Menopausal hormone therapy alternatives

Author :Richard J Santen, MD Section Editor:Peter J Snyder, MD William F Crowley, Jr, MD Deputy Editor: Leah K Moynihan, RNC, MSN, Kathryn A Martin, MD

INTRODUCTION — During a woman’s reproductive years, the body produces a variety of hormones, including estrogen. Estrogen is important for normal menstrual periods and fertility, and it promotes bone strength. Estrogen levels fall at the time of menopause, causing well-known symptoms such as hot flashes.
Hormone replacement therapy (HRT) is the term used to describe the two types of hormones, estrogen and progestin, that are the most effective treatments available to relieve bothersome symptoms of menopause. However, some women cannot or do not want to take hormone replacement therapy. There are a number of alternate treatments that may be considered for these women; one or more of these may be a reasonable option.
This topic review discusses alternatives to postmenopausal hormone replacement therapy. A separate topic review discusses the risks, benefits, and types of available hormone replacement therapy options. (See “Patient information: Menopausal hormone therapy”).
PREVENTING AND TREATING OSTEOPOROSIS — When estrogen levels fall, bone density and strength begin to decline. Over time, this can lead to osteoporosis and an increased risk of fractures. A test to monitor bone density can detect early bone loss and is usually recommended for all women beginning at age 65. Younger women and men may also benefit from bone density testing, as described in a separate topic review. (See “Patient information: Osteoporosis causes, diagnosis, and screening”).
Several alternatives to HRT can help keep bones strong and prevent fractures caused by osteoporosis. The most effective treatments include a combination of a healthy diet, lifestyle, and medication. (See “Patient information: Osteoporosis prevention and treatment”).
Calcium — Calcium is an essential component of bones; calcium from foods we eat can help strengthen bones. However, calcium alone cannot always prevent osteoporosis.
All postmenopausal women need 1500 mg of calcium each day. Most women will need to eat a well-balanced diet and take a daily supplement that contains 1000 mg of calcium, usually in the form of calcium carbonate, calcium citrate, or an equivalent calcium compound. A list of calcium-rich foods and guidelines for choosing calcium supplements is available in the table (show table 1). (See “Patient information: Calcium and Vitamin D for bone health”).
Vitamin D — Vitamin D helps the body absorb and incorporate calcium into bone. Many older adults, particularly those over 70 years, have vitamin D deficiency. All postmenopausal women should get at least 800 IU of vitamin D each day through their diet or with a supplement; more than 2000 IU of vitamin can be toxic and is not recommended. Some calcium supplements and multivitamins include vitamin D, so it is important to read the label to determine how much is consumed.
Exercise — Bones remain stronger when they are used in day-to-day activities; inactivity increases the rate of postmenopausal bone loss. At least 30 minutes of weight-bearing exercise three times a week can reduce this loss. Weight-bearing exercise includes activities such as walking, aerobics, or tennis, but do not include bicycling or swimming.
Medications — Several medications, such as alendronate, risedronate, ibandronate, zoledronic acid, tamoxifen, and raloxifene can help prevent or even reverse osteoporosis by boosting bone density. These medications can even benefit women who have already suffered fractures. Women taking these medications should continue to take calcium, eat a healthy diet, and exercise to promote bone strength. These treatments are described in detail in a separate topic review. (See “Patient information: Osteoporosis prevention and treatment”).
PREVENTING CARDIOVASCULAR DISEASE — The decrease in estrogen levels after menopause increases the risk of developing and dying from heart disease. Oral estrogen replacement does not lower this risk in women over 60 years of age. Alternatives to HRT can reduce some of the risk factors associated with cardiovascular disease, such as high cholesterol levels.
Smoking cessation — Quitting smoking is probably the most important change a woman can make to decrease her risk of developing heart disease. Be sure to ask your doctor about methods for successfully quitting. (See “Patient information: Smoking cessation”).
Dietary modification — A low-fat, low-cholesterol diet may be recommended initially to reduce cholesterol levels. If this approach is successful, medication may not be necessary. If cholesterol levels are not controlled with diet alone, a cholesterol-lowering medication may be recommended. (See “Patient information: Diet and health”).
Cholesterol-regulating medication — In postmenopausal women with high cholesterol levels in the blood, medications such as statins lower levels of total and low-density lipoprotein (LDL) cholesterol (“bad” cholesterol). These medications also decrease the risk of heart disease, unlike HRT, which does not prevent heart disease. (See “Patient information: High cholesterol and lipids (hyperlipidemia)”).
CONTROLLING HOT FLASHES — Alternate treatments for hot flashes are effective in many women. None work nearly as well as estrogen, but relief from these agents is about 70 percent as effective as estrogen. Some women do not require treatment for hot flashes since they typically subside after one to two years, even without treatment. Some of the treatments that can give partial relief of hot flashes include:
Antidepressants — Venlafaxine (Effexor®) and paroxetine (Paxil®) were developed to treat depression, but studies show that they are an effective treatment for hot flashes. Venlafaxine has been more extensively studied than the others. Fluoxetine (Prozac®) is also effective.
Antidepressant medications are recommended as a first line treatment for hot flashes in women who cannot take estrogen. Paroxetine and sertraline (Zoloft®) interfere with the action of tamoxifen. Other antidepressant side effects and interactions are discussed in detail in a separate topic review. (See “Patient information: Depression treatment options for adults”).
Clonidine — Clonidine, a blood pressure lowering drug, helps relieve hot flashes in some women. Clonidine is absorbed into the bloodstream from a skin patch (Duraclon®), oral medication (Catapres®), or a combination of both. Clonidine seems to work well in some patients but is completely ineffective in others. Only a trial of medication can identify those women who will benefit. Side effects can range from dry mouth and constipation to dizziness and sedation.
Gabapentin — Gabapentin (Neurontin®) is a drug that is primarily used for the treatment of seizures. Although it has not been as well studied as the SSRIs, it appears to be moderately effective for treatment of hot flashes. To minimize side effects, gabapentin is often recommended at bedtime, to decrease hot flashes that awaken a woman from sleep. This approach would not reduce daytime symptoms, although many women are less disturbed by hot flashes in the daytime than nighttime.
Progesterone — The injectable progestin birth control hormone, medroxyprogesterone acetate (Depo-Provera®) may help to reduce hot flashes. Depo-Provera® may be used long-term, although it can cause side effects such as weight gain and loss of bone density.
Plant-derived estrogens (phytoestrogens) — Plant-derived estrogens have been marketed as a “natural” or “safer” alternative to hormones for women with menopausal symptoms. However, there is no evidence that phytoestrogens are safe or effective. There are three main types of phytoestrogens: isoflavones, coumestans, and lignans. Phytoestrogens are found in many foods, including soybeans, chickpeas, lentils, flaxseed, lentils, grains, fruits, and vegetables. Isoflavones are found in red clover.
There is no evidence that phytoestrogens are beneficial in reducing symptoms of hot flashes or night sweats. In addition, phytoestrogens might increase the risk of breast cancer risk because they act like estrogen in some tissues of the body. Women who have a history of breast cancer are cautioned against the use of phytoestrogens.
Herbal treatments — A number of herbal treatments have been also been promoted as a “natural” remedy for hot flashes. These include black cohosh, ginseng, dong quai, evening primrose oil, wild yam, and others.
Studies of black cohosh, alone or as part of a multibotanical regimen, show that it does not appear to be more effective than placebo in reducing symptoms of menopause [11] . In addition, there are safety concerns about black cohosh and its effect on the breast (similar to that of estrogen). As a result, black cohosh is not recommended for women with breast cancer or those at high risk for breast cancer.
Other complementary or alternative treatments, including ginseng, dong quai, or evening primrose oil, acupuncture, wild yam, and progesterone creams, have also been studied and found to be ineffective in reducing hot flashes. Traditional medicinal Chinese herbs, reflexology, and magnetic devices have all been studied and have no beneficial effect [11] .
TREATING VAGINAL DRYNESS — When estrogen production falls, the lining of the vagina thins, leading to vaginal dryness and sometimes causing pain with sexual intercourse. Several alternatives to estrogen can help control these symptoms. (See “Patient information: Sexual problems in women”).
Moisturizers and lubricants — Regular use of vaginal moisturizing agents, such as Replens® or KY Long Lasting®, can help relieve vaginal dryness and irritation. These agents must be used regularly. They work by moisturizing the vaginal tissues.
Lubricants can prevent pain during sexual intercourse and are used immediately before intercourse. Water-soluble lubricants, such as Astroglide®, are more effective for intercourse than surgical lubricants such as K-Y® jelly. Products such as petroleum jelly or hand and body lotions should not be used to relieve vaginal dryness since they can be irritating to the vaginal tissues.
Vaginal estrogens — Estrogen creams, such as Premarin® or Estrace®, can be applied directly to the vagina. Low doses of vaginal estrogen can improve the health of the vaginal tissues without increasing levels of estrogen in the bloodstream. Vaginal estrogen creams are given every day for two to three weeks, and then only once or twice weekly to maintain the effects. They are more effective than moisturizers and lubricants for relieving vaginal symptoms. The lowest dose that is effective should be used.
Other vaginal estrogen products are available, including a tablet (Vagifem®) and a low-dose vaginal estrogen ring (Estring®). These products are as effective and may be less messy and more convenient than estrogen cream.
Vaginal ring — The estrogen vaginal ring (Estring®) is inserted into the vagina and releases estrogen in a controlled fashion over three months. Very small amounts are released into the vagina. The estrogen appears to act only on the tissues of the vagina with little to no estrogen absorbed into the bloodstream.
Studies show that women using the ring experience very few side effects. The ring is changed once every three months by the woman or her healthcare provider. The low dose vaginal ring should not be confused with the estrogen replacement vaginal ring (Femring®), which releases a higher dose of estrogen and is intended to relieve hot flashes.
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 patients 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)
• The Mayo Clinic
(www.mayoclinic.com)
• U.S. Department of Health and Human Services
Agency for Healthcare Research and Quality
(www.ahrq.gov)
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REFERENCES
1 Loprinzi, CL, Levitt, R, Barton, D, et al. Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7. J Clin Oncol 2006; 24:1409.
2 Loprinzi, CL, Kugler, JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000; 356:2059.
3 Stearns, V, Beebe, KL, Iyengar, M, Dube, E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003; 289:2827.
4 Loprinzi, CL, Sloan, JA, Perez, EA, et al. Phase III Evaluation of Fluoxetine for Treatment of Hot Flashes. J Clin Oncol 2002; 20:1578.
5 Stearns, V, Slack, R, Greep, N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 2005; 23:6919.
6 Hsia, J, Langer, RD, Manson, JE, et al. Conjugated Equine Estrogens and Coronary Heart Disease: The Women’s Health Initiative. Arch Intern Med 2006; 166:357.
7 Grodstein, F, Manson, JE, Stampfer, MJ. Hormone Therapy and Coronary Heart Disease: The Role of Time since Menopause and Age at Hormone Initiation. J Womens Health (Larchmt) 2006; 15:35.
8 Pinkerton, JV, Santen, R. Alternatives to the use of estrogen in postmenopausal women. Endocr Rev 1999; 20:308.
9 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.
10 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.
11 Nedrow, A, Miller, J, Walker, M, et al. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med 2006; 166:1453.