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Coronary heart disease (CHD) is the single leading cause of death and a significant cause of morbidity among American women. Despite this fact, there are surprising trends in the prevalence and management of CHD risk factors in women. Smoking rates are declining less for women than for men. The prevalence of obesity is increasing, and 25% of women report no regular sustained physical activity. Approximately 52% of women under 45 years of age have elevated blood pressure, and 40% of women under 55 years of age have elevated serum cholesterol. (Mosca, 1999). A recent report by the Centers for Disease Control and Prevention National Ambulatory Medical Care Survey (MMWR,1998) indicated that health care professionals were missing opportunities to prevent CHD. In this study of 29,273 routine office visits, women were counseled less often than men about exercise, nutrition, and weight control. These trends present justification and an opportunity for experienced fitness professionals to collaborate with physician groups to organize systematic patient exercise and disease prevention programs.
Recent findings from the Heart and Estrogen Replacement Study (HERS) (Hulley, 1998) have challenged previous observational data regarding the role of estrogen in preventing subsequent cardiovascular events. HERS was the first large-scale, randomized clinical trial in older postmenopausal women with confirmed CHD to test the efficacy and safety of hormone replacement therapy (HRT) on clinical cardiovascular outcomes (CHD death or non fatal heart attack) in postmenopausal women. They studied 2763 women with established CHD randomly assigned to estrogen/progesterone per day or placebo over and average of 4.1 years. Surprisingly, after 1 year, HERS showed an increase in cardiovascular events in the treatment arm, but in years 4 & 5, fewer events occurred than in the placebo arm. Hypothetically, the early adverse effects of estrogen in women with CHD may have been due to a procoagulant (increased blood clotting tendency) that may have been later offset by an anti atherosclerosis (heart disease) benefit. As a result, the American Heart Association in collaboration with the American College of Cardiology have issued a consensus recommendation that for women with CHD already on estrogen therapy for less than 1 year, it may be reasonable to continue therapy while awaiting the results of a HERS follow-up study and other ongoing trials of estrogen therapy with clinical endpoints. The HERS results may not apply to women free of vascular disease and these results do not take into consideration the other potential benefits of hormone replacement therapy (HRT).
Estrogen and Cancer
The issue of whether estrogen use effects the risk of breast cancer was addressed by a recent study by Gapstur and associates as part of the Iowa Women?s Health Study (Gapstur, 1999). They conducted a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 breast cancer cases occurred in the at-risk cohort of 37,105 women. Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. The researchers also noted that this relationship appeared to be stronger for current users compared with past users. According to the researchers, despite the positive effects of HRT on reducing menopausal symptoms, reducing risk of osteoporosis and a potentially beneficial effect on primary prevention of coronary heart disease, concerns about breast cancer cause many women not to take estrogens. HRT?s association with breast cancer is controversial. A considerable amount of epidemiological data supports a modest increase in risk of breast cancer with long-term hormone use. In view of recent observations on the benefits and risks of HRT women should consult with their physicians before deciding to adopt HRT. Family history of estrogen-dependent cancer (e.g.. breast and ovarian cancer), CHD, and osteoporosis along with lifestyle factors will play a major role in this decision process.
Exercise and Menopause
Up to 75% of women in the climacteric menopause years experience hot flashes, and up to 10% are still experiencing them 15 years later. Estrogen administration increases endogenous endorphin levels, which may account, in part, for the effectiveness of estrogen treatment for hot flashes. According to Margaret Burghardt, a staff physician at the Fowler-Kennedy Sports Medicine Clinic, University of Western Ontario Faculty of Medicine in Ontario Canada (Burghardt, 1999), ?For some women, regular exercise appears to be a promising alternative or adjunct to estrogen therapy: It, too, increases central opioid activity (e.g.. Endorphins) and thus may decrease the incidence and/or severity of hot flashes?.
Numerous studies have demonstrated reduced frequency and/or intensity of hot flashes after participating in an aerobic exercise program. Wallace and associates (1982) found that both premenopausal women (mean age, 43.1 ? 2.8 years) and postmenopausal women (mean age, 53.7 ? 3.7 years) showed increased levels of estrogen after participating in an aerobic training program, and 55% of the postmenopausal women experienced a decrease in the severity of hot flashes.
In a Swedish study, Hammar (1990) and colleagues found that the incidence of moderate-to-severe hot flashes in a physically active group of women (n=142) was nearly half that reported by the control group (n=1246) (22% Vs 44%).This cross-sectional study did not look at the physical activity level of the control group, however, and there may have been a self-selection bias among the subjects, with the degree of physical activity somewhat contingent upon and secondary to the magnitude and effects of vasomotor symptoms in individual menopausal women.
Prince and coworkers (1991), in a 2-year study of 120 women and 42 controls, found that fewer postmenopausal women (mean age, 56 years) in the exercise-plus-ERT (n=40) group had hot flashes than in the exercise-only and the exercise-plus-calcium groups (n=41 and n=39, respectively). However, the proportion of women experiencing hot flashes decreased significantly in all 3 groups.
COMMENT: Regarding HRT, a reasonably balanced approach to regular exercise can generate similar benefits as HRT and usually without unnecessary risks. Both HRT and regular exercise can result in:
- Favorable alterations in the blood lipid profile (decreased LDL/HDL-cholesterol ratio)
- Decreases blood pressure and exercise-induced ischemia
- Antioxidant properties
- Decreased depression and anxiety scores
- Reduction in hot flashes
- Increases in central endorphin activity
- Increases in bone mineral content and/or decreased bone turnover
- Arterial vasodilatation
- Decreased blood fibrinogen levels
- Decreased risk of stroke
- Decreased symptoms of depression
This is not to say that women should discard their estrogen patches in favor of step aerobics but it does perhaps demonstrate that there are potential alternatives to HRT for many women, at least such that there may be a lower HRT dosing requirement with the implementation of a well-balanced exercise program.
Gender Differences and Heart Disease
Two recent studies in the July 22 issue of New England Journal of Medicine examined gender differences in heart attack, hospitalization and death rates. One study found higher heart attack death rates in women than men. Another study found differences in the types of heart attacks between the sexes.
Heart attack death rate during hospitalization was 16.7 percent for women and 11.5 percent for men according to the study by Vaccarino and colleagues (Vaccarino, 1999). Their study included 155,565 women and 229,313 men who had been enrolled in the National Registry of Myocardial Infarction 2 study, also found that among women over 50 years of age, the rate of death was even higher, about twice that of men.
In a second study (Hochman, 1999) researchers found that women had more complications than men during hospitalization and a higher death rate after 30 days. They found that compared with men, women who developed or died of a heart attack were usually older, and more likely to have diabetes and high blood pressure, risk factors for heart disease. But even when these factors were taken into account, researchers found differences in death rates. The research project included 3,662 women and 8,480 men.
In addition, researchers found gender differences in the type of heart attacks. Women made up a higher proportion of cases of unstable angina (severe chest pain but no permanent clot), while men were more likely to have a myocardial infarction with ECG abnormalities, which is a heart attack that is generally associated with a permanent blood clot. However, women who did have heart attacks with ECG abnormalities had a less favorable outcome than men, while those women with unstable angina (unpredictable chest discomfort) had a better survival rate than their male counterparts.
According to Lynn A. Smaha, MD, Ph.D., president of the American Heart Association, ?These observations provide some of the most solid evidence so far that there are sex differences in the causes and types of heart attacks. It also appears that women under 50 years of age who have heart attacks face a higher risk of dying than their male counterparts. Taken together, these studies suggest that there are gender-specific factors at play in heart attacks that are not necessarily related to differences in care but to the underlying disease process. Understanding these factors should advance our ability to treat heart attacks for both our male and female patients.?
Cancer and Exercise
The estrogen-dependent cancers (breast, endometrial, and ovarian) are among the leading causes of morbidity and mortality in American women. Increased incidence of these cancers is predicted in the future, and the need for primary prevention is clear. According to a literature review by Kramer and Wells (1996) sufficient evidence has accumulated to warrant an analysis of the relationship between physical activity and estrogen-dependent cancer. Estrogen-dependent cancers are those associated with high levels of exogenous or endogenous estrogen. Recent epidemiological studies confirm an inverse relationship between physical activity and estrogen-dependent cancer, with stronger associations appearing for occupational activity than for leisure time or non-occupational activity. Several hypothesized mechanisms are described for the prevention of estrogen-dependent cancer by physical activity: 1) maintenance of low body fat and moderation of extraglandular estrogen, 2) reduction in number of ovulatory cycles and subsequent diminution of lifetime exposure to endogenous estrogen, 3) enhancement of natural immune function, and 4) the association of other healthy lifestyle habits. Although the mechanisms are not well defined, several lines of evidence support the inclusion of low-to-moderate physical activity as a preventive strategy for estrogen-dependent cancer.
Breast Cancer Prevention Update
Breast cancer accounts for approximately one-third of all cancers and is the second most common cause of cancer death in American women. Each year 180,000 women learn they have breast cancer. Additionally, it is estimated that 1 in 8 women will be diagnosed with breast cancer in her lifetime. Currently, the following risk factors have been identified as risk factors for breast cancer:
- Increased age
- Family history of breast cancer
- Benign breast cancer
- Presence of BRCA1 or BRCA2 gene
- Early menarch (before age 12)
- Late menopause (after age 55)
- Late age at first pregnancy
- Exogenous estrogens (eg. estrogen replacement therapy)
- Obesity
- Alcohol use
- Caucasian race
Detection and Prevention
Early detection of breast cancer is the key to increased survival and improved quality of life. Breast cancer can be detected by mammogram up to 2 years before it is palpated. However, the effectiveness of mammography is controversial for women between 40-49 years of age and, as a rule, has not been established to be effective in women under 50 years of age. Other options for prevention are:
- Prophylactic mastectomy
- Weight loss
- Alcohol abstinence
- Estrogen avoidance
- Chemoprevention (see antiestrogen therapy below)
- Antiestrogens (this section is a component of Breast Cancer Prevention Update)
A growing number of epidemiological and experimental studies have supported the role of estrogen in development and growth of breast cancer cells. Exogenous estrogen, eg estrogen replacement therapy, has been shown to increase a woman?s risk of breast cancer. This risk is thought to increase with a prolonged duration of estrogen therapy. The results from the Women?s Health Initiative, an ongoing large, randomized study of the benefits and risks of estrogen replacement therapy will help answer these important questions. Breast cancer chemoprevention targets the role of estrogen, with research focusing on the development and study of antiestrogens. Antiestrogens such as tamoxifen and raloxifene ideally would inhibit estrogen?s action however such agents have a much more complex role than a mere estrogen-blocking effect. Tamoxifen, for example, is a pill that has been used for more than 20 years to treat patients with breast cancer. This drug works against breast cancer, in part, by interfering with the activity of estrogen, a female hormone that promotes the growth of breast cancer cells. For this reason, tamoxifen is often called an ?anti-estrogen?. Raloxifene is a useful alternative to hormone replacement therapy in prevention of osteoporosis for women at increased risk of breast cancer. However, the current research literature does not support the use of raloxifene for prevention of breast cancer outside of the clinical trials.
According to Fugate and Franks (Fugate,1999), both PhD pharmacists, tamoxifen should be considered as an option for reduction in breast cancer incidence in post menopausal women at increased risk of breast cancer. The National Cancer Institute has developed a breast cancer risk assessment tool to assist patients and health care providers. This tool, the most accurate assessment method to date, consists of 7 questions requiring approximately 3 minutes to complete. (EDITOR: I am still waiting to insert these seven questions, they are in route mail to me from the NCI ? it would be an appropriate sidebar/BOX)
According to the National Cancer Institute (see resource and website below) the Breast Cancer Prevention Trial, a large multicenter, randomized, double blind study of 13,388 women, demonstrated that breast cancer was diagnosed half as often in the women who were assigned to take tamoxifen compared with women who were assigned to take the placebo. Tamoxifen offered this benefit along with no apparent increased risk of serious side effects for women ages 35 to 49, but the benefit for women ages 50 and older came with an increased risk of serious side effects. Women over age 50 who took tamoxifen had an increased chance of developing three rare but serious health problems: endometrial cancer (cancer of the lining of the uterus), pulmonary embolism (a blood clot in the lung), and deep vein thrombosis (blood clots in major veins). As we await results of numerous clinical trials on the safety and efficacy of these drugs there is great promise for a preventive role for existing and safer antiestrogens.
Role of Soy Phytoestrogens (Part of Breast Cancer Prevention Update)
Another alternative to traditional HRT is soy phytoestrogen. Soy products contain high levels of genistein, a phytoestrogen that is a potent inhibitor of cell proliferation and angiogenesis (growth of new blood vessels, in this case induced by tumors for their own nutrient supply). Genistein has been found to inhibit the growth of carcinogen-induced cancers in rats and human leukemia cells transplanted into mice. Current research recommends women consume 50-70 grams of soy protein a day. Soy is touted to reduce breast cancer risk and lower cholesterol levels. Good sources of soy protein include soybeans, tempeh, soy flour, tofu, textured soy protein, or soy milk.
Information Resources from the National Cancer Institute
For more information and free publications on the prevention, early detection, diagnosis and treatment of breast cancer, call the National Cancer Institute?s Cancer Information Service at 1-800-4-CANCER. Specially trained staff provide the latest scientific information in understandable language. CIS staff answer questions in English and Spanish. For easy access to clinical trials information from NCI, go to http://cancerTrials.nci.nih.gov on the World Wide Web.
Physical Activity for Postmenopausal Women
Postmenopausal women can improve their chances of living a longer life by exercising regularly, according to findings of a recent study. The study (Kushi, 1997) included data from 40,417 postmenopausal women in Iowa (age 55-69), over a seven-year period (1986 to 1993). Dr. Lawrence H. Kushi, Sc.D., from the Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, and his colleagues evaluated the association between physical activity and mortality in these postmenopausal women. This study was one of the largest of its kind to include women. Data were collected through the use of mailed questionnaires over the seven year period. Participants rated their participation in regular physical activity with respect to the frequency of exercise and intensity of the physical activity. Examples of moderate physical activity included in the questionnaire are bowling, golf, gardening, or taking long walks, while examples of vigorous activities are jogging, swimming, aerobics, racket sports or strenuous sports. Participants rated their exercise levels from ?rarely or never? to ?more than four times a week.? The principle measure of success was survival; 2,260 of the study?s participants (5.6%) died during the seven years of the study. Dr. Kushi and his team measured self-reported physical activity levels among the surviving group, and found three levels of activity which were related to the overall risk of mortality.
The researchers adjusted the data to exclude women who stated that they had heart disease or cancer, as well as those who died within the first three years of the study. After these adjustments were made, the researchers found that even a minimal amount of physical activity resulted in a reduced mortality risk. More frequent and intense levels of activity resulted in greater reductions in risk; among the self-reportedly most active respondents, the overall mortality risk decreased by 30% compared with the least-active (or non-active) participants. Those women who exercised once a week benefitted from a 12% reduced mortality risk compared to sedentary women in the study. Reductions in mortality rates were most dramatic in the areas of cardiovascular and respiratory diseases. Those women who were the most active were the least likely to die from cardiovascular and respiratory illnesses. These findings are similar to prior studies, most of which were conducted on men, which found that exercise can reduce the risk of cardiovascular disease.
COMMENT: It is commonly held that the benefits of exercise in promoting both general good health and, more specifically, cardiovascular health are equally distributed among men and women. However, only seven of 51 major studies conducted through 1995 that examined the relationship of physical activity and coronary disease reported data on women. More recently, there has been a profusion of research substantiating the benefits of exercise in women with over 50 peer-reviewed published trials on women and exercise since 1995. What most of this research teaches us is even with moderate increases in physical activity there are at least as many benefits to be derived from exercise for women as there are for men. Perhaps the most intriguing aspect of exercise and women?s health is that regular balanced exercise appears to be capable of very similar benefits compared to estrogen-replacement therapy without increasing the risk of cancer. The good news for modern woman is that modest increases in activity in middle-aged non-athletic women can help prevent some of the debilitating effects of aging and coronary heart disease. Greater increases in activity may reap even greater rewards depending on initial level of fitness and risk. The health-related benefits derived from exercise need not be accompanied by substantial weight loss. Since coronary disease is an equal opportunity killer (striking men and women alike), this is important information for all women.
Balanced Exercise
In order to achieve a near full range of health benefits from physical activity women (and men) will need to participate in a consortium of physical activity beyond just weekly aerobics classes. The following are characteristics of a balanced exercise program which may optimize health benefits:
? Regular aerobic exercise of varying intensity 3x/ week
? Resistance exercise (eg. weight training, weight bearing exercise, eg. hatha yoga) 2x/week
? Utilitarian exercise (household chores, yard work, gardening, etc.) 4-7x/week
? Mindful exercise (quiet reflective time combined with moderate exercise, eg. hatha yoga, meditation walking, tai chi, etc.) 2x/week
* Note: the above characteristics are not mutually exclusive, eg. select components of aerobic, resistance, and mindful exercise can be creatively combined in either organized workouts or local utilitarian activity.
Osteoporosis
One of the most noteworthy papers published thus far in 1999 was the quantitative review of the controlled studies by Wolff and others at the Institute fora Research in Extramural Medicine in Amsterdam on the effects of exercise training programs on bone mass, measured as bone mineral density (BMD) or bone mineral content (BMC), of the lumbar spine (LS) and the femoral neck (FN) in pre- and postmenopausal women. The literature from 1966 through December 1996 was searched for published randomized and nonrandomized controlled trials. Study treatment effect is defined as the difference between percentage change in bone mass per year in the training group and the control group. Of the 62 articles identified, 25 met the inclusion criteria and were maintained for further analyses. The overall treatment effects for the RCTs showed very consistently that the exercise training programs prevented or reversed almost 1% of bone loss per year in both LS and FN for both pre- and postmenopausal women.
At the University of Pittsburgh The Women?s Healthy Lifestyle Project, a study performed by Salamone and colleagues (1999) demonstrated the clear association between the loss of body weight and decreased bone mineral density. They examined the effect of a lifestyle intervention aimed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy, premenopausal women aged 44-50 y All women were randomly assigned to intervention or control groups. Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial. The intervention group (n = 115) experienced a mean weight loss of 3.2 kg over the 18 mo compared with a weight gain of 0.42 kg in the control group (n = 121) (P < 0.001). The annualized rate of hip BMD loss was 2-fold higher (P < 0.015) in the intervention group than in the control group; a similar, although nonsignificant pattern was observed for the loss in spine BMD: in the intervention and control groups, respectively. Large increases in physical activity slowed spine BMD loss, but had no significant effect on BMD loss at the hip. The intervention group, who modified their lifestyle to lose weight, had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group. Recommendations for weight loss by health promotion professionals must be made with consideration that such an endorsement may result in BMD loss.
Gregg and others (1998) at the National Center for Chronic Disease Prevention and Health Promotion in Atlanta evaluated physical activity patterns and bone fracture incidence in 9704 older women. They found that higher levels of leisure time, sport activity, and household chores and fewer hours of sitting daily were associated with a significantly reduced relative risk for hip fracture after adjustment for age, dietary factors, falls at baseline, and functional and health status. Very active women had a statistically significant 36% reduction in hip fractures compared with the least active women. The intensity of physical activity was also related to fracture risk: moderately to vigorously active women had statistically significant reductions of 42% and 33% in risk for hip and vertebral fractures, respectively, compared with inactive women. Women who did lower-intensity activities, such as walking, gardening, or social dancing, for at least 1 hour per week also had significant reductions in risk for hip fracture. It was suggested that low-intensity activities may be the most prudent recommendation for sedentary older women.
An Update on the treatment choices for Osteoporosis
In the U.S. today, 10 million individuals already have osteoporosis and 18 million more have low bone mass, placing them at increased risk for this disease. One out of every two women and one in eight men over 50 will have an osteoporosis-related fracture in their lifetime. The following is an update on current treatments for osteoporosis: A comprehensive osteoporosis treatment program includes a focus on proper nutrition, exercise, and safety issues to prevent falls that may result in fractures. In addition, your physician may prescribe a medication to slow or stop bone loss, increase bone density, and reduce fracture risk.
Nutrition
The foods we eat contain a variety of vitamins, minerals, and other important nutrients that help keep our bodies healthy. All of these nutrients are needed in a balanced proportion. In particular, calcium and vitamin D are needed for strong bones as well as for your heart, muscles, and nerves to function properly.
Exercise
Exercise is an important component of an osteoporosis prevention and treatment program. Exercise not only improves your bone health, but it increases muscle strength, coordination, and balance and leads to better overall health. While exercise is good for someone with osteoporosis, it should not put any sudden or excessive strain on your bones. As extra insurance against fractures, your doctor and/or exercise practitioner can recommend specific exercises to strengthen and support your back.
.The Therapeutic Role of Medication for Osteoporosis
Currently, estrogen, calcitonin, and alendronate are approved by the U. S. Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. Estrogen, raloxifene and alendronate are approved for the prevention of the disease.
Estrogen. Estrogen replacement therapy (ERT) has been shown to reduce bone loss, increase bone density in both the spine and hip, and reduce the risk of hip and spinal fractures in postmenopausal women. ERT is approved for both the prevention and treatment of osteoporosis. ERT is especially recommended for women whose ovaries were removed before age 50. Estrogen replacement should also be considered by women who have experienced natural menopause and have multiple osteoporosis risk factors, such as early menopause, family history of osteoporosis, or below normal bone mass for their age. As with all drugs, the decision to use estrogen should be made after discussing the benefits and risks and your own situation with your doctor.
Raloxifene. Raloxifene (brand name Evista?) is a drug that was recently approved for the prevention of osteoporosis. It is from a new class of drugs called Selective Estrogen Receptor Modulators (SERMs) that appear to prevent bone loss at the spine, hip, and total body. Raloxifene?s effect on the spine does not appear to be as powerful as either estrogen replacement therapy or alendronate, but its effect on the hip and total body are more comparable. While side-effects are not common with raloxifene, those reported include hot flashes and deep vein thrombosis, the latter of which is also associated with estrogen therapy. Additional research studies on raloxifene will be ongoing for several more years.
Alendronate. Alendronate (brand name Fosamax?) is a medication from the class of drugs called bisphosphonates. Like estrogen, alendronate is approved for both the prevention and treatment of osteoporosis. In postmenopausal women with osteoporosis, the bisphosphonate alendronate reduces bone loss, increases bone density in both the spine and hip, and reduces the risk of both spine fractures and hip fractures. Side effects from alendronate are uncommon, but may include abdominal or musculoskeletal pain, nausea, heartburn, or irritation of the esophagus. The medication should be taken on an empty stomach and with a full glass of water first thing in the morning.
Calcitonin. Calcitonin is a naturally occurring non-sex hormone involved in calcium regulation and bone metabolism. In women who are at least 5 years beyond menopause, calcitonin slows bone loss, increases spinal bone density, and according to anecdotal reports, relieves the pain associated with bone fractures. Calcitonin reduces the risk of spinal fractures and may reduce hip fracture risk as well. Studies on fracture reduction are ongoing. Calcitonin is currently available as an injection or nasal spray. While it does not affect other organs or systems in the body, injectable calcitonin may cause an allergic reaction and unpleasant side effects including flushing of the face and hands, urinary frequency, nausea, and skin rash. The only side effect reported with nasal calcitonin is a runny nose.
Fall Prevention
Fall prevention is a special concern for men and women with osteoporosis. Falls can increase the likelihood of fracturing a bone in the hip, wrist, spine or other part of the skeleton. In addition to the environmental factors listed below, falls can also be caused by impaired vision and/or balance, chronic diseases that impair mental or physical functioning, and certain medications, such as sedatives and antidepressants. It is important that individuals with osteoporosis be aware of any physical changes they may be experiencing that affect their balance or gait, and that they discuss these changes with their health care provider.
Personal trainers can play an integral role in fall prevention. Recent studies have demonstrated fewer falls in those who engage in regular physical activity especially activities that train balance, eg. tai chi.
Resources for More Information and Materials for Health Promotion Professionals: National Institutes of Health Osteoporosis and Related Bone Diseases~National Resource Center 1150 17th St., NW, Suite 500, Washington DC 20036 202-223-0344 or 800-624-BONEFax (202) 223-2237 E-Mail: orbdnrc@nof.org To find the location of a bone density testing center near you, call 1-800-464-6700.
REFERENCES Burghardt M. ?Exercise at Menopause: A Critical Difference? Medscape Women?s Health eMed Journal, Jan/Feb 1999; Vol. 4 (www.medscape.com/Medscape/WomensHealth/journal) Fugate S and Franks A. Breast Cancer Prevention: The role of antiestrogens. American Journal of Managed Care 1999: 5:925 Gapstur SM, Morrow M, Sellers TA. ?Hormone Replacement Therapy and Risk of Breast Cancer With a Favorable Histology: Results of the Iowa Women?s Health Study? JAMA 1999;281:2091 Gregg E. et. al. ?Physical activity and osteoporotic fracture risk in older women? by Gregg, EW. Ann Int Med 15 July 1998. 129:81-88 Hully S, Grady D, Furberg C. et.al. Heart and Estrogen/progestin Replacement Study (HERS). JAMA 1998;280:605-613. Hochman JS, Tamis JE, Thompson T. et. al. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. NEJM 1999; 341:226-232.
Hammar M, Berg G, Lindgren R: Does physical exercise influence the frequency of postmenopausal hot flushes? Acta Obstet Gynecol Scand 1990; 69:409-412. Kushi L, Lee RM, Folsom, AR. et. al. Physical Activity and Mortality in Postmenopausal Women JAMA 1997;277:1287-1292 Mosca L, Grundy S, Judelson D. et.al. Guide to preventive cardiology for women. Circulation 1999; 99:2480-2484. MMWR. Missed opportunities in preventive counseling for cardiovascular disease: United States, 1995. MMWR Morbidity and Mortality Weekly Report. 1998; 47:91-95. Poehlman ET, Goran MI, Gardner AW et. al. Metabolic determinants of the decline in resting metabolic rate in aging females. Am J Physiol 1993; 264: E450-E455. Poehlman, E., Arciero, P. & Goran, M. Endurance Exercise in Aging Humans: Effects on Energy Metabolism. In: Exercise and Sport Sciences Reviews Vol. 22 (Hollozy editor). pp,251-284, 1994. Prince RL, Smith M, Dick IM, et al: Prevention of postmenopausal osteoporosis: A comparative study of exercise, calcium supplementation and hormone-replacement therapy. N Engl J Med 1991; 325(17):1189-1195. Salamone L, Cauley J, Black D et. al.
Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA 15261, Am J Clin Nutr 1999 Jul;70(1):97-103 Thune I, Bren T, Lund E. & Gaard M. Physical activity and the risk of breast cancer. N Eng J Med. 1997; 336:1269. Kramer M & Wells C. Does physical activity reduce risk of estrogen-dependent cancer in women? Med & Science in Sports and Exercise, 1996; 28:322-334 Vaccarino V, Parsons L, Every N et.al. Sex-Based Differences in Early Mortality after Myocardial Infarction. NEJM 1999; 341: 217-225. Wallace JP, Lovell S, Telano C: Changes in menstrual function, climacteric syndrome, and serum concentrations of sex hormones in pre- and post-menopausal women following a moderate intensity conditioning program. Med Sci Sports Exerc 1982; 14:154 Wolff I; van Croonenborg JJ; Kemper HC; Kostense PJ; Twisk JW The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in pre- and postmenopausal women. Osteoporos International 1999; 9:1-12
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