COMMENTARY

January 2003: The Year in Review. Part 2. Highlights in Women's Health

Ursula Snyder, PhD

Disclosures

January 15, 2003

Introduction

Last month we reviewed some of the highlights in 2002 in obstetrics and gynecology. We continue this month with a selective glance at some other predominant issues in women's health over the past year. We chose to focus on breast cancer, bone health and osteoporosis, cardiovascular disease, and HIV/AIDS, as they were issues that were covered in some depth on Medscape Ob/Gyn & Women's Health. We also invited readers to contribute their opinion as to key issues in women's health, and you can find these in our reader's choice (sidebar).

One can get a good sense of what has occurred in the field over the past year by reading the summaries from our coverage of the San Antonio Breast Cancer Symposium (SABCS), the premier breast cancer conference in North America. Most of the authors of these summaries are themselves leading researchers in the field. Our coverage is also a 2-part CME program, the first section on breast cancer biology, risk, and prevention, and the second on breast cancer therapy.

The mammography debate. In the United States, the mammography debate seems to be heavily weighted in favor of screening women in their 40s. Dr. Robert Mocharnuk provides an overview of the issue as presented at SABCS in his summary. In addition, a study published in the first 2003 issue of the journal Cancer found that women between the ages of 42 and 49 without a prior history of breast cancer who received mammograms at least every 2 years were 44% less likely to be diagnosed with a later stage of breast cancer compared with women who had not received regular mammograms. However, it is very clear that mammography has significant limitations and that more accurate technologies are needed for screening. A European view is expressed in a Medscape Newsmaker Interview with Michael Baum, MD, ChM, FRCS, FRCR (University College in London, UK). He also makes the point that

Unfortunately, in the United States, screening is a huge commercial industry, and in the United Kingdom, it's a politically charged issue guaranteed to win votes. Everyone wants to fight cancer, so screening seems like a quick fix, but the long-term fix will involve spending more money on treatment and research. It's time for those in charge of health policy to do what's best for the patient, and to put aside these other considerations.

Therapy. According to Medscape Ob/Gyn & Women's Health board member Kathleen Pritchard, MD (University of Toronto, Ontario, Canada), the publication of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) data showing that the aromatase inhibitor anastrozole is slightly superior to tamoxifen when given for 5 years as adjuvant therapy for estrogen-receptor positive postmenopausal women with breast cancer has been an exciting development. Although the American Society of Clinical Oncology Technology Assessment suggested that anastrozole should not yet be standard therapy, it certainly recommends it for women who are unable to tolerate tamoxifen for whatever reason. These data may presage a change in drugs used in adjuvant therapy. Dr. Pritchard also points to the first publication of the IBIS data, a randomized study of tamoxifen vs placebo confirming that tamoxifen given for 5 years can reduce the risk of developing breast cancer in women at high risk. These data and the accompanying meta-analysis of the data from the Oxford Overview, the Italian, and the Royal Marsden studies have confirmed a hazard ratio somewhere between 0.5 and 0.7 for tamoxifen in relation to the risk of developing breast cancer in this setting.

Nutrition and physical activity for prevention of breast cancer. What is not addressed in our SABCS coverage is the role of nutrition and physical activity. The role of physical activity in breast cancer prevention may be primarily related to maintenance of proper weight or weight reduction in overweight individuals. Obesity, consumption of trans fatty acids and saturated fatty acids, and alcohol consumption have been linked to an increased risk in breast cancer. On the other hand, good nutrition with a high vegetable intake may be protective against breast cancer.[1] However, data from the California Teachers Study cohort produced no evidence that recent macro- or micronutrient composition of adult diet has a direct effect on breast cancer risk.[2] At least 2 studies published this year have not found that meat intake per se is associated with an increased risk of breast cancer.[1,3] The role of milk in breast cancer prevention is controversial,[3,4] and we can anticipate more research in this area. The role of isoflavone derivatives was a major focus of study this past year; still, no definitive results were obtained.

One study found an association between high soy intake and a reduced risk of mammographic parenchymal patterns that are associated with high breast cancer risk.[5] A small randomized placebo-controlled study found that in premenopausal women, isoflavone intake over a 3-month period altered estrogen metabolism and menstrual cycle length (longer cycles).[6] However, a 1-year trial using a higher dosage of isoflavones found no effect on menstrual cycle length.[7] At least 2 animal studies published in 2002 suggest that timing of isoflavone intake may be important.[8,9] Perhaps we can look forward to more interesting studies of soy in relation to breast cancer prevention in 2003.

For a comprehensive guide to of all the content on Medscape about breast cancer, please visit the Breast Cancer Resource Center.

Osteoporosis was a key topic over the past year on Medscape Ob/Gyn & Women's Health. We covered 4 major conferences on osteoporosis, all as CME programs (which are still active -- please visit the CME Center to access them), established an "Ask the Experts" on osteoporosis (have questions? send them in), published articles in Medscape Women's Health eJournal, and posted numerous articles in journal scans and from our Publisher's Circle colleagues. The easiest way to find all of this information is to visit our Osteoporosis Resource Center

Bone health and osteoporosis prevention. Osteoporosis is a disease of aging, but as world-renowned researcher and Medscape author Ego Seeman, MD (University of Melbourne, Australia) colorfully puts forth in his report from the World Congress on Osteoporosis held in Lisbon this past summer:

Bone fragility in old age has its origins in youth, if not during intrauterine growth. The variations in size and structural organization (including abnormalities) of the skeleton originate in the genetic code but are modified by environmental factors that act during growth as well as during adulthood. Maternal leptin levels may affect bone mass in the fetus; vitamin D deficiency, protein malnutrition, and sex hormone deficiency in growth all influence peak skeletal size and density. Exercise is probably most important during the early years of growth when the skeleton is particularly responsive to loading and will adapt to greater loads by modifying its size, shape, and architecture. Indeed, it is possible that our children, leashed to an electronic image of the world and moving no further than the distance between the computer and the wall adapter, may develop a lower peak bone mass. As suggested by many studies presented at this meeting, elevators, escalators, automatic 4-wheel drives, the desire for slimness, avoidance of dairy products for fear of fatness and cholesterol, low-protein diets; tobacco use, avoidance of sunlight in fear of skin cancer, may be contributing to reduced peak bone mass during growth and bone loss in adulthood.

Board member Dr. Susan A. New (University of Surrey, Guildford, England, UK) would no doubt add "low consumption of fruits and vegetables throughout life" to the list -- the role of fruits and vegetables in relation to bone health is a principal focus of research for Dr. New. She presented her team's recent research on fruit and vegetable consumption in postmenopausal women at the World Congress this summer. Their study showed that total fruit and vegetable intake was significantly correlated to bone mineral density (BMD) at the lumbar spine and femoral neck and that the relationship remained significant after adjustment for the important confounding factors.

Two studies published in 2002 showed the importance of exercise for bone health in postmenopausal women.[10,11] Walking can significantly reduce the risk of hip fracture[10] and help maintain radius BMD.[10] The JAMA study -- a 12-year prospective study of 61,200 mostly white (98%) postmenopausal women aged 40-77 years -- showed that active women had a 55% lower risk of hip fracture compared with sedentary women. Women with a lower risk of hip fracture because of higher body weight also achieved reduction in risk with higher levels of activity. Of note is that the risk of hip fracture decreased linearly with increasing level of activity among women not taking postmenopausal hormones but not among women taking hormones. Among women who did no other exercise, walking for at least 4 hours a week was associated with a 41% lower risk of hip fracture compared with those who walked less than 1 hour a week. These are important results, and clinicians should be encouraging their postmenopausal patients to walk for bone health as well as heart health.

Osteoporosis therapy. The news this past year included the US Food and Drug Administration approval of the recombinant human parathyroid hormone fragment rhPTH(1-34), teriparatide, for treatment of severe osteoporosis. One of the hot research questions this year centered around the use of this bone anabolic agent in conjunction with antiresorptive therapy. A continuing focus of research is the mechanism of action of antiresorptive therapy and, in particular, the effect of antiresorptive agents on bone structure and what may be potential consequences of prolonged antiresorptive therapy. Do drugs that suppress remodeling reduce or increase the risk of fracture in the long term? We don't know the answer.

A consequence of the results of the Women's Health Initiative (WHI) is that long-term estrogen/progestin (specifically conjugated equine estrogens and medroxyprogesterone acetate) for osteoporosis prevention will no longer be standard therapy. Of course, this has afforded a substantial marketing opportunity for other antiresorptive therapies. Raloxifene is notable in this regard, partly because it is a selective estrogen receptor modulator that has demonstrated the potential to decrease risk of invasive breast cancer in older postmenopausal women and partly because it has cardiac effects. However, it should be noted that raloxifene is approved only for the prevention and treatment of osteoporosis; it is not approved for the prevention of breast cancer or cardiovascular disease. Other antiresorptive therapies, namely the bisphosphonates, are targeted to bone only. Calcitonin seems to have some analgesic properties.

Stephen Harris, MD (University of California, San Francisco), provides a useful review of currently approved therapies for osteoporosis in the CME program, New Considerations in the Selection of Current Therapies to Prevent and Treat Osteoporosis. Marc Hochberg, MD, MPH (University of Maryland, Baltimore), discusses the bisphosphonates, which to date are the most potent antiresorptive agents for the prevention of fracture, in a CME program that will post in the near future.

When should preventive antiresorptive therapy be initiated in postmenopausal women? This has been a common question for our experts. Perhaps readers would find of interest the responses from Dr. Seeman and Jean Yves Reginster, MD, PhD (University of Liège, Liège, Belgium), in this regard.

Of course, new therapies seem always to be in development, and one of the more interesting is strontium ranelate, which has both antiresorptive and bone anabolic properties. The first major presentation of data on this agent was also at the World Congress this past summer, and you will be able to read more about it another CME program on new osteoporosis treatments by Dr. Reginster that will post early in 2003.

Finally, as has been pointed out at past conferences by L. Joseph Melton III, MD (Mayo Clinic and Mayo Foundation, Rochester, Minnesota), the treatment of osteoporosis cannot be universal because cost-effective use of available medical resources, which vary dramatically from country to country, must inform the decision of when and how to treat. "Widespread BMD testing with long-term pharmacologic therapy for osteoporosis prevention or treatment will only be feasible in the most wealthy societies."

Perhaps the most distressing news in women's health this year has been the increase in the number of women with AIDS: for the first time, about half of the adults infected with HIV worldwide are women. In sub-Saharan Africa, 58% of the women are infected. At the same time, African women are in the midst of a famine. In an editorial in TheNew York Times, Kofi Annan states: "This is no coincidence: AIDS and famine are directly linked... More than 30 million people are now at risk of starvation in southern Africa and the Horn of Africa. All of these predominantly agricultural societies are also battling serious AIDS epidemics."[12] He continues:

... [A]s AIDS is eroding the health of Africa's women, it is eroding the skills, experience and networks that keep their families and communities going. Even before falling ill, a woman will often have to care for a sick husband, thereby reducing the time she can devote to planting, harvesting and marketing crops. When her husband dies, she is often deprived of credit, distribution networks or land rights. When she dies, the household will risk collapsing completely, leaving children to fend for themselves. The older ones, especially girls, will be taken out of school to work in the home or the farm. These girls, deprived of education and opportunities, will be even less able to protect themselves against AIDS.

Because this crisis is different from past famines, we must look beyond relief measures of the past. Merely shipping in food is not enough. Our effort will have to combine food assistance and new approaches to farming with treatment and prevention of HIV and AIDS. It will require creating early-warning and analysis systems that monitor both HIV infection rates and famine indicators. It will require new agricultural techniques, appropriate to a depleted work force. It will require a renewed effort to wipe out HIV-related stigma and silence.

Former President Bill Clinton also urged action in a World AIDS Day editorial in The New York Times[13]:

Confronted with these awful facts, we can offer the historians of the future our excuses: too many countries are still in denial about the scope of the problem and what has to be done about it; many countries lack the nationwide health infrastructure to treat such a disease; most countries don't have enough health-care personnel to run a complicated treatment program; the necessary drugs are expensive and unavailable to people in the poorest, hardest-hit countries. But those facts only serve to outline the extent of the problem. They do not justify our failure to recognize the moral and practical imperatives to mount a full-throttle treatment program in conjunction with ongoing education and prevention efforts.

But HIV/AIDS is not just affecting women in developing countries. In the United States, of the approximately 40,000 new HIV infections occurring annually, 30% are in women. Roughly 75% of women are infected through heterosexual sex and 25% through injection drug use. And HIV/AIDS is affecting African American women disproportionately. According to the Centers for Disease Control and Prevention (CDC), of newly infected women, approximately 64% are black, 18% are white, 18% are Hispanic, and a small percentage are members of other racial/ethnic groups.[14]

As Clinton says, " we can and must do more to stop the spread of AIDS by doing more to treat people who already have it. Now that we have the medical capacity to save and improve the lives of millions of people, there is no other moral or practical choice."

It is projected that as soon as 2020, CVD will surpass infectious disease as the world's leading cause of death and disability.[15] High blood pressure and high blood cholesterol levels, tobacco use, excessive alcohol consumption, obesity, physical inactivity, and low fruit and vegetable consumption -- now the dominant risks in all middle- and high-income societies -- are becoming more prevalent even in the developing world.[16]

CVD remains the number 1 killer of women in the United States. The lifetime risk of coronary artery disease is > 20% in women, and in 2000, 41% of all female deaths in the United States were attributable to cardiovascular events.

Important differences in the presentation and clinical course of heart disease between men and women were the subject of Medscape conference coverage from the 51st Scientific Session of the American College of Cardiology. Sadly and inexcusably, there remains racial and gender disparity with respect to cardiovascular procedures performed in the United States. One study from Maryland published in 2002 suggested that African American women fare the worst, receiving less high-technology cardiac treatment than any other race/ethnic and gender category.[17]

More than 23 million women living in the United States are obese, and the prevalence of obesity among US adults has increased by 74% since 1991, according to the CDC.[18] And, although there is clearly a link between education/socioeconomic status and obesity/diabetes (see, for example, a study published in one of our Publisher's Circle journals, and the CDC report on women, socioeconomic status, and diabetes[18]), a CDC study has shown that obesity and diabetes in the United States continue to increase in both sexes regardless of age, educational level, and smoking level.[19]

A recent meta-analysis by Hu and Willet[20] highlights the evidence that diets using nonhydrogenated unsaturated fats, whole grains, lots of fruits and vegetables, and adequate omega 3 fatty acids are protective against cardiovascular disease. The authors conclude: "Such diets, together with regular physical activity, avoidance of smoking, and maintenance of a healthy body weight, may prevent the majority of cardiovascular disease in Western populations." A study of the diet and exercise habits of patients with diabetes, dyslipidemia, cardiovascular disease, or hypertension revealed that many continue to consume a diet high in fat and low in fruits and vegetables and engage in very little physical exercise.[21] The authors conclude the obvious: "New strategies are needed to help patients adopt and maintain healthful dietary practices that will reduce their risk." The words of John E. Hall, PhD, and Daniel W. Jones, MD (University of Mississippi Medical Center, Jackson), hit hard in this regard: "It is ironic that obesity, the most easily observed and measured manifestation of disease risk found in most patients with hypertension, has not been taken seriously by a majority of physicians... As a result, the problems of obesity and its consequences continue to grow..."[22] But obviously it is not just a medical problem, and the underlying situation is certainly not one that clinicians can improve on their own.

How to provide an environment and means for people to engage and adhere to healthy lifestyle on a national scale? It is difficult to be hopeful. In poorer communities, even finding healthy food can be a formidable task. A study by Morland and colleagues[23] looked at the locations of grocery stores in Maryland, Minnesota, Mississippi, and North Carolina. They found that poor neighborhoods had fewer supermarkets and gas stations with convenience stores than did wealthy neighborhoods. There were 4 times as many supermarkets located in white neighborhoods as in black neighborhoods. They conclude that "Without access to supermarkets, which offer a wide variety of foods at lower prices, poor and minority communities may not have equal access to the variety of healthy food choices available to nonminority and wealthy communities."

Nonetheless, a small study showed that if real means are provided to encourage healthy lifestyles -- consistent exercise in this example, with access to free supervised classes, free transportation to and from classes when necessary, and a dedicated staff -- compliance and good health outcomes can result.[24] And a companion study to that of Morland and colleagues showed that the more supermarkets a neighborhood had, the higher the consumption of fruits and vegetables by its residents. This particular study found that in black communities, produce consumption rose by 32% for each additional supermarket.[25]

In this and the December column, we have touched on just a few of the many issues confronting clinicians and health professionals caring for women this past year. Some of these same issues will be present under even more dire circumstances if current trends continue, and no doubt new issues will confront us in 2003. A recent Institute of Medicine report points out what many already know and experience in the United States:

We spend more than $1 trillion on healthcare annually, we have extraordinary knowledge and capacity to deliver the best care in the world, but we repeatedly fail to translate that knowledge and capacity into clinical practice." As one of the study authors said, "The hardest thing, it seems, will be getting people to be 'creatively intolerant' with the way things are in the current health system."

At Medscape Ob/Gyn & Women's Health, we aim to provide clinicians and health professionals with the best information available to us. It is up to us all as providers, health professionals, patients, and citizens to successfully translate this knowledge into real change and improved health outcomes. Here's to continued good work and creative intolerance in 2003.

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