Menopause

Introduction

As women reach their late forties or early fifties, their menstrual periods generally become much less frequent and then stop. Sometimes called the ?change of life? or the ?climacteric?, menopause is not really a ?pause? ? a temporary interruption in menstruation. It is actually the time when menstrual periods end. Some women see menopause as a time for celebration; others dread the physical signs of aging; most treat it as a normal stage of life.

What is it?

Menopause simply means the end of menstruation. Usually defined as not having had a menstrual period for 12 months in a row, menopause may be natural or it may occur after a hysterectomy (surgical removal of the uterus). In the United States, the average age of natural menopause is 51 years, but it may occur naturally at any time between the ages of about 45 and 55 years.

Menopause results from decreased production of the female sex hormones, estrogen and progesterone. After menopause, few eggs remain in the ovaries. As a result, both estrogen and progesterone levels fall. The extreme decline in hormone production is a major cause of symptoms, such as hot flashes and mood disorders, which frequently accompany the start of menopause. Lowered estrogen and progesterone levels also contribute to increased risk among postmenopausal women for certain health problems, such as heart disease, osteoporosis, and urinary incontinence (the inability to control urine flow). When levels of both hormones decline, menstruation stops and fertility essentially ends, as well.

Perimenopause is the time just before and after the onset of menopause. It averages 4 years in length, but it may be much shorter or longer for individual women. Because women may still may release eggs during perimenopause, they can still get pregnant. Common symptoms that may begin in perimenopause include:

• Changes in menstrual periods
• Hot flashes
• Insomnia
• Mood changes
• Night sweats

Postmenopause refers to the time after menopause. This is the time when some of the distress from the changes from menopause will start to fade. The symptoms described above may become milder, while energy levels and emotions stabilize.

What causes it?

Menopause is a natural part of the aging process for women. Each girl is born with a limited number of immature eggs in her ovaries. A complex balance of female hormones promotes the maturation and release of the eggs by the ovaries. With each menstrual period, some of the eggs are lost. As the number of eggs in the ovaries decreases, less estrogen is produced and menstrual periods usually become irregular before they stop completely. For most women, the process is gradual, but some women experience abrupt physical and emotional changes. For unknown reasons, some young women undergo menopause many years before expected. Women of any age enter menopause if the ovaries are removed surgically or if they are damaged - by chemotherapy or radiation, for example. In menopause caused by ovarian surgery or damage, the production of estrogen and progesterone drops suddenly.

Who has it?

All women will experience menopause. The average age is in the early fifties, but some women undergo menopausal changes much earlier or later in life. Emotional stress, certain illnesses, some medications, or excessive exercise can cause even very young women to stop menstruating temporarily. In rare cases, temporary cessation of the menstrual cycle may become permanent if the underlying cause is not corrected. Women who smoke cigarettes generally enter menopause a few years earlier than non-smokers.

What are the risk factors?

Risk factors are characteristics that make individuals more likely to develop a disease or condition. For menopause, the only risk factors are being female and approaching 50 years of age. However, younger women with certain risk factors can experience menopause earlier in life. For example, women who undergo surgical treatments such as hysterectomy (removal of the uterus), have genetic disorders that affect the ovaries, or who use certain types of cancer therapies may experience menopause at a younger age.

Menopause increases risk factors for other health conditions. When a woman stops producing female hormones naturally, she loses the possible protective effects of those hormones. For example, her rate of bone loss speeds up, making the development of osteoporosis causing broken bones more likely. Her risk of heart disease also increases, partly due to higher cholesterol levels that occur after the production of female hormones stops. Estrogen and progesterone were formerly prescribed widely to help prevent heart disease among postmenopausal women. However, the results of large studies have found they not only do not protect against heart disease, they may actually increase heart disease risk for some women. The American Heart Association (AHA) now recommends against the use of estrogen and progesterone if they are taken only to prevent heart disease. If hormones are taken to relieve the symptoms of menopause, some guidelines now suggest they be used no longer than needed ? 5 years, at the most.

What are the symptoms?

Menopause is usually associated with distinctive symptoms. Although many women have very little trouble dealing with menopausal symptoms, about 40% of American women report symptoms that disrupt their normal functioning to some extent. Approximately 85% of women experience vasomotor symptoms ? most often hot flashes. Vasomotor refers to the interactions of muscles and nerves that cause blood vessels to shrink and expand. Although the exact causes of vasomotor menopausal symptoms are not yet known, they are associated with disruption of the body?s temperature regulation by changing hormone levels. Hot flashes are sudden, unprovoked feelings of heat ? usually on the face, head, neck, and chest. They may be accompanied by rapid heartbeats, reddened skin, and/or heavy sweating. Typically beginning a year or more before menopause, individual hot flashes may last for a few seconds or for several minutes; they may occur singly or in groups; only a few may occur per day or they may occur frequently; they may happen at any time of the day or night; and they may persist for several years. Generally, however, both the length and the number of hot flashes decrease gradually until they disappear eventually for most women.

Other symptoms of menopause may include:

• Decreased interest in sexual intercourse
• Difficulty in concentrating
• Dry, thin, easily bruised skin
• Inability to control urine
• Insomnia
• Mood changes (such as anxiety, depression, and/or irritability)
• Night sweats
• Spotting (small amounts of blood from the vagina) and/or abnormal vaginal bleeding
• Thinning or lost hair
• Vaginal dryness
• Urinary Tract Infections
• Vaginal infections
• Waking up earlier than usual

How is it treated?

For nearly 50 years, the standard treatment for menopausal symptoms has been replacing one or both of the major female hormones, estrogen and progesterone. Hormone replacement therapy, often abbreviated as "HRT", restores both estrogen and progesterone. Since estrogen alone may increase the risk of uterine cancer, HRT is frequently prescribed for menopausal women who have not had surgery to remove the uterus. Progesterone decreases the risk of endometrial cancer and so, is said to ?oppose? the uterine cancer-promoting side effects of the estrogen. Progesterone also regulates fluid balance, restores libido, and helps to build bone. Replacement of estrogen alone (estrogen replacement therapy or ERT) is often used for women who have had a hysterectomy (surgical removal of the uterus) since they no longer have a risk for uterine cancer.

It is important to realize that there are different types of estrogen, each playing a different role in the body. Estradiol is the principal estrogen found in a women's body and helps to relieve menopausal symptoms. It is protective against heart disease, osteoporosis (by slowing bone loss), and Alzheimer?s disease. It also improves mood by increasing serotonin and endorphin levels. Supplementation reduces LDL (bad cholesterol) and reduces instances of insulin resistance. Estriol is the estrogen that increases tremendously during pregnancy and is essential for successful gestation. It is useful in protecting the urogenital region and promoting its health. Estrone is the weakest of the three estrogens and estradiol 17-B has benefits of protecting against osteoporosis by opposing the breakdown of bone. It (antagonizes osteoclasts) (JAMA. 2003;290:1042-1048), improves vasomotor symptoms, reduces LDL, protects against atherosclerosis (Ann Intern Med. 2001;135:939-953), and reduces incidence of insulin resistance / DM Type 2 (Diabetes Care. 2003;27:645-649). Estriol is protective estrogen with weak estrogenic properties that binds to receptor sites in breast to prevent estradiol binding.

In addition, either HRT or ERT may decrease the risk of colorectal cancer.

Taking HRT or ERT may not be a good decision for some women, however. Other types of treatment may be more appropriate for women who:

• Have or have had breast cancer
• Have mothers or sisters who have or have had breast cancer or ovarian cancer
• Experience abnormal bleeding from the uterus
• Receive active treatment for blood clots in the legs

Bioidentical hormones may be an option for women who are at risk for certain types of cancer and/or have failed treatment with prescription estrogens and progesterone. The terms "natural" or "bioidentical" hormone therapy are used to describe hormone treatment with individually compounded recipes of certain hormones in various dosage forms. Based on the results of a person's salivary or blood hormone levels, the final composition of the compounded dosage form is individualized to that specific person. It is important to consider that saliva testing has not been proven accurate or reliable, and blood testing only provides hormone levels present in the blood at the time of testing. This may be a problem because blood hormone levels can vary throughout the day. Also, the desired levels of these hormones in the blood and saliva are unknown.

Proponents claim that NHT is better tolerated than manufactured products. Most manufactured oral hormone products require metabolism by the body to be broken down into a form that the body can use. Metabolites are left behind that your body does not use and are the likely culprits of causing side effects. Bioidentical hormones are chemically identical to the hormones which your body produces and do not require metabolism. However, there is no approved preparation method for these compounded products, and methods will differ from one pharmacist or pharmacy to another. This can result in patients receiving inconsistent amounts of medication. Currently this treatment option is not recommended over FDA-approved prescription products.

For more information on some commonly asked questions regarding treatment options for menopause, click on the links below:

Are herbal or natural products safe and effective for managing menopause?

Due to negative results from large studies of ERT and HRT, more women may be turning to herbal or natural products ? such as black cohosh, dong quai, soy isoflavones, and wild yam ? to control symptoms of menopause. However, the effectiveness and safety of these alternative products may vary. For short-term use, the American College of Obstetricians and Gynecologists (ACOG) states that hot flashes may be reduced somewhat by soy isoflavones (for up to 2 years) or black cohosh (for up to 6 months). However, the ACOG also cautions women that the manufacture of most natural products is not regulated by the U. S. Food and Drug Administration (FDA). Thus, consumers cannot be assured of the actual content or quality of natural products.

Additionally, many natural therapies contain chemicals that may act like estrogen in the body, possibly making them inappropriate for women with estrogen-dependent conditions such as endometriosis and some types of breast cancer. Some natural products may interact with other drugs or cause estrogen-like side effects that may be worse than menopausal symptoms for some women. Women who consider taking natural products should discuss the use of those products with a doctor or pharmacist before starting to use them.

Should I take estrogen replacement therapy (ERT) or hormone replacement therapy (HRT)?

The decision to take ERT, HRT, or neither must be based on an individual's personal risk profile. Women without short-term symptoms of reduced estrogen levels and women whose symptoms are mild may decide not to use prescription drug therapy. Mild symptoms may respond well to lifestyle modifications such as avoiding caffeine and spicy foods. Some women find relief with alternative therapies such as acupuncture.

Estrogen Replacement Therapy (ERT)

ERT is commonly used to decrease short-term discomfort from menopause-related symptoms, such as hot flashes, insomnia, and mood swings. Estrogen also plays a significant role in preventing osteoporosis by building and maintaining bone. ERT can prevent the decline of bone density and may reduce the incidence of fractures. While calcium, vitamin D, diet and exercise are important first steps for maintaining healthy bone, the loss of estrogen after menopause speeds up the rate of bone loss for all women.

Some women should not take estrogen. Women who have not had a hysterectomy (the surgical removal of the uterus) are considered to have an ?intact? uterus. When estrogen is taken alone, the risk of uterine cancer increases for a woman with an intact uterus; therefore taking estrogen alone is not advisable for those women. The risk increases with long-term use (5 years or longer). Others who should avoid ERT are women who have or ever have had:

• Abnormal vaginal bleeding
• Blood clots or clotting disorders
• Breast cancer
• High triglyceride levels
• Liver disease

Potential side effects of ERT include:

• Bloating
• Breast tenderness
• Headaches
• Nausea
• Vaginal bleeding

Some of estrogen?s side effects may be eliminated by reducing the dose or changing the way the estrogen is delivered to the body. Lower-dose oral estrogen products that have become available in the last 20 years are often an option for women who experience side effects with higher estrogen doses. Lower-dose estrogens have been shown to reduce menopausal symptoms and reduce bone loss about as well as higher doses.

Although estrogen traditionally has been given as oral tablets, alternative dosage forms, including gels, lotions, and patches that are applied to the skin, have been developed. Vaginal rings containing hormones have also become available in the last few years. While some women find these topically-applied or vaginally-inserted forms easier to use, estrogen side effects may still be associated with all of them. The side effects may be lessened, however, because not as much estrogen may enter the blood. Irritation on the skin where gels, lotions, or patches have been applied is common. Some women experience abdominal pain or vaginal irritation from using the estrogen ring.

Hormone Replacement Therapy (HRT)

HRT usually refers to a combination of estrogen and progesterone. Taking progesterone in combination with estrogen not only adds to the control of menopausal symptoms, it also offsets or ?opposes? the possibility that estrogen will increase the risk of uterine cancer for women who have not had a hysterectomy (surgical removal of the uterus).

Benefits

Either ERT or HRT decreases:

• Bone loss
• Colon cancer risk
• Hot flashes
• Pain associated with intercourse
• Vaginal dryness and thinning of the vaginal walls

Either ERT or HRT may possibly:

• Decrease the risk of fractures
• Decrease urinary incontinence (the inability to control urine flow)
• Improve skin texture, collagen content, and skin thickness
• Improve mood
• Relieve insomnia and other sleep disturbances

Risks

Both ERT and HRT should be avoided by women who have or ever have had:

• Blood clots or clotting disorders
• Breast cancer
• Gall stones or gallbladder disease
• Liver disease
• Other estrogen-dependent cancer (such as endometrial or ovarian cancer)

HRT may increase the risk of:

• Breast tenderness
• Mood changes

Either ERT or HRT may increase the risk of:

• Breast cancer (slightly) - especially when taken for 5 years or longer
• Gallbladder disease
• Heart attacks for women who already have heart disease
• Vaginal bleeding

Talking with your healthcare provider

Women should be involved in their own healthcare in all stages of life, including peri- and postmenopause. Perimenopausal women should talk with their doctors about postmenopausal hormone replacement therapy and possible alternatives. Although each woman will have individual concerns, examples of general questions that may be asked include:

• Should I take estrogen and/or progesterone?
• What is the best dose for me?
• Do I need to take ERT or HRT for the rest of my life?
• Am I at risk for osteoporosis?
• What other therapies are available for me?

For further information:

Several organizations have developed informational materials or web sites on the management of menopause. Below are a few links to web sites that have additional information.

MedLine Plus

http://www.nlm.nih.gov/medlineplus/menopause.html

National Institute on Aging

http://www.niapublications.org/engagepages/menopause.asp

North American Menopause Society

http://www.menopause.org

Planned Parenthood

http://www.plannedparenthood.org/WOMENSHEALTH/menopause.htm

Helping Yourself

Replacing female hormones is not the only treatment for the symptoms of menopause. Throughout life, women can prepare for menopause by exercising, maintaining good general health, and getting adequate amounts of calcium and vitamin D to build strong bones. Peri- and postmenopausal women can make changes in their daily habits or use non-prescription products that may help to relieve many common symptoms. For example:

Hot Flashes

Hot flashes occur commonly during the perimenopausal and early postmenopausal years. For some women, hot flashes are simply a nuisance. Other women experience hot flashes that are intense enough to interfere with work, social activities, and/or sleep. Some non-hormonal ways to relieve hot flashes include the following:

• Avoid highly-seasoned and spicy foods
• Avoid hot places as much as possible
• Drink plenty of water or cool, noncaffeinated beverages
• Limit the intake of alcohol, caffeine (coffee, tea, cola), and chocolate
• Try to determine what triggers hot flashes, and then avoid these triggers
• Wear layers of cotton or other lightweight clothing that can be removed as needed

While early results for non-prescription menopause treatments appear promising, they have not yet been proved more effective than placebos (sugar pills). However, many women have found relief by taking:

• Foods rich in isoflavones (such as soy-based foods)
• Vitamin E (no more than 400 units per day)
• Vitamin B (up to 50 mg per day)

Vaginal Dryness/Pain with Intercourse

The loss of estrogen associated with menopause may cause the lining of the vagina to become thin and dry. As a result, having sex may become painful. Vaginal infections may also be more likely to occur. Some non-hormonal suggestions for relieving vaginal dryness include the following:

• Drink plenty of water to help vaginal tissues stay moist
• Have regular sexual intercourse, which can maintain vaginal flexibility
• Use a vaginal moisturizer or a vaginal lubricant to make having sex more comfortable

Note: Hand creams, petroleum jelly, and baby oil are not good vaginal lubricants, though, because scented or oil-based products are more likely to irritate vaginal tissue. They may also interfere with the effectiveness of condoms.

Urinary Incontinence

After menopause, accidental leakage of urine is fairly common ? especially during exercise. Coughing, laughing, or sneezing may also cause urine leaks for some women. However, urinary incontinence after menopause may be temporary and it may be treatable. Non-hormonal prescription drugs (such as oxybutinin) are available to help control it. In addition, the following actions may also help lessen urinary incontinence:

• Limit salt and caffeine intake
• Perform kegel (KEE-gul) exercises several times throughout the day. Kegel exercise involves tightening the muscles used to stop urination. Recommendations are to tighten muscles for 10 seconds then relax them. The sequence should be repeated several times a day for a total of 50 to 100 repetitions. For more detailed information on Kegel exercises, see: http://www.nlm.nih.gov/medlineplus/ency/article/003975.htm

What is on the horizon?

Recently, two large, long-term studies and several smaller ones concentrated on defining the risks and benefits associated with ERT and HRT. In 1998, results form the Heart and Estrogen-Progestin Replacement Study (HERS) found no heart disease prevention benefit from HRT. Those findings were confirmed in a follow-up study (HERS II) that concluded in 2002. The good news, however, is this study showed that after an initial treatment period of 2 years with hormones, the risk of blood clots declined to a non-significant difference. Therefore, long-term there seems to be no increased risk of blood clots. The HERS II study also demonstrated that there were no differences between the hormone group and the placebo (inactive pill) group in the incidence of any types of cancer.

An even larger study, the Women's Health Initiative (WHI) sponsored by the National Heart, Lung and Blood Institute of the U.S. National Institutes of Health also examined the use of both ERT and HRT by thousands of women. The part of WHI that concerned HRT began in 1993 and ended in 2002 ? well before the planned end date. It was stopped when higher rates of breast cancer, heart disease, stroke, and blood clots in the lungs were found in women who were taking HRT than in women taking a placebo.

The estrogen-only part of the WHI, scheduled to end in 2005, was also stopped early (in February 2004) after results showed that estrogen apparently increased the risk of both stroke and dementia (decreased mental functioning). Benefits from treatment in this study included a reduction in fractures, conferring protection from osteoporosis. Neither part of WHI found any benefit for ERT or HRT in preventing heart disease.

The Women's International Study of Long Duration Oestrogen After Menopause (WISDOM) was a study performed in the United Kingdom, Australia, and New Zealand that was designed similar to the Women?s Health Initiative study. The trial was stopped early following the publication of results from the Women's Health Initiative study. Reports of results from the portion of the WISDOM study that was completed were consistent with those from the Women?s Health Initiative. Older women beginning HRT many years after the start of menopause were at greater risk for cardiovascular events and blood clots. The investigators suggested that research is needed to assess the long term risks and benefits of starting HRT in younger women, who may have different effects than older women starting HRT.

To investigate this issue, a substudy of the estrogen-only part of the Women?s Health Initiative was recently undertaken. The results of this substudy demonstrated that younger postmenopausal women who had had a hysterectomy and who took ERT had significantly less buildup of calcium plaque in their arteries compared to those who did not take hormone therapy. This is good news for younger women who have had a hysterectomy and want to use short-term estrogen therapy to relieve the symptoms of menopause. However, more studies in this age group are needed, and it should be noted that these findings do not alter the previous recommendation that hormone therapy should not be used to prevent heart disease.

In other research:

The National Center for Complimentary and Alternative Medicine (NCCAM), a division of the U.S. National Institutes of Health, is currently conducting several clinical trials investigating the effectiveness and safety of natural menopause treatments. Black cohosh, soy and other isoflavones, and red clover are the primary agents being studied. However, clinical studies to date have failed to demonstrate positive results with these natural products.

Some evidence suggests that antidepressant drugs may help to control hot flashes. In small studies involving women with hot flashes, drugs known as selective-serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, and paroxetine, relieved hot flashes up to twice as well as placebo. Another type of antidepressant, venlafaxine, has also shown effectiveness. Possible side effects from antidepressants include constipation or diarrhea, dry mouth, insomnia, nausea, and sexual dysfunction. In addition, antidepressant drugs may interfere with the effectiveness of tamoxifen, a drug used to treat breast cancer.

Gabapentin, a drug used to control epileptic seizures and some types of pain, has also shown some promise for controlling hot flashes. A recent study has demonstrated that gabapentin appears to be as effective as estrogen in treating menopausal hot flashes. The exact mechanism of action in menopause is not completely understood, but it may help to normalize the body?s temperature. In clinical and case studies of its use, women taking gabapentin reported reductions in other menopausal symptoms, such as mood changes and muscle aches, as well. Side effects ? mainly dizziness, tiredness, and swelling in the hands or feet ? were generally mild and appeared to be similar to those experienced by women taking estrogen only. Usually, side effects lessened after a few days of therapy. Gabapentin does not interfere with tamoxifen therapy for women who have breast cancer.

Also under study is the drug clonidine, which is commonly used to treat high blood pressure. Like gabapentin, clonidine can be used at the same time that tamoxifen is being taken. In case reports, clonidine relieved the length, number, and severity of hot flashes, at least mildly, for many women who were taking it. However the effects of clonidine on hot flashes wore off more quickly than anti-depressants or gabapentin. In addition to oral tablets, clonidine is available as a transdermal patch, which may be easier for some women to use. However, women taking clonidine experienced more problems with sleeping than women who were taking a placebo.

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Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. Journal of the American Medical Association. 2003;289(21):2827-2834.

The North American Menopause Society. Understanding the Controversy: Hormone Testing and Bioidentical Hormones. Proceedings from the Postgraduate Course presented prior to the 17th Annual Meeting of The North American Menopause Society October 11, 2006. Available online at: http://www.menopause.org/edumaterials/PG06monogrpah.pdf. Accessed August 20, 2007.

U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Annals of Intern Medicine; 137(10): 834-839.

WHI study finds no heart disease benefit, increased stroke risk with estrogen alone [Press release]. National Institutes of Health. U.S. Department of Health and Human Services. April 30, 2004. Available at: http://www.nhlbi.nih.gov/new/press/04-04-13.htm. Accessed December 3, 2004.

Writing group for the PEPI trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1995;273:199-208.

The American Heart Association. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501. Epub 2007 Feb 19. Available at: http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.181546. Accessed August 20, 2007.

Association of Women for the Advancement of Research and Education. Project AWARE: A website by women, for women... offering objective and comprehensive health information, especially related to menopause, perimenopause, and postmenopause. Available at: http://www.project-aware.org/index.shtml Accessed August 20, 2007

Vickers MR, MacLennan AH, Lawton B, et al. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ. 2007 Aug 4;335(7613):239. Epub 2007 Jul 11

WHI Study of Younger Postmenopausal Women Links Estrogen Therapy to Less Plaque in Arteries [press release]. National Institutes of Health. U.S. Department of Health and Human Services. June 20, 2007. Available at: http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=288 Accessed: August 20, 2007.

Menopause Health Condition Last Updated: August 2007

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.

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