) and blood clots in the lungs (pulmonary embolus) by about 2 or 3 fold. However, it is important to remember that these conditions are extremely rare in healthy women. Thus, the true increase in risk for healthy women is minimal. Women with a personal or family history of these blood clots should review this issue when considering hormone therapy (HT).
  • Uterine Cancer (endometrial cancer): Research shows that women who have their uterus and use estrogen alone are at risk for endometrial cancer. Today, however, most doctors prescribe the combination of estrogen and progestin. Progestin protects against endometrial cancer. If there is a particular reason why a woman with a uterus cannot take some form of progesterone, her doctor will take a sample of tissue from her uterus (endometrial biopsy) to check for cancer annually while she is taking estrogen. Women without a uterus (women who have had a hysterectomy) have no risk of endometrial cancer.
  • Breast cancer: Recent research indicates that hormone therapy (HT), and especially EPT, increases the risk of breast cancer, although the increase in risk is very small. For example, the Women's Health Initiative, a reliable large study of hormone therapy (HT) in menopausal women, predicted that there were approximately eight extra cases per 10,000 women who took hormone therapy (HT) for 1 year, compared to women taking a placebo pill. The increase in risk of breast cancer associated with hormone therapy (HT) likely increases with duration of use and is especially increased with five or more years of use.
  • Abnormal vaginal bleeding: Women on hormone therapy (HT) are more likely than other postmenopausal women to experience abnormal vaginal bleeding. What is called "abnormal bleeding" depends on the type of hormone therapy (HT). With cyclic therapy, in which monthly bleeding is expected, bleeding is abnormal if it occurs when it is not expected or is excessively heavy or long in duration. With daily continuous therapy, irregular bleeding can last for six months to a year, therefore, irregular bleeding that lasts for more than a year is considered abnormal. When abnormal bleeding occurs, a doctor usually takes a sample of the lining of the uterus (endometrial biopsy) to rule out an abnormality or cancer in the uterus. This procedure is usually done in the office. After the evaluation is done, if nothing is found to be wrong, hormone therapy (HT) doses will often be adjusted to minimize further abnormal bleeding.
  • Stroke: Hormone therapy (HT) slightly increased the risk of stroke in women studied in the Women's Health Initiative. The WHI predicted that there were 8 extra strokes per 10,000 women taking hormone therapy (HT) for one year, compared to women taking a placebo (sugar pill). Because of the possibility of increased breast cancer, stroke, and heart disease risks, women who have no major menopause symptoms may choose to avoid hormone therapy (HT). The effects of other types of hormone therapy (HT) (aside from the Women's Health Initiative types) on breast cancer risk are still unclear.

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What are the types of hormone therapy (HT)?

Doctors usually prescribe hormone therapy (HT) as a combination of estrogen and another  female hormone, progesterone. Synthetic progesterone compounds are referred to as progestins. Long-term estrogen use without progesterone increases the risk of uterine cancer (endometrial cancer), whereas addition of progesterone counteracts this risk. Therefore, estrogen without progestin is usually only recommended for women who have had their uterus removed (hysterectomy). Estrogen is available as pills, tablets, patches, creams, mist sprays, or vaginal preparations (vaginal rings, vaginal tablets, or vaginal cream). The choice of estrogen preparation recommended by the doctor depends on the women's symptoms. For instance, vaginal creams, vaginal tablets, and vaginal rings are used for vaginal dryness, while pills or patches are used to ease hot flashes. Estrogen pills are also useful for vaginal dryness and are sometimes used along with vaginal creams, tablets, or rings.

Although progestin is usually taken in pill form, it is also available, together with estrogen, in patch form.

Doctors may prescribe different schedules for taking hormone therapy (HT). Every woman's hormone therapy (HT) treatment and schedule should be individualized based on her particular situation. Below are some standard forms of hormone therapy (HT) that are used:

Pills (oral therapy)

In order to avoid monthly vaginal bleeding, some women choose to take small doses of estrogen and progesterone together every day. This is called daily continuous therapy. Sometimes, daily continuous therapy can cause some irregular, unexpected vaginal bleeding for the first several months of treatment, especially in younger women entering menopause. For these women, and for some other women, planned cyclic bleeding is more acceptable. In these women, progesterone is usually added to estrogen for the first 12 calendar days of the month.

Patches and spray mists (transdermal therapy)

Hormone therapy (HT) skin patches are to be worn on a continuous basis. Newer patches need to be changed once or twice per week. Combination estrogen/progesterone patches are available for women who have not undergone hysterectomy to prevent cancer of the uterus. Patches are as effective as oral hormone therapy (HT) for controlling hot flashes. Spray mists for ET are available as a transdermal spray used once daily.

Vaginal tablets, rings, and Creams

Estrogen vaginal tablets and creams are generally prescribed nightly for 2 weeks, and then reduced to twice per week as a long-term "maintenance therapy." There is a low level of absorption of estrogen into the body with the use of vaginal preparations as directed. Circulating blood levels of estrogen are slightly increased from vaginal estrogen use, and the long-term safety of vaginal estrogen rings, creams and tablets has not been clearly established (for example risk of uterine cancer, heart disease, or breast cancer). For this reason, occurrence of vaginal bleeding during any type of vaginal estrogen use should be promptly evaluated.

Vaginal estrogen rings are approved to treat genital dryness and irritation that can occur due to the lack of estrogen in women after menopause. A higher dose vaginal ring is available to treat hot flashes, so the hormone released from this higher dose ring clearly reaches sufficient levels to affect other parts of the body besides the genital area. The vaginal ring remains in place for 12 weeks, after which it can be changed by either the woman herself or her physician. The long-term safety of estrogen rings is not yet clear, but there is a low level of absorption of the hormone into the bloodstream with use of the vaginal estrogen ring.

Bioidentical hormone therapy

There has been increasing interest in recent years in the use of so-called "bioidentical" hormone therapy for perimenopausal women. Bioidentical hormone preparations are medications that contain hormones that have the same chemical formula as those made naturally in the body. The hormones are created in a laboratory by altering compounds derived from naturally-occurring plant products. Some of these so-called bioidentical hormone preparations are U.S. FDA-approved and manufactured by drug companies, while others are made at special pharmacies called compounding pharmacies, which make the preparations on a case-by-case basis for each patient. These individual preparations are not regulated by the FDA, because compounded products are not standardized.

Advocates of bioidentical hormone therapy argue that the products, applied as creams or gels, are absorbed into the body in their active form without the need for "first pass" metabolism in the liver, and that their use may avoid potentially dangerous side effects of synthetic hormones used in conventional hormone therapy. However, studies to establish the long-term safety and effectiveness of these products have not been carried out.


If menopause occurs in a woman younger than ___ years, it is considered to be premature.
See Answer

Who should take hormone therapy (HT)?

  • Women with hot flashes, especially when they are causing sleep disturbance, can consider hormone therapy (HT). Estrogen given short-term is the most effective treatment for hot flashes, and benefit of short-term (less than 5 years) use outweighs potential risks for most women.
  • Because the risks outweigh the benefits of long-term hormone therapy (HT) for most women, women who are at risk of, or who have been diagnosed with, osteoporosis should talk to their doctors about non-estrogen medications such as alendronate (Fosamax), risedronate (Actonel), raloxifene (Evista), teriparatide (Forteo), and calcitonin (Miacalcin) in preventing and treating osteoporosis.
  • Women with vaginal dryness or itching due to menopause can consider HT. Oral pills, skin patches, gel, or vaginal forms of estrogen can be used. Women who only have vaginal menopause symptoms and are not experiencing hot flashes should pick a vaginal form of estrogen, whereas women with both hot flashes and vaginal symptoms can use any form of ET. Sometimes, if a woman has both hot flashes and vaginal symptoms, both oral and vaginal forms of ET will be prescribed together, especially if vaginal symptoms do not improve with oral ET alone.
  • It is recommended that women who do choose to take hormone therapy should take the lowest effective dose for the shortest time period possible.

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Who should not take hormone therapy (HT)?

  • Contrary to common myth, women with high blood pressure that is controlled by medication can take hormone therapy (HT) because hormone therapy (HT) does not cause significant elevations in blood pressure. A major medical reason for not taking hormone therapy (HT) is a personal medical history of breast cancer or uterus cancer. Women with abnormal vaginal bleeding should have an evaluation prior to embarking on hormone therapy (HT) to exclude the presence of cancer of the uterus. Similarly, routine mammograms and breast examinations are important to exclude the presence of breast cancer.
  • While hormone therapy (HT) may be used in women with migraines or liver disease, certain types of hormone therapy (HT) (often a patch or vaginal form) may be chosen to try to avoid aggravating these conditions.
  • Women should not be taking hormone therapy (HT) to prevent heart disease, and should initiate hormone therapy (HT) only with caution if they already have been diagnosed with coronary artery disease (such as past heart attack), as hormone therapy (HT) may be increase the risk of heart attacks.
  • Women with a personal history of deep vein thrombosis (blood clots in the veins) should avoid hormone therapy (HT).
  • Women with phosopholipid antibodies, including cardiolipin antibodies or lupus anticoagulant, should not take HT because of the added risk of blood clotting and thrombosis.

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What medical checkups are advised for women on hormone therapy (HT)?

All women receiving hormone therapy (HT) should undergo a medical checkup every year. At that time, the doctor or nurse will perform a breast exam and order a mammogram (a special X-ray picture of the breasts) to check for masses in the breasts that might possibly be cancer. At, or even prior to these check-ups, a woman should discuss her bleeding pattern with her physician to be sure it is within the expected pattern for her specific type of hormone therapy (HT). Other routine screening evaluations may also be performed at this annual check-up.

What if a woman decides against hormone therapy (HT)?

If a woman decides against hormone therapy (HT), there are other methods to deal with the symptoms of menopause. Although hormone therapy (HT) is by far superior to other medications in relieving hot flashes, other prescription non-hormonal medications can also reduce hot flashes. Likewise, personal lubrication products such as a water-soluble jelly (not petroleum jelly) can be applied to the vagina to reduce dryness.

A woman may also want to ask her doctor about non-hormonal prescription osteoporosis medications. These new treatments appear safe and effective in preventing fractures.

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