Postmenopausal hormone therapy
Author
Robert L Barbieri, MD Section Editor
Peter J Snyder, MD
William F Crowley, Jr, MD Deputy Editor
Leah K Moynihan, RNC, MSN
Kathryn A Martin, MD
POSTMENOPAUSAL HORMONE THERAPY OVERVIEW — Menopause is defined as the time in a woman’s life, usually between 45 and 55 years, when the ovaries stop producing eggs and menstrual periods end. The average age of menopause is between 50 and 51 years.
For several years before menopause, menstrual periods become irregular, and many women develop hot flashes, night sweats, and vaginal dryness. This stage is called perimenopause or the menopausal transition. A woman is said to be postmenopausal when she has not had a menstrual period for at least 12 months.
There are a number of options available to ease the symptoms of menopause, including estrogen. However, the risks and benefits of estrogen can be difficult to understand due to the large number of studies that have been published. This article discusses the most common symptoms of menopause, explains how estrogen works, and discusses the risks and benefits of both short and long-term hormone use.
Other articles about treatment options during menopause are also available. (See “Patient information: Postmenopausal hormone therapy alternatives” and see “Patient information: Postmenopausal hormone therapy and breast cancer”).
SIGNS AND SYMPTOMS OF MENOPAUSE — The most common symptoms of menopause include hot flashes, night sweats, and vaginal dryness. However, not all women experience these symptoms.
Hot flashes — Hot flashes occur because of a fall in estrogen levels. Estrogen levels fall as the ovaries slow and then stop producing eggs. Hot flashes often begin several years before menopause and may continue for several years after menopause. They are far more common at night, when they can cause night sweats, which can disrupt sleep. As a result of sleep disruption, many women also experience symptoms such as fatigue, irritability, difficulty concentrating, and mood swings. Estrogen is the most effective treatment available for hot flashes.
Vaginal and urinary symptoms — During or after menopause, many women begin to experience vaginal dryness. These problems are related to a decrease in estrogen levels. Vaginal dryness is best treated with lubricants and/or very low doses of vaginal estrogen (cream, tablets, or ring). (See “Patient information: Vaginal dryness”).
Other symptoms — Estrogen has important effects on many other organs, such as the brain, skin, blood vessels, heart, bone, and breast. Without estrogen, the bones are at greater risk of developing osteoporosis, which causes the bones to become weakened and increases the risk of fractures. In addition, the risk of heart disease increases after menopause. However, estrogen is not recommended to prevent heart disease. (See “Patient information: Osteoporosis prevention and treatment”).
WHAT IS HORMONE THERAPY? — Hormone therapy is the term used to describe the two hormones, estrogen and progestin, that are given to relieve bothersome symptoms of menopause. Estrogen is the hormone that relieves the symptoms. Women with a uterus must also take progestin (a progesterone-like hormone) to prevent uterine cancer. This is because estrogen alone can cause excessive growth of the uterine lining.
Women who have had a hysterectomy do not have a uterus and therefore do not need to take progestin. They are treated with estrogen alone.
Types of estrogen — Estrogen can be taken as a pill, or absorbed through the skin from a patch (transdermally), or inserted into the vagina.
Estrogen pill — There are many types of estrogen pills (show table 1). The most commonly used brand, called Premarin®, is made from the urine of pregnant horses (mares). Other preparations are derived from plant sources. Both types of estrogen are effective for relieving menopausal symptoms.
Women with a uterus who take an estrogen pill must also take a progestin, either in a combination product or separately, to minimize the risk of developing uterine cancer. Pills that include both estrogen and progestin are available. (See “Types of progestin” below).
Low dose birth control pill — Very low dose birth control pills are a good option for perimenopausal women in their 40’s who have bothersome menopausal symptoms, irregular bleeding and who still need a reliable form of birth control. Birth control pills are NOT recommended for postmenopausal women because the dose of estrogen is higher than necessary. (See “Patient information: Hormonal methods of birth control”).
Estrogen patch — There are many brands of estrogen patches. A combination estrogen and progestin patch is also available. Some patches need to be replaced every few days, while other are only replaced once a week.
Estrogen patches are as effective as oral estrogens in increasing bone density and in treating menopausal symptoms. Women with a uterus who use an estrogen patch must also take a progestin to decrease the risk of uterine cancer (see “Types of progestin” below).
Vaginal estrogen — Vaginal estrogen is discussed in a separate article. (See “Patient information: Vaginal dryness”).
Types of progestin — In women with a uterus, progestins are routinely recommended in addition to estrogen.
Oral progestins — The most commonly prescribed progestin pill is medroxyprogesterone acetate. Other types of progestin pills (norethindrone, norgestrel) are also available. There is no advantage of one type over another.
A natural progesterone, called Prometrium®, is another option. Natural progesterones have no negative effect on lipids, and may be a good choice for women with high cholesterol levels. While there are theoretical advantages to natural progesterone, it has not yet been proven to be safer than standard progestin products.
Intrauterine progesterone — An intrauterine device (IUD) that releases progestin (called Mirena®) is used by younger women for contraception, but it has also been used in some menopausal women to minimize the risk of developing uterine cancer. However, the IUD is not approved for use in menopausal women. An IUD for menopausal women, which contains a lower dose of progestin, is available in Europe.
“Natural” or “bioidentical” products — Many postmenopausal women are turning to “natural” or “bioidentical” hormone therapy as an alternative to conventional hormone preparations. The “bioidentical” approach generally refers to use of an individualized dose of hormones that is made by a pharmacy as pills, creams, or vaginal suppositories. The quality of these products is not regulated and may be inferior in some cases.
The hormones most commonly included in bioidentical products are estradiol, estrone, estriol, progesterone, testosterone, and DHEA. Women typically are asked to provide a saliva or blood sample to measure baseline hormone levels. Based upon the results, the prescriber selects the individual hormones and doses to be compounded.
Proponents of this approach claim that these preparations are effective for menopausal symptoms and that these products are safer and better tolerated than commercially available preparations. However, there is no evidence that these hormones have any advantage over conventional hormone therapies and their safety has not been established [3] .
STUDIES OF RISKS/BENEFITS — The Women’s Health Initiative (WHI) was a large study designed to find out if hormone therapy would reduce the risk of coronary heart disease (CHD) after menopause. Participants were postmenopausal women between the ages of 50 and 79 years. Women who had a uterus were assigned to a trial that compared combined estrogen-progestin therapy to placebo, while women who had undergone hysterectomy were assigned to a separate trial that compared estrogen-alone therapy to placebo.
Both trials were stopped early. In the combined estrogen-progestin trial, researchers did not see a lower risk of CHD with hormone treatment. In fact, they saw a slight increase in risk, and an increase in stroke as well. Other findings included:
An increase in breast cancer
An increase in blood clots
A decrease in colon cancer
A decrease in fractures from osteoporosis
Overall, researchers concluded that the risks of combined estrogen-progestin therapy outweighed the benefits. However, it is important to note that the actual or “absolute” risk of having any of the complications was quite low for an individual woman.
The results of the estrogen-only study were quite different. The trial was stopped early because of a small increase in stroke risk. There was a small increase in the risk of blood clots, but there was no increased risk of heart disease or breast cancer.
Coronary heart disease — As noted above, the initial reports from the WHI suggested that combined estrogen-progestin therapy was associated with an overall increase in the risk of coronary heart disease. This caused great concern for all postmenopausal women and their physicians.
However, the WHI researchers subsequently reported that the risk of coronary heart disease (CHD) appeared to be age dependent; women who became menopausal less than 10 years before starting treatment or who were 50 to 59 years old did not have an increased risk of CHD as a result of hormone replacement therapy [6] . On the other hand, women who were further from menopause or over age 60 years were at increased risk for CHD with estrogen-progestin therapy.
Breast cancer — The risk of breast cancer was slightly increased in women who took combined estrogen-progestin therapy, but not in women who took estrogen alone. This suggests that the progestin component of HRT is an important factor in the risk of developing breast cancer. It is important to note that the actual risk of developing breast cancer because of hormone therapy is very low. This is discussed in detail separately. (See “Patient information: Postmenopausal hormone therapy and breast cancer”).
Endometrial hyperplasia and cancer — Studies have found that postmenopausal women with a uterus who are treated with estrogen alone have an increased risk of endometrial cancer and hyperplasia (a precursor to cancer). Within one year, 20 to 50 percent of women who have a uterus and take estrogen alone develop endometrial hyperplasia (overgrowth of the uterine lining). However, women with a uterus who take estrogen are routinely treated with a progestin, which minimizes this risk. (See “Patient information: Endometrial cancer diagnosis and staging”).
Gallbladder disease — There is considerable evidence that taking estrogen, especially in pill form, increases the risk of gallbladder disease. The risk of requiring a cholecystectomy (removal of the gallbladder) increases the longer a woman uses hormone therapy. The risk decreases substantially within one to three years after a woman discontinues hormone therapy. (See “Patient information: Gallstones”).
Osteoporotic fracture — The risk of osteoporotic fracture was reduced at the hip and spine in women who took combined estrogen-progestin and estrogen alone. (See “Patient information: Osteoporosis prevention and treatment”).
Colorectal cancer — The risk of colorectal cancer was reduced in women who took combined estrogen-progestin. This benefit was not seen in women who took estrogen alone. (See “Patient information: Colon cancer screening”).
Cognitive function and dementia — There was no significant improvement in overall cognitive function or decrease in the risk of dementia in women who took combined estrogen-progestin. The impact of estrogen alone is not known.
Hot flashes — Estrogen is the most effective treatment available for menopausal symptoms, such as hot flashes.
Quality of life — Women with severe menopausal symptoms often describe a dramatic improvement in their quality of life when they are treated with estrogen. This is usually due to relief of hot flashes and restoration of normal sleep.
Vaginal dryness — Vaginal dryness can also be treated with vaginal estrogen. Other products, such as vaginal lubricants and moisturizers, may also be helpful. (See “Patient information: Vaginal dryness”).
Depression — Estrogen may improve mood and decrease depression in some menopausal women. One study showed that estrogen plus progestin was effective in relieving symptoms of depression in perimenopausal women. However, estrogen replacement or hormone replacement therapy is not a standard treatment for depression, and is not usually recommended unless there are other bothersome symptoms such as hot flashes. (See “Patient information: Depression in adults”).
WHO SHOULD TAKE HORMONE THERAPY? — Data from large clinical trials have led to changes in recommendations for who should consider hormone therapy [4,7] . The primary reason to consider hormone therapy is to treat bothersome menopausal symptoms such as hot flashes. Most experts agree that hormone therapy is safe and reasonable for healthy postmenopausal women who need to take it to relieve symptoms. When it is used, is should be taken for the shortest period of time possible.
Short term use of estrogen does not increase the risk of breast cancer, but endometrial hyperplasia and cancer can occur after as little as six months of estrogen therapy (when taken without progestin); as a result, a progestin is a required part of hormone therapy for women who have not had a hysterectomy.
The goal of hormone therapy is to relieve symptoms, and then to eventually decrease and stop the treatment (unless there is a compelling reason to continue it long-term). One way to do this might be to omit one pill per week. Many women are able to stop hormones without any return in menopausal symptoms.
Dose of estrogen — It is possible that lower doses of estrogen may be safer than the standard dose of estrogen while still effectively treating menopausal symptoms. The “standard” dose of conjugated estrogen is 0.625 mg, although 0.3 mg or the equivalent dose of other estrogens (estradiol, estrogen patch) have been shown in some, but not all studies to relieve menopausal symptoms and prevent bone loss.
However, it is not clear if lower doses of estrogen or different hormone therapy preparations are safer than standard doses in regards to breast cancer and cardiovascular risks. Therefore, it is safest to assume that other doses carry some risk.
Long-term therapy — Only a minority of women who are unable to successfully stop estrogen should continue it long-term. If hormone therapy is required, the lowest dose possible should be used, and the woman is encouraged to try decreasing the dose at a later date. Women who choose to take long-term hormone therapy should discuss the risks of breast cancer, heart disease, blood clots, strokes, and other potential complications with their healthcare provider on a regular basis.
Who should avoid estrogen? — Estrogen or combined estrogen-progestin therapy is not recommended for women with the following:
Current or past history of breast cancer
Coronary heart disease
A previous blood clot or stroke
Women at high risk for these complications
Women with breast cancer — Women with breast cancer often experience early menopause as a result of their breast cancer treatments. In these women, estrogen or hormone replacement therapy (by mouth or patch) is not generally recommended due to an increased risk of a recurrence of their breast cancer. (See “Patient information: Postmenopausal hormone therapy and breast cancer”).
Alternatives to hormone therapy are available and are often effective in relieving bothersome menopausal symptoms. These alternatives are discussed in detail in a separate article. (See “Patient information: Postmenopausal hormone therapy alternatives”).
ALTERNATIVES TO ESTROGEN — Some women are not able or willing to take hormone replacement; effective alternatives are available. These are discussed in detail in a separate article. (See “Patient information: Postmenopausal hormone therapy alternatives”).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Hormone Foundation
(www.hormone.org/public/menopause.cfm, available in English and Spanish)
[2-5,7,8]
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REFERENCES
1 Canonico, M, Oger, E, Plu-Bureau, G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007; 115:840.
2 Takahashi, K, Manabe, A, Okada, M, et al. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas 2000; 34:169.
3 Boothby, LA, Doering, PL, Kipersztok, S. Bioidentical hormone therapy: a review. Menopause 2004; 11:356.
4 Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288:321.
5 Anderson, GL, Limacher, M, Assaf, AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004; 291:1701.
6 Rossouw, JE, Prentice, RL, Manson, JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297:1465.
7 Grady, D, Herrington, D, Bittner, V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:49.
8 Holmberg, L, Anderson, H. HABITS (hormonal replacement therapy after breast cancer–is it safe?), a randomised comparison: trial stopped. Lancet 2004; 363:453.
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