Prescription Drugs Information
HEALTH GUIDE / Prescription Drugs / Hormone Replacement Therapy

Hormone Replacement Therapy

HRT, Estrogen Replacement Therapy, Progestin Replacement Therapy


About Hormone replacement therapy

Hormone replacement therapy (HRT) uses medications to replace the hormones lost during menopause. It may be taken in various forms, including pills, skin patches, vaginal creams, vaginal rings, suppositories or injections. HRT helps relieve symptoms and prevent diseases brought on by a decrease in the level of estrogen and progesterone experienced by women during and after menopause. About six million American women take a combination of estrogen and synthetic progesterone after menopause, according to the National Heart, Lung and Blood Institute.

Hormones are chemical substances that carry important information and instructions from one group of cells to another. The two most important sex hormones are estrogen and testosterone. They contribute to the growth and development of sexual characteristics and reproduction. Both women and men produce estrogen and testosterone. However, women have much higher proportions of estrogen, whereas men have much greater proportions of testosterone.

Estrogen is a major female hormone that appears to offer women a number of important health benefits such as:

  • Helps prevent bone loss
  • Helps prevent buildup of plaque in the arteries
  • Keeps the vagina lubricated and supple
  • Keeps the lining of the urethra from thinning, which helps prevent urinary tract infections

During the years just prior to menopause (around age 50), a woman’s ovaries begin to shrink, causing levels of estrogen and progesterone hormones to drop. When estrogen is no longer produced in large amounts by a woman’s ovaries, she will gradually cease to menstruate. However, she also loses the health benefits of estrogen. As a result, she may experience various adverse symptoms (including hot flashes and vaginal dryness) or face increased risks of heart disease, osteoporosis, Alzheimer’s disease and other health risks.

HRT provides benefits to women during and after menopause, including:

  • Reduces symptoms associated with menopause. Such symptoms include:
    • Hot flashes. This is warmth in the face, neck and chest that can have a range of effects, from mild to severe heat and sweating. It also manifests as night sweats and may cause headaches.
    • Vaginal dryness. During menopause, vaginal skin may become dry and thin. Sex may become painful, and vaginal itching (pruritus) or burning may occur.
    • Mood swings.
  • Protects against other diseases. Hormones are known to help prevent certain diseases, such as colon cancer and osteoporosis (a thinning and weakening of the bones). New evidence indicates that HRT may help prevent heart disease in younger women who start treatment shortly after menopause.

Women receiving HRT usually take one of the following:

  • Estrogen. Given to women who no longer have a uterus. It is made synthetically from plants and other sources, or made from the urine of pregnant horses.
  • Estrogen with progesterone. Given to women who still have a uterus. The progesterone helps prevent overgrowth of cells (hyperplasia) in the lining of the uterus that can lead to cancer. Progesterone that is made synthetically is called progestin. Another form of progesterone is known as “natural progesterone” or “micronized progesterone.” It is very similar to the natural hormone.

Women usually remain on HRT for anywhere between several months to a few years. For years, physicians regularly prescribed HRT for menopausal and post-menopausal women. However, the Woman’s Health Initiative (sponsored by the National Institutes of Health) — a 15-year study of more than 160,000 post-menopausal women that ended in 2002 — revealed health risks associated with HRT that have made physicians more cautious about prescribing these drugs. Because of this study, the current recommendation is for most menopausal women to not take HRT indefinitely.

Many health risks are now known to be associated with HRT, including blood clots, breast cancer, uterine cancer and others. The Food and Drug Administration (FDA) currently requires manufacturers of estrogen medications to include information about these risks in the labeling and packaging that accompanies the drugs. However, despite the possible risks, it should be emphasized that the likelihood of adverse effects due to HRT is very low in any individual woman.

In addition, recent findings challenge some of the results of the WHI’s 2002 study. According to a new study conducted by researchers from Cornell and Stanford universities, the risk of heart disease may be lowered in women who begin taking HRT before the age of 60 or shortly after onset of menopause. It should be noted, however, that for women who begin HRT after age 60 the same study had mixed results. For the older group of women participants, HRT increased the risk of heart attacks in the first year of treatment, but after two years of treatment hormone replacement therapy began to reduce this risk. The risk of heart disease and stroke varies with age and the health of a woman. Women of menopausal or post-menopausal age must discuss with their physician whether HRT is right for them.

Studies have found that women who use HRT are more likely to:

  • Have entered menopause due to surgery (e.g., hysterectomy, oophorectomy) rather than from normal aging
  • Be Caucasian than African-American or Hispanic
  • Have higher levels of education and income
  • Have been counseled about HRT by a physician or other healthcare provider

Women who choose not to undergo HRT can still take several steps to improve their health. These include:

  • Have regular checkups with their physician, especially their gynecologist
  • Avoid tobacco products
  • Eat a balanced diet and maintain a healthy body weight
  • Ask a physician about taking calcium or vitamin D supplements to improve bone health
  • Exercise regularly
  • Check blood pressure, cholesterol and blood sugar
  • Schedule breast exams and mammograms

In addition, new findings link the current national decline in the rate of breast cancer to a decrease in use of HRT by women. A study released in 2006 indicated that the incidence, or new cases, of invasive breast cancer declined in the period from mid-2002 to 2003. The American Cancer Society statistics for 2001 to 2003 indicate that new breast cancer cases leveled off after 20 years of increases. Many factors may contribute to this change, including a major decrease in the use of HRT by women after menopause. However, the cause and effect of such changes are difficult to establish, especially in the short term.


Types and differences of HRT

There are two primary types of hormone replacement therapy (HRT):


Comparable to the hormone testosterone in men, estrogen is a major female hormone that affects both the brain and the body. During puberty, it is primarily responsible for secondary sexual characteristics (e.g., breast development, pubic hair, broadening of the hips). It is also chiefly involved in the internal physical changes that allow a woman to carry a pregnancy.

There are three types of estrogen:

  • Estrone (E1). Produced by the ovaries.
  • Estradiol (E2). Produced by the ovaries, it is the most abundant estrogen.
  • Estriol (E3). Produced by the placenta during pregnancy.

Normal concentrations of estrone are produced in body fat. Women who are exceptionally thin will not have monthly periods because there is not enough fat to produce estrone. Estrone and estradiol are the two types of estrogen produced in the ovaries — the two organs leading to a woman’s uterus (womb) that contain eggs (ova). The ovaries begin producing estrogen around the age of eight or nine years and gradually stop producing it around the time of menopause (12 months after the last menstrual period). Not only is estrogen responsible for processes related to the female reproductive organs, but it is also present in hundreds of other tissues in the female body.

Estrogen treatment is given to women who no longer have a uterus. It is made synthetically from plants and other sources, or made from the urine of pregnant horses. Estrogen may be taken by pill, skin patch, vaginal cream, vaginal ring, suppository or injection. The method of delivery may depend on the nature of the symptoms. For example, a cream may ease vaginal dryness, whereas a pill or skin patch may help reduce hot flashes.

For many years, menopausal and post-menopausal women were given estrogen to help reduce symptoms associated with menopause. Known as estrogen replacement therapy (ERT), this treatment was used because it was recognized that estrogen is the main sex hormone that produces menopause-related changes.

However, when ERT is taken alone, it can lead to abnormal thickening of the uterine lining (uterine hyperplasia), which significantly increases the risk of uterine cancer and endometrial cancer (cancer in the lining of the uterus). This is because a postmenopausal woman’s ovaries not only stop producing estrogen, but they also stop producing another sex hormone called progesterone, which protects the uterus. Because postmenopausal women do not have enough progesterone to take ERT without increasing the risk of uterine and/or endometrial cancer, ERT is now recommended only for women who have had a hysterectomy (the surgical removal of the uterus).

Estrogen and progesterone

For women who still have a uterus, estrogen is usually taken with a form of progesterone. The form of progesterone most often prescribed is chemically produced: a synthetic progestin, almost always given in pill form. This type of HRT can be administered according to different schedules, including:
  • Cyclical estrogen and progestin. This involves taking estrogen daily and adding progestin between 12 and 14 days every month. During five or six days each month, the patient takes no hormones. The regimen is often used in women who are still having menstrual periods at the time they begin HRT. Most women will experience a light period during the days when they are not taking hormones.
  • Daily estrogen and progestin. Also known as “continuous combined HRT,” it involves taking both estrogen and progestin every day. Women who have not had a period for at least six to 12 months often use this regimen. Many will initially experience episodes of irregular spotting or bleeding that usually ends within six to eight months.
Type of HRTBrand Name(s)


Cenestin, Estratab, Estrace, Gynediol, Menest, Ogen, Premarin

Estrogen patches

Alora, Climara, Estraderm, FemPatch, Vivelle

Vaginal estrogen

Estring, Femring, Vagifem


Amen, Cycrin, Provera

Natural progesterone



Conditions of concern with HRT

Patients should not take hormone replacement therapy (HRT) drugs if they have been diagnosed with or experienced any of the following conditions:

  • Pregnancy
  • Vaginal bleeding
  • Stroke or heart attack in past year
  • Blood clots
  • Liver disease
  • Some forms of cancer, including those of the breast, endometrium and uterus

Women with noncancerous (benign) tumors of the uterus (uterine fibroids) may find that HRT makes the fibroids grow larger, but this is not typical. In addition, HRT has been linked with increased breast density in some women undergoing the therapy making it more difficult to read mammograms.

Benefits and risks

Potential benefits and risks of HRT

Women who undergo hormone replacement therapy (HRT) often report a dramatic improvement in their quality of life due to a reduction of symptoms typically associated with menopause. According to the Food and Drug Administration (FDA), HRT is the most effective treatment for the following conditions related to menopause:

  • Hot flashes
  • Vulvar or vaginal atrophy

In addition, HRT is an option for preventing osteoporosis (thinning of the bones) in women whose risk of the disease outweighs the risk of treatment. HRT can reduce the amount of calcium lost from the bones. Women will usually receive the most effective protection against osteoporosis if they begin HRT around the time of menopause and continue to use it indefinitely.

Other non-estrogen drugs that can be used to prevent osteoporosis include bisphosphonates (such as alendronate and risedronate) and selective estrogen receptor modulators (such as raloxifene). However, these drugs are relatively new, so their long-term effectiveness is unknown.

Many women report that HRT is effective at relieving other symptoms associated with menopause, including:

  • Sleep disturbances
  • Depression
  • Pain during intercourse
  • Urinary tract infections

However, HRT also carries serious risks for some patients. These include increased risk of certain illnesses, such as:

  • Blood clots
  • Breast cancer
  • Dementia
  • Gall bladder disease
  • Heart attack
  • Ovarian cancer
  • Strokes
  • Uterine cancer
  • Uterine fibroids

Women who still have their uterus while undergoing HRT have a greater risk of developing endometrial cancer (cancer of the uterine lining). Adding progestin lowers this risk. In addition, not only does use of HRT drugs raise the risk of breast cancer, but it also makes tumors harder to detect, which can lead to dangerous delays in diagnosis.

A follow-up study to the Woman’s Health Initiative (WHI) found that the combination of estrogen and progestin increases the risk of dementia in women 65 years and older while failing to prevent memory loss. However, women who start HRT earlier in life — before they turn 65 — could reduce their risk of developing Alzheimer’s or dementia, according to a new study.

Common side effects associated with HRT include:

  • Headache.
  • Breast pain or tenderness. Women who develop this side effect while using HRT may be forming denser breast tissue, according to recent findings. Studies have shown that women with denser breasts are at higher risk for developing breast cancer.
  • Irregular vaginal bleeding or spotting.
  • Stomach cramps.
  • Nausea and vomiting.
  • Hair loss.
  • Skin discoloration.
  • Dizziness.
  • Fluid retention.
  • Mood changes.

Side effects can be reduced by taking the lowest possible effective dose of the hormone for the shortest period of time possible. In some cases, patients may find relief from side effects by switching to an alternative form of HRT.

In recent years, the benefits and risks of HRT have been studied in depth. Initially, HRT was believed to help prevent cardiovascular disease in older women. However, the WHI study completed in 2002 revealed that HRT may not protect women from heart disease. In addition, findings indicated a slight increase in the risk of breast cancer, blood clots, stroke and heart attack.

Although HRT may not help prevent heart disease in older women, the therapy may be beneficial for younger postmenopausal women. New results of the WHI Estrogen-Alone Trial show that younger postmenopausal women — age 50 to 59 — who take estrogen-alone hormone therapy have significantly less buildup of calcium plaque in their arteries compared to women who do not take hormone therapy. Coronary artery calcium is a known risk factor for heart disease. However, experts caution that the heart disease effects of HRT remain unclear.

Despite the potential risks, it should be emphasized that the likelihood of adverse effects due to HRT remains low in most women. The risks also gradually decrease in the years after a woman stops HRT. According to the FDA, for every 10,000 women taking HRT, there are:

Health Benefits

6 fewer cases of colon cancer

5 fewer cases of hip fracture

Health Risks

8 more cases of breast cancer

7 more cases of heart attack

8 more cases of stroke

18 more cases of blood clots in the lungs and legs

23 more cases of dementia in women over 65 years of age

In addition, postmenopausal women taking progestin as part of HRT may experience greater hearing loss than women taking estrogen alone or no hormones at all, according to a recent study.

It should be noted that the health risks associated with HRT (e.g., heart disease) can vary with age and the health of a woman. Women need to discuss the risks and benefits of using HRT with their physicians to determine the best course of treatment following menopause.

Questions for your doctor

Patients may wish to ask their doctor or healthcare professional the following questions about hormone replacement therapy (HRT):
  1. Based on my medical history, am I a good candidate for HRT?
  2. When is the best time to start HRT?
  3. Will I need any tests prior to starting on the medications?
  4. How quickly will I notice relief from menopausal symptoms once I start on HRT?
  5. How long will I need to stay on HRT?
  6. Is one type of HRT better for me than another?
  7. How will I benefit from using HRT?
  8. What are my risks with using HRT?
  9. After starting HRT, will I need any additional monitoring?
  10. What are the signs that HRT is causing potential problems?

©2007-2012. All rights reserved. This site is for information and support only.