What is hormone therapy?
Hormone therapy (HT), also called menopausal hormone therapy, is a treatment for women who are going through or have gone through menopause. The female hormone estrogen is the most common type of hormone therapy. Because taking estrogen alone may increase the risk of uterine cancer, it is usually combined with another type of hormone called a progestogen.1 Estrogen alone is only given to women who have had a hysterectomy (had their uterus surgically removed).2
See also: Age & Menopause
What is hormone therapy used for?
Hormone therapy is used to treat menopausal symptoms such as hot flashes, night sweats, sleep disturbances, and vaginal dryness.
Hormone therapy has also been investigated as a way to prevent or treat many diseases that become common after menopause—from heart disease, stroke, and cancer to Alzheimer's disease and osteoporosis—but results have generally been disappointing so far.
What are the different kinds of hormone therapy?
There are three main types of hormone therapy:
- Estrogen-only therapy (ET)
- Progestogen-only therapy
- Combined estrogen-progestogen therapy (EPT)
There are many variations on these main themes: hormone therapies come in different combinations of estrogens and progestogens, with different dosing strengths and schedules. It is generally recommended that you use the lowest dose that controls your symptoms.
Hormone therapy can be applied in many ways. It is usually given as a pill, but can also be given as an injection, or absorbed through the skin as a patch, gel, cream, or spray, or as a vaginal cream, ring, or tablet. For a list of the different hormone therapy formulations available in the US and Canada, visit http://www.menopause.org/edumaterials/htcharts.pdf.
How do my body's natural hormones affect my risk of stroke?
Women tend to develop stroke and heart disease later in life than men. This delay is thought to be largely due to the protective effects of estrogen. Estrogen alters the levels of cholesterol and fat in your blood,2 changes the way your blood forms clots,3 affects how well your blood flows though the body and how the blood vessels respond,4, 5 and has an impact on many factors related to the buildup of fatty plaque in the arteries. All of these processes influence the development of heart disease and stroke.6
When a woman goes through menopause, her body stops producing estrogen and these protective effects are lost. After menopause a woman's risk of heart disease and stroke begins to increase. It was therefore thought that replacing the lost estrogen might help prevent heart and blood vessel disease.
Does hormone therapy increase my risk of having a stroke?
Yes. Hormone therapy, either estrogen alone or combined with progestin, increases your risk of stroke and does not prevent you from having a heart attack or dying of heart disease.7, 8 In the past, some doctors prescribed hormone therapy in an attempt to lower the risk of heart and blood vessel disease, but current guidelines state that hormone therapy should not be used to treat or prevent heart disease or stroke in women.9
Early studies that compared women who chose to take hormone therapy with those who didn't showed that hormone therapy users had a lower risk of heart disease and the same risk of stroke, but that they were likely to have less severe strokes.1, 10, 11, 12 However, when more tightly controlled experiments randomly assigned women to hormone therapy or a dummy pill, the results were not positive.
The Women's Health Initiative study of more than 16,000 healthy postmenopausal women found that a combination of estrogen and progestin provided no protection from heart attack, stroke or heart disease.7 In fact, hormone therapy users had a slightly higher risk of heart disease, stroke, and blood clots.13 The trial was stopped early because women taking hormone therapy also began to show an increased risk of breast cancer. The Women's Health Initiative also found that estrogen alone increased the risk of stroke and blood clots and had no effect on the risk of heart disease or breast cancer.14 Overall, researchers decided that while the risk of harm is small from using hormone therapy to prevent heart disease and stroke, it still outweighs any potential benefits.
The increases in stroke risk when using hormone therapy to treat menopausal symptoms is relatively small. Over 1 year, if 10,000 healthy women were to take combination hormone therapy, 8 more women would suffer a stroke compared with a group of 10,000 women not taking hormone therapy.13 In women with a hysterectomy who are taking estrogen-only hormone therapy, there would be 12 additional strokes per 10,000 women treated. See also: What are the Risks and Benefits of Hormone Therapy?
Most studies of hormone therapy have only looked at one type of estrogen-plus-progesterone pill, called Prempro, and one type of estrogen alone pill, called Premarin. It is not known whether other forms of hormone therapy have the same effects. Some research has shown that when hormones are imbedded in a patch and absorbed through the skin, they affect the body differently.13
Do the stroke risks of hormone therapy change with age?
When women of all ages are looked at together, using hormone therapy increases the risk of stroke and heart disease. Results from the Women's Health Initiative study of hormone therapy found that younger women taking hormone therapy within 5 years of menopause may not be at increased risk for heart disease, and may actually have a slightly lower risk.15 The effects of younger age on stroke were smaller, with an increased stroke risk regardless of years since menopause. However, while stroke risk did not decrease in women of any age taking hormones, in women aged 50 to 59 there was no significant increase in risk with therapy.15
For now, hormone therapy should not be taken to prevent heart disease or stroke even among very young postmenopausal women. However, the results of studies like the Women's Health Initiative should reassure younger women who want to take HT for menopausal symptoms that they need not be scared off by the possible stroke risks.16
Can I take hormones for menopausal symptoms if I have a history of stroke?
No. If you have had a stroke or blood clots in the past, or have been diagnosed with heart disease, you should not take hormone therapy.17 A study of women who had already had a stroke or transient ischemic attack (TIA) found that estrogen-only hormone therapy did not decrease the risk of having another stroke, and actually doubled the risk of having a recurrent stroke in the first 6 months of therapy.18 Among women who had another stroke, those who were taking estrogen therapy were 3 times as likely to die; those who survived had worse mental and functional disabilities. Combination hormone therapy increases the risk of stroke and blood clots and increases the risk of heart attack in the first year of therapy.19-23
What alternatives to hormone therapy are being studied?
Currently, researchers are looking into a group of drugs called Selective Estrogen-Receptor Modulators (SERMs), which have also been called "designer estrogens." They are compounds that have beneficial effects on bone density like estrogen, but without estrogen's negative effects on the breast or lining of the uterus. The hope is that these new compounds will provide the benefits of replacement estrogen without the negative side effects, such as stroke, heart problems, and cancer. So far, most studies of SERMs have found that although they have better risk profiles for heart disease, like hormone therapy they increase the risk of stroke and blood clots.
The most studied of the four FDA-approved SERMs is raloxifene (Evista), used to prevent and treat postmenopausal osteoporosis (thinning of the bones) and to prevent breast cancer in women at high risk. In the RUTH trial, over 10,000 women with heart disease or multiple risk factors received raloxifene or a dummy pill once a day for more than 5 years. Raloxifene cut the risk of breast cancer and spine fractures, and did not increase the risk of heart attack, hospitalization for heart disease, or dying of heart disease. However, women taking raloxifene had a slightly higher risk of dying of a stroke or having blood clots in the leg veins, which can move to other parts of the body.24
Current guidelines state that, like hormone therapy, SERMs should not be used for the prevention or treatment of heart disease or stroke in women.9
- For a summary of the overall benefits and risks of hormone therapy, click here
- For information on how to decide whether or not to take hormone therapy and the alternatives to hormone therapy, click here
- Click here for information on the relationship between hormone therapy and heart disease risk
For More Information
National Heart Lung and Blood Institute Facts about menopausal hormone therapy
FDA Menopause & Hormones Information
National Women's Health Information Center – Menopause & Menopause Treatments
List of Hormone Products for Postmenopausal Use in the United States and Canada
The North American Menopause Society
- Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. Dec 15 1992;117(12):1016-1037.
- Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. Jan 18 1995;273(3):199-208.
- Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA. Oct 6 2004;292(13):1573-1580.
- Collins P, Rosano GM, Sarrel PM, et al. 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. Jul 1 1995;92(1):24-30.
- Reis SE, Gloth ST, Blumenthal RS, et al. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation. Jan 1994;89(1):52-60.
- Mendelsohn ME, Karas RH. The Protective Effects of Estrogen on the Cardiovascular System. N Engl J Med. June 10, 1999;340(23):1801-1811.
- Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. Aug 7 2003;349(6):523-534.
- Wathen CN, Feig DS, Feightner JW, Abramson BL, Cheung AM. Hormone replacement therapy for the primary prevention of chronic diseases: recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. May 11, 2004;170(10):1535-1537.
- Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ. Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update. Circulation. 2007;115:1481-1501.
- Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis. Nov-Dec 1995;38(3):199-210.
- Heckbert SR, Weiss NS, Koepsell TD, et al. Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women. Arch Intern Med. Jun 23 1997;157(12):1330-1336.
- Hurn PD, Brass LM. Estrogen and Stroke: A Balanced Analysis. Stroke. February 1 2003;34(2):338-341.
- Writing Group for the Women's Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial. JAMA. July 17, 2002;288(3):321-333.
- 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. Apr 14 2004;291(14):1701-1712.
- Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. Apr 4 2007;297(13):1465-1477.
- Lobo RA. Menopause and stroke and the effects of hormonal therapy. Climacteric. Oct 2007;10 Suppl 2:27-31.
- Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Circulation. Mar 14 2006;113(10):e409-449.
- Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med. Oct 25 2001;345(17):1243-1249.
- Clarke SC, Kelleher J, Lloyd-Jones H, Slack M, Schofiel PM. A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Bjog. Sep 2002;109(9):1056-1062.
- Alexander KP, Newby LK, Hellkamp AS, et al. Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up. J Am Coll Cardiol. July 1, 2001;38(1):1-7.
- Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. Aug 19 1998;280(7):605-613.
- 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. Jul 3 2002;288(1):49-57.
- Executive summary. Hormone therapy. Obstet Gynecol. Oct 2004;104(4 Suppl):1S-4S.
- Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. Jul 13 2006;355(2):125-137.