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Menopause

Highlights

Menopause

Menopause is a natural process that occurs as a woman’s ovaries stop producing eggs, and production of the hormones estrogen and progesterone declines. (Menopause can also occur if a woman’s ovaries are surgically removed.) Menopause usually happens gradually between the ages of 45 - 55. During this transition time, called “perimenopause,” menstrual periods become more irregular and begin to taper off. When menstrual periods have completely stopped for 12 months, a woman is considered to have reached menopause. On average, women reach menopause around the age of 51, but menopause can occur at younger or older ages.

Perimenopausal Symptoms

During perimenopause, women may have various symptoms. Symptoms vary among women, and may range from mild to severe. Some women have no symptoms.

Hot flashes, an intense sudden build-up of body heat, are the most common symptom. Other symptoms can include heart pounding, mood changes, vaginal dryness, sleep disturbances, and thinning hair. These symptoms are caused by changes in estrogen and progesterone levels. After most women pass through menopause, many symptoms eventually subside and disappear.

Treatment

Menopause is a natural condition. It is not a disease that needs medical treatment. However, some women seek treatment for the relief of perimenopausal symptoms -- especially hot flashes. Hormone replacement therapy (HRT) is the most effective drug treatment for hot flashes, but long-term use (more than 5 - 7 years) can increase the risks of heart disease, stroke, blood clots in the lungs, breast cancer, ovarian cancer, and endometrial cancer. Therefore, doctors recommend that women who use HRT should take the lowest possible dose for the shortest possible time.

Other prescription drugs, such as antidepressants, are also sometimes used to manage hot flashes and mood changes. Although some women try herbal remedies for symptom management, little scientific evidence supports their effectiveness.

Menopause and Heart Health

When a woman reaches menopause, her risk for heart disease increase. It is important for postmenopausal women to follow preventive lifestyle modifications (healthy diet, exercise, not smoking) to ensure heart health.

Introduction

The ovaries have 200,000 - 400,000 follicles, tiny sacks that 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:

• They are essential for the reproductive process and the development of the female organs.
• Estrogens determine the characteristic female distribution of body fat on the hips and thighs, which develops during adolescence.
• They also are involved in tissues in the central nervous system (including the brain), the bones, the liver, and the urinary tract.

Estrogen has different forms:

• The most potent form is estradiol.
• The other important, but less powerful, estrogens are estrone and estriol.

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.

As a woman ages, her supply of eggs declines. Menopause occurs naturally after a woman's ovaries fail to function 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:

• Early Stage. The beginning of perimenopause can begin in some women in their 30s, but most often it starts between ages 40 - 44. It is marked by changes in menstrual flow and in the length of the cycle. There may be sudden surges in estrogen.
• Middle Stage. In the middle cycle, periods become irregular, but they are not skipped.
• Late Stage. In the late stages, women begin missing the periods until they finally stop. About 6 months before menopause estrogen levels drop significantly. The fall in estrogen triggers the typical symptoms of vaginal dryness and hot flashes (which can last from half a year to more than 5 years after onset of menopause).

Menopause. At the point at which menopause occurs, the following hormonal changes occur:

• Ovarian secretion of estrogen and progesterone ends.
• Once the ovaries have stopped producing estrogens, however, they still continue to produce small amounts of the male hormone testosterone, which can be converted to estrogen (estradiol) in body fat.
• In addition, the adrenal gland continues to produce androstenedione (a male hormone), which is converted to estrone and estradiol in the body fat.

Click the icon to see an image of the adrenal glands.

• The total estrogen produced after menopause, however, is far less than that produced during a woman's reproductive years.

The average age of women at menopause today is 51.4 years although it can occur as early as age 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 complications. 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.

Symptoms

The most prominent symptoms of the transition to menopause include:

• Hot flashes and night sweats. Women often feel hot flashes as an intense build-up in body heat, followed by sweating and chills. Some women report accompanying anxiety as the sensation builds. In most cases, hot flashes go away within 2 years of menopause, although they may linger in some women for years. Women who have a hysterectomy (surgical removal of the uterus) are less likely to have hot flashes than women who have a natural menopause. However, women who have surgical removal of both ovaries, and who do not receive hormone replacement therapy, may have more severe hot flashes than women who enter menopause naturally.
• Heart pounding or racing can occur, with or without hot flashes.
• Difficulty sleeping. Insomnia is common during perimenopause. It may be caused by the hot flashes, or it may be an independent symptom of hormonal changes.
• Mood changes. Mood changes are most likely to be a combination of sleeplessness, hormonal swings, and psychological factors as a woman undergoes this intense passage in her life. Once a woman has reached a menopausal state, however, depression is no more common than before, and women with a history of premenstrual depression often have significant mood improvement.
• Sexuality. Sexual responsiveness tends to decline in most women after menopause, although other aspects of sexual function, including interest, frequency, and vaginal dryness vary. It is useful to remember that the symptoms of menopause eventually go away.
• Forgetfulness. This appears to be one of the few symptoms that are common across most cultural and ethnic groups.
• Urine leakage.
• Vaginal dryness.
• Joint stiffness.

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 had far fewer menopausal symptoms, except for forgetfulness. All groups complained about this symptom.

Complications

After a woman reaches menopause, her average life expectancy is 30 - 40 years. During those years, however, 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 - 3 times the risk for Alzheimer's disease compared to men.

Heart disease is the number one killer of women. Although young women have a much lower risk for cardiovascular disease than young men, after menopause women catch up. After age 51, women’s risk of dying from heart disease is very close to that of men. Estrogen loss is believed to play a major role in this increased risk. Woman who reach menopause before the age of 35 have a significant increase in risk for heart disease as they age. This increase is primarily due to a rise in levels of the harmful low-density lipoprotein (LDL) cholesterol. [For more information, see In-Depth Report #3: Coronary artery disease.]

Women who take hormone replacement therapy are at risk for thromboembolism -- blood clots that block a vessel. This action may explain the higher rates of adverse heart events now observed in women with heart disease who take HRT.

Click the icon to see an image of thromboembolism.

Osteoporosis 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 1 in 3 and that for hip fracture is 1 in 6. Furthermore, 10 - 20% of women who break their hip die within a year, and about 25% need nursing home treatment.

Click the icon to see an image of osteoporosis.

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:

• Estrogen's most important effect on osteoporosis appears to be prevention of bone break down (resorption). Some research suggests that estrogen may control the lifespan of osteoclasts, the cells responsible for bone breakdown.
• Part of estrogen's beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Risk factors for osteoporosis include:

• Being tall and thin
• Being Caucasian
• Smoking
• Taking thyroid hormone
• Being sedentary
• Early menopause or surgical menopause (removal of ovaries)

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 doctor. [For more information, see In-Depth Report #18: Osteoporosis.]

Depression may occur as a woman transitions into menopause (perimenopause), even among women with no history of clinical depression. Hormonal changes and declines in estrogen levels are probably involved in this process. Research suggests that a depressive disorder is 2.5 times more likely to develop during perimenopause than premenopause. Women who reach menopause at a younger age are at increased risk of a first episode of depression.

Symptoms of clinical depression include:

• Loss of interest or pleasure in activities once enjoyed
• Persistent (longer than 2 weeks) sad mood
• Decreased energy
• Sleep problems (insomnia or oversleeping)
• Feelings of guilt, worthlessness, and hopelessness
• Difficulty concentrating

Some of these symptoms may overlap with other symptoms that typically accompany perimenopause. Women who have these symptoms should talk to their doctor. Depression is treatable. [For more information, see In-Depth Report #8: Depression.] For many women, depression eases once they reach menopause.

Estrogen, the primary female hormone, appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. About 40% of women who are either perimenopausal or menopausal complain of forgetfulness.

Estrogen 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.

Estrogen, progesterone, or both appear to protect against cataracts.

Click the icon to see an image of a cataract.

Studies also indicate that estrogen helps prevent glaucoma and macular degeneration.

Click the icon to see an image of glaucoma.

Click the icon to see an image of macular degeneration.

The drop in body estrogen levels brought on by menopause may contribute to both urinary stress and urge incontinence.

Women are at increased risk for recurrent urinary tract infections after menopause. Research suggests that estrogen may prevent infection by increasing the number of lactobacilli, a microorganism that fights infection by preventing bacteria from adhering to vaginal cells.

Estrogen may help prevent slackness and dryness in the skin and reduce wrinkles.

Menopause is associated with more sleeping problems, including inability to fall asleep and nighttime wakefulness.

Lifestyle Changes

Simple changes in lifestyle and diet can help control menopausal symptoms such as hot flashes. Avoid hot flash triggers like spicy foods, hot beverages, caffeine, and alcohol. Dress in layers so that clothes can be removed when a hot flash occurs. For vaginal dryness, moisturizers, and non-estrogen lubricants, such as KY Jelly, Replens, and Astroglide are available.

When women reach menopause, they are at increased risk for heart disease. A heart-healthy diet is an important way to control cholesterol and blood pressure levels. [For more information, see In-Depth Report #42: Heart-healthy diet.]

In 2007, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

• Balancing calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 - 90 minutes, of daily exercise.)
• Consuming a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
• Choosing whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
• Eating fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to a reduced risk of sudden death and death from coronary artery disease. Women with heart disease may also consider taking a daily dietary supplement of 850 - 1,000 mg of EPA and DHA.
• Limiting daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
• Using little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
• Cutting down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
• If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 1 drink per day for women.
• The AHA does not recommend antioxidant supplements (such as vitamin E, C, or beta carotene) or folic acid supplements for prevention of heart disease.

Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans).

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. The majority of studies have found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still recommends soy foods, but not supplements, as a healthy food choice. The benefits of soy on menopausal symptoms are mixed, according to research (see below in Alternative Therapies). A 2006 study reported that increased soy intake does not help reduce the frequency or severity of hot flashes and night sweats.

A combination of calcium and vitamin D is important for helping to prevent bone loss. [For more information, see In-Depth Report #18: Osteoporosis.]

Calcium. Women should consume low-fat dairy products or calcium-enriched orange juice to get enough calcium and vitamin D in their diet. Calcium supplements may be another option for some women. For calcium supplements, calcium citrate (Citracal) is better absorbed than calcium carbonate (Tums, Os-Cal) and other types of calcium compounds. Calcium citrate was the first calcium supplement reported to preserve bone density after menopause.

Click the icon to see an image of the benefits of calcium.

The standard recommended calcium dose for adults age 50 years and older is at least 1,200 mg per day, depending on risk factors. 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.)

Click the icon to see an image of calcium sources.

There are differing views on the use of calcium and vitamin D. Some doctors recommend that women over age 60 should take calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether you should take calcium supplements.

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. Some studies suggest that vitamin D protects against osteoporosis only in combination with calcium.

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. Levels also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of vitamin D sources.

Daily dosage guidelines vary, ranging from 400 - 800 IU per day. The higher dose range is generally recommended by the National Osteoporosis Foundation.

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, as well as salmon, fresh tuna, and mackerel) are also important dietary sources of vitamin D. Wild salmon has a much higher vitamin D content than farmed salmon.

Effect 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. Three or more drinks per day are considered a risk factor for brittle bones and osteoporosis.

Effect on Breast Cancer. Women who drink have an increased risk for breast cancer, but the risk associated with mild-to-moderate drinking is small.

Many 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, diabetes, and many other health problems.

Click the icon to see an image of different types of weight gain.

For 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. Several studies report that exercise can help control hot flashes. A healthy diet plus regular, consistent exercise can also help ward off the weight gain associated with menopause. Weight-bearing exercises are specifically helpful for protecting against bone loss. Women should get at least 30 minutes of exercise each day (for weight loss, 60 - 90 minutes is preferred). While more exercise is better, any exercise is helpful. A 2007 study showed that postmenopausal sedentary women who exercised only 75 minutes a week experienced improvement in fitness levels.

If a woman smokes, she should quit. Smoking is linked to a decline in estrogen levels. Women who smoke reach menopause about 2 years earlier than nonsmokers. Smoking doubles a woman’s odds of developing heart disease and is a major risk factor for osteoporosis.

Aspirin. The American Heart Association recommends daily low-dose aspirin for all women age 65 years and older who can safely take aspirin. High-risk women may need 75 - 325 mg per day; lower-risk women may benefit from 81 mg a day or 100 mg every other day. [For more information, see In-Depth Report #03: Coronary artery disease.]

There are many unproven methods for relieving 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.

Women often try herbal or so-called natural remedies to treat menopausal symptoms. There have been numerous studies conducted on various herbal products and other complementary and alterative therapies. These studies have not found that these approaches have any benefit. Some can have adverse side effects.

Many studies have researched plant estrogens (phytoestrogens), which are generally categorized as isoflavones (found in soy and red clover) and lignans (found in whole wheat and flaxseed). No evidence to date indicates that phytoestrogen supplements provide any benefit for hot flashes or other menopausal symptoms. Nevertheless, foods containing them may be healthful.

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.

The following herbs are sometimes used for menopausal symptoms and have certain risks:

• Black cohosh (Cimicifuga racemosa), also known as squaw root, is the herbal remedy most studied for menopausal symptoms. Although it contains a plant estrogen, this substance does not act like an estrogen in the human body. Studies have shown mixed results in preventing hot flashes. High-quality studies have found that black cohosh works no better than placebo for treating hot flashes and night sweats. While it may be ineffective, black cohosh appears to be safe. Headaches and gastrointestinal problems are common side effects.
• Dong quai (Angelica sinensis) does not appear helpful for hot flashes or other menopausal symptoms. Do not use dong quai with blood-thinning drugs, such as warfarin, because it may cause bleeding complications.
• Ginseng (Panax ginseng) may help menopausal symptoms of depression and sleep problems, but it has no effect on hot flashes.
• Kava (Piper methysticum) may relieve anxiety but it does not help hot flashes. This herb is generally considered unsafe, due to several reports of liver failure and death, especially in people with liver disease.
• Wild yam (Dioscorea villosa) is an herb sometimes used for menstrual problems as well as menopausal symptoms. It contains a plant progesterone. However, like black cohosh, there is no evidence that the human body can convert this substance into a hormone. Patients should be aware that some commercial herbal wild yam products contain prescription progesterones.
• Dehydroepiandrosterone (DHEA) is a weak male hormone secreted by the adrenal gland. It is available as a dietary supplement. DHEA has no benefit for hot flashes and may increase the risk of breast cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration to sell their products. Just like with drugs, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctors before using any herbal remedies or dietary supplements.

Medications

Doctors used to believe that HRT could help reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. The results of an important study, called the Women's Health Initiative (WHI), led doctors to revise their recommendations regarding HRT.

The WHI, started in 1991, enrolled 161,809 women ages 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. Analysis of the data from this ongoing study has produced many changes in the way hormone therapy is prescribed.

While the WHI studies indicate that HRT generally should not be prescribed solely for prevention of chronic diseases (heart disease, stroke, breast cancer), many doctors still accept and recommend its use for short-term treatment of moderate-to-severe hot flashes and other menopausal symptoms. Current guidelines supports short-term (up to 5 - 7 years) use of HRT for treatment of hot flashes and other vasomotor symptoms in recently menopausal women who have a low risk for stroke, heart disease, or breast cancer. Beginning estrogen replacement therapy years after menopause has occurred is generally not recommended.

In general, doctors recommend that patients who choose HRT take the lowest possible dose for relief of symptoms for the shortest amount of time.

When a woman stops taking HRT, perimenopausal symptoms may recur. There is some debate about whether it is better to abruptly stop the medication or to taper it off gradually. Gradual discontinuation of HRT may delay -- but not prevent -- the reappearance of symptoms. However, when a woman reaches full menopause, symptoms will eventually go away.

Hormones Used in HRT. Hormone replacement therapy uses either estrogen alone (known as ET or unopposed estrogen) or in combination with forms of progesterone (known as combined hormone therapy or EPT).

Estrogens may be natural, synthetic, or plant derived. The primary reason for using estrogen is the relief of hot flashes, night sweats, and vaginal dryness. Estrogen replacement therapy may take several forms:

• Oral tablets or pills
• Skin patches
• Vaginal cream or tablet
• Vaginal ring
• Nasal spray
• Pellets inserted below the skin
• Topical gel

Progesterone is referred to by one of several names:

• Progesterone is the name for the natural hormone.
• Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects.
• Progestogen is any hormone that has effects similar to progesterone.

Progesterones are available in pill form, as a skin patch, or as vaginal cream. The primary reason for using progesterone is to reduce the risk of uterine (endometrial) cancer by using it in combination with estrogen.

Estrogens or progesterones may be administered in a number of different ways, including:

• Estrogen therapy alone
• Progesterone therapy alone
• Estrogen combined with progesterone

When estrogen and progesterone are prescribed together, recommended schedules include:

• Cyclical estrogen, with a progesterone dose given 10 -14 days of each month
• Continuous low-dose progestogen taken on a daily basis

Woman who should probably not take estrogen therapy include those with the following conditions:

• Current, past, or suspected breast cancer
• Vaginal bleeding of unknown cause
• Current or past history of blood clots
• High blood pressure that is untreated or poorly managed
• Angina that is currently symptomatic or heart attack that occurred recently
• Active liver problems

Periomenopausal and Menopausal Symptoms. HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness, sleep problems, and mild depression. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair.

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. HRT may be useful for some women at high risk for osteoporosis, although other drugs, such as bisphosphonates, should be considered first-line treatment. HRT increases and helps maintain bone density. Studies also report reductions in fractures (especially hip fractures) among women taking HRT, but these 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 for life for maximum protection against osteoporosis, therefore increasing the risk of side effects. [For more information, see In-Depth Report #18: Osteoporosis.]

Heart Disease. Younger women with a natural or surgically induced menopause are at increased risk for heart disease and probably benefit from estrogen replacement therapy.

Heart Disease. HRT does not prevent heart disease except in women with premature menopause and may increase the risk for heart disease and heart attack, especially in older women. Results from the Women’s Health Initiative study found that women who began HRT within 10 years of menopause had less risk of heart disease than women who begin HRT later on. This study suggests that HRT may be safest for women younger than age 60, and should be avoided by women older than age 60. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated. Estrogen can increase the risk for heart attack in women who have advanced heart disease.

Stroke. HRT may increase the risk of stroke, regardless of years since menopause. It is certainly no longer recommended as a strategy to prevent stroke. In addition, HRT appears to worsen the outlook for women who are at increased risk for stroke and women who have had a stroke.

Mental Decline. Reviews of the Women’s Health Initiative Memory Study, as well as other more recent studies, have found that combined HRT does not reduce the risk of cognitive impairment, and may actually increase the risk of cognitive decline.

Thromboembolism. HRT is associated with a higher risk for thromboembolism, in which blood clots form in deep veins. This places women at risk for pulmonary embolism, in which the blood clot travels to the lungs.

Click the icon to see an image of a pulmonary embolism.

Breast Cancer. Because breast tissue growth is highly sensitive to estrogens, it is generally felt that the more a woman is exposed to estrogen over her lifetime, the higher the risk for breast cancer. A small but increased risk for breast cancer may be present for women who take prolonged hormone replacement therapy. However, risk for breast cancer does not seem to be increased during the first 5 - 7 years of estrogen therapy. Therefore, use of hormone therapy for most women to treat active menopausal symptoms is considered safe regarding risk for breast cancer.

Breast tissue density increases with HRT, which makes mammograms more difficult to read and leads to more breast biopsies. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

Of interest, a recent study noted that breast cancer rates have fallen as HRT use has declined.

Endometrial (Uterine) Cancers. Estrogen overstimulates the tissue lining the uterus (the endometrium) and causes uncontrolled cell growth, a condition known as hyperplasia, which is a strong risk factor for cancer. Taking unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer at least five-fold. Adding progestin to HRT appears to pose no risk for this cancer. However, a 2007 study indicated that short-term treatment (3 years) with ERT is associated with a relatively low risk of endometrial cancer. Women who take ERT should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests.

Ovarian Cancer. HRT appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop ovarian cancer and die from it than women who had never taken HRT.

Gallstones. HRT is associated with a higher risk for gallstones.

Despite its risks, hormone replacement therapy appears to be the best treatment for hot flashes. There are many nonhormonal treatments for hot flashes and other menopausal symptoms.

Antidepressants. The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used for managing mood changes and hot flashes. They include fluoxetine (Prozac), sertraline (Zoloft), venlafaxine (Effexor), and paroxetine (Paxil, Asimia). A 2006 review of nonhormonal therapies, found that paroxetine in particular may help hot flashes. However, paroxetine, like other antidepressants, can cause headache, anxiety, and sexual problems. A 2007 study suggested that the antidepressant citalopram (Celexa), given alone or with HRT, may help treat hot flashes.

An investigational antidepressant, desvenlafaxine (Pristiq), is also being studied for treatment of hot flashes, night sweats, and perimenopausal sleep problems. Research presented at the 2007 meeting of the American College of Obstetricians and Gynecologists indicated that desvenlaxafine, which is related to venlaxafine, showed promise in improving symptoms.

Gabapentin. Several small studies suggest that gabapentin (Neurontin), a drug used for seizures and nerve pain, may relieve hot flashes. Gabapentin may cause drowsiness, dizziness, fatigue, and swelling of the hands and feet.

Clonidine. Clonidine (Catapres) is a drug used to treat high blood pressure. Studies show it may help manage hot flashes. Side effects include dizziness, drowsiness, dry mouth, and constipation

Testosterone. Some doctors prescribe combinations of estrogen and small amounts of the male hormone testosterone to improve sexual function and increase bone density. Side effects of testosterone include increased body hair, acne, fluid retention, anxiety, and depression. Testosterone also adversely affects cholesterol and lipid levels, and combined estrogen and testosterone may increase the risk of breast cancer. No good evidence supports the safety or effectiveness of testosterone for treatment of menopausal symptoms.

Resources

• www.menopause.org -- North American Menopause Society
• www.acog.org -- American College of Obstetricians and Gynecologists
• www.nia.nih.gov -- National Institute on Aging
• www.nhlbi.nih.gov/whi/recommend.htm -- Women's Health Initiative Study
• www.nih.gov/PHTindex.htm -- National Institutes of Health -- Menopausal Hormone Therapy Information
• http://nccam.nih.gov/health/menopauseandcam -- National Center for Complementary and Alternative Medicine

References

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