Hormone replacement therapy (HRT)

Examples

Hormone replacement therapy (HRT) refers to the use of estrogen plus progestin for the treatment of perimenopausal symptoms.

Estrogen and progestin combinations (pills or tablets)

Generic Name Brand Name
conjugated estrogens/medroxyprogesterone Premphase, Prempro
estradiol/norethindrone acetate Activella

Transdermal combination preparations (a patch placed on the skin that continuously releases estrogen and progestin)

Generic Name Brand Name
estradiol/norethindrone acetate CombiPatch

Oral progestin (pills or tablets; used along with an estrogen-only preparation)

Generic Name Brand Name
medroxyprogesterone Provera
micronized progesterone Prometrium
norethindrone Micronor, Nor-QD
norethindrone acetate Aygestin

Progestin intrauterine device (IUD; used along with an estrogen-only preparation)

Generic Name Brand Name
levonorgestrel Mirena

Estrogen-progestin hormone therapy, or HRT, is recommended for all women with a uterus who choose to take estrogen. Using estrogen without progestin greatly increases your risk of endometrial cancer. Taking progestin with estrogen eliminates this increased risk.1

How It Works

HRT increases the estrogen and progestin levels in your body. There are several standard hormone replacement therapy schedules, including continuous and cyclic along with higher-dose and low-dose.

Combining progestin with estrogen:

  • Protects against endometrial cancer (which can develop with estrogen-only therapy).
  • Is not needed for women who have no uterus.
  • May trigger monthly withdrawal bleeding when progestin is used periodically (such as in cyclic HRT).

Patch warning. Direct sunlight or high heat can increase, then lower, the amount of hormone released from a patch. This can give you a big dose at the time and leave less hormone for the patch to release later in the week. Avoid direct sunlight on the hormone patch. Also avoid using a tanning bed, heating pad, electric blanket, hot tub, or sauna while you are using a hormone patch.

Why It Is Used

The estrogen in hormone therapy is used by some postmenopausal women to increase estrogen levels. This helps prevent osteoporosis and perimenopausal symptoms, such as hot flashes and sleep problems.

But HRT slightly increases risks of some serious health problems. This means that in a small number of women, HRT is known to cause breast cancer, ovarian cancer, blood clots, or dementia. In women who are 10 or more years past menopause, using HRT slightly raises the risk of heart disease.2

The U.S. Food and Drug Administration (FDA) recommends HRT only for:

  • Short-term treatment of menopausal symptoms, at the lowest effective dose for as short a time as possible.3
  • Osteoporosis prevention and treatment, in select cases. Most experts recommend that HRT only be considered for women with significant risk of osteoporosis that may outweigh their risks of taking HRT.4 Women are now encouraged to consider all possible osteoporosis treatments and to compare their risks and benefits.5 For more information, see the topic Osteoporosis.

Who should not use HRT

You should not use HRT if you:

  • Could be pregnant.
  • Have a personal history of breast cancer or ovarian cancer.
  • Have a personal history of certain endometrial cancers.
  • Have a personal history of pulmonary embolism, deep vein thrombosis, heart attack, or stroke.1
  • Have vaginal bleeding from an unknown cause.
  • Have active liver disease. You may be able to use an alternative to oral estrogen that bypasses the liver, such as estrogen delivered from a skin patch (transdermal) or vaginal cream.

How Well It Works

HRT increases estrogen levels, which:6, 7

  • Helps prevent postmenopausal osteoporosis by slowing bone loss and promoting some increase in bone density.7
  • Reduces hot flashes, depression, and sleep problems in most, but not all, women.7, 8
  • Maintains the lining of the vagina, reducing irritation.
  • Increases skin collagen levels, which drop as estrogen levels naturally decrease. Collagen is responsible for the stretch in skin and muscle.
  • Reduces the risk of dental problems, such as tooth loss and gum disease.
  • May slightly lower the risk of colon cancer.6

Side Effects

Risks of hormone replacement therapy

Hormone replacement therapy was part of a large set of clinical trials called the Women's Health Initiative (WHI). The HRT portion of these trials showed a small increase in the rate of breast cancer among the women taking a combination of 0.625 mg of estrogen plus 2.5 mg of progestin daily. WHI data also showed an increased rate of blood clots, heart disease, ovarian cancer, and dementia with HRT use.

HRT risk slightly raises the risk of several serious health problems. This means that in a small number of women, using HRT causes a serious health problem.

The risks linked to HRT are relatively low in the general population of postmenopausal women. Your personal risk from hormone therapy may be significantly lower or higher than the general population. Your own risk depends on your family history and health. Not all possible risk factors are known.

  • HRT-related breast cancers first become apparent after 4 years of HRT use. The number of HRT-related breast cancers increased with each additional year of HRT use. Women taking HRT generally had larger, more advanced tumors than women who developed breast cancer while taking placebo treatment.6
  • HRT slightly increases stroke risk in all healthy postmenopausal women, regardless of risk factors.6, 9 The increase in strokes first becomes apparent during the second year of HRT use.10
  • In women who are 10 or more years past menopause, HRT slightly raises the risk of heart disease. Early signs of heart disease can first become apparent during the first year of hormone use.11, 12, 2
  • HRT slightly raises the risk of blood clots in the lungs (pulmonary embolism) and legs (deep vein thrombosis) in all healthy postmenopausal women regardless of risk factors.10
  • HRT raises the risk for Alzheimer’s disease and other dementias in women ages 65 and older. The increased risk first becomes apparent in women taking HRT for more than 4 years. The WHI researchers have concluded that HRT does not provide protection from dementia or cognitive impairment, as was previously believed.13
  • HRT slightly raises ovarian cancer risk. This means that for a small number of women, taking HRT causes ovarian cancer.14
  • Among HRT users, the number of abnormal mammograms increases by approximately 4% each year, first apparent after 1 year of HRT use. (Daily estrogen plus progestin increased breast density compared with estrogen alone or placebo.) Although the abnormal mammograms required additional medical evaluation, they were not linked to the increase in breast cancer. Studies are ongoing to determine the significance of this finding.15

Experts do not yet know whether lower-dose, shorter-term HRT reduces or eliminates these risks.

Estrogen side effects

Side effects that can occur with all forms of estrogen but are more frequent with oral estrogen include:

  • Irregular vaginal bleeding.
  • Headaches.
  • Nausea.
  • Vaginal discharge.
  • Fluid retention.
  • Weight gain.
  • Breast tenderness.
  • Spotting or darkening of the skin, particularly on the face.
  • Asthma . Newly diagnosed asthma appears to be more common among women taking HRT or estrogen-alone (ERT) than women who are not. (Estrogen is thought to be a factor that causes asthma or makes it worse over the life span.)16
  • Gallstones . Women who use estrogen replacement therapy are more likely to have gallstones that cause symptoms than women who do not use ERT. (High estrogen levels are linked to gallbladder disease.)
  • In rare cases, an increased growth of preexisting uterine fibroids or a worsening of endometriosis.

In addition, the estrogen patch (transdermal estrogen) may cause skin irritation.

Some of these side effects, such as headaches, nausea, fluid retention, weight gain, and breast tenderness, may go away after a few weeks of use.

Progestin side effects

The side effects of progestin often cause women to stop using hormone replacement therapy (HRT). Adjusting the progestin dose, changing the dosing schedule, or changing the type of progestin may reduce side effects. The progestin intrauterine device (IUD) reduces or eliminates side effects that are common with oral progestin.1

Progestin side effects include:

  • Mood changes, such as anxiety, irritability, or depression.
  • Headache.
  • Breast pain or tenderness.
  • Abdominal pain or bloating (distention).
  • Dizziness or drowsiness.
  • Diarrhea.
  • Vaginal discharge.

Cyclic progestin (taken 10 to 14 days a month) is more likely to cause:

  • Premenstrual-like symptoms, such as bloating, cramping, breast tenderness, nausea, and depression.
  • Monthly withdrawal bleeding.

The combination transdermal patch may cause skin irritation.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

If you have been taking HRT, talk with your doctor about your reasons for taking it. Are you taking it to help with perimenopausal symptoms or for long-term health reasons? Consider changing to another treatment, depending on the problem you are using HRT to treat. If HRT seems like the best choice for you, plan to use the lowest possible effective dose.

If you are unable to tolerate the side effects of progestin in hormone replacement therapy and you have not had a hysterectomy, try nonhormonal treatment options.

The British Million Women Study has confirmed the Women's Health Initiative findings and has provided more information about estrogen, progestin, and breast and endometrial cancers.17 This is important information for women deciding whether to take estrogen without progestin, as described above.

When given with a skin patch, estrogen-progestin enters the bloodstream directly, without passing through the liver. The estrogen and progestin in pills must be processed by the liver before entering the bloodstream. This is why women with liver or gallbladder disease can usually use a patch form of HRT.

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References

Citations

  1. Speroff L, Fritz MA (2005). Postmenopausal hormone therapy. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 689–777. Philadelphia: Lippincott Williams and Wilkins.
  2. Rossouw JE, et al. (2007). Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA, 297(13): 1465–1477.
  3. North American Menopause Society (2007). Position statement: Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of the North American Menopause Society. Menopause, 14(2): 168–182.
  4. National Heart, Lung, and Blood Institute (2007). Postmenopausal hormone therapy: Questions and answers about estrogen-plus-progestin hormone therapy. Available online: http://www.nhlbi.nih.gov/health/women/q_a.htm.
  5. American College of Obstetricians and Gynecologists (2003). Statement of the American College of Obstetricians and Gynecologists on hormone therapy for the prevention and treatment of postmenopausal osteoporosis. ACOG News Release. Available online: http://www.acog.com/from_home/publications/press_releases/nr10-07-03.cfm.
  6. Rossouw JE, et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative randomized controlled trial. JAMA, 288(3): 321–333.
  7. Speroff L, Fritz MA (2005). Menopause and the perimenopausal transition. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 621–688. Philadelphia: Lippincott Williams and Wilkins.
  8. Rapkin AJ, et al. (2002). The clinical nature and formal diagnosis of premenstrual, postpartum, and perimenopausal affective disorders. Current Psychiatry Reports, 4(6): 419–428.
  9. Manson JE, et al. (2003). Estrogen plus progestin and the risk of coronary heart disease. New England Journal of Medicine, 349(6): 523–534.
  10. Wassertheir-Smoller S (2003). Effect of estrogen plus progestin on stroke in postmenopausal women. The Women's Health Initiative: A randomized trial. JAMA, 289(20): 2673–2684.
  11. Grodstein F, et al. (2006). Hormone therapy and coronary heart disease: The role of time since menopause and age at hormone initiation. Journal of Women's Health, 15(1): 35–44.
  12. Prentice RL, et al. (2006). Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease. American Journal of Epidemiology, 163(7): 589–599.
  13. Shumaker SA, et al. (2003). Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women's Health Initiative memory study: A randomized controlled trial. JAMA, 289(20): 2651–2662.
  14. Beral V, et al. (2007). Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet, 369(9574): 1703–1710.
  15. Chlebowski T, et al. (2003). Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women's Health Initiative randomized trial. JAMA, 289(24): 3243–3253.
  16. Barr RG, et al. (2004). Prospective study of postmenopausal hormone use and newly diagnosed asthma and chronic obstructive pulmonary disease. Archives of Internal Medicine, 164(4): 379–386.
  17. Million Women Study Collaborators (2003). Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet, 362(9382): 419–427.

Last Updated: May 16, 2008

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