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MenopauseHighlightsNew Research Soy. Soy products may reduce bone loss, particularly in young menopausal women. Researchers are not sure whether isoflavones, a chemical found in soy, are responsible for the apparent benefit. Soy may also reduce a woman’s risk of endometrial cancer and decrease plaque-related build up that leads to Alzheimer’s disease. Alcohol. Moderate wine consumption appears to boost bone mineral density (BMD) in men and women, respectively. Study findings released in late 2004 revealed that postmenopausal women who drank one to two glasses of wine daily improved their hip BMD by 5%. Resveratrol, a substance found in grapes and wine, may benefit bones. Raloxifene. Raloxifene (Evista) can reduce invasive breast cancer recurrence by two-thirds in postmenopausal women. Hormone Replacement Therapy (HRT). Although HRT appears to reduce the risk of bone fractures, experts say its benefits to bone don’t outweigh its risks. Studies have found that HRT can increase the risk of heart attack, stroke, and dementia. A recent study found that patients on HRT also have poorer stroke outcomes. Celiac disease. Researchers reporting in the Archives of Internal Medicine have found that patients with osteoporosis have a higher risk for celiac disease, a hereditary intolerance to the glutein protein found in wheat. The finding suggests that osteoporosis patients should be screened for the disease. Drug Approvals Alendronate (Fosamax) is now available in a once-a-week pill that also contains vitamin D. Ibandronate (Boniva) now comes in a once-a-month dose. Medication Risks Nonsteroidal anti-inflammatory drugs (NSAIDs) can offer relief from menopause symptoms, but they should be used with caution and under the advice of a doctor. Certain NSAIDs may increase one’s risk for cardiovascular problems and gastrointestinal bleeding. Symptoms of Menopause may include:
IntroductionThe ovaries contain between 200,000 and 400,000 follicles, tiny sacks contain the materials needed to produce mature eggs, or ova. The ovaries produce two major female hormones: estrogen and progesterone. ![]() The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth. Estrogen. Estrogens have an effect on about 300 different tissues throughout a woman's body:
Estrogen also has different forms:
Most of the estrogens in the body are produced by the ovaries, but they can also be formed by other tissues, such as body fat, skin, and muscle. Progesterone. Progesterone, the other major female hormone, is necessary for thickening and preparing the uterine lining for the fertilized egg. Menopause and PerimenopauseAs a woman ages, her supply of eggs declines. Menopause occurs naturally after the woman's supply of follicles has been depleted and menstruation ends completely. (Menopause may also be induced if the ovaries are surgically removed.) Perimenopause. Menopause does not occur suddenly. A period called perimenopause usually begins a few years before the last menstrual cycle. Some experts believe there are three stages in the transition:
Menopause. At the point at which menopause occurs, the following hormonal changes occur:
The average age of women at menopause today is 51.4 years (although it can occur as early as 40 to as late as the early 60s). Women now have a life expectancy of more than 80 years. Currently, women can expect to live some 30 or 40 years of their life in the postmenopausal state. Menopause is not a disease. However, many conditions are associated with estrogen depletion, including heart disease, osteoporosis, and other problems. Fortunately, effective treatments are available for these conditions. In a number of studies, most women have reported menopause as a positive experience and have welcomed it with relief and as a sign of a new stage in life. One study found no link between menopause and a woman's state of mind. In fact, middle-aged women overwhelmingly reported satisfaction with their home and work lives. ComplicationsAfter a woman reaches menopause, her average life expectancy is 30 years. During those years, however, she faces certain health risks due to lower levels of estrogen that cause accelerated bone loss and an increase in LDL cholesterol (the so-called bad cholesterol). Her risks for serious disorders are estimated at 46% for heart disease, 20% for stroke, and 15% for hip fracture. In addition, about 8% of people over 75 have dementia, with postmenopausal women having 1.4 to three times the risk for Alzheimer's disease compared to men. Effects on the HeartHeart disease is the number one killer of women. In 2002, more than 480,000 women died from diseases of the heart and circulation (cardiovascular diseases). Although young women have a much lower risk for cardiovascular disease than young men, after menopause women catch up, so that after age 51 their risk of dying of heart disease is very close to that of men. Estrogen loss is believed to play a major role in this increased risk. Estrogen has the following effects:
![]() Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.
Effect of Menopause on Bone DensityOsteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. At age 65, about 30% of women have osteoporosis, and nearly all of them are unaware of their condition. After age 80, up to 70% of women develop osteoporosis. Osteoporosis is a major risk factor for fracture in the spine and hip. The lifetime risk of spinal fracture in women is about one in three and that for hip fracture is one in six. Furthermore, between 10% and 20% of women who experience a hip fracture die within a year and about 25% require nursing home treatment. Experts are still puzzled by the extreme speed-up of bone breakdown (resorption) after menopause. Estrogen may have an impact on bone density in various ways:
Risk factors for osteoporosis include:
Women at risk for osteoporosis should have a bone density test to measure their bone mass and then make a decision about treatment after consulting their physician. Estrogen Loss and Mental DeclineEstrogen, the primary female hormone, appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Among estrogen's effects on the brain are the following:
Gum Disorders and Tooth LossEstrogen therapy has been associated with reduced gum bleeding and with decreased bone loss around the teeth, and women who take estrogen are less likely to lose their teeth. Thus, the same principle that helps prevent bone loss in osteoporosis is also at work in preventing bone loss in the mouth. Eye DisordersEstrogen, progesterone, or both appear to protect against cataracts. Studies are also indicating that estrogen helps prevent glaucoma and macular degeneration. IncontinenceThe drop in body estrogen levels brought on by menopause may contribute to both stress and urge incontinence. WrinklesSome evidence exists that estrogen may help prevent slackness and dryness in the skin and even reduce wrinkles. Urinary Tract InfectionsWomen are at increased risk for recurrent urinary tract infections after menopause. Researchers suggest that estrogen may resist infection by increasing the number of lactobacilli, a microorganism that fights infection by preventing bacteria from adhering to vaginal cells. (Studies are finding that vaginal creams or rings containing estrogen dramatically lower the incidence of recurring infections. It is not clear whether taking oral estrogen has the same benefit. Some studies, in fact, reported a higher incidence of urinary tract infections in women taking oral estrogen.) Sleep DisordersMenopause is associated with more sleeping problems, including inability to fall asleep and nighttime wakefulness. SymptomsThe most prominent symptoms of menopause tend to be the following:
Women from different ethnic and or cultural groups report different menopausal symptoms. For example, in one study hot flashes occurred in about 30% of Caucasians and 45% of African-Americans. Hispanic women tended to complain of urine leakage, vaginal dryness, and heart pounding. Japanese and Chinese women experienced far fewer menopausal symptoms, except for forgetfulness. All groups complained about this symptom. Over-the-Counter MedicationsNSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs) include the common painkillers aspirin and ibuprofen (Advil, Motrin) among many others, and they may be sufficient for relief of menopausal symptoms. Taking aspirin or any NSAID on a regular basis can increase the risk for gastrointestinal bleeding, and therefore any decision to take such medications regularly should be discussed with a physician. Lubricants for Vaginal Dryness. For vaginal dryness, moisturizers, and non-estrogen lubricants, such as KY Jelly, Replens, and Astroglide are available. (Frequent sexual activity helps preserve the lining of the vagina and maintain an acidic environment to protect against infection.) Vitamin E. Vitamin E supplements may help some women with hot flashes. Alternative TherapiesThere are many unproved methods for alleviating menopausal symptoms, some more effective than others. Acupuncture, meditation, and relaxation techniques are all harmless ways to reduce the stress of menopause and some people report great benefit from these practices. ![]() Acupuncture, hypnosis and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body. Many women also try herbal or so-called natural remedies. Some may have proven benefits, but others have no value and can have adverse side effects. The following agents are sometimes use for menopausal symptoms and carry certain risks:
Lifestyle ChangesEveryone should maintain a healthy diet rich in fresh fruits, vegetables, whole grains, and low in saturated fats (found in dairy and animal products) and trans-fatty acids (found in shortening, commercial baked goods, and hard margarines). Reducing salt intake is also important as people age. Whole Grains, Fresh Fruits, and VegetablesVegetables, fruits, whole grains, nuts, and legumes (beans and peas) contain fiber and many nutrients that are important for the heart and overall health. Of note, vitamin supplements are not recommended in place of healthy foods. Research is increasingly suggesting that high supplement doses, even of vitamins E and C, may have harmful effects. Mineral-Rich Fruits and Vegetables. Studies specifically suggest that diets rich in fresh fruits and vegetables are high in potassium and magnesium and can help preserve bones. Many of these foods also help protect against heart disease and cancers. Potassium-rich fruits include bananas, oranges, prunes, and cantaloupes, and vegetables that contain potassium include carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados and broccoli. Foods rich in magnesium include dairy products, spinach, potatoes, beets, nuts, sole, and halibut. Avoid Fast Foods and Limiting Salts. Reducing salt is important for protecting both the heart and the bones. High sodium intake interferes with calcium retention. Limiting table salt is not sufficient, since most salt in the Western diet comes from fast foods and commercial food products. Such foods are often also high in dangerous fats called trans-fatty acids and are harmful to the heart. Effects of Fiber. Fiber is important for the heart. Of some concern are reports of estrogen loss with high amounts of wheat bran (but not oat or corn) and calcium loss with any high-fiber diet. Calcium supplements can help offset this effect. Protein from Soy and AnimalsSome studies report a lower risk for diseases associated with estrogen and a high intake of so-called plant estrogens (phytoestrogens), which are generally categorized as isoflavones (found in soy and red clover) and lignans (found in whole wheat and flaxseed). At this time there is insufficient evidence on the benefits and risks of phytoestrogens to recommend them as an to approach menopausal health. Nevertheless, foods containing them may be healthful. Soy is of particular interest, however. It is rich in both soluble and insoluble fiber, healthy fatty acids, and provides all essential proteins. Soy products, many of which contain calcium, are widely available. The following are some forms and the amount of soy they contain:
Soy appears to have numerous effects on the body, many positive but some potentially negative ones as well. For example, supplements containing specific isoflavones found in soy--typically the estrogen-like compounds genistein and daidzein--do not appear to provide any benefits compared to the whole soy protein. Taking them separately may, in fact, cause harm, including a possible increase in estrogen-related cancers or a drop in white blood cells in infants. (Studies suggesting this have used animals or laboratory evidence. To date, there is no evidence of harm for humans who eat soy products.) More research is needed. Effect on Menopausal Symptoms. Studies have been mixed on whether soy relieves menopausal symptoms. One report suggested that if it did have any benefits, they were short lived. Effects on the Heart. A number of studies have indicated that subjects who consume at least 25 grams of soy protein improve cholesterol levels. Not all studies are consistent about particular effects, but the majority shows improvements in at least one of the cholesterol components. (Soy diets may also reduce high blood pressure in men, although not in women.) Powdered whole soy protein that contains at least 60 mg of isoflavones may provide similar benefits. Effect on Bone. The role of protein in osteoporosis is not entirely clear. An important 2000 study confirmed earlier reports that adequate protein is important for bone health. Other studies have also reported thinner bones in people who were deficient in protein. Investigators are trying to determine benefits, if any, from either animal or vegetable protein.
![]() Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with IBD (inflammatory bowel disease).
The effect of protein on bone is complicated, however, and laboratory studies suggest that high protein intake may increase calcium loss. And indeed some studies have reported higher bone loss associated with a high intake of protein, particularly when calcium or potassium intake was low. Of particular, note, there is some evidence that popular high-protein low-carbohydrate diets, such as the Atkins diet, may cause osteoporosis. The bottom line may be that in order for protein to be protective, or even not harmful, individuals should also eat plenty of mineral-rich foods. In any case, the best sources of protein for bone protection are oily fish and soy. Effects on Cancer. The effects of phytoestrogens on cancer are less clear. In general, Asian women have a lower incidence of reproductive and breast cancers as well as a higher intake of soy. A 2000 study of 120 Asian women reported an association between high levels of soy compounds in the urine and a lower risk for breast cancer, as much as 50% lower. A 2005 study of Asian Americans found that soy intake during adolescence was associated with a lower risk for breast cancer in adulthood. A 2001 Chinese study found that regular consumption of soy reduced the risk of endometrial cancer. The effects of phytoestrogens, however, in all cases are far from settled. Of concern are studies that report breast cell proliferation with low levels of genistein (one of the important isoflavones compounds in soy). In one study, the compound actually reversed the protective properties in tamoxifen, which is used to prevent breast cancer in high-risk women. In general, women at risk for breast cancer should avoid consuming large amounts of plant products with high levels of phytoestrogens until more is known about their effects. More research is needed on the effects of soy on breast and reproductive cancers. Effects on the Brain. A 2004 animal study reported that soy appeared to protect the brain against plaque build-up associated with Alzheimer’s disease. Of concern, however, was a study of older men that found an association between a high intake of tofu in middle age with later mental decline and brain atrophy, a finding that researchers were at a loss to explain. In general, any evidence on the effects of soy on menopause symptoms is weak, with some studies reporting no benefits. More clinical trials on soy are necessary before conclusions about its myriad effects can be drawn, and experts say it is too early to recommend soy as a replacement for estrogen. FatsBenefits of Fats and Oils. Although no one wants to be overweight, even a slight excess of fat helps protect bones. In fact, in one 2000 study, women who ate more fat in their diet were, on average, better able to absorb calcium than were women who had been put on a low-fat, high-fiber diet. Fats that contain fish oil or oils, such as olive or canola, may also be healthy for the heart. Dangers of Fats and Oils. Everyone should avoid saturated fats (found in animal products) and trans-fatty acids (found in hydrogenated fats, fast foods and commercial products). And of course, women should be aware that all fats, regardless of the type, are high in calories. No one should over-eat any fat or oil. -Calcium and Vitamin DCalcium. Women should be sure they have sufficient calcium and vitamin D in their diet by consuming low-fat dairy products or calcium-enriched orange juice. The standard recommended dose for older people is between 1000 and 1500 mg per day, depending on risk factors. Even doses of 1000 mg may help preserve bone in many postmenopausal women without osteoporosis, especially during winter months (when bone loss is greatest). In women who have already experienced osteoporosis-related fractures, however, 1000 mg daily may not add any protective benefits without bone-building medication. Calcium citrate (Citracal) is better absorbed than many other calcium compounds and was the first reported calcium supplement to preserve bone density after menopause. High doses (over 2,500 mg per day) of calcium supplements may increase the risk for kidney stones. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.) Vitamin D. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones. Vitamin D is manufactured in the skin using energy from the ultraviolet rays in sunlight. It can also be obtained from dietary supplements. As a person ages, vitamin D levels decline. They also fall during winters months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels. Current adult guidelines recommend the following:
Drinking milk fortified with vitamin D and sunlight exposure supply most people's need for vitamin D. (One cup of whole milk provides about 100 IU of vitamin D.) Oily fish (sardines especially, also salmon, fresh tuna, mackerel) are also important dietary sources of vitamin D. Of concern, however, is the increasing use of sunscreen to prevent skin cancers and the intake of milk products (such as yogurt and skim milk) that may have little vitamin D. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.) It should be noted that some studies suggest that vitamin D agents can protect against osteoporosis only in combination with calcium and that they do not appear to be protective in isolation. Caffeinated BeveragesTea. Tea may have a very positive effect on the heart. Although it contains caffeine, it also is rich in flavonoids and other substances that offer protection against damaging forms of LDL. A 2002 study also suggested that drinking tea regularly may help protect bones. Green tea is often cited for its health benefits, but black tea may also be beneficial. In one study, higher intake of black tea, particularly by women, was associated with a reduced risk for severe coronary artery disease. Tea also contains folic acid, which reduces homocysteine levels, a possible factor in coronary artery disease. Coffee. Some evidence suggests that, coffee, like red wine, contains phenol, which helps prevent oxidation of LDL cholesterol. One study also suggests that it may boost estrogen levels. The caffeine in coffee may reduce a woman’s risk for Parkinson’s disease, suggests one study, but hormone-replacement therapy might block this benefit. One 10-year study reported the highest rates of fatal heart disease in non-coffee drinkers, and women who increased their coffee intake reduced mortality rates. Regular intake of coffee does have a harmful effect on blood pressure in people with existing hypertension. (Caffeine causes a temporary increase in blood pressure in everyone, an effect thought to be harmless in people with normal blood pressure.) Of note: Unfiltered coffee (Turkish coffee, Scandinavian boiled or French pressed coffee, and espresso) contains an alcohol called cafestol, which may raise cholesterol levels. Filtered coffee does not contain this residue. Studies have been conflicting about the association between caffeine and low bone mass. In one trial, consumption of lots of coffee, nine or more cups per day, was associated with an increased risk of hip fractures in women, but not in men. Nevertheless, a 2001 animal study reported that coffee consumption did not cause bone loss. And other studies suggest that when calcium intake is sufficient, coffee does not harm bones. Note: The enhancing effects of coffee on estrogen may be harmful for women with risk factors for breast or ovarian cancer or premenopausal women with estrogen-related disorders, such as endometriosis. AlcoholEffect on the Heart. One drink a day in women who are not at risk for alcohol abuse may be beneficial for the heart. Red wine in particular contains a substance called resveratrol, which is classified as a phytoestrogen and has estrogen-like effects. Effect on Bones. Alcohol has different effects on bones depending on how much is consumed. A 2004 study found that moderate wine consumption was linked to improved bone mineral density in postmenopausal women. Alcohol, in moderate amounts, may increase estrogen levels. Excessive drinking, however, has been associated with brittle bones. Effect on Breast Cancer. Women who drink face an increased risk for breast cancer, but the risk associated with mild to moderate drinking is small. Controlling Weight GainMany women need to increase physical activity and reduce caloric intake before and after menopause. Weight gain is common during these years, and it can be sudden and distressing, particularly when habitual exercise and eating patterns are no longer effective in controlling weight. Gaining weight around the abdomen (the so-called apple shape) is a specific risk factor for heart disease and diabetes and many other health problems. ExerciseFor protection against all aging diseases, women, whether or not they are taking hormone replacement therapy, should pursue a lifestyle that includes a balanced aerobic and weight resistance exercise program appropriate to their age and medical conditions. Brisk walking, stair climbing, hiking, dancing, and tai chi are all helpful. One study reported that exercise alleviated hot flashes. In another study, a healthy diet plus regular, consistent exercise helped ward off the weight gain associated with the menopause. Weight-bearing exercises are specifically helpful for protecting against bone less. A recently designed successful program for older women employs weighted vests instead of traditional weights. In a 2001 study, after more than five years women on the program lost less than 1% of hip bone mass compared to 3.8% in women not on the program. Quit SmokingIf a woman smokes, she should quit. Smoking is linked to a decline in estrogen levels. Women who smoke experience menopause about two years earlier than nonsmokers. Smoking doubles a woman’s odds of developing coronary heart disease and is a major risk factor for osteoporosis.
MedicationsStatins inhibit the liver enzyme hMG-CoA reductase, which is used in the manufacturing of cholesterol. They may also benefit the heart by mechanisms beyond lowering cholesterol levels, but what these are exactly is as yet unknown. They are the most effective drugs for the treatment of high cholesterol and are now strongly recommended as the first choice for lipid-lowering treatment for older women with heart disease. They may have other benefits for women as well. Specific Statin Drugs. The statins include the two groups:
All are effective and safe. All are approved for lowering LDL. Although at this time only lovastatin and pravastatin are approved for prevention of heart disease and stroke, studies are showing the same benefits in the others. The differences among them are currently under investigation. Benefits of Statins. Their potential benefits for older women are the following:
![]() A heart attack or acute myocardial infarction (MI) occurs when one of the arteries that supplies the heart muscle becomes blocked. Blockage may be caused by spasm of the artery or by atherosclerosis with acute clot formation. The blockage results in damaged tissue and a permanent loss of contraction of this portion of the heart muscle.
Adverse Effects of Statins. Side effects may include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet). Statins can affect the liver, so periodic liver function tests should be performed. They can also damage muscle tissue, particularly among Asians, and when combined with fibrates (other cholesterol lowering drugs). Kidney failure has also been reported among people taking statins. The risk, however, is very low compared to their benefits. Statins should never be taken by women during pregnancy or breast-feeding, and they must be used with extra caution by people with liver disease. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering agents. Grapefruit juice and sour oranges (found in marmalades and other condiments, not in juice) may increase their potency. Selective Estrogen-Receptor Modulators (SERMs)Drugs known as selective estrogen-receptor modulators (SERMs) have been designed to produce the benefits of estrogen, such as bone protection, without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. Currently available SERMs include raloxifene (Evista) and tamoxifen (Nolvadex). Tibolone (Livial) is a synthetic hormone that acts more like a progestin. It has minimal side effects and patient compliance in clinical trials has been high. It is not yet available in the US. Other SERMs under investigation include lasofoxifene. They all have some common properties but may vary according to benefits and adverse effects. Osteoporosis and SERMs. Raloxifene (Evista) is the first SERM to be approved for preventing spinal fractures. (It does not appear to have any protective effect on other fractures, including those in the hip.) Raloxifene appears to have fewer side effects than hormone replacement therapy and women tend to stay on it. Low-dose tamoxifen may reduce the risk for fractures, but it has not been approved for this purpose. Heart Disease and SERMs. Raloxifene may have some benefits on cholesterol levels. A 2002 study further reported possible heart protection in women with existing heart disease, although the findings could have been due to chance. SERMs still pose a risk for deep vein blood clots, which may have long-term implications on heart problems. Longer studies are needed on possible risks and benefits. Breast Cancer and SERMs. Tamoxifen (Nolvadex) is the best-studied SERM and is now being used to prevent breast cancer in high-risk women and to prevent recurrence in women who have been treated for breast cancer. Researchers investigating raloxifene announced in 2004 that the drug reduced the risk of invasive breast cancer in postmenopausal women by 66% over an eight-year period. Common Side Effects. Most SERMs do not relieve menopausal symptoms, and some exacerbate them. As with estrogen therapy, most SERMs increase the risk for blood clots. Tamoxifen, but not raloxifene, increases risk for uterine cancer. Tamoxifen is associated with worse mental function. Raloxifene studies are mixed, with an important 2001 study reporting no benefits. BisphosphonatesThe bisphosphonates inhibit osteoclast activity, increase bone mass, and are among the primary drugs against osteoporosis in postmenopausal women and in people taking corticosteroids or hormonal agents that suppress estrogen. They are proving to reduce the risk of both spinal and hip fractures in women who have had prior bone breaks. Brands. A number of bisphosphonates in different forms are available or under investigation.
Candidates. National Osteoporosis Foundation's guidelines recommend that the following people should take or consider bisphosphonates:
Alendronate has also now been approved for men with osteoporosis. Both alendronate and risedronate are approved for both men and women who take corticosteroids. Side Effects. The most distressing side effects are gastrointestinal problems, particularly stomach cramps and heartburn, which are very common, occurring in nearly half of patients. Patients should strictly adhere to instructions for taking the drug (although gastrointestinal problems may still occur).
Long-Term Risk for Ulcers. Evidence to date suggests that agents do not harm the upper GI tract (the esophagus and throat). Of concern, however, are studies reporting a higher risk for long-term injury and ulcers in the stomach and small intestine. Some of these cases may be due to osteoporosis and other factors that also put women at risk for ulcers and bleeding. One 2002 study, however, reported a significantly higher risk for ulcers (38%) in people who regularly took both Fosamax and naproxen compared to either drug alone. (The risk for ulcers was 8% with Fosamax alone and 12% with naproxen alone.) Naproxen (e.g., Aleve) is one of the NSAIDs, which are common pain relievers used for many conditions. Others include aspirin and ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen, ketoprofen (Actron, Orudis KT). Long-term use of NSAIDs alone is known to increase the risk of ulcers, so both agents may have a double effect on the stomach lining. It is not known yet if the risks for these adverse actions are as high with other combinations. For example, ibuprofen may have a lower risk for ulcers than naproxen, and Actonel may have fewer adverse effects on the stomach than Fosamax. Because so many older people take NSAIDs regularly clarifying these effects is very important. Other Adverse Effects. Risedronate was associated with higher risk for lung cancer in one study, although not in others. (This association has not been found with other bisphosphonates.) More research needed. Hormone Replacement TherapyBased on early studies, many physicians used to believe that HRT might be beneficial for reducing the risk of heart disease and bone fractures caused by osteoporosis (thinning of the bones) in addition to treating menopausal symptoms. The results of a new study, called the Women's Health Initiative (WHI), has led physicians to revise their recommendations regarding HRT. The WHI, started in 1993, has enrolled 161,809 women between the ages of 50-79 in 40 different medical centers. Part of the study was intended to examine the health benefits and risks of hormone replacement therapy, including the risks of breast cancer, heart attacks, strokes, and blood clots. In July 2002, one component of the WHI, which studied the use of estrogen and progestin in women who had a uterus, was stopped early because the health risks exceeded the health benefits. The main reason for stopping the estrogen-progestin study was a 26% increase in breast cancer. In March 2004, a second component of the WHI, which studied estrogen-only therapy in women who no longer have a uterus, was stopped early. This was primarily because of an increase in the risk for strokes. And other randomized clinical trials have linked HRT to an increased risk of heart attack and cognitive decline while conferring some protection against osteoporosis and colon cancer. It should be noted that overall, these risks are still quite small. While the WHI study suggests that HRT should not be prescribed for prevention of chronic diseases, many physicians still accept its use for short-term treatment of moderate to severe hot flushes and other menopausal symptoms, and in women undergoing premature menopause for medical or other reasons. Hormones Used in HRT. Hormone replacement therapy can either use estrogen alone (known as unopposed estrogen) or in combination with forms of progesterone (known as combined hormone therapy or HRT). Progesterone is referred to by one of several names:
Both ERT and HRT are available in many forms, including oral tablets, skin patches, and vaginal and skin applications. A new form approved by the FDA in 2004 is a a topical estrogen gel which is applied to the arm. Menopausal Symptoms and HRT. At this point HRT is mainly recommended for relieving menopausal symptoms, including vaginal atrophy and dryness, hot flashes, sleep problems, and mild depression. HRT does not prevent certain other problems associated with menopausal changes such as thinning hair. Even short-term use of HRT poses some risk for blood clots and adverse heart events in some women. Furthermore, according to studies in 2002 and 2003, other than relieving hot flashes and other symptoms, taking HRT does not improve quality of life. In fact, in one study women who did not have hot flashes and took HRT generally had a worse quality of life, including fatigue and decline in physical functioning. Oral hormonal medications and skin patches are equally effective in reducing hot flashes, mild depression, and sleep problems. Progestins may sometimes be prescribed alone for hot flashes and other acute menopausal symptoms, though they can cause side effects, such as mood swings, bloating, and breast tenderness. Estrogen creams, rings, or vaginal tablets restore vaginal elasticity and lubrication and improve sexual pleasure. Osteoporosis and HRT. HRT may also be useful for some women at risk for osteoporosis, although other agents, such as bisphosphonates, should be considered first. It increases bone density and also appears to improve balance and protects against falling. Studies also report reductions in fractures (especially hip fractures) among women taking HRT, but the benefits may not outweigh the risks of HRT. It appears that the beneficial effects wear off soon after therapy is stopped. Estrogen must be taken life long for maximum protection against osteoporosis, which then increases the risk for adverse health effects. A 2002 study suggested that low doses may still be bone protective, and might also reduce health risks associated with HRT. Other Possible Benefits of HRT
Adverse Effects of HRT.
Other Prescription Agents Used For OsteoporosisCalcitonin. Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and in injected form (Calcimar). Calcitonin is not used to prevent osteoporosis; it is used to treat osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture. Low-Dose Parathyroid Injections. Although high persistent levels of parathyroid hormone can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulates bone production. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped. Teriparatide (Forteo), an agent made from selected amino acids found in parathyroid hormone, has now been approved for treatment of osteoporosis in postmenopausal women. Studies suggest it significantly lowers the risk of fracture and increases bone mineral density. In one small study, parathyroid significantly reduced spinal fractures compared to hormone replacement therapy. Prescription Agents Used for Menopausal SymptomsOral Contraceptives. Oral contraceptives (OCs) contain both estrogen and progestins. They generally use more potent forms of estrogen than those used for HRT and had not been thought suitable for replacement therapy. However, during the months before menopause, when periods may be irregular but contraception is still needed, low-dose forms of OCs may reduce the risk for bone loss and alleviate early menopausal symptoms, such as hot flashes. Like HRT they may protect bones in women approaching menopause (although they may have adverse effects on bones in young women.) Unlike HRT, they also protect against ovarian and endometrial cancers and do not appear to increase the risk for breast cancer. (Most studies on OCs, however, have been conducted with young women. The risks for women reaching menopause are not yet clear). Antidepressants. The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) may be used for managing mood changes and hot flashes. They include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil, Asimia). Testosterone. Some doctors are now prescribing combinations of estrogen and small amounts of the male hormone, testosterone. Estratest, for example, adds small doses of testosterone to estrogen therapy and appears to increase bone mass, improve sexual drive (when taken in higher doses), and improve mental alertness. A testosterone patch is also showing some promise in improve sexual function and well-being. Side effects of testosterone include increased body hair, acne, fluid retention, anxiety, and depression. It also adversely affects cholesterol and lipid levels. Long-term benefits or other adverse effects are unknown. Bellergal. Bellergal is the only non-hormonal drug specifically approved for hot flashes and other menopausal symptoms. This drug contains phenobarbital and belladonna and can be addictive. It relieves symptoms about half the time. It is not recommended in most cases. Gabapentin. Several small studies suggest that gabapentin (Neurontin, a drug used for many neurologic conditions) may alleviate hot flashes. More research is needed. The drug is expensive and may cause sleepiness, dizziness, and clumsiness. Resources
ReferencesEspeland MA, Rapp SR, Shumaker SA et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004; 291: 2959–2968. Messina M, Ho S, Alekel DL. Skeletal benefits of soy isoflavones: a review of the clinical trial and epidemiologic data. Curr Opin Clin Nutr Metab Care. 2004;7(6):649-658. Ridker, PM, Cannon, CP, Morrow, D. C-Reactive Protein Levels and Outcomes after Statin Therapy. N Engl J Med. 2005;352(1):20-28.
Review Date:
5/12/2005 Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-
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