Understanding the Connection:

Understanding the Connection: Menopause and Cardiovascular Disease in Women Osteopathic physicians must encourage women to make lifestyle changes that reduce their risk of cardiovascular disease. Research in the July 13, 2005, issue of the Journal of the American Medical Association (JAMA) shows that half of the older women who took combination hormone therapy (Estrogen+Progesterone) for an average of six years suffered a recurrence of menopause symptoms when they stopped the therapy. Study findings suggest that combination therapy delays symptoms rather than eradicates them. More research is needed to see which dosage is most effective, as well as whether tapering off the dosage would work better. Many women in the study successfully tackled menopausal symptoms by drinking more fluids, exercise, yoga, and meditation. Women who question combination therapy for menopausal symptom relief will undoubtedly consult their physicians on risks and benefits. Evidence shows risks for heart disease, stroke, breast cancer and Alzheimer s disease from long-term combination hormone replacement therapy. Women can benefit from taking hormones for moderate-to-severe symptoms of menopause when the hormones are given at the lowest effective dose and for shortest possible time. While this is the current recommendation, the tide is changing on this thought. See Dr Phillips interview on page 10. Joining us for a discussion of these issues are Joyce Flory, PhD, a Chicagobased healthcare researcher and journalist who serves as moderator; Kedrin E. Van Steenwyk, DO, a gynecologist at Sycamore Women s Center, Miamisburg, Ohio; Suzanne Steinbaum, DO, preventive cardiologist and director of Women s Cardiac Care Network at Beth Israel Medical Center, New York, NY; Gary S. Packin, DO, a reproductive medicine and fertility specialist at South Jersey Fertility Center, Turnersville, NJ; Teresa A. Hubka, DO, a gynecologic women s health specialist at Comprehensive Women s Care, Chicago. What do we know about cardiovascular disease (CVD) in women? Dr Van Steenwyk: CVD is the leading cause of death in women and is responsible for more deaths each year than all other medical causes combined. Heart attacks in women increase dramatically following menopause. However, the exact role of menopause is still unclear. Coronary heart disease (CHD) mortality is also higher in women than in men. Dr Bushman: More than 500,000 women die yearly from CVD. More often than not, there are no symptoms and the disease goes unnoticed. Dr Hubka: Women s primary health concern has always been breast cancer, although more women die each year from cardiovascular disease. Women don t perceive CVD as a women s disease, although more women are affected by CVD than men. CHD accounts for the majority of CVD deaths in women and 5

should therefore be a primary target for prevention. Haven t we experienced a reduction in CHD mortality? Dr Packin: Much of the decline in CHD is due to a reduction in risk factors such as smoking or dyslipidemia. The Nurses s Health Study, which followed close to 86,000 women for 14 years, revealed a 31% reduction in CHD over a two-year period. The most significant risk reductions took place in women over 65. Even though the number of smokers declined by 41%, the number of subjects deemed overweight zoomed 38%. This led researchers to conclude that while smoking and diet accounted for 13% to 16% declines in CHD, obesity accounted for an 8% increase in CHD. Dr Hubka: Although we ve had a decline in mortality from CHD due to lifestyle changes such as smoking cessation, the morbidity due to inactivity and poor dietary habits has lead us to an epidemic level of obesity, metabolic syndrome, gastrointestinal disorders and mood disorders. Given the rising rates of obesity in this country, do we face a significant problem? Dr Steinbaum: Yes. Cardiovascular disease remains the most common cause of death and disability in women in this country. Even though we ve reduced the death rate from coronary heart disease (CHD) since 1980, CHD still accounted for 35% of mortality in women as of 1995 and continues to be the greatest health threat to women. Dr Packin: What we have to remember is that between the ages of 45 to 64, one in nine women develop complications related to CVD. In the over-65 age category, the ratio skyrockets to one in three women. Dr Steinbaum: Physicians are finding high blood pressure and hyperlipidemia in children and adolescents. For the first time in decades, we ve observed a decline in life expectancy. Especially troubling is the disconnect between the intellectual understanding of CVD risk factors and the assumption of personal responsibility for lifestyle management. Dr Hubka: Obesity affects many other comorbid conditions, including diabetes, digestive disorders, metabolic syndrome, and depression. How can DOs encourage better lifestyle management? Dr Van Steenwyk: Osteopathic physicians need to check thyroid and cholesterol levels more frequently, as well as offer more bone density scans to our female patients. Many women don t see a primary care physician on a regular basis, although they typically see a gynecologist. This means that both the primary care physician and gynecologist must do a better job of screening women for CVD. Dr Bushman: We must encourage women to make lifestyle changes that reduce their risk of CVD. This includes not smoking. Don t start smoking, quit if you already smoke, and avoid second hand smoke. Exercise regularly by doing 30 minutes of moderate-intensity physical activity daily. Maintain an appropriate weight, including a BMI between 18.5 and 24.9 and a waist circumference of less than 35 inches. Consume a heart healthy diet featuring fruits, vegetables, whole grains, low-fat dairy, and protein low in saturated fat. Dr Steinbaum: Drops in estrogen are accompanied by increases in LDL, weight, and blood pressure, as well as declines in HDL. It s essential to tackle issues such as diet, diabetes, blood pressure, stress, smoking, and exercise in perimenopausal and menopausal women. Ideally, we should begin when women are still in their 20s or even during adolescence. Dr Bushman: A woman with hypertension should use lifestyle change and antihypertensive medication to keep her blood pressure at or below 140/90 preferably 120/80. Women with elevated LDL-C or low HDL-C should use diet, exercise and medication to maintain LDL-C below 100 mg/dl and HDL-C above 50 mg/dl. The same recommendations apply to pre-, periand postmenopausal women. Dr Van Steenwyk: Take the case of an otherwise healthy woman who exercises regularly. If either her mother or father takes a statin, there may be a family tendency toward high cholesterol levels. By age 40, that woman should have a baseline cholesterol test. She may decide then and there to watch her eating and exercise. As DOs, we need to screen regularly and more often in higher risk patients. Of course, such screening depends upon lifestyle, family history, BMI, weight and exercise. Dr Hubka: DOs should assess risk factors such as family history of CVD and lifestyle behaviors, as well as health status (lipid profile, diabetes screening (Hgb A1C), thyroid panel, bodyweight with waist circumference, and blood pressure. It s important to encourage smoking cessation, appropriate physical activity, and healthy dietary habits. How would you evaluate women s level of knowledge concerning CVD, menopause and heart disease? Dr Steinbaum: Although more than 50% of women are aware that heart disease is the number one killer of women, only 13% 6

of women say that they themselves are at risk for heart disease. They fail to understand the link between personal risk factors such as excess weight and smoking and the development of heart disease. Women need to understand that what physicians and scientists say about heart disease applies to them and that risk factors develop early and show up later in life. Dr Hubka: In my office I utilize a general health screening tool, which asks women about symptoms of menopause, lifestyle behaviors, and awareness of health conditions. I would recommend the AHA risk assessment tool/questionnaire. How should providers approach gender differences? Dr Steinbaum: Physicians have noticed gender differences in CHD epidemiology, diagnosis, treatment and prognosis. Gender bias is rooted in the belief that women don t have heart disease. A 2005 survey of primary care physicians revealed that women who had the same CVD risk factors as men were less likely to receive preventive treatment. Dr Bushman: Despite the fact that more women die from CVD than men each year, CVD in men has been studied more thoroughly. Until recently, women haven t had the opportunity to participate in clinical trials involving heart attack or unstable angina. Although the medical community has started to study women, we continue to extrapolate data from studies involving men. But women are different from men. For example, they tend to have asymptomatic diseases more frequently than men. Dr Steinbaum: The situation is changing. Until recently, only 25% of CVD studies featured female subjects. Now, if you apply for a grant from the AHA or another entity, you must demonstrate how you plan to incorporate women subjects. Dr. Packin: Because women with CHD tend not to be referred for further diagnosis and treatment as often as men are, women s outcomes tend to be worse than those of men. On the other hand, some experts believe these differences are due not to gender, but to risk factors such as age, diabetes, or hypertension. Dr Steinbaum: Men with CHD often present 10 years later than men and have more risk factors. Women may initially present with anginal symptoms rather than an acute heart attack. In the Framingham study, for example, 80% of women had uncomplicated angina, as compared to the 66% of men whose angina followed a heart attack. Women are also less likely than men to have typical angina, and very often present with different symptoms than classic chest pain. Dr Hubka: Physicians need to know that CVD is a critical concern in women s health. They need to discuss signs, symptoms and risk factors with patients. They need to address symptoms immediately and initiate testing early on. Since most women fail to have symptoms prior to a fatal event, physicians must also make strong preventive recommendations. How did physicians rely on HT to prevent CVD, and how did the WHI findings change that approach? Dr Van Steenwyk: Before the Women s Health Initiative (WHI) study, more than 30 studies supported estrogen for primary and secondary prevention. Physicians prescribed estrogen and progesterone for anyone who was menopausal and had a uterus. At the time, the message seemed clear: By taking estrogen women could reduce their risk of a first heart attack by at least 50%. Women who already had heart disease also seemed to benefit from taking estrogen. Dr Steinbaum: Clinical trials failed to agree with the findings of earlier studies. The WHI study and Heart and Estrogen/ progestin Replacement Study (HERS) trials took a closer look at primary and secondary prevention of heart disease. HT not only failed to prevent heart disease, but also had the potential to increase heart disease risk. Dr Van Steenwyk: It s interesting to note that the unopposed estrogen arm of the WHI reported no increase in CHD risk. In fact, estrogen seemed to have a small protective effect in younger women. The HERS trials of close to 3,000 post-menopausal women with a history of heart disease took a closer look at secondary prevention. After seven years of follow-up and ongoing estrogen-progestin therapy women with established CHD failed to reduce their risk of a CHD event. How do you evaluate the WHI findings? Dr Packin: They ve certainly had an impact. Within a year of the announcement of the WHI findings in 2002, hormone therapy prescriptions dropped close to 40%. Between 1995 and 2001, the percentage of women taking hormone therapy jumped from 33% to 42%. By 2003, the percentage of women taking hormone therapy went down to 28%. Physicians appear to have been influenced by educational programs, informed patients, and electronic alerts, as well as a re-evaluation of the standard of care. Dr Van Steenwyk: The WHI has yet to prove that hormones generate negative consequences across the board. Instead of forcing women to make decisions based on fear and panic, I offer them information that supports informed choice. I also share my opinion that WHI has never demonstrated why an otherwise healthy, newly menopausal woman between the ages of 48 and 53 shouldn t be on hormone therapy. The inflammatory presentation of WHI has set back women s healthcare 20 years. We ve allowed one study to cloud our professional judgment at a time when I truly believe we don t yet have all the answers about hormone therapy. Dr Packin: We have to look at the evidence on risk very carefully. In the WHI study, the rate of events (relative risk) such as heart 7

attack was almost 25% higher in women taking HT. While this increase appears substantial, there were slightly fewer than 40 CHD events annually for each of the 10,000 women who took HT (absolute risk). This compares to 33 CHD events annually in the 10,000 women who received placebos. These differences showed up in the first year of the study and persisted through year five. Dr Bushman: We don t have the full story yet. There s conflicting evidence, as well as fear of litigation. The American Heart Association guidelines recommend not starting women on hormonal therapy for CVD prevention. But women who suffer from hot flashes and vaginal atrophy are begging for relief. Physicians are confused and patients are confused. Dr Van Steenwyk: We need to look at the quality of a woman s life as intensely as we look at longevity. If a woman is miserable, doesn t sleep through the night, and can t function normally, hormone therapy is appropriate for an abbreviated period of time. Dr Packin: Before WHI we treated many women with hormones, assuming the hormones would deliver multiple benefits. WHI has helped to put hormone therapy into proper perspective. Hormone therapy must be tailored to the individual patient. Unfortunately, conflicting findings have deprived many women of the opportunity to receive short-term treatment for very debilitating symptoms. Dr Bushman: Research will continue. An article in the March 2005 issue of Fertility and Sterility says that beginning hormonal therapy at the onset of menopause may produce a decrease in CHD over time. Starting hormone therapy in a woman who s well into menopause is associated with an initial increase in cardiovascular risk followed by some benefit. In women who require progestogens for uterine protection, these benefits are attenuated. In my practice, I start patients on hormonal therapy at the onset of menopause but for relief of menopausal symptoms, not for CVD protection. I avoid starting women who are well into menopause on hormone therapy because of the increased risk of CV events. Dr Hubka: Management of menopausal symptoms is important to the quality of a woman s life. Hormone therapy has many benefits, as well as potential risks. I assess a woman s risk factors for CVD, breast cancer, mental health conditions and osteoporosis. HT is appropriate for the otherwise healthy woman who s entered menopause. I counsel this woman on personal risk factors and health conditions and, working together, we develop a health plan. It s important to involve a woman in decision making through education and awareness. What have you said to women who are on hormone therapy to prevent heart disease or stroke? Dr Packin: I advise women that I can no longer recommend hormone therapy to prevent heart disease or stroke. Then I explore other methods for lowering heart disease risk factors. I explain that we can try to lower blood pressure and cholesterol through smoking cessation, exercise, and diet. If that doesn t work, we can move to medications such as statins, beta-blockers, or ACE-Inhibitors. Dr Steinbaum: Before recommending hormone therapy, I always review possible lifestyle changes such as diet and exercise, including weight-bearing exercise. Hormone therapy has a number of psychosocial benefits, such as an enhanced quality of life. So it s definitely part of the solution for women who are symptomatic and not at high risk for breast cancer or cardiovascular disease. What can we conclude about the benefits of ER/HT? Dr Packin: We know hormone therapy is effective for the treatment of symptoms such as atrophic vaginitis, urinary symptoms, and hot flashes. It improves qualify of life by reducing hot flashes and restoring sleep patterns. While it can t improve urinary incontinence, it tends to decrease the frequency of urinary tract infections. It can also help to reduce depression in post-menopausal women, while mood changes in perimenopausal women can be improved in some patients using hormone therapy. Dr Van Steenwyk: The main reason for hormone therapy is controlling menopausal symptoms. Unless a post-menopausal woman has a history of breast cancer, CHD, blood clot or stroke, she can probably receive hormone therapy. Dr Steinbaum: Perimenopausal women between the ages of 40 and 50 can find symptom relief, as well as bleeding control and contraception through low-estrogen oral contraceptives. While low-dose and conjugated estrogens can relieve symptoms and bone loss, the jury is still out on whether they increase breast cancer and cardiovascular risk. Women whose symptoms persist must work with their physician to evaluate the risks and benefits of long-term therapy. Do the various forms of estrogen make a difference? Dr Packin: Premarin is the most commonly used preparation. While some women prefer plant-derived estrogens, there s no evidence that they work better than other forms. Patches are as effective as pills in 8

generating symptom relief and increasing bone density. But there s no evidence that patches have a positive impact on cholesterol levels. Dr Van Steenwyk: Some women prefer the vaginal ring because they can leave it in for as long as three months and don t have to remove it during bathing or intercourse. It also works for women who have experienced vaginal prolapse or have trouble using vaginal creams. Women who can t tolerate medroxyprogesterone acetate sometimes turn to natural progesterone. What types of patients challenge you most? Dr Bushman: Among the most challenging patients are those who resist lifestyle changes and have comorbidities. Another is the patient who needs to increase activity but has debilitating arthritis and knee mobility problems. Then there s the patient who has severe menopausal symptoms but refuses to consider hormonal therapy because of negative effects promoted through the media. These same women are willing to use herbal or natural remedies with no consideration of the risks involved. Dr Hubka: Among the most challenging patients are those with every excuse as to why they can t make changes. They will say they don t have enough money to eat well, they don t have the time to exercise, or they were born overweight. They come to the conclusion that it s impossible to change. What does the future hold for diagnosis and treatment of CVD? Dr Steinbaum: In the future, the treatment goal of the LDL will be lower and management to reach these goals will not only be with drugs such as Lipitor, but with diet and exercise. Coronary artery calcium scores can help us determine how aggressively we want to work with a patient who has an intermediate risk of heart disease, such as suffering with high blood pressure and cholesterol. Dr Hubka: Stress has a great impact on women s heart health. Playing a key role in preventive therapy for CVD in women will be stress management, modifications in dietary habits and activity levels, lifestyle behavioral changes for smoking cessation, weight reduction, and blood pressure and lipid control. What about the role of the media and public health in fostering better health among women? Dr Hubka: The AHA and affiliated or-ganizations have initiated Go Red for Women, while the Office of Women s Health of the Department of Health and Human Services has launched Heart Truth. Dr Steinbaum: Our consciousness is profoundly affected by what we see on television. Breast cancer organizations have done a wonderful job of educating women on early detection. Heart disease campaigns need a similar level of clout and credibility. Dr Packin: The public has become very discerning and polarized. The level of health and medical information available to patients and practitioners is very high but remains conflicting and confusing. Among the top Internet sites are those of the North American Menopause Society, American Society of Reproductive Medicine, and American College of Obstetrics and Gynecology. Dr Steinbaum: The campaign against heart disease must reach women of all ages, including the 25-year-old mother who thinks it s OK to feed her two-year-old potato chips. I recently said to one such parent, Don t you know how bad this is for your baby? There are so many other foods you could use. She replied, I thought potato chips were OK. Potatoes are vegetables. Dr Hubka: The AOA s Women s Health Advisory Committee and the American Osteopathic Foundation have partnered with AHA, Pfizer and Vitality Communications to address heart disease. Working with American College of Osteopathic Obstetricians and Gynecologists (ACOOG), these organizations hosted a CME event at the 2005 Unified Osteopathic Convention in Orlando. This educational program will be made available to state osteopathic associations, as well as physicians offices. It s a great opportunity to influence women s heart health. ww Resources American Heart Association www.americanheart.org, go to science and professional Women s Health Initiative www.whi.org Office of Research on Women s Health www.od.nih.gov National Institutes of Health- Menopausal Hormone Therapy Information www.nih.gov/phtindex.htm National Heart Lung & Blood Institute www.nhlbi.nih.gov/health/ women/index.htm, see also information for health professionals National Women s Health Information Center www.4woman.gov National Women s Health Network www.healthywomen.org Centers for Disease Control and Prevention www.cdc.gov, go to health top-ics, women s health North American Menopause Society www.menopause.org Food and Drug Administration Office of Women s Health www.fda.gov/ womens. 9