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Menopause: Hormones and Other Therapies

Sorting Out The Options

Date: 04/23/2000

What is menopause?

• Menopause is the time in a woman's life when menstruation stops. Menopause is usually a gradual process. The ovaries begin to produce lower amounts of hormones. The reduced amounts of hormones cause menstrual periods to become irregular and eventually to stop completely. This process of irregular menses and fluctuating hormone levels can take several months to 5 years and is often called "perimenopause" or "transition."
• Most women go through menopause between ages 45 and 60. In the U.S. the average age for menstrual periods to stop completely is 51. There may be a genetic link for the age of onset. Smoking lowers the age at which menopause begins.
• Menopause can also occur when the ovaries are surgically removed.
• The hormonal changes often cause other symptoms.

What are the symptoms?

• You may have both physical and psychological symptoms during menopause. Symptoms may occur for a few weeks, a few months, or sometimes over several years. Your symptoms may come and go, or they may occur regularly.
• These physical symptoms are common during menopause:
• Irregular menstrual periods
• Hot flashes- flushing of face and upper trunk; may occur with heart palpitations, dizziness, headaches
• Night sweats
• Disturbed sleep patterns- depression and irritability may result from insomnia
• Vaginal dryness and shrinkage of genital tissues, sometimes resulting in discomfort or pain or bleeding during sexual intercourse, itching
• Dry skin- facial hair growth and wrinkles
• Cold hands and feet
• More frequent urination, burning, or leakage of urine (urinary incontinence)
• More frequent minor vaginal and urinary infections.
• Menopause usually occurs at a time in life when other dramatic changes take place. Some of these changes may include loss of parents, adjustment to children growing up and leaving home, becoming a grandparent, retirement, or career changes. These changes, in addition to the changes in your body, may result in psychological or emotional stress. Psychological symptoms of menopause may include:
• Anxiety
• Depression
• Tearfulness, irritability
• Sleeplessness
• Less desire for sex
• Lack of concentration
• More trouble remembering things.
• Medical conditions that can results from menopause include
• Osteoporosis-bone breaks become more likely
• Coronary heart disease (CHD)-twice as many women die from CHD than cancer

How is it diagnosed and what tests can be ordered?

• Menopause can often be diagnosed through your medical history.
• A pelvic exam and Pap smear may show effects of decreased estrogen.
• Traditional blood tests to confirm menopause is an elevated LH or FSH.
• A few, but growing number of physicians, may order estrogen, progesterone, testosterone and DHEA levels in order to best individualize a women's hormone replacement therapy. This can be done by blood or saliva measurements. Some feel that saliva measurements better reflect tissue levels of hormones. Saliva hormone tests are very new and therefore not covered by some insurances.
• Furthermore, there is now available urine estrogen metabolite testing that can assess estrogen metabolite patterns that may put a woman at higher risk for breast cancer.
• There are advantages and disadvantages to each of these methods that can be discussed in more detail by your health care provider.

How is it treated?

• Menopause is a natural part of a woman's life cycle. It is not a disease and does not necessarily require any treatment. However, certain health problems, such as osteoporosis and increased heart disease, are associated with low estrogen. To help prevent such problems, many women choose to take estrogen to replace what their body is no longer producing. This treatment is called estrogen replacement therapy (ERT), or hormone replacement therapy (HRT).
• You and your health care provider should discuss the pros and cons of hormone replacement therapy for you. Factors such as your age, race, family history, and health history will be considered in the discussion. Hormone replacement therapy is effective for treatment for preventing and treating osteoporosis (loss of bone density). ERT also has heart protective effects and possibly brain protective effects. The benefits and risks (pros and cons) of HRT are discussed in detail later in this monograph.
• However, it is not the right treatment for every woman. Women who have had some types of breast cancer or other cancer, blood clots, or certain liver disease should not take estrogen.
• There are additional non-hormonal drug and non-drug therapies that can address the issues of menopause and will be discussed after hormone therapy is reviewed in detail.
• Before you read any further, it is important to emphasize the following aspects concerning hormone treatment for menopause. In our opinion, a women has the following options:
• Standard prescription estrogens and progesterones, which are commonly prescribed by the majority of physicians. This includes both synthetic hormones and bio-identical hormones, which are the exact same molecular structure as a woman's own natural hormones.
• Compounded "natural" estrogens and progesterone made from yam and soy. These are "bio-identical" hormones and usually must be obtained from a special "compounding pharmacy." However, "progesterone creams" are included here and are available at many health food stores.
• Herbal (Phyto) hormones: Cohosh, Red Clover, Soy and others. These natural items contain natural compounds that act like hormones but do not contain the actual hormones.
• No hormone treatment at all

Each of these hormone options has their own pluses and minuses, risks and benefits. The details of such discussion will be the topic of the rest of this monograph.

What Are Natural Estrogens and Progesterone?
Estrogen is actually a group of some 20 related compounds in the body the chief of which are: estrone (E1), estradiol (E2) and estriol (E3). Estrogens have an effect on about 300 different tissues throughout a woman 's body--not only those involved in the reproductive process, such as the uterus, breasts, and external genitalia--but also tissues in the central nervous system (including the brain), the bones, the liver, and the urinary tract. Estrogens determine the characteristic female distribution of body fat on the hips and thighs, which develops during adolescence.

The high estrogen levels that occur during the reproductive years derive from the ovaries, which produce two major female hormones, estrogen and progesterone. The most potent form of estrogen is estradiol. The other important--but less powerful--estrogens are estrone and estriol. Although the ovaries produce most of the estrogens in the body, other tissues, such as body fat, skin, and muscle, can also form them. After menopause, some amounts of estrogen continue to be manufactured in body fat. Even when the ovaries have stopped producing estrogens, they continue to produce small amounts of the male hormone testosterone, which converts into estradiol. In addition, the adrenal gland continues to produce androstenedione, which is converted to estrone, some of which is then converted to estradiol. The total estrogen produced after menopause, however, is far less than that produced during a woman's reproductive years. A woman also naturally produces small amounts of testosterone and DHEA ("male hormones") from her adrenal gland.

What Is Hormone Replacement Therapy (HRT)?
Women currently can expect to live thirty or forty years of their life in the postmenopausal state. The lower amount of estrogen during these decades puts them at greater risk for cardiovascular disease, osteoporosis, and possibly even Alzheimer 's disease (it's still in dispute whether estrogen protects against Alzheimer's). Hormone replacement therapy is proving to reduce many of these risks, but obtaining specific health benefits depends on the selection of the appropriate hormone therapy.

• Estrogen replacement therapy (ERT) uses estrogen alone, called unopposed estrogen, to combat diseases related to estrogen loss, particularly heart disease and osteoporosis. Unfortunately, ERT significantly increases the risk for endometrial (uterine) cancer. Women who have had hysterectomies are generally good candidates, then, because their uteruses have been removed. (Although not yet scientifically accepted, we feel that the addition of natural progesterone is still a good idea even for women without a uterus). This will be discussed in more detail later on.
• Hormone replacement therapy (HRT) combines estrogen with natural progesterone or its synthetic version, called progestin, which offsets the risk for uterine cancer. The HRT combination appears to offer benefits similar to those of ERT and is now the usual choice for many postmenopausal women who are at risk for osteoporosis or heart disease. Adding a synthetic progestin to estrogen may offset some of the heart benefits of unopposed estrogen and may also increase the risk of breast cancer above the risk of estrogen use alone.
• There are a number of other considerations, however, as well as alternatives to HRT that women should discuss with their physician.

Timing
For women who choose hormone replacement therapy, the next question is when to start it.

• Some experts believe that HRT should begin as soon as possible after menopause to achieve maximum benefits for the heart and bones and possibly the brain.
• Because of possible increased risks for breast cancer with long time use, some physicians suggest that therapy should continue for about ten years or until a woman reaches her mid-sixties and then stop. The problem with this approach is that the protective value of HRT declines and ceases five years after stopping.
• Some experts, then, advise waiting 10 years after menopause before taking hormone therapy and then staying on HRT to life. They argue that HRT still protects against osteoporosis and heart disease--even after age 60--but the odds of a woman then developing HRT-related cancers before the end of her life are very low.

It is a difficult issue, and women should discuss the problem with their physician, in the context of their particular risks and needs.

Forms of Hormone Medications
Hormone replacement therapies are available in many natural and synthetic forms. Estrogens can be given alone (unopposed estrogen) or in combination with progesterone/progestins (combined hormone therapy). Each regimen and form of administration has specific benefits and risks. No one method can prevent all the diseases associated with loss of estrogen and aging. If a woman chooses to begin estrogen (ERT) or hormone replacement therapy (HRT), she must then pick the types of hormones to use based upon the known and theoretic benefits and risks of each type. Let's start with types of estrogens, and then we will discuss types of progesterone and other hormones (DHEA and Testosterone).

Estrogens
Taking estrogen alone (ERT), called unopposed estrogen, rather than in combination with progesterone or a progestin, is the most proven protective medication against heart disease in women. However, without progesterone to balance the hormonal cycle, estrogen over stimulates the tissue lining the uterus (the endometrium) and causes uncontrolled growth, a condition known as hyperplasia. Hyperplasia, if abnormal and untreated, may develop into uterine (endometrial) cancer. In general, only women who have had their uteruses removed should take unopposed estrogen. Any woman with an intact uterus who is taking estrogen therapy alone (no progesterone) should have annual endometrial biopsies (tissue samples of her uterus) and report any vaginal bleeding immediately.

Standard Estrogen drug formulations:

• Conjugated estrogen is marketed as Premarin, which contains a mixture of estrogens derived from the urine of pregnant horses. It is the most commonly prescribed drug for estrogen therapy.
• Plant-derived conjugated estrogens, called esterified estrogen, are usually made from modified soy (Estratab, Menest). These regimens may increase bone density with fewer side effects than conjugated equine estrogen, although whether they reduce fractures is not yet known. These formulations are made up of a mixture of several estrogens, the chief of which is usually estrone (E1).
• Estradiol (E2), the most potent estrogen, is available as tablets (Estrace), in skin patch form (Estraderm, Alora, Climara, Vivelle, FemPatch, Evorel), as a vaginal ring (Estring), through injections, and as pellets inserted under the skin twice a year. This formulation is equivalent (bio-identical) to the estradiol naturally found in a woman's body.
• Estropipate (Ogen, Ortho-Est) is a version of estrone, a weaker form of estrogen. A vaginal tablet (Vagifem) has also been developed. Very small (nickel-sized), water-resistant patches are also available.
• Synthetic estrogens, which are more potent than natural estrogens, are generally used for oral contraceptives (OCs) and not for replacement therapy after menopause. However, during the months before the last period (perimenopause) when periods are infrequent but contraception is still needed, low-dose forms of OCs may reduce the risk for bone loss and alleviate early menopausal symptoms, such as hot flashes.
• Using patches, vaginal devices, or gels to deliver hormones may avoid problems, such as gallstones and blood clots, which can occur with the use of oral (pill) estrogens.

Compounded Bio-identical Estrogen formulations. These are made by specially licensed compounding pharmacies with a prescription from your doctor. They are made (derived) from either soy or wild yam and are 100% equivalent to the estrogens in your body. The term used to describe these compounded forms of estrogen is called "bio-identical" because they are totally equivalent to your own estrogens. It should be noted that the standard prescription estradiol formulations listed above are also considered a bio-equivalent estrogen. These compounded hormones were popularized and developed by Jonathan Wright, M.D., who in the 1980's, performed urinary estrogen levels with a variety of compounded preparations and found that a formulation of "tri-estrogen" was tolerated the best and gave the most "optimal urinary estrogen levels." More recent investigation on estrone metabolites and the risk of breast cancer has now lead to the concept that "bi-estrogen" may be the preferred form. These compounded hormones are frequently but not always covered by insurance plans and tend to be more expensive than the standard estrogens listed above.

These formulations emphasize estriol (E3) as the natural estrogen of choice. Estriol is frequently referred to as the "forgotten" estrogen (Follingstad, JAMA, 1978). There is limited and small research that suggests estriol is the "safest" of the estrogens in terms of breast cancer risk, but this has yet to be conclusively proven. Estriol may be as beneficial to the heart but it has not been well studied in heart disease. Like other estrogens, estriol given to a woman with a uterus and without additional progesterone (unopposed) can cause hyperplasia and even uterine cancer (Weiderpass, Lancet, 1999). Because estriol is relatively weak, high doses of estriol are usually needed when prescribed by itself to control menopausal symptoms.

In our opinion, and until further studies are performed, we believe that estriol is a "safer" estrogen option. However, it is unclear if it has the same good benefits to the bones and heart as the standard estrogen preparations listed above. Clearly, estriol needs much further scientific study in order to give good answers on its theoretic status as the "safest" estrogen and its effects on a woman's bone and heart. At this time, most physicians would state that the scientific data on estriol is too small to make a recommendation for a woman to use this form of estrogen for estrogen replacement therapy.

Compounded bio-identical estrogens can be given orally by mouth or a cream rubbed on the skin. They can also be mixed with natural micronized progesterone (see below). They are usually prescribed in one of several formulations:

• Tri-estrogen: contains 10% estrone (E1), 10% estradiol (E2) and 80% estriol (E3). According to Dr. Wright, 2.5 mg of tri-estrogen is roughly equivalent to 0.625 mg of conjugated estrogen (Premarin).
• Bi-estrogen: contains 10-20% estradiol (E2) and 80-90% estriol (E3) but no estrone (E1)
• Estriol- alone without any estradiol or estrone. A 2 mg dose of estriol is roughly equivalent to 0.6 mg of conjugated estrogen

Progesterone
Progesterone is referred to by one of several names:

• Progesterone is actually the name for the natural hormone and
• Progestin is usually used to refer to synthetic derivative of progesterone.

Progesterone/progestins may sometimes be prescribed alone for hot flashes and other acute menopausal symptoms. However, they are usually used with estrogen to protect against the uterine cancer side effect of estrogen used alone. Progesterone/progestins come in several formulations:

• Progestins include medroxyprogesterone (Provera, Amen, Curretab, Cycrin, Depo-Provera), norethindrone acetate (Aygestin, Norlutate, Activelle) synthesized from male hormones, and norgestrel.
• A natural form of finely ground progesterone made from wild yams, known as micronized progesterone (Prometrium), has been recently approved by the FDA and has been found to be significantly protective against heart disease when used in combination with estrogen. Prometrium comes in a gel capsule with peanut oil and those with peanut allergy or sensitivity should not take this product. It only comes in certain doses making it less flexible for individualized dosing.
• A natural progesterone gel, Crinone, which is administered vaginally, may prove to be very effective in combination with an estrogen of choice; it blocks the processes that can lead to uterine cancer and has very few side effects. Compliance appears to be excellent.
• Micronized Progesterone may also be made by a compounding pharmacy in any individual dose recommended by your physician. It can come in a capsule, which contains any oil of choice (usually olive or sesame is used) to increase absorption. At times, this may be a more affordable option to Prometrium or Crinone.
• Over The Counter Progesterone Creams- There are variety of progesterone creams sold at many health food stores, pharmacies and mail order companies. Unfortunately, there are no standardized dosages of these creams and some contain over 400 mg per ounce whereas others contain less the 2 mg per ounce (Aeron Life Cycle Labs, 1996).

Natural progesterone has some known and additional theoretical advantages over synthetic progestins that require some discussion. Natural progesterone does not have as many side effects as progestins do and is therefore tolerated much better. One survey of 176 women revealed that 34% were more satisfied with natural progesterone over synthetic progestin, 50% reported better improvement of hot flashes, 42% reported better improvement of depression and 47% reported better improvement in anxiety (Fitzpatrick, May Clinic Women's Healthsource, Aug 1999). Natural progesterone may have breast cancer inhibitory effects. Breast cancer cells grown in a petri dish culture were inhibited by natural progesterone (Formby, Annal Clin Labor Sci, 1998). One epidemiological study found that women with low progesterone levels were at higher risk for developing breast and other cancers (Cowan, Am J Epidem, 1981). Natural progesterone cream applied to the breasts was found to decrease the estrogen stimulating effect on breast cells (Chang, Fertil Steril, 1995). Women who had breast cancer surgery at the time of her cycle when progesterone was at its highest had better prognosis and longer survival than those who had the same surgery at a time when the progesterone was at its lowest (Mohr, Br J Can, 1996 and Hrushesky, Lancet, 1989). Animal studies have revealed bone-building properties to natural progesterone (Prior, Endocrin Rev, 1990). John Lee, MD, reported increased bone density using natural progesterone cream (Lee, Int J Clin Nutr Rev, 1990). However, other human studies have failed to confirm his observation (PEPI Trial, JAMA, 1995 and Leonetti, Obstet Gynec, 1999). There is currently underway a FDA approved long-term trial to see if topical progesterone cream can indeed improve osteoporosis. Natural progesterone may have advantages concerning the heart compared to synthetic progesterones. This will be reviewed in more detail later. Natural progesterone may facilitate thyroid function, normalize blood sugar levels in hypoglycemia and normalizes zinc/copper levels. These preliminary encouraging beneficial effects of natural progesterone have not yet been confirmed with large randomized human trials. The body metabolizes natural progesterone more rapidly than synthetic progestins, thus requiring more frequent dosing. Increasing the dose can sometimes cause drowsiness.

Combined Hormone Replacement Therapy (HRT)
To avoid the risk of uterine (endometrial) cancer, physicians generally prescribe estrogen along with a progestin or progesterone, known as combined hormone replacement therapy.

• Cyclic HRT: this combination regimen mimics the natural menstrual cycle. Estrogen is taken for the first 25 days of the month, and progesterone/progestin is added for days 13 (actually anywhere from day 10-16) through day 25. No hormones are taken for the next five or six days. Since the body 's premenopausal hormone balance is being mimicked, mild vaginal bleeding will usually occur at the end of the cycle. Such bleeding does not indicate any significant health problem, nor does it indicate a return of fertility, but some women find it unpleasant.
• Continuous HRT: Reduces end-of-cycle bleeding significantly by using both estrogen and progesterone/progestin together on a daily basis. If a synthetic progestin is used, this simultaneous approach may not be as heart protective and some studies indicate it still carries a risk for uterine cancer. Transdermal HRT (the patch form) may be as heart protective as this oral HRT regimen according to one study, but more research is needed. It appears that natural progesterone does not decrease the heart benefits of estrogens like the synthetic progestins do.
• Oral drug forms that combine both estrogen and progestins together are: Prempro, Premphase, and Ortho-Prefest (has a different synthetic progestin that appears to better tolerated than the usual provera).
• Compounded bio-identical estrogens (triestrogen, biestrogen or estriol) can be combined with micronized progesterone with an individual dose the best meets the needs of the individual women. These formulations require a prescription from your physician and must be filled at a specialized "compounding" pharmacy.

Selective Estrogen-Receptor Modulators: SERMs
Selective estrogen-receptor modulators (SERMs), also called "designer estrogens", act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. These drugs are designed to produce the benefits of estrogen without increasing hormone-related cancers.

• Tamoxifen is the best-known SERM, and a recent study indicated that even in low-doses it might reduce the risk for fractures. The drug is also being studied for protection against breast cancer. Unlike estrogen, tamoxifen appears to offer little protection for the heart.
• Raloxifene (Evista) is actually the first SERM to be approved for preventing spinal fractures. This drug may also reduce the risk of cardiovascular disease, although it is not as protective for the heart as estrogen. It does not appear to increase the risk of uterine or breast cancer, but more research is needed.
• Both raloxifene and tamoxifen increase the risk for blood clots.
• Droloxifene and tiboline (Livial) are investigational SERMs that appear to protect against bone loss without increasing cancer risks. Tiboline also reduces menopausal symptoms and improves sexual function in postmenopausal women.

"Male" Hormones: Testosterone and DHEA
Testosterone and DHEA are often considered "male hormones" but women have them too, just in much smaller amounts. Some women may benefit from adding low doses of these hormones to their HRT program. This should be individualized to each woman and be performed only under medical supervision of your doctor.

• Testosterone
• Methyltestosterone is a synthetic testosterone and increases libido (sex drive) and may decrease osteoporosis of the spine. A bio-identical form of testosterone call oral micronized testosterone is also available from compounding pharmacies.
• Testosterone added to estrogen therapy appears to increase bone mass, improve sexual energy, offers heart protective benefits and improves mental alertness (Gelfand, Contemp OB/GYN, 2000).
• Possible side effects of testosterone include those of estrogen, as well as body hair growth, acne, fluid retention, anxiety, and depression.
• Dehydroepiandrosterone (DHEA)
• Is a weak male hormone secreted by the adrenal gland. It is available over the counter and through compounding pharmacies.
• Benefits: There are some claims that it increases bone density and increases the "sense of well being" (Labrie, J Clin Endocrinol Met, 1997). It appears helpful for depression and memory (Wolkowitz, Biol Psychiartry, 1997). One small study revealed reduction of triglyceride levels and improvement in insulin sensitivity (Casson, Fertil Steril, 1995). Its benefits on decreasing body fat and increasing muscle mass appears to occur only in men but not in women (Yen, Ann NY Acad Sci, 1995).
• Other Effects: DHEA may be converted in the body to estrogen and thus raise estrogen levels in the body just by taking DHEA. DHEA can also be converted to testosterone. This conversion process is different in every women- some make lots of estrogen or testosterone from DHEA and others make little to none.
• Down side: The hormone may, however, reduce HDL, beneficial cholesterol levels, and its effect on cancer-cell growth is unknown. Long-term safety studies have lasted only 1-2 years.
• Until more studies are done, our approach to DHEA use in menopause is to establish estrogen, DHEA and testosterone levels prior to its use and to carefully monitor levels while on therapy (either blood or saliva). We feel that achieving mid-normal blood levels of DHEA that occur in a woman in her age 20's-30's (serum levels of 200-250 ug/dl would be considered mid normal for this age group) is unlikely to cause any harm and may offer some of the benefits listed above. If side effects do occur, then simply stopping the DHEA results in them going away. In any case, DHEA is not regulated and brands vary widely in their content. No one should take DHEA without consulting a physician.

What Are The Benefits Of Hormone (Estrogen/Progesterone) Therapy?

Relief of Menopausal Symptoms
Hormone therapy can alleviate bothersome symptoms associated with menopause, particularly vaginal atrophy and dryness, hot flashes (and their associated sleeplessness), and increased urinary frequency and urgency. Oral medications and skin patches are equally effective in reducing these menopausal symptoms. Estrogen creams restore vaginal elasticity and lubrication and improve sexual pleasure. Estrogen vaginal creams are not effective against osteoporosis and heart disease. Estrogen does not prevent other problems associated with menopausal changes--such as thinning hair, increased weight, and changes in body fat distribution.
Effects on Heart Disease and Stroke
Most recent reports suggest that HRT (premarin + provera) increase the risk of both heart disease and stroke.

• In contrast to synthetic progestins, natural progesterone is heart protective and does not negative the good heart benefits of estrogen. One study found that the use of micronized progesterone with estrogen raised HDL levels almost as high as unopposed estrogen (PEPI Trial, JAMA, 1995). Natural progesterone protected monkeys from chemically induced heart artery spasm (the synthetic progestin monkey group had near fatal spasms) (Heresmeyer K, J Am Coll Card, 1997). Furthermore, women with known heart artery disease were given estrogen + a synthetic progestin or estrogen + natural progesterone and those in the latter group were found to be able to exercise longer than the former group (Am College of Cardiology Meeting, Feb 1999). It appears that based on these few studies, natural progesterone may be the preferred form of progesterone concerning the heart.
• On the downside, hormone replacement therapy increases triglyceride levels that may be a risk factor for heart disease in some women.
• Estriol was found to lower both cholesterol and triglyceride levels and increase good HDL levels in Japanese postmenopausal women (Nishibe, Nippon Ronen Igakkai Zasshi, 1996). There are no studies directly assessing whether estriol has heart protective effects.
• For women who are not good candidates for HRT or choose not to use it, there are other proven steps to take to reduce your risk for heart disease. These steps are often forgotten in the discussion concerning heart prevention and HRT.

Effects on Bones

• Osteoporosis is a disease of the skeleton in which the amount of calcium present in the bones slowly decreases until the bones become brittle and susceptible to fracture. It causes more than 1.5 million fractures in the U.S. each year. About 80% of the 24 million Americans who have osteoporosis are women, and almost 90% of them are over 75. After menopause, calcium depletion accelerates. As much as 6% of calcium is lost per year for as long as 10 years. Estrogen's most important effect appears to be prevention of bone break down. In older women, estrogen therapy prevents the loss in bone density, and major studies are now reporting that women who have received postmenopausal estrogen therapy, with or without progesterone, experience fewer hip fractures as well as fractures of all types than untreated women. Even low doses of estrogen may provide significant protection from bone loss. As with protection against heart disease, hormone therapy must be taken throughout life to sustain protection against hip fracture. Women who take estrogen therapy even for ten years after menopause and then stop begin to lose bone density.
• Calcium, magnesium, and vitamin D are important companions to estrogen therapy for prevention and treatment of osteoporosis. Women who use high-dose calcium (1,500 to 1,700 mg) lose bone more slowly than those who take no calcium, and a combination of calcium and estrogen is optimal for preserving and even increasing bone density.
• It is not known how much Estriol helps bones. Only studies that have shown a bone protective effect of estriol have come from three Japanese studies and the high amount of soy phytoestrogens in the Japanese diet may have something to do with this beneficial effect (Head, K, Alt Med Rev, 1998). One small Chinese study could not find a bone benefit (Yang, Chinese Med J 1995) nor could a study performed in Scotland (Lindsay R, Maturitas, 1979)
• Osteoporosis is discussed in much more detail in our separate handout on this subject.

Effects on Joints
Estrogen therapy may even be protective against osteoarthritis, also known as degenerative joint disease, which accounts for most of the hip and knee replacement operations in the elderly. As with osteoporosis, women who stop using estrogen therapy lose this protection over time.
Alzheimer's Disease and Effects on Mental Function
Estrogen may have properties that protect against the memory loss and lower mental functioning associated with normal aging including both Alzheimer's and dementia in Parkinson's disease. Some studies have reported that women taking hormone replacement therapy (in various combinations) score better on memory and learning than women not on HRT. However, other studies have found no association between estrogen levels and mental functioning. Until more conclusive research has been conducted, women should not choose hormone replacement therapy solely prevent Alzheimer's disease.
Effects on the Bladder

• Urinary Incontinence- The drop in postmenopausal estrogen levels may contribute to urinary loss (incontinence). Urge incontinence occurs when a person has an urge to urinate and cannot control that impulse. It affects 70% of incontinent people. Stress incontinence occurs when coughing or sneezing triggers urine leakage because of weak muscles in the pelvic region or loss of function in the urethra. Estrogen therapy helps restore the urethral lining in women with stress incontinence, and estrogen cream desensitizes the bladder, helping those with urge incontinence. Full benefit may take a year although improvement often begins in six weeks.
• Urinary Tract Infections- Some women are at increased risk for recurrent urinary tract infections after menopause. One study found that postmenopausal women who used an estrogen vaginal cream had a dramatically lower incidence of recurring infections than women not using the cream. Researchers suggest that estrogen may resist infection by increasing the number of lactobacilli, a microorganism that fights infection by preventing bacteria from adhering to vaginal cells. It is not clear whether taking oral estrogen has the same benefit. Some studies, in fact, reported a higher incidence of urinary tract infections in women taking oral estrogen.

Colon (Colorectal) Cancer
Studies continue to show that hormone replacement therapy, with or without progesterone, protects against colon cancer. Risk reduction for colon cancer is also associated, however, with a healthy lifestyle, and it is still not yet known whether estrogen protects against colon cancer or if women who take HRT tend to perform other healthy lifestyle behaviors that are colon cancer protective.
Teeth, Eyes, and Skin Problems
Estrogen therapy has been associated with reduced gum bleeding and with decreased bone loss around the teeth; 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. Studies are also indicating that estrogen helps prevent glaucoma and macular degeneration. Some evidence exists that estrogen therapy may help prevent slackness and dryness in the skin and even reduce wrinkles. Estrogen creams have proven to be beneficial in tests, reducing fine lines and increasing skin thickness. Estrogen may also have wound-healing properties that may prove to help women with varicose veins.
Diabetes
Studies indicate that HRT may help post-menopausal women with diabetes control their blood sugar levels more effectively. It may even help prevent diabetes type 2 after menopause. More research is needed in this area.

What Are The Negative Effects Of Hormone (Estrogen/Progestin) Therapy?
Taking hormone replacement therapy for five years or less is generally acknowledged to pose little or no danger. Studies are under way to conclusively define the risks that might occur in older women or those taking HRT for long periods and will be finished by 2005. Women who are overweight tend to have higher levels of estrogen, which may put them at higher risk for negative effects of HRT.
Distressing Side Effects

• Estrogen or hormone replacement therapy can cause a number of distressing side effects, including bloating, nausea, breast tenderness, vaginal bleeding, and fluid retention.
• Some women report weight gain with HRT, but studies have found no evidence to support these reports; in fact, one detected a trend toward less weight gain than in other postmenopausal women. (It should be noted that many women gain weight after menopause, with or without HRT.) That being said, we have observed roughly a 3-5 pound wt gain is some, but not all, women on HRT.
• Breast soreness usually subsides in three to four months and can be relieved with over-the-counter pain killers, decreasing caffeine intake and adding vitamin E.
• Vaginal bleeding is a primary reason why many women stop treatment. Some women suffer depression and mood swings, although it is not clear if negative emotions are side effects of the medications or provoked by other causes. Some studies, in fact, indicate that estrogen may improve depression. Side effects can often be reduced or relieved with lower dosages or a different type of regimen.

Endometrial Cancer
There is at least a five-fold increased risk of endometrial (uterine) cancer in those taking unopposed estrogen replacement therapy. Supporters of ERT argue that its protective value against heart disease--a far greater killer--outweighs the risk of endometrial cancer, which is rare. Nevertheless, combined hormone therapy eliminates the increased risk of endometrial cancer and is the preferred choice for women whose uteruses are still intact.
Breast Cancer

• Because breast tissue is highly sensitive to estrogens, the longer a women is exposed to estrogen over her lifetime, the higher the risk for breast cancer. Of major concern are studies that have indicated an increased risk for breast cancer in women taking hormone replacement therapy (HRT). Many of them indicate that any danger exists only with long-term therapy (greater than 10 years), although a major 1997 analysis of 51 studies reported that even one year of HRT could increase the chances of breast cancer and the risk increases by 2.3% for each additional year. Even in this study, however, the real danger for most women was still very low and it ceased five years after therapy was stopped. Even among women with a family history of breast cancer, this risk failed to offset the increased overall survival rates that they experienced after taking HRT. The Iowa Women's Health Study evaluated 37,000 women over from 1986 to 1996 and found that HRT was associated with an increased risk of breast cancer but that those who got breast cancer had a very good prognosis and survival (Gapstur, JAMA, 1999). Most recently, a 15 year study of 46,000 women found that women who took estrogen plus a synthetic progestin had a 40% higher risk of developing breast cancer than those who took no hormones and those who took estrogen alone had a 20% higher risk of developing breast cancer than those who took no hormones (JAMA, 2000). These findings were confirmed by another study revealing an increased risk of developing breast cancer when estrogen is combined with a synthetic progestin (J Natl Cancer Inst, 2000).
• Women with benign breast disease who take HRT do not appear to have any higher risk for cancer than those without these abnormalities.
• Other studies have found no significant increase in breast cancer, and one suggested that it may exist only in women who take HRT and consume one or more alcoholic drinks a day. In addition, breast cancers that occur in women taking hormone replacement therapy tend to be smaller and less aggressive.
• On the other hand, some experts argue that the risk of breast cancer from HRT may be underestimated. Until recently, women who took HRT tended to be at risk for osteoporosis or heart disease and so were likely to have low estrogen levels to begin with. Studies, then, may not yet be reporting the risks for women who are now taking HRT to reduce menopausal symptoms or to prevent Alzheimer's disease and may be starting with normal or even high estrogen levels. Of further concern for women taking HRT, breast tissue density increases and mammograms may miss some breast cancers.
• Many experts believe that any risk from HRT should be weighed against the protection it offers against heart disease and osteoporosis, far greater killers in older women than breast cancer.
• Estriol may be a "safer" form of estrogen as far as breast cancer is concerned. Mice studies revealed that estriol did not cause breast cancer (estrone and estradiol did!) and might have even been breast cancer protective (Lemon, JAMA, 1966 and Lemon, Acta Endocrinol Suppl, 1980). In addition, a small study of postmenopausal women with advanced spreading breast cancer were given estriol- 37% of them experienced an arrest of the cancer spread (Lemon, Cancer Res, 1975). The studies looking at a women's natural estriol level and her risk of breast cancer is conflicting: some suggest the higher the estriol level the lower the risk (Lemon, JAMA, 1966); however, one study revealed a higher breast cancer risk with a higher estriol level (Key, Br J Cancer, 1996). More research is clearly needed to assess whether estriol is the safest estrogen as far as breast cancer is concerned.

Ovarian and Cervical Cancers
Although some studies have reported an increased risk for certain ovarian cancers in women taking HRT, others have found no association either with short- or long-term use of HRT. Evidence is unclear about the effects of HRT on cervical cancer. Some studies indicate that there is no effect and, in fact, because women on HRT tend to have regular check-ups, they may actually be more protected against advanced cervical cancer.
Asthma
Some experts have long suspected an association between estrogen levels and asthma in adolescent and adult women. Postmenopausal women who take hormone-replacement therapy, both with and without progesterone, have a higher than average risk for late-onset asthma. (It should be noted, however, that the chance for developing asthma among all older women is extremely small.) Women taking hormone replacement therapy who experience asthma might withdraw for a while to see if asthmatic symptoms subside.
Non-cancerous Conditions in the Uterus
Women with a recent history of endometriosis may be advised not to take estrogen replacement therapy for several months after menopause because it might reactivate the condition and cause pain. Postmenopausal women who have a history of submucous fibroids and abnormally heavy bleeding may find that when they start hormone replacement therapy the heavy bleeding recurs, although some studies have found that standard HRT doses do not increase the risk for recurring fibroids in most postmenopausal women.
Gallstones
Estrogen stimulates the liver to remove cholesterol from blood and divert it into the gallbladder. If too much cholesterol is dumped by the liver into the gallbladder, it may form gallstones. As a result, postmenopausal women taking high doses of estrogen face an increased risk for gallstones. Low doses poses little problem.
Thromboembolism (Blot Clots)

• Some studies are showing that women who take hormone replacement therapy have a higher risk for venous thromboembolism (blood clots that obstruct blood vessels), with a particular risk for clots that travel to the lung (pulmonary embolism). It should be noted, however, the risk for this condition is still extremely low. Only women with a previous history of thromboembolism or other risk factors for it should avoid HRT for this reason.
• One study found that estriol had less potential to cause blood clots than synthetic estrogens (Toy, Br J Obstet Gynaecol, 1978).

High Blood Pressure

• Some women taking oral contraceptives are at risk for high blood pressure, although this is very unlikely in postmenopausal estrogen therapy. In fact, according to a recent Dutch study, HRT may actually lower blood pressure in women with normal pressure.
• An 8 years study of estriol found no negative effects upon blood pressure elevation (Erkkola R, Maturitas, 1978).

Headaches and Facial Pain
Many menopausal women report decreased migraine headaches after taking hormone replacement therapy. However, other women, particularly those who had experienced menstruation-related migraines, might experience flare-ups of severe headaches while on HRT. Estrogen replacement therapy also may increase the risk for temporomandibular disorders (TMD), chronic pain in the bones, joints, and muscles of the jaw.
Liver Disease Complications
Estrogens do not damage the liver, but they metabolize more slowly in women with diseased livers, which can increase the effects of estrogen.
Cataracts
Estrogen, progesterone, or both may play a mixed role in cataracts. They appear to protect against cortical cataracts, those that form on the outside of the lens of the eye, but they increase the risk for posterior subcapsular cataract, which form in the back of the membrane surrounding the lens.
Raynaud's Phenomenon
A recent study suggests that the use of unopposed estrogen more than doubles the risk of Raynaud's phenomenon, which affects circulation in the hands and feet, causing changes in skin color and sensation, including tingling, coldness, or numbness. (HRT combinations with progestins to do not carry this risk.)

What Are The Alternatives To Hormone Therapy?
The following non-hormonal options will be reviewed:

• Soy Phytoestrogens
• Other Herbal Phytoestrogens
• Diet and Nutrition and other supplements
• Healthy Life style behaviors
• Non-hormonal Medications
• Other Complementary and Alternative Therapies
• Waiting out menopause

What are Phytoestrogens?
Phytoestrogens are plant-based compounds that have weak estrogen effects in the body and can be found in a variety of foods (soy beans and flax seed), herbs (Black Cohosh, licorice, red clover, thyme, hops, and verbena) and spices (tumeric) (Zava, Proc Soc Exp Biol Med, 1998). Some studies report an association between a lower risk for diseases (breast cancer and heart disease in particular) and lower menopausal symptom severity associated with a high dietary intake of phytoestrogens (Aldlercreutz, Ann Med, 1997, Baillieres Clin Endocr Metab, 1998 and Ingram, Lancet, 1998).

There are still many unanswered questions concerning phytoestrogen therapies: What are the exact activities of the various phytoestrogen preparations? What dosages of each one will provide the most benefit? What are the toxic and harmful effects? When should we not use them? The effects of unopposed phytoestrogen (without a progesterone) are unknown. Until more is known about phytoestrogens, we recommend adding small amounts of natural progesterone to anyone choosing therapeutic phytoestrogens. This recommendation will of course change with any new scientific evidence on the subject. Furthermore, any women on therapeutic doses of phytoestrogen who experiences abnormal uterine bleeding should be seen by a physician to determine whether an endometrial biopsy is needed.

Soy Phytoestrogens

• Soy contains soy isoflavones (the phytoestrogens specifically found in soy), which may relieve hot flashes and vaginal symptoms and offer increased protection from osteoporosis and breast cancer. The names for these soy phytoestrogens are Genistein and Daidzein. Typical traditional Asian diets contain 25-45 mg of these isoflavones per day and traditional Japanese diets contains 60-200 mg per day. Japanese women have a much lower rate of heart disease and breast cancer than American women, and so most studies on plant estrogens are being conducted using soy. There are 1-2 mg of isoflavones in each 1 gram of soy protein. Not all soy products contain isoflavones as some soy products have been processed with an alcohol extraction that removes the good isoflavones. Soy isoflavones phytoestrogens may play specific beneficial roles in preventing cardiovascular disease, osteoporosis and cancer (Tham, J Clin Endocrinol Metab, 1998). They act as weak estrogens and can bind to estrogen receptors in the uterus, breast, brain, bone and arteries. They can both augment and antagonize estrogen effects in the body and thus are referred to as "Natural SERMS." Other effects of soy isoflavones include antiviral, antibacterial, antifungal, and antioxidant effects.
• Menopause Symptoms: In randomized, double blind trial of 104 menopausal women, 45% of women who took 76 mg/d of soy isoflavones had reduction in their hot flashes after 12 weeks, compared to 30% of those who took placebo (Albertazzi, Obstet Gynaecol, 1998). In another study, 50% of women had reduction in mild to moderate hot flashes with 80 mg/d of soy isoflavones; little relief was noted at 40 mg/d (Woods, Second International Symposium on Soy, Belgium, 1996). However, in another randomized, double blind trial, 34 mg/d of soy isoflavones in healthy perimenopausal women resulted in improvement in the severity of menopausal symptoms (Washburn, Menopause, 1999). Based on these few trial, it appears that soy isoflavones have value in the control of menopausal symptoms.
• Cancer: The effects of soy phytoestrogens on cancer are still being investigated. There are some conflicting results and can be explained by the fact that isoflavones are selective as to where in the body they are a "pro-estrogen" and where they act as an "anti-estrogen." They may also be pro or anti estrogen depending on the dose- at low doses isoflavones have an estrogen-like stimulating effect, while at higher doses it appears to have anti estrogen effects. In the absence of any estrogens, genistein in low doses has a weak pro estrogen effect on breast cancer cells in a test tube (Hsieh, Cancer Res, 1998). However, in that same test tube, when adding higher doses of genistein, it inhibits the growth of breast cancer cells (Zava, Nutr Cancer, 1997 and Peterson, Cell Growth Diff, 1996). That being said, in over 150 test tube studies, genistein has been found to inhibit the growth of cancer cells (Messina, Adjuvant Nutrition in Cancer Treatment Symposium, 1995 and Fotsis, Baillieres Clin Endocrinol Metab, 1998). Soy phytoestrogens inhibit the proliferative effect of both estrogens and xenoestrogens (chemicals that act like estrogens in the promotion of breast cancer) (Herman, J Nutr, 1995 and Verma, Nutr Cancer, 1998). One study revealed that at high doses of ERT, eating soy acts like progesterone and protects against breast and uterine cell proliferation. Of the 25+ animal studies performed with soy, roughly 65% of them revealed a cancer preventing effect of soy (Messina, Nutr Cancer, 1994). Epidemiological studies that have looked at the amount of soy in the diet and the incidence of breast cancer have reported that soy may be protective against cancer (Persky, J Nutr, 1995). One case controlled study of 144 pairs of Australian women with newly diagnosed early breast cancer found three was a substantial reduction in breast cancer risk among women with high intake of phytoestrogens (Ingram, Lancet, 1997). Another human study revealed soy consumption decreased total estrogen and the estrogen metabolites that may be cancer stimulating (Xu, Cancer Epidemiol Biomarkers Prev, 1998). In somewhat contradiction to these studies, other human studies have shown the soy isoflavones can stimulate the growth of normal breast tissue (McMichael-Phillips, Am J Clin Nutr, 1998 and Petrakis, Cancer Epidemiol Biomarkers Prev, 1996). Although encouraging, the human studies on soy and cancer are small, preliminary and are by no means conclusive. There are no well-controlled randomized human trials evaluating soy and female cancers.
• Heart Effects: One study indicated that monkeys who consumed 1206 milligrams of soy phytoestrogens were protected against heart disease as effectively as those who took ERT. One human study found that eating 17-25 grams of soy a day reduces cholesterol by 9.3%, decreased LDL by 13% and triglycerides by 10% in six weeks. There was no effect on HDL (Erdman, NEJM, 1995). Isoflavones also demonstrated beneficial biochemical effects on plaque formation in clogged arteries (Raines, J Nutr, 1995). Furthermore, soy isoflavones exhibit antioxidant activity against the harmful oxidized LDL cholesterol (Kapiotis, Arterioscler Thromb Vasc Biol, 1997). A trial of 4 weeks of soymilk in healthy human subjects did not affect cholesterol levels but did show protection against harmful oxidation of lymphocytes (Mitchell, Eur J Nutr, 1999). In a randomized, double blind, placebo controlled trail using 55 mg of soy isoflavones per day for 8 weeks did not change lipid levels in human subjects who had "average" cholesterol levels (Hodgson, J Nutr, 1998). However, in a study of 156 men and women with LDL levels from 140-200 and on a Step I cholesterol diet, soy diets containing 62 mg of isoflavones lowered total cholesterol by 6% and LDL by 4%. Furthermore, those with the highest LDL levels (greater than 160) had a 9% decrease. HDL and triglyceride levels were not changed in this study (Crouse, Arch Intern Med, 1999).
• Bone Effects: Spinal bone density increased in a double-blinded trial of women given a high soy isoflavones, 90 mg/d (Potter, Am J Clin Nutr, 1998). In another report, 3 months of a daily soy isoflavones intake of 40-60 mg/d increased bone formation (Endocrine Society Meeting, 1999).
• Ipriflavone is a synthetic derivative of soy isoflavones (separate and distinct from Genistein and Daidzein) but is not found naturally in soy foods. A total of 60 studies world wide totaling 2800 patients have been conducted on Ipriflavone. 16 randomized human studies have confirmed maintenance or increase in bone density. Further studies concerning Ipriflavone and osteoporosis are underway. It is well tolerated and is available over the counter without a prescription in the US.
• Precautions and Potential Concerns:
• High doses (200 mg/d) of soy isoflavones may inhibit thyroid function (Divi R, Biochem Pharmacol 1997)
• High doses (100-200 mg/d) of soy isoflavones can decrease estrogen levels in the premenopausal women. This may be good in women with an estrogen dominant state but may be undesirable in a women with a low estrogen state (Kronenberg, Menopause, 1999)
• High soy diet was shown to interfere with coumadin (warfarin) therapy in patients with high cholesterol and after by pass surgery (Gaddi, Curr Ther Res Clin Exp, 1989).
• Soy beans can be difficult for some to digest and cause gas and stomach upset
• Soy contains high amounts of phytates that can block to absorption of calcium, magnesium, iron and zinc. Fermented soy products such as tempeh and miso have reduced amounts of phytates due to the fermentation process. Eating soy with meat or fish reduces the mineral blocking effect of phytates.
• Some express concerns about high dose processed soy products and recommend just using the fermented types (tempeh and miso) and soy sprouts until more is known about the effects of high dose soy (Fallon and Enig, Health Freedom News, 1995).
• Forms and Doses: Soy powders, soluble in juice or milk, that list amounts of isoflavones per serving are now available in health food stores. Different products contain different amounts of isoflavones; be sure to check labels. Some experts recommend 40 to 80 milligrams of soy isoflavones a day. See the chart on soy foods and the amount of isoflavones they contain.

Soy Food	Amount	Isoflavones (mg)
Textured soy protein granules	1/4 cup	62
Roasted soy nuts	1/4 cup	60
Tofu	1/2 cup	35
Tempeh	1/2 cup	35
Soy beverage powders	1-2 scoops	25-90 varies with products
Regular soy milk	1 cup	30
Low fat soy milk	1 cup	20
Roasted soy butter	2 tbsp	17
Cooked soybeans	1/2 cup	150
Soy isoflavones pills	Varies with product, check labels
Fermented soy isoflavones pills	Contains lower amounts but may be better absorbed

Other Herbal Phytoestrogens

• Black Cohosh (Cimicifuga racemosa) relieves menopausal symptoms as well or superior to conjugated estrogens (Warnecke, Med Welt, 1985 and Stoll, Therapeuticum, 1987). Remifemin is the most tested extract of black Cohosh and is approved by the German FDA (BGA) for the treatment of menopause in Germany. Long-term use is safe. Small limited studies revealed inhibitory effects on breast cancer cells but long term human studies have not been done. Remifemin comes as a standardized 20mg pill to be take twice per day. Herbs may be used as dried extracts (capsules, powders, teas), glycerin extracts, or tinctures (alcohol extracts). Teas should be made with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers; 10 to 20 minutes for roots. Drink 2 to 4 cups per day.
• Red Clover- contains a isoflavones phytoestrogen. There is one study showing that at a dose of 40-80 mg/day resulted in increased artery elasticity which might be heart and blood vessel beneficial (Nestel, J Clin Endocrinol Metab, 1999). It had poor relief of menopausal symptoms. There are no other studies on red clover and menopause. It comes in a trade preparation called Promenstil in 40 mg standardized pill.
• Chaste tree (Vitex agnes-castus) is widely used in Europe for PMS, painful and irregular periods and menopause symptoms relief. Unfortunately, there are no scientific studies performed concerning its use in menopause.
• Angelica (Angelica archangelica) traditional use to relieve some menopausal symptoms. There are no scientific studies on this herb to date concerning menopause.
• Licorice (Glycyrrhiza glabra), an estrogen-balancing herb especially for chronic stress. Again, there are no studies concerning its use in menopause. Typical doses are 250 mg three times a day, 30 to 60 drops tincture three times a day, or 1 cup of tea three times a day. Doses above 400 mg/day can result in elevated blood pressure, fluid retention and potassium loss in the susceptible individual. Do not use if you have high blood pressure.
• Dong Quai- Is traditionally used in Chinese herbal medicine as one of several or many herbs for female support and has reported phystoestrogen effects. However, the only study conducted on dong quai used alone for menopause found no additional benefits for menopausal symptoms compared to placebo (Hirata, Fertil Steril, 1997).
• Wild Yam, Dioscorea villosa- It has been shown to have very mild progesterone like effects. However, many wild yam creams purport to have a progesterone effect. This has been referred to as the "Wild Yam Scam." Although, it is true that natural bio-identical progesterone can be made from wild yam in the laboratory, your body cannot convert wild yam to progesterone. Any "wild yam" cream that raises progesterone levels in the body actually has natural progesterone in the tube. Some list the actual amount of progesterone, but most do not.

Dietary Factors
Everyone should maintain a healthy diet that is outlined in our diet handout titled Basic Health Maintenance Diet.

• Fiber- In one study, premenopausal women who took high supplements of wheat bran as part of high fiber diets experienced estrogen loss. However, estrogen levels in those taking supplements of oat or corn were not affected. High fiber foods also decrease absorption of calcium, although taking calcium supplements can offset this problem. Perhaps the best fiber for the menopausal women is flax seed fiber. Flax contains some phytoestrogens and the ground seeds are an excellent source of fiber.
• Cruciferous Vegetables- contain phytochemicals by the names of DIM, PEITC and sulfophorane, which modulate estrogen metabolism and may decrease cancer risk. These vegetable include broccoli, cabbage and cauliflower. (Zeligs, J of Medicinal Foods, 1998 and Michnovica, J Natl Cancer Inst, 1997)
• Caffeine- reducing caffeine may help relieve some of the anxiety and sleeplessness associated with menopause. Caffeine increases calcium excretion.
• Alcohol- a glass of wine 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. Red wine also contains a substance called pycnogenol, which is a potent antioxidant. Studies indicate that women who drink more than one or two alcoholic drinks a day, however, face an increased risk for breast cancer, particularly if they are also taking HRT.

Vitamins and Other Supplements

• Vitamin E- supplement of 400-1,600 IU per day may help women with hot flashes. Vitamin E also raises estriol levels, which is the theoretic "safer" estrogen as previously discussed (London, Cancer Res, 1981). Vitamin E also has heart protective benefits. High doses are not recommended for women with high blood pressure.
• Calcium (1,000 to 2000 mg per day) and vitamin D (600 to 800 IU) may help slow progression of osteoporosis after menopause. Calcium citrate is better absorbed than many other calcium compounds and was the first reported calcium supplement to preserve bone density after menopause. Supplement of vitamin D can be toxic in high doses (more than 2000 IU per day). Vitamin D is found in fortified milk and is manufactured in the body by exposure to sunlight.
• Other Minerals- Magnesium, boron, silica and other trace minerals are also important for bone support. Magnesium also has muscle relaxing properties and cardiovascular benefits.
• Vitamin A- Some studies indicate that high amounts of dietary vitamin A might reduce increase the risk for osteoporosis.
• Vitamin C- A combination of vitamin C (1,200 mg), hesperidin (900 mg), and hesperidin methyl chalcone (900 mg) may relieve hot flashes.
• Gamma-oryzanol (from rice bran oil)- 300 mg per day gives partial or total relief of hot flashes in over 80 percent of users.

Healthy Life Style

• Exercise- For protection against all aging diseases, women--whether or not they are taking hormone replacement therapy--should pursue a life style that includes a balanced aerobic and weight resistance exercise program appropriate to their age and medical conditions. One study reported that exercise alleviated hot flashes. Exercise increases endorphin release, which helps relieve pain and elevates mood. Brisk walking, stair climbing, hiking, and dancing are all helpful. Weight-bearing exercise helps reduce the risks for osteoporosis. Walking, swimming, and biking are less stressful on the joints.
• Stress Management- Stress is associated with an increase in heart disease and reduced immune response. Talk and share feelings with a friend or family member who understands what you are experiencing. You may wish to join a support group for women who have been or are going through menopause. For more information on stress management techniques, see our handout titled Stress Fitness: Keys to Stress Mastery.
• Sex- Frequent sexual activity helps preserve the lining of the vagina and maintain an acidic environment to protect against infection.
• Smoking Cessation- for women who smoke, quitting is essential whether hormone replacement is taken or not. Smoking is linked to a decline in estrogen levels; women who smoke start menopause about two years earlier than nonsmokers. Smoking also accounts for 41% of heart-related deaths in women and is a major risk factor for osteoporosis.

Non-Hormonal Medications
A number of drugs, normally used for other medical conditions, may have properties that help menopausal symptoms.