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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 differ 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 vaginal dryness, sleep disturbances, and mood changes. 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, heart attack, stroke, blood clots in the lungs, breast 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 increases. 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.

Uterus
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 strongest 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.

Menopause and Perimenopause

As a woman ages, her supply of eggs decreases. 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. There are two stages in the transition:

  • Early Stage. Perimenopause can begin in some women in their 30s, but most often it starts in women 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.
  • Late Stage. The late stages of perimenopause usually occur when a woman is in her late 40s or early 50s. In the late stages of the menopausal transition, 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. Menopause is considered to have occurred when a woman has gone a full 12 months without a period. Menopause is marked by the following hormonal status:

  • 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.
Adrenal glands

 Click the icon to see an image of the adrenal glands. 
  • The total estrogen produced after menopause is, however, far less than that produced during a woman's reproductive years.

The average age that women reach menopause is 51 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 lives 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 as a sign of a new stage in life.

Symptoms

The most prominent symptoms of the transition to menopause include:

  • Irregular menstrual periods. In the years preceding menopause, women experience changes in their menstrual cycle. The time between periods can become shorter or longer and periods may last a longer or shorter number of days. Bleeding can be heavier or lighter, and change in flow from month to month. It is also normal for periods to skip a cycle.
  • 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 continue to occur for 3 - 5 years, although they may linger in some women for years after menopause. 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.
  • 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.
  • Vaginal dryness. Decrease in estrogen can cause thinning and drying of the vaginal membrane (vaginal atrophy also called atrophic vaginitis), which can cause itching and pain during sex (dyspareunia).
  • Mood changes. Mood changes and irritability are most likely to be a combination of sleeplessness and hormonal swings. Some women find the menopausal transition to be psychologically stressful. 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.

Although forgetfulness is often mentioned as a symptom, evidence indicates that menopause does not affect memory or other cognitive functions. It is normal for both men and women to experience some memory lapses as part of the natural aging process.

Complications

The decline in estrogen after menopause can increase the risk for a number of health problems for women.

Menopause and Heart Health

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 60, 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 LDL (“bad” cholesterol) and triglycerides, and a decrease in levels of HDL (“good”)cholesterol). [For more information, see In-Depth Report #3: Coronary artery disease.]

Thrombus

 Click the icon to see an image of thromboembolism. 

Menopause and Bone Density

Osteoporosis is a disease of the skeleton in which bones become "thin" and prone to fracture. In other words, the bone loses calcium and 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 decrease in bone density can also lead to bone loss in the jaw and subsequent tooth decay. [For more information, see In-Depth Report #18: Osteoporosis.]

Osteoporosis

 Click the icon to see an image of osteoporosis. 

Urinary Incontinence

The drop in body estrogen levels brought on by menopause can thin the linings of the urethra and bladder, which may contribute to both urinary stress and urge incontinence. [For more information, see In-Depth Report #50: Urinary incontinence.]

Urinary Tract Infections

Because of vaginal drying, women are at increased risk for recurrent urinary tract infections after menopause. [For more information, see In-Depth Report #36: Urinary tract infections.]

Weight Gain

Weight gain is common during a woman’s middle-aged years, especially between the ages of 50 - 59 years. The hormonal changes associated with menopause contribute to these body changes. Gaining weight around the abdomen (the so-called apple shape) is a specific risk factor for heart disease, diabetes, and many other health problems. Higher body mass index (BMI) may also be associated with increased risk for more frequent or severe hot flashes.

Different types of weight gain

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

Skin and Hair Changes

Estrogen loss can contribute to slackness and dryness in the skin and wrinkles. Many women experience thinning of their hair and some have temporary hair loss.

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.

Heart Health Recommendations

When women reach menopause, they are at increased risk for heart disease. A heart-healthy diet and other lifestyle changes are important ways to control cholesterol and blood pressure levels. [For more information, see In-Depth Reports #42: Heart-healthy diet and #03: Coronary artery disease.]

Heart-healthy recommendations include:

  • Quit smoking. 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.
  • Balance 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.) Aerobic exercise will reduce the risk of heart disease, while weight-bearing and resistance exercise will reduce the risk of osteoporosis.
  • Consume 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.
  • Choose 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.
  • Eat 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.
  • Limit 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.
  • Use little or no salt in your foods. Reducing sodium (salt) can lower blood pressure and decrease the risk of hypertension, heart disease, and heart failure.
  • Cut 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 American Heart Association (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.
  • For women ages 55 - 79 years who are at risk of heart disease, a daily low dose (75 - 81 mg) of aspirin may be helpful for primary prevention, particularly stroke. Women who have coronary artery disease or a previous stroke should take low-dose aspirin for secondary prevention.

Calcium and Vitamin D

A combination of calcium and vitamin D can reduce the risk of osteoporosis, the bone loss associated with menopause. [For more information, see In-Depth Report #18: Osteoporosis.]

Calcium. Women should consume low-fat dairy products and other foods rich in calcium (dark green vegetables, sardines), or calcium-fortified foods and beverages (orange juice, cereal), to get enough calcium in their diet. Calcium supplements may be an option for women who do not consume adequate amounts of calcium in their diets. Calcium supplements include calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions.

Calcium benefit

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

The standard recommended calcium dose for women age 50 years and older is at least 1,200 mg per day. High doses (over 2,500 mg per day) of calcium supplements may increase the risk for kidney stones.

Calcium source

 Click the icon to see an image of calcium sources. 

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 made in the skin using energy from the ultraviolet rays in sunlight. As people age, their vitamin D levels decline. Levels also fall during winter months and when people have inadequate exposure to sunlight.

Vitamin D source

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

The recommended daily intake of vitamin D is 800 - 1,000 IU a day after age 50. Dietary sources of vitamin D include fatty fish (salmon, mackerel, tuna), egg yolks, liver, and vitamin D-fortified foods and beverages (milk, orange juice, soy milk, cereals). However, many older women do not get enough vitamin D solely from diet or sunlight and may need to take a supplement. Vitamin D supplements are available either as D2 (ergocalciferol) or D3 (cholecalciferol). They work equally well for bone health.

Calcium and vitamin D supplements can be taken as separate supplements or as a combination supplement. If separate preparations are used, they do not need to be taken at the same time. Like calcium supplements, vitamin D supplements may increase the risks for kidney stones. If you have a history of kidney stones, discuss with your doctor whether these supplements are appropriate for you.

Alcohol

Effect on the Heart. One drink a day in women who are not at risk for alcohol abuse may be beneficial for the heart. However, the American Heart Association recommends that women have no more than one drink per day.

Effect on Bones. Excessive alcohol consumption increases the risk for brittle bones and osteoporosis.

Effect on Breast Cancer. Any woman who is at high risk for breast cancer should consider not drinking at all or drinking very sparingly.

Controlling Weight Gain

Many women need to increase physical activity and reduce caloric intake in the years 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. In addition to reducing risk factors for heart disease, weight loss may help lessen frequency and severity of hot flashes.

Exercise

Women 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, weight lifting, and tai chi are all helpful. Some studies report that exercise may help reduce 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 amount of exercise is helpful.

Alternative Therapies

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. Some women report great benefit from these practices, but there is no scientific proof of effectiveness.

Acupuncture
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.

Herbs and Supplements

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 alternative therapies. These studies have not found that these approaches are beneficial. Some herbs and supplements can have adverse side effects.

Phytoestrogens and Isoflavones. 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 foods or supplements provide any benefit for hot flashes, night sweats, or other menopausal symptoms. They also do not appear to help lower cholesterol or prevent heart disease. Nevertheless, soy is a healthy food choice. The best sources of soy protein are soy food products (tofu, soy milk, soybeans), not supplements.

Soy isoflavones contain genistein and daidzein, which are estrogen-like compounds. While some studies have suggested that soy food consumption may protect against estrogen-responsive cancers such as breast and endometrial cancer, other studies have indicated that high intakes of soy may increase the risks of these cancers. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy food and avoid taking dietary supplements that contain high amounts of isoflavones.

Other Herbs and Supplements. The following herbs and dietary supplements 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. Headaches and gastrointestinal problems are common side effects. This herb has been associated with liver toxicity.
  • 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) has been reported to possibly 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 dangerous. There have been several reports of it causing 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. (For more information on progesterone, see Hormone Replacement Therapy in Medications section.)
  • Evening primrose oil has not been shown to be superior to placebo. It may increase the risk for seizures when taken with certain types of drugs associated with seizures.
  • 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

Hormone Replacement Therapy (HRT)

Hormone replacement therapy, also known as menopausal hormone therapy (MHT) or hormone therapy (HT), uses medications that contain the female hormones that the body has stopped producing after menopause. The primary reasons that women use HRT are for the relief of hot flashes, night sweats, and vaginal dryness.

Hormone replacement therapy uses either estrogen alone (known as estrogen therapy [ET]) or estrogen in combination with progestogen (known as EPT). (The term “progestogen” encompasses both progesterone and progestin. Progesterone is the name for the natural hormone that the body produces. Progestin refers to a synthetic hormone that has progesterone effects.)

  • Women who have a uterus (have not had a hysterectomy) receive estrogen plus progesterone or a progestin (EPT). Progestogen is added to estrogen to protect the uterine lining (endometrium) and reduce the risk of endometrial cancer.
  • Women who do not have a uterus (have had a hysterectomy) receive estrogen alone (ET).

General Recommendations for HRT

Current guidelines support the use of HRT for the treatment of hot flashes. Specific recommendations:

  • HRT may be started in women who have recently entered menopause.
  • HRT should not be used in women who have started menopause many years ago.
  • HRT should not be used for longer than 5 - 7 years.
  • Women should not take HRT unless they have a low risk for stroke, heart disease, blood clots, and breast cancer

Initiating Therapy. Before starting HRT, your doctor should give you a comprehensive physical exam and take your medical history to evaluate your risks for heart disease, stroke, blood clots, osteoporosis, and breast cancer. While taking HRT, you should have regular mammograms and pelvic exams and Pap smears.

Discontinuing Therapy. 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.

Because HRT offers protection against osteoporosis, when women stop taking HRT their risks for bone thinning and fractures increases. For women who have used HRT for several years, doctors should monitor their bone mineral density and prescribe bone-preserving medications if necessary.

Safety Concerns. Until 2002, doctors used to routinely prescribe HRT to reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. That year, 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, is an on-going health study of nearly 162,000 postmenopausal women. Part of the study focuses on the benefits and risks of hormone replacement therapy. Analysis of the data from this ongoing study and other studies have raised concerns about that HRT use is associated with an increased risk of developing breast cancer, heart attacks, strokes, and blood clots.

As a result of these studies’ findings, there have been a number of changes in the way hormone therapy is prescribed. In general, doctors recommend that patients who choose HRT take the lowest possible dose for relief of symptoms for the shortest amount of time.

Woman who should not take hormone replacement therapy include those with the following conditions:

  • Current, past, or suspected breast cancer
  • History of endometrial 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

HRT Forms and Regimens

HRT comes in several forms:

  • Oral tablets or pills
  • Skin patches
  • Vaginal cream or tablet
  • Vaginal ring
  • Topical gel or spray

Vaginal forms of HRT are called “local” therapy. Pills and skin patches are considered “systemic” therapy because the medication delivered affect the entire body. Doctors generally prescribe vaginal applications of HRT to specifically treat symptoms such as vaginal dryness. For treatment of hot flashes, systemic therapy is recommended.

There are various dosing regimens for combination hormone therapy, although there is no consensus as to which is best. When estrogen and a progestogen are prescribed together, dosing schedules include:

  • Cyclic hormone therapy is often recommended when a woman is starting menopause. With this therapy, estrogen is taken in pill or patch form for 25 days, with progestin added somewhere between days 10 - 14. The estrogen and progestin are used together for the remainder of the 25 days. Then, no hormones are taken for 3 - 5 days. There may be monthly bleeding with cyclic therapy.
  • Continuous, combined therapy involves taking estrogen and progestin together every day. Irregular bleeding may occur when starting or switching to this therapy. Most women stop bleeding within 1 year.

"Biodentical" Hormones. Bioidentical” hormone replacement therapy is promoted as a supposedly more natural and safer alternative to commercial prescription hormones. Bioidentical hormones are typically compounded in a pharmacy. Some compounding pharmacies claim that they can customize these formulations based on saliva tests that show a woman’s individual hormone levels.

The FDA, and many professional medical associations, warn patients that “bioidentical” is a marketing term that has no scientific validity. Formulations sold in these pharmacies have not undergone FDA regulatory scrutiny. Some of these compounds contain estriol, a weak form of estrogen, which has not been approved by the FDA for use in any drug. In addition, saliva tests do not give accurate or realistic results, as a woman’s hormone levels fluctuate throughout the day.

FDA-approved hormones available by prescription come from different synthetic and natural sources, including plant-based. (For example, Prometrium is a progesterone derived from yam plants.)

Benefits of HRT

Periomenopausal and Menopausal Symptoms. HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness and accompanying pain during sexual intercourse, and sleep problems. Evidence is mixed as to whether HRT helps improve mood; the progestogens in EPT may worsen mood in some women. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair or weight gain.

Osteoporosis. Estrogen increases and helps maintain bone density. HRT may be useful for some women at high risk for osteoporosis, but for most women the risks do not outweigh the benefits. Other drugs, such as bisphosphonates, should be considered first-line treatment for osteoporosis. [For more information, see In-Depth Report #18: Osteoporosis.]

Colon Cancer. Combination estrogen-progesterone HRT may provide some protection against colon cancer.

Adverse Effects of HRT

Heart Disease and Heart Attack. Giving HRT in order to prevent heart disease is not recommended. However, using HRT for a short period of time in younger women (ages 50 - 59 years) within 10 years after menopause does not appear to raise the risk for heart disease.

Stroke. HRT may increase the risk of stroke in some age groups. It is no longer recommended as a strategy to prevent stroke, either a first stroke or a second 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.

Pulmonary embolus

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

Breast Cancer. Many studies have reported a higher risk for breast cancer in postmenopausal women who take combination estrogen-progesterone hormone replacement therapy for more than 3 - 5 years The risk appears higher for women who begin EPT before or soon after menopause. This risk declines within 3 years of stopping combination HRT.

Estrogen-only HRT (ET) does not significantly increase the risk of developing breast cancer if it is used for less than 10 years. If used for more than 10 years, it may increase the risk of breast (and ovarian) cancers, especially for women already at increased risk for breast cancer. The North American Menopause Society does not recommend ET use in breast cancer survivors as it has not been proven safe and may raise the risk of recurrence.

Both estrogen-only and combination HRT increase breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take HRT should be aware of the need for regular mammogram screenings.

The North American Menopause Society recommends that women who are at risk for breast cancer avoid hormone therapy and try other options to manage menopausal symptoms. Recent studies have noted that breast cancer rates have fallen as HRT use has declined.

Endometrial (Uterine) Cancers. Taking estrogen-only replacement therapy (ET) for more than 3 years increases the risk of endometrial cancer at least five-fold. If taken for 10 years, the risk is ten-fold. Adding progesterone or a progestin to estrogen (EPT) helps to reduce this risk. Women who take ET should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests. No type of hormone replacement therapy is recommended for women with a history of endometrial cancer.

Ovarian Cancer. Long-term use (more than 5 - 10 years) of estrogen-only HRT may increase the risk of developing and dying from ovarian cancer. The risk is less clear for combination estrogen-progesterone therapy.

Lung Cancer. While it is not clear if HRT use is associated with increased risk of lung cancer, women who smoke and who are past or current users of HRT should be aware that some evidence indicates that EPT may promote the growth of lung cancers.

Other Drugs Used for Menopausal Symptoms

Despite its risks, hormone replacement therapy appears to be the most effective treatment for hot flashes. There are, however, 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, generic), sertraline (Zoloft, generic), venlafaxine (Effexor), desvenlafaxine (Pristiq), paroxetine (Paxil, generic), and escitalopram (Lexapro).

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, generic) 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 therapy 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. It is unclear whether testosterone is safe or effective for treatment of menopausal symptoms.

Vaginal Lubricants. Lubricants (such as KY Jelly, Replens, Astroglide) are helpful for vaginal dryness and dyspareunia (painful sexual intercourse).

Resources

References

American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. ACOG Committee Opinion No. 420, November 2008: hormone therapy and heart disease. Obstet Gynecol. 2008 Nov;112(5):1189-92.

Beral V, Reeves G, Bull D, Green J; Million Women Study Collaborators. Breast cancer risk in relation to the interval between menopause and starting hormone therapy. J Natl Cancer Inst. 2011 Feb 16;103(4):296-305. Epub 2011 Jan 28.

Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa): a systematic review of adverse events. Am J Obstet Gynecol. 2008 Nov;199(5):455-66.

Brunner RL, Aragaki A, Barnabei V, Cochrane BB, Gass M, Hendrix S, et al. Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial. Menopause. 2010 Sep-Oct;17(5):946-54.

Chlebowski RT, Kuller LH, Prentice RL, Stefanick ML, Manson JE, Gass M, et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. 2009 Feb 5;360(6):573-87.

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Review Date: 9/13/2011
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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