What is Osteoporosis? From birth until the mid-twenties, our bones become thicker and denser. Then this bone growth peaks. Next comes a slow but steady decline, and our bones begin to thin. Eventually, thinner bones become more brittle, and more breakable. This process is called osteoporosis. Men usually are spared the risk of bone fracture from osteoporosis because their bones are thicker than women's to begin with, so it takes longer for them to reach the critical point of fracture. In addition, women lose bone mass at a faster rate than men. The loss of estrogen at menopause is believed to be responsible. Do all women eventually get osteoporosis and have a bone fracture? No. Bone loss can be more rapid in some than others, and some women with thick bones may never lose enough bone mass to be at risk of a fracture. But other women are definitely at risk for osteoporosis - particularly petite, light-complexioned women; and women who smoke, don't exercise or have a family history of osteoporosis. Young women who experience early menopause also are at risk for osteoporosis. Among its other benefits, estrogen helps slow bone-thinning. The loss of estrogen during menopause can make a woman increasingly susceptible to broken bones - a wrist fracture, for example, is very common. Bones in the spine also become increasingly fragile; as a result, just the weight of the body may occasionally cause these bones to be crushed spontaneously. Thinning bones result in the curving of the spine so often seen in older men and women; this also may lead to back pain. How do you stop this bone-thinning? Exercise and calcium supplements may help. If you decide to take extra calcium, you'll need to take a lot of it - at least 1,500 mg, or 1.5 grams, a day if you are not taking ERT and 1,200 mg if you are taking estrogen. It's probably best to do it in divided doses - for example, take 500 mg in the morning, and again at noon and dinnertime. But, though calcium and exercise might slow bone loss, it is not clear whether they can protect the bones from further loss or injury. It is pretty clear, however, that taking estrogen during menopause is helpful in preventing future bone loss. Several drugs are approved by the Food and Drug Administration (FDA) for this purpose. Drugs designed to prevent bone loss include alendronate (dispensed under the brand name Fosamax(tm)), raloxifene (dispensed under the brand name Evista(tm)), risedronate (marketed under the brand name Actonel (tm)), and three types of calcitonin. Alendronate and risedronate are from a class of drugs called bisphosphonates, which reduces bone loss, increases bone density in the hip and spine and decreases the risk of fractures. Side effects are uncommon but could include nausea, abdominal pain, heartburn or irritation of the esophagus. The medicine must be taken on an empty stomach, at least 30 minutes before eating, and the person must stay upright during those 30 minutes. Raloxifene, from a new class of drugs called Selective Estrogen Receptor Modulators (SERMs), prevents bone loss throughout the entire body, helps increase bone mass and reduces the risk of spine fractures by 50 percent after three years of usage. SERMs are not as strong as estrogen, but they also produce decreases in the bad LDL cholesterol that may result in a protection against heart disease. But unlike estrogen, SERMs do not seem to stimulate breast or uterine tissue. Side effects are rare, but have included hot flashes and clotting in veins. Special cells in the thyroid gland make calcitonin, a hormone that affects bone metabolism. It slows bone loss in women who are at least five years beyond menopause, increases spinal bone density, lowers the risk of spinal fractures and relieves the pain associated with bone fractures. Calcitonin is available as a nasal spray or an injection. Very recently the FDA approved a synthetic form of parathyroid hormone known as teriparatide, marketed under the brand name Forteo, for use in the treatment of osteoporosis. This drug must be administered daily by subcutaneous injection and is recommended only for those individuals who have already had a bone fracture believed to be a consequence of osteoporosis.

If injected, calcitonin may result in an allergic reaction and side effects, including flushing of the hands or face, skin rash, urinary frequency or nausea. A runny nose is the principal side effect reported with nasal calcitonin. Several types of estrogen and two types of estrogen delivering systems can prevent osteoporosis and reduce the risk of bone fractures. These are conjugated equine estrogen contained in Premarin(r), Prempro(r) and Premphase(r); esterified estrogens contained in Estratab; estropipate contained in Ogen; micronized estradiol contained in Estrace and Ortho-Prefest; ethinyl estradiol contained in Femhrt; and estradiol contained in transdermal dispensing systems, i.e., the patches Vivelle, Climara, Alora and Combipatch. To measure bone density or thickness, bone mass measurement (also called bone mineral density tests) is done. There are several test options - all are painless, safe and noninvasive. Often patients don't even have to change into an examination robe. The tests that measure the bone density in the spine, hip or wrist, the most common fracture-sites due to osteoporosis are done with a central machine. The FDA recently has approved tests using peripheral machines that measure the middle finger, the heel and the shinbone. DEXA (Dual Energy X-ray Absorptiometry) measures the spine, hip or total body. SXA (Single Energy X-ray Absorptiometry) measures the wrist or heel. PDXA (Peripheral Dual Energy X-ray Absorptiometry) measures the wrist, heel or finger. RA (Radiographic Absorptiometry) uses an X-ray of the hand and a small metal wedge to calculate bone density. DPA (Dual Photon Absorptiometry) measures the spine, hip or total body; SPA (Single Photon Absorptiometry) and QCT (Quantitative Computed Tomography) measure the wrist. Ultrasound aims soundwaves at the heel, shin bone and kneecap to measure density. Test results, known as T-scores, which are standard deviations, compare an individual's bone density with that of normal adult young women. If your bone density is 1 standard deviation less than the peak bone mass for young women, you may need treatment that rebuilds bone and prevents broken bones due to osteoporosis.

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What about Colon Cancer? The third leading cause of cancer death among women is colon cancer. The incidence of this disease, which is more common in women than men, begins to rise in women at age 40 and peaks between 60 and 75 years. Studies suggest that use of estrogen replacement therapy may decrease the risk for developing colorectal cancer in postmenopausal women. Data from retrospective studies appears to indicate a 30 percent to 40 percent reduction in risk of colon cancer in women using hormone replacement. In the recent WHI prospective randomized double blind clinical trial a significant reduction in risk from colon cancer was observed in women taking Prempro versus placebo. An explanation for this benefit remains to be determined and there is no data to show whether estrogen replacement therapy will help prevent recurrence or further spread of the disease in women already diagnosed with colon cancer.

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What about Changes in the Skin?Skin is composed of an outer layer of cells called the epidermis, which rests on the dermis, a base of connective tissue that lies just above the body fat. Skin thickness refers to the combined width of the epidermis and dermis. As we age, our skin becomes thinner. The dermis contains a protein called collagen, which is responsible for more than 70 percent of the thickness of the skin. Attempts have been made to show that a drop in this collagen causes the skin to thin with aging. (This is not yet certain, however.) Studies do show that most menopausal women who take estrogen have an increase in skin thickness as well as skin collagen. It is believed that estrogen stimulates dermal skin cells to produce collagen, which forms the bulk of skin. Increasing the dose of estrogen beyond the minimal level therefore is required to increase skin thickness. Recent studies show that women who use estrogen are 25 percent to 30 percent less likely to have dry and wrinkled skin.

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What about Changes in the Urethra, Bladder and Vagina? Estrogen has a significant influence on cells that make up the lining of the urethra and vagina. When estrogen de-creases in menopause, there is a corresponding drop in the number of cells lining the vagina; its natural lubrication diminishes, and its lining becomes thin and easily injured - and having sex may become painful. A drop in estrogen also may thin the cells lining the urethra - which are important in preventing urine from leaking. This may increase the chance of urinary incontinence, as a thinner lining lowers the pressure inside the urethra, and allows the urine to escape more easily. ERT may help ease some of these symptoms.

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What about Psychological Changes? As women age, the frequency of depression increases, as do memory problems, dementia and Alzheimer's disease. For every man with Alzheimer's, there are two women who have the disease. Do changes caused by menopause contribute to an increase in mental health problems? This question remains unresolved. Some women report, however, that the use of estrogen has helped aid with depression, memory problems and even things such as improved sleep, which can have a significant impact on how a person feels psychologically. Research from at least a half dozen observational studies suggests that women who use estrogen replacement therapy are less likely to be diagnosed with Alzheimer's disease in later life. Some data appears to indicate that hormone replacement therapy reduces the risk of Alzheimer's disease by 30 percent to 40 percent. That can only be validated through randomized clinical trials.

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What about Quality of Life? For most women, hormone replacement reduces the number of hot flashes, and allows them to feel more comfortable. Some women have noticed benefits ranging from "improved skin tone" to a decrease in such urinary symptoms as incontinence or frequency and urgency, to an increase in vaginal moisture and less-painful intercourse.

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RISKS

What about the Risk of Uterine Cancer? For a woman who is 50 years old and just entering menopause, her lifetime risk of developing endometrial cancer is approximately 2.5 percent, with a very small - less than 1 percent - chance of dying from this type of cancer in her lifetime. Studies show that women who take only estrogen as hormone replacement will, on average, have twice the risk of developing endometrial cancer as women who take no estrogen. This risk will increase, depending on how long the estrogen replacement is used. Surprisingly, although the risk of having endometrial cancer increases with estrogen use, the risk of dying from endometrial cancer does not. That is to say that women taking estrogen who develop endometrial cancer live longer than women who never took estrogen and never developed endometrial cancer. And, if progestins are taken along with estrogen and women are carefully followed by their physician, the risk of developing endometrial cancer is not increased. Due to the publicity surrounding cases in which women took only estrogen for long periods of time (one or more years), many menopausal women, fearing the risk of uterine cancer, have been reluctant to take estrogen. Yet it should be re-emphasized that the risk of developing uterine cancer is small and the risk of dying from it smaller still, and most importantly: the risk of developing osteoporosis and its complications are much greater.

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What about the Risk of Breast Cancer? Breast cancer, although most feared by women, is a disease associated with aging. Most breast cancers occur after menopause when estrogen levels are lowest. During the years of peak estrogen, the risk of developing breast cancer is extremely low. For a woman just entering menopause at age 50, her future risk of developing breast cancer is approximately 10 percent with a 3 percent chance of dying from this disease. Women who live to be older than age 85 have a 12.5 percent risk of developing breast cancer. Women have a greater risk of developing breast cancer if they have a family history of the disease, begin menstruating at an early age, experience menopause at a later age, never give birth to children, have their first child at an older age, have a history of radiation therapy, use alcohol, are overweight or are taller than average. Some women, however, develop breast cancer without having any risk factors and some women with many risk factors never develop breast cancer.

Over the years, there has been much controversy as to whether taking estrogen alone or both estrogen and progesterone increases a woman's risk of developing and/or dying of breast cancer. Studies reveal conflicting findings and many women are understandably hesitant to take the medication. For example, one recent report indicated there was a 1.46 percent increased relative risk of breast cancer in women using hormone replacement for more than five years. At the same time, another study reported no increased risk of breast cancer in women using estrogen alone or estrogen and progestin as a replacement for longer than five years. It's no wonder women are confused. Most of the studies report a modest or no increased risk of developing breast cancer. But other studies show a significant increase in long-term hormone replacement users. Recently, a re-review of 51 previously published epidemiologic studies on breast cancer was published. Using the raw data from the original studies, the authors did a re-analysis of all the combined data. The data included 54,000 menopausal women, of whom 18,000 had breast cancer and 36,000 did not.

The median age at diagnosis was 60. The analysis found that if no hormone replacement had been used for at least five years, there was no increased risk for breast cancer. Researchers believe this shows that exposure to estrogen stimulates or promotes the growth of preexisting disease, rather than stimulating the formation of a new cancer. Scientists believe it may refute the hypothesis that prolonged exposure to estrogen increases the risk of being diagnosed with breast cancer. It also should be mentioned that biases could affect studies. More women who use estrogen replacement therapy may be diagnosed with breast cancer because they have more frequent mammograms, are of higher socio-economic status and use alcohol more frequently. Estrogen non-users may show a lower risk of breast cancer because they do more physical activity or have lower bone density. One paradox exists from most of the epidemiologic studies. While an increase in the diagnosis of breast cancer is reported in hormone replacement users, there is either no change or a decrease in mortality from breast cancer when diagnosed in these same people There is no consensus yet. But it appears that there is little risk of breast cancer following estrogen replacement therapy for less than five years. Long-term use does appear to increase risk, but this risk disappears five years after stopping hormone use. Women must still weigh the possibility of an increased risk of breast cancer with estrogen therapy against the reduced risk of osteoporosis and (possibly heart disease) that estrogen provides. For most women, the benefits of therapy probably outweigh the risks. Additional studies now under way should help in the development of definitive guidelines regarding hormone therapy and breast cancer.

IS ERT FOR YOU?
The Decision Rests with You. A physician can give you all the facts, and even make recommendations, but in the end it's up to you to make this decision. Weigh the risks and benefits to health and quality of life mentioned in this guidebook, and consider your family history of heart disease, osteoporosis and cancer. Many women who begin taking estrogen experience some of the side effects discussed in the preceding pages. Sharing these concerns with your physician is important. Sometimes your physician can alter your medication to alleviate symptoms you may be experiencing.

What are My Options for Hormone Replacement Therapy During Menopause? First, it's important to remember that during menopause the amount of estrogen made by the ovaries drops significantly - by about 90 percent. The purpose of taking estrogen during menopause is to put back as much of this estrogen as is safely possible. Many of the serious problems that have been associated with estrogen use - such as stroke or heart attack - occurred in young women who took birth-control pills, which contain estrogen. These women's ovaries were already making estrogen. And, the extra estrogen in the birth-control pill was three to five times greater than what's usually given for hormone replacement. The ovaries produce an estrogen called estradiol, which binds to receptors in the body's tissues. The various types of estrogen used in ERT also affect these same receptors. So, for example, although the estrogen-replacement drug Premarin may not be an estradiol, it still works in the same way as the body's natural estrogen. Estrogens commonly given during hormone replacement are conjugated estrogens - extracted from the urine of pregnant horses. (When estrogen is conjugated, this means a sugar or sulfate molecule is attached to the estrogen chemical in the liver.) Other types of replacement estrogens include micronized estradiol or Estrace(tm). In this medication, the estradiol is prepared in very small, or micro-amounts, to help increase its absorption when taken by mouth. Oral estrogen also may be given as estrone. Another oral estrogen is ethinyl estradiol, the form of estrogen that's present in birth-control pills. Oral estrogen is metabolized by the body differently from estrogen that was naturally produced by the ovaries. Consequently, blood levels of estrogen fluctuate rapidly.

Directions for taking oral estrogens may vary, depending on your doctor's recommendations. Some physicians tell women to take estrogen every day; others may advise taking it Monday through Friday, and some may recommend taking it for the first 25 days of each month. Which regimen is the best? That's not clear. It is clear, however, that symptoms of estrogen withdrawal such as hot flashes occur after estrogen is stopped - even if it's only for two days. Before menopause, the ovaries produce estrogen continuously. Then, for two weeks after release of the egg at ovulation, the ovary that released the egg makes the hormone called progesterone. Together, these two hormones are responsible for the menstrual period if pregnancy does not occur.

Biologically, it's very important that the uterus be exposed to progesterone after it has been exposed to estrogen. Estrogen stimulates the cells lining the wall of the uterus to divide; if progesterone is not introduced, these cells keep dividing. (If this continues unabated, eventually the lining will grow until it becomes thick. In some women, it can become hyperplastic, a condition that can lead to cancer.) But when the lining of the uterus is exposed to progesterone, these cells stop dividing. If the progesterone level falls, the uterus is stimulated to shed its lining. This causes a menstrual period. During menopause - because they no longer ovulate - the ovaries no longer make progesterone. If estrogen alone were given to a menopausal woman, the lining of her uterus could become thick and possibly cancerous. To avoid this risk, it's vital that hormone replacement also include a compound similar to progesterone in women who have their uterus. Medications that mimic progesterone are called progestins. One progestin is medroxyprogesterone acetate, frequently dispensed under the brand name Provera(tm). Another, which is less frequently prescribed, is norethindrone acetate, dispensed under the brand name Norlutate. Women may be told by their physician to take these drugs on different days or in different dosages. For example: Provera may be given as a 10 mg-tablet for 10 to 14 days each month while the estrogen tablet is being taken every day. Some doctors may prescribe only 5 mg of Provera for 10 days each month or every other month. Other physicians may even give a low dose of Provera, such as 2.5 mg every day, in addition to estrogen. The goal is to prevent the uterine lining from overgrowing, while keeping the side effects of the progestins to a minimum. Oral contraceptive pills have been used by some physicians as hormone replacement. However, the estrogen dose of the birth-control pill is from three to five times greater than the dose needed for average hormone replacement. That's why some doctors question use of the pill for routine hormone replacement. (However, it may be suitable for some women in certain circumstance, such as during perimenopause, the transition period before menopause.) Sometimes an estrogen patch is prescribed. The small adhesive is worn near the navel during which time it releases estrogen. Depending on the type of patch used, it may be changed weekly or twice a week. The estrogen passes through the skin and is not first absorbed by the liver as are oral estrogens, but circulates directly through the bloodstream. It is unclear whether this method of taking estrogen will offer the same protection against cardiovascular disease as estrogen taken orally. If the potentially beneficial effect of estrogen on the heart is due to the effect on the coronary vessel then there should be positive effect with estrogen administered orally or by a patch. But if the major benefit of estrogen is due to its effect on lipids, then the greater effect would be by estrogen administered orally, not by a patch. Studies are currently under way to answer this question. Due to the amount of progesterone that needs to be absorbed, a progesterone-containing patch is not currently available. However, a combined estrogen and progestogen patch using estradiol and nonrethindrone has been introduced as the Combi-patch(tm).

When Should Women Begin to Take Estrogen? Women begin taking estrogen replacement therapy at different times in their lives. Some physicians may prescribe estrogen replacement therapy at the first signs of declining estrogen when a woman may begin experiencing symptoms of menopause. Many women seek their physician's advice about estrogen when they stop menstruating. At the present time taking estrogen for treatment of menopausal symptoms is entirely appropriate. Taking estrogen to prevent chronic disease such as heart disease remains to be proven.

How Long should Women Take Estrogen?
What about side effects? Side effects are an inevitable risk of any medication - even aspirin. However, just because a relative or neighbor experiences a problem does not mean that you will, too. While some women may experience some of these side effects, few women experience all these ailments. Estrogen may keep the kidney from excreting all of the salt that it normally would from the urine. Retaining salt and water causes bloating; this problem may be greater for some women than others. (Use of fluid pills or diuretics are discouraged, since this fluid retention is expected and use of the fluid pill may cause serious medical problems such as a lowering of the potassium level.) Estrogen also may cause headaches. Because of its effects on the liver and gallbladder, a small number of women may notice nausea; a few may even develop gallbladder symptoms. Many women who take replacement hormones may notice breast tenderness, fullness and enlargement. For women who find breast tenderness intolerable, it may help to try different estrogen preparations, try different doses or change the method of administration - try a patch instead of a pill. With progestins, some women may notice a mood change, frequently described as feeling "blue" or mildly depressed. Also, some women may notice a return of some premenstrual symptoms - breast tenderness, food cravings and increased irritability. (This and all side effects should be discussed with your physician.) Some women taking estrogen and progestin may notice vaginal bleeding or spotting, which can vary with each regimen of medication. As a result of the recent WHI findings it has suggested that estrogen therapy to treat menopausal symptoms be used only for the shortest possible time. How this is to be determined remains uncertain.

What about Alternative Strategies? There are a number of other ways to reduce symptoms of menopause, but the effectiveness of many of the methods remains unproved. Women who exercise regularly have fewer hot flashes than women who do not exercise. Deliberate deep breathing may reduce the frequency of hot flashes by 40 percent. Herbs and acupuncture also are successful for some women, although scientific studies are lacking in this area. However, using herbs to treat hot flashes may be risky because some herbal preparations used by men with prostate cancer have caused breast tenderness, loss of sex drive and problems with blood clotting. Other herbs used by men and women have caused liver damage and problems with blood not clotting. Various medications also will help control hot flashes including alpha-adrenergic agonists such as Clonidine hydrochloride (Catapres(tm)) and Lofexidine. Side effects such as dry mouth, insomnia, headaches, fainting, nausea and dizziness have been reported. An anti-dopaminergic drug, Veraliperide(tm), has helped significantly to reduce the frequency of hot flashes but side effects include painful breasts. A medication consisting of ergotamine tartrate, belladonna alkaloids and phenobarbital (Bellergal-S) also has been used to reduce the frequency of hot flashes but side effects include a burning sensation on the skin, palpitations and dry mouth. And phenobarbital may be addictive. Another nonhormonal agent sometimes used is ethamsylate. Use of dietary supplements such as soy protein reduces the frequency of hot flashes by 45 percent; however, women given a placebo, casein, showed a 30 percent reduction. More than 10 percent from each group dropped out because of gastrointestinal symptoms. Androgens and progestins also have been used to treat hot flashes. Danazol (Danocrine(tm)) a derivative of testosterone has been effective in low doses. Medroxyprogesterone acetate has been shown to markedly reduce the frequency of hot flushes. For women with a history of ovarian or endometrial cancer, androgen or progestin therapy may not appear to be controversial because high-dose progestin therapy is used in treatment for those cancers. But research does not exist on the actual risk of recurrence of the diseases when these hormones are taken. In addition, the use of androgen and estrogens to suppress hot flashes in women previously treated for breast cancer is problematic because duct and alveolar growth within the breast may respond to progestins and the effect of androgens on breast cancer has not been well studied.

Johns Hopkins Estrogen Consultation
Johns Hopkins has assembled a team of reproductive endocrinologists, gynecologists and cardiologists to help women assess their personal health and to decide if ERT is right for you. At Hopkins, we've been fortunate to participate in numerous clinical trials advancing the understanding of ERT and how to modify these therapies to benefit our patients. Scientists have extended the Heart Estrogen Progestin Research Study (HERS) in which menopausal women with heart disease are given hormone replacement therapy, to monitor long-term results. Also, we are participating in studies of hormone replacement involving a new progestin, as well as the use of a new estrogen patch. As research continues, more answers will be found. But for now, we're able to help you make an informed decision about ERT and advise our patients and manage the resulting course of therapy and its ramifications. Women who choose to schedule an appointment or whose physicians refer them to Hopkins specialists will receive a careful physical evaluation, on-site laboratory testing, mammography and osteoporosis testing, if necessary, and screening for other medical problems, including heart disease and hypertension. After reviewing the results, the physicians will discuss their recommendations with you. If you are referred by your physician, he or she also will receive a report. You'll be seen at Johns Hopkins at Greenspring Station which offers easy and convenient parking. For more information, or to schedule an appointment, please call 410-583-2749 between 8 a.m. and 4:30 p.m., Monday through Friday.

Personalized Profile
Use this simple outline to assess your risks.