dm01.gifResearching and writing about the latest developments in healthcare is more interesting than your average job, and that goes double for this month’s Women’s Health disease management section.
   From osteoporosis to ovarian cancer and heart disease, there is no shortage of female-related health topics to cover. The public has an insatiable appetite for information on living longer and healthier. And women, the primary healthcare gatekeepers for families, are the biggest consumers of this deluge of information.
   This month’s disease management section, looks at a few of the latest research and development efforts on women’s health from the scientific community.
   Good news for women suffering in the advanced stages of osteoporosis came out of this year’s meeting of the Society of Cardiovascular and Interventional Radiologists. Researchers in Maryland, Ohio and across the country are injecting medical-grade bone cement into the fractured vertebrae of women to stabilize and prevent further collapse of the spine. The procedure, vertebroplasty, also helps relieve the pain associated with fractured vertebrae. A similar process, kyphosis, which involves injecting bone cement and a small balloon inside the vertebrae, may help relieve the pain and restore some height loss to more acutely injured patients.
   In other news, a three-year study of 28,263 post-menopausal women found that testing for C Reactive Protein is useful in assessing risk of cardiovascular disease. The study, published in the March 22nd New England Journal of Medicine, concludes that adding the test to standard lipid panels now in use may improve the opportunity to identify women most at risk for cardiovascular events.
— Coleen Curran

Dowager’s hump relief with vertebroplasy and kyphoplasty
The pain, height loss and deformity caused by osteoporotic fractures of the vertebrae may be prevented or even partially reversed in some patients with the help of a liquid bone cement and small balloons.
   Two non-surgical techniques performed by interventional radiologists — vertobroplasty and spine balloon therapy (kyphoplasty) — offer help to those who have no treatment options besides pain killers. Information on the procedures recently was presented at the 25th Annual Scientific Meeting of the Society of Cardiovascular and Interventional Radiology (SCVIR) in San Diego.
   Multiple vertebral fractures lead to height loss and kyphosis, or “dowager’s hump.” Vertebroplasty involves injecting a medical grade bone cement into the fractured vertebra to stabilize it, stop the pain and prevent further collapse. Research shows vertebroplasty is more than 80 percent successful in people with osteoporotic vertebral fractures, including young people whose bones have become fragile due to the use of steroids for diseases such as lupus, asthma and rheumatoid arthritis.
   A new approach to vertebroplasty will include the use of cements, currently in development, that will convert bone or stimulate bone growth. Kyphoplasty, another new approach to vertebroplasty, involves inserting a small balloon at the point where the vertebra has collapsed, inflating the balloon to raise the bone and then injecting cement into the space. Researchers hope the procedure will restore lost height.
   Ten million American women have osteoporosis, a disease that causes 700,000 vertebral fractures annually, according to the National Osteoporosis Foundation. Osteoporosis leads to more than twice as many vertebral fractures as hip fractures.
   In the near future, we’ll likely be using vertebroplasty preventively to treat fragile osteoporotic vertebrae in some at-risk patients before they fracture,” said John M. Mathis, M.D., M.Sc., chairman of the radiology group at Lewis-Gale Medical Center in Salem, Va., and associate clinical professor of radiology, neurosurgery and orthopedic surgery at Johns Hopkins Medical Institutions in Baltimore. Mathis helped introduce vertebroplasty to the United States and at the SCVIR meeting.

photoPartially collapsed vertebra which has been treated with vertebroplasty. The cannula for cement delivery is still in place and the dark material represents the cement that has been injected.

   Vertebroplasty may help prevent severe deformity and gets people up and walking around,” said Gregg H. Zoarski, M.D., director of diagnostic and interventional neuroradiology at the University of Maryland Medical Center, and associate professor of radiology at the University of Maryland School of Medicine in Baltimore. “This helps prevent devastating complications such as pneumonia or pulmonary embolism.”
   “After a vertebra is fractured, typically there’s an initial loss of only 20 or 30 percent of the height of the vertebra. But over several weeks, fractures may re-occur, and the vertebra pancakes out until eventually there’s a 70 to 90 percent loss. Gradually, the back hunches over and the person loses height, especially if several vertebra are involved. If we treat patients soon after each fracture, we can stop the vetebral height loss before deformity occurs.”
   “It gets people who are often in hospital beds and on constant medication back on their feet, and probably lengthens their lives,” said Mathis.
   At least four of five patients who have had vertebroplasty reported significant pain relief, according to two studies presented at SCVIR.
   In the University of Maryland study, 24 of 30 patients (80 percent) reported significant and durable pain relief two weeks after having vertebroplasty.
   “The physicians involved in our study have helped about 400 patients, and we have not had complications in any of them,” said Zoarski, lead author of the University of Maryland study.
   “In another study at St. Vincent Mercy Medical Center in Toledo, Ohio, 95 percent of 45 patients who had vertebroplasty reported significant improvement in pain and motility,” Mathis said.
   Vertebroplasty also is performed on people with vertebral fractures caused by cancer in the spine. Several thousand procedures have been performed within the last several years and it is now available across the country.

   “We are on the cusp of vertebroplasty becoming the standard of care for compression fractures of the spine,” said Mathis. The technique involves making a nick in the skin and inserting a cocktail straw-sized needle into the fractured vertebra using X-ray guidance. Bone cement is used to fill tiny holes and crevasses inside the vertebra to shore up the fractured outer bone. The procedure takes less than an hour. Patients need only light sedation.
   Vertebroplasty most often is used to treat vertebrae in the lower- and mid-spine, which are prone to fracture when they become brittle. In a third of the cases, the bone is so weak that the fracture occurs when the patient is simply rolling out of bed or coughing, said Zoarski. Because the patient can’t recall a specific trauma, vertebral fracture frequently is diagnosed incorrectly.
   Patients with vertebral fractures caused by osteoporosis have few options besides bed rest and pain killers. Surgery to stabilize the fracture with spine screws usually is not possible because bone is too weak to hold the screws and surgery is risky in these patients.
   “About 5 to 10 percent of my patients are under 50,” said Mathis. “Young patients do extremely well with vertebroplasty. I treated seven crushed vertebrae in one patient who had osteoporosis because of the sterioids she had taken to treat lupus. Four years later, at age 39, she remains pain free.”
   “It’s also significant that we can get rid of the pain in an 80-year old who might otherwise be put to bed for six weeks and never get back to the level of activity he or she had previously enjoyed,” Zoarski said.

Spine balloon may restore height
The spine balloon technique (kyphosis) has been performed in about 150 patients nationwide and, although no clinical investigations are published yet, early results are promising, according to Mathis.
   The technique is similar to vertebroplasty, except that before cement is injected, a small balloon is passed through a needle (similar to that used in vertebroplasty) into the inside of the vertebra and expanded. The one-to-two-hour procedure typically is performed while the patient is under general anethesia.
   Both vertebroplasty and kyphosis have a place, said Mathis. “Vertebroplasty will continue to be extremely useful in treating the majority of these fractures, while kyphoplasty may be helpful in more acutely injured patients who have greater height loss,” he said “The most opportune time to use kyphoplasty is soon after the vertebrae fractures, so the break is fresh and the bone is more malleable.”
— Coleen Curran

photoMore questions than answers surround hormone replacement
Talk to your doctor.
   That is still the best course of action for menopausal and post-menopausal women who are facing the prospect of hormone replacement therapy, according to the American Cancer Society.
   As researchers continue to explore the side effects of estrogen and estrogen-progesterone therapies, questions arise about the cancer risks to women.
   A major study released by the National Cancer Institute this year reports a greater risk of breast cancer for women receiving estrogen-progesterone combination therapy as compared with estrogen therapy alone.
   Calling the research “an important study,” Joann Schellenbach, a spokesperson for the American Cancer Society, said it still does not provide the answer as to what is the best treatment for women.
   “It raises a question that each woman should discuss with her physician,” Schellenbach said of the study. “But you can’t make a blanket statement from it — care has to be individualized based on consultation with a physician and a woman’s medical and family history.”
   Using data from more than 46,000 postmenopausal women, the study found a “marked” increase in breast cancer risk to those receiving combination estrogen-progesterone therapy as opposed to estrogen alone. Combination therapy was associated with a 10 percent breast cancer risk for each five years of use, according to study data.
   Steven R. Goldstein, M.D., professor of Obstetrics and Gynecology at New York University School of Medicine, said that many doctors currently recommend some form of hormone replacement therapy to treat symptoms of menopause and reduce the risk of osteoporosis. Progesterone reduces the risk of uterine cancer, and the combination therapy of estrogen and progesterone is considered standard treatment in women who have not had a hysterectomy.
   “This study isn’t good news for women,” Goldstein said of the national research, but he added that women receiving hormone therapy should not be unnecessarily alarmed by the results.
   Goldstein, who has written extensively about treatment options for menopausal and perimoneopausal women, stressed that women today have many more options available to them as compared to 20 years again when research for the study began.
   Today, Goldstein said, newer types of progesterone, such as natural oral micronized progesterone and natural vaginal progesterone, are readily available and are safer than the progesterone likely used by the women in the study. Also, he said, some physicians are now treating women with fewer doses of progesterone a regime called “sporadic progesterone.”
   Schellenbach said that the study results were not a surprise. Other studies have shown an increased cancer risk with combination hormone therapy, she said, and more data is currently being collected by other studies including the national Women’s Health Initiative.
   Established by the National Institutes of Health, the initiative is a long-term study of more than 164,000 women to determine the effects of diet and hormone replacement therapy on heart disease, cancer and bone disease.
   Regarding hormone replacement therapy, Schellenbach said, “Nobody feels that the definitive research has been done yet. The information continues to come in. Meanwhile, each woman has to make her own decision with her doctor.”
— Barbara R. Rice

dm04.jpg NEJM study finds C Reactive Protein is cardio risk indicator in post-menopausal women
A recent study in the New England Journal of Medicine confirms that Dade Behring’s N High Sensitivity C-reactive protein (CRP) assay is useful in assessing risk of cardiovascular and peripheral vascular events, such as heart attack and stroke.
   The study, C Reactive Protein and Other Markers of Inflammation in the Predication of Cardiovascular Disease in Women, was authored by Paul M. Ridker, M.D., M.P.H., cardiologist and associate professor of medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston and colleagues. The FDA-cleared assay can detect levels of CRP in the blood down to 0.175mg/L.
   The researchers studied 28,263 healthy postmenopausal women over three years. To assess the risk of cardiovascular events associated with baseline levels of markers of inflammation, results from 122 participants who suffered a cardiovascular event were compared to the levels of 244 women who did not.
   Of the 12 markers measured, high sensitivity CRP was found to be the most significant indicator of the risk of future cardiovascular events, with relative risk of 4.4 for women in the highest quartile as compared with the lowest quartile.
   Conclusions suggest that the addition of high-sensitivity CRP to lipid screening may provide an improved method of identifying persons at risk for cardiovascular events.
   C-reactive protein is an acute-phase protein, which rises due to infection, tissue injury, or inflammatory processes such as rheumatoid arthritis, cardiovascular disease and peripheral vascular disease.
— Melissa R. Mac

dm04.jpg Ovarian tumor index helps identify malignant from benign masses
In an effort to save thousands of women from unnecessary surgeries and ensure appropriate treatment for those who do, researchers at the Dallas University of Texas Southwestern Medical Center have developed an ovarian cancer tumor index to help physicians accurately distinguish between benign or malignant ovarian tumors.
   Many ovarian tumors, confirmed though ultrasound, are found to be benign after surgery. Unfortunately, diagnosis is difficult before surgery so many physicians recommend aggressive treatment.
   The index evaluates characteristics of malignant and nonmalignant masses using ultrasonic measurements of flow, structure and color mapping.
   The most definitive diagnostic characteristic turned out to be patient age. Younger patients were more likely to have benign tumors. Large vascular tumors with abnormal appearances were more likely to represent malignant disease.
   The index interprets a complex set of ultrasound findings in a way that helps physicians plan for clinical management. Information from the index may help physicians decide whether they should perform surgery or refer the patient to a cancer specialist. The index also can indicate which patients would benefit from serum monitoring, or laproscopic surgery.
   “We were frustrated with many of the pre-existing algorithms used for determining if an ovarian mass might be cancerous,” said David Miller, M.D., director of gynecologic oncology and professor of obstetrics and gynecology at The UT Southwestern Medical Center and one of the study researchers. “Many of those were black and white, and unfortunately many things in biology are gray.”
   Researchers studied the many formulas for evaluating masses with ultrasound and then compiled a detailed prospective evaluation on a group of their ovarian tumor patients. These were patients they were concerned about but did not know if their masses were malignant.
   A year or two later they followed up to see what had happened to those patients, and whether or not their masses were malignant. The results of that analysis were used to sort and make risk estimates based on the score of each patient’s ultrasound scan.
   Of the 304 women in the study, 244 had follow-up care at UT Southwestern, allowing their outcomes to be correlated with prospective ultrasounds. Of the 244 women, 214 were diagnosed with non-cancerous masses, 30 had neoplasms that proved cancerous, and 85 of the non-cancerous masses were benign neoplasm-type tumors. The study included peri-, post-, and menopausal women. As the researchers suspected, patient age and the size, appearance, and blood flow of the mass were significantly different in cancerous and non-cancerous lesions.
   Miller said the tumor index study is ongoing. Researchers at UT continue to use the new tool, and judging from the number of phone calls he has received, other clinicians are at least evaluating it. Since about 20 percent of ovarian masses are cancer, Miller said the main value in the index is that it can help physicians identify the kind of expertise they will need to have available at the time of the patient’s surgery, such as a cancer surgeon.
   “If the mass is at low risk for malignancy, then most gynecologists are very capable of taking care of that,” Miller said. “If it is at a high risk for malignancy, then that patient may benefit from having a gynecologic oncologist in attendance at the surgery.”
— Melissa R. Mac

dm06.jpg (9451 bytes)Ovarian cancer facts

• Ovarian cancer is very treatable when detected early, but the majority of cases are not diagnosed until it is too late.
• When ovarian cancer is detected before it has spread beyond the ovaries, 95% of women will survive longer than five years.
• Only 25% of U.S. ovarian cancer cases are diagnosed in the beginning stages.
• When diagnosed in advanced stages, the chance of five-year survival is only 28%.
• Symptoms, which are easily confused with other diseases, include abdominal pressure or bloating, constant and progressive changes in bowel or bladder patterns, persistent digestive problems, excessive fatigue, abnormal bleeding and pain during intercourse.
• Increased risk factors for developing ovarian cancer include: increasing age, family history of ovarian, breast, or colon cancer, and not bearing a child.
• 90% of women diagnosed do not have a family history that puts them at higher risk.
• No reliable and easy to administer screening test such as the Pap or mammogram currently exists.
• The National Cancer Institute spent only $62 million in 2000 on ovarian cancer research, even though one-third as many women die of ovarian cancer as die of breast cancer. NCI is spending only one-seventh as much money for ovarian cancer as for breast cancer research this year.

dm07.jpg (7908 bytes)C-sections performed too early in labor
Nearly one-quarter of women undergoing cesarean section (c-sections) may have had the procedure too early in their labor, according to a new Agency for Healthcare Research and Quality (AHRQ) study. The study, conducted by researchers at RAND, Brown University and the University of California and funded by AHRQ, is in the April 1, 2000, issue of Obstetrics and Gynecology.
   Of the one million c-sections performed annually, about 294,000 of them are done because of lack of progress in labor. In this study, researchers found that 24 percent of the c-sections may have been performed too early. These women had c-sections with a dilation of only zero to three centimeters contrary to recommendations of the American College of Obstetrics and Gynecology (ACOG) that the cervix should be dilated to four centimeters or more before diagnosis is made. In addition, many repeat c-sections occur subsequent to previous c-sections done for lack of progress.
   According to the researchers, doctors may be more at ease with risks associated with c-sections than with those associated with abnormal labors that are not progressing as rapidly as expected. They also concluded that doctors either disagree with ACOG recommendations or interpret them differently. As a result, doctors may formulate their own definitions of “lack of progress in labor.” The authors suggest that more research is needed to understand the health effects of diagnosing lack of progress earlier in labor and why doctors do not follow the ACOG recommendations.
   Researchers reviewed medical records and collected postpartum telephone surveys from 733 women who delivered full term, nonbreech infants by unplanned c-sections. The data were captured from 30 hospitals in Los Angeles County and Iowa between March 1993 and February 1994.
— Coleen Curran

dm08.jpg (9843 bytes)More osteoporosis treatments being studied
One third of American women over age 65 will experience a spinal fracture or vertebral or compression fracture, according to The Osteoporosis Center in Modesto, Calif.
   As a major public health problem in this country, osteoporosis numbers are frightening. More than 250,000 hip fractures occur annually in the United States with approximately 65,000 of those cases resulting in death.
   There are several drugs available for the treatment and prevention of osteoporosis, including alendronate, calcitonin and raloxifene. Fosamax (alendronate) is in a class of drugs called biphosphonates to treat osteoporosis in post-menopausal women. It has been shown to build healthy bone, thereby reducing the risk of spinal fractures and the resulting loss of height.
   Fosamax has been studied in more than 1,800 women in five clinical trials. Data have shown that over three years, the drug can build healthy bone at the spine, hip and other sites by as much as 10 percent, as compared with patients treated with a placebo, whose bone mineral density decreased. The drug reduced the number of women suffering from new spinal fractures by 48 percent compared to women treated with placebo.
   Merck & Co. Inc., the West Point, Pa., distributor of Fosamax, reports that the drug has been taken in the United States by more than 2.5 million post-menopausal women with low bone mass. Fosamax also is used to treat osteoporosis in men and women receiving corticosteroid medications such as prednisone.
   Calcitonin, which is produced in the body by the thyroid gland, regulates calcium levels by inhibiting osteoclastic activity, or the breakdown of bone. Once osteoclasts are inhibited, osteoblasts can work to build up bone mass. In clinical trials involving women with osteoporotic syndromes, therapeutic results using calcitonin from salmon, such as Calcimar and Miacalcin, have been conflicting, according to the Osteoporosis Center. Some studies showed a slowdown in annual bone loss rates, and others showed significant dose-related increases in vertebral and long bone mass. Generally, calcitonin appears to increase bone mass by about 2 percent after two years.
   Calcitonin may have additional benefits for older women who are already suffering from full-blown osteoporosis. Its analgesic properties can help relieve the bone pain associated with established osteoporosis.
   In December 1999, Unigene Laboratories, Inc. of Fairfield, N.J., announced that an Investigational New Drug application was filed by Warner-Lambert with the U.S. Food and Drug Administration to begin clinical testing of an oral formulation of calcitonin that was developed by the two companies. Phase I studies, which are slated to begin following FDA review of the application, will mark the first human studies for this product in the United States. It was tested on humans in 1999 in the United Kingdom.
   In January, the company filed its own IND application with the FDA to begin clinical testing of its proprietary nasal calcitonin formulation. On Feb. 7, Unigene announced it had begun U.S. clinical studies for its calcitonin nasal spray product under the IND application filed earlier this year. The study design is similar to that used in the company’s U.K. pilot study of its nasal formulation, which was completed last June.
   Unigene also announced it has filed a patent application for its nasal formulation with the U.S. Patent and Trademark Office.
   On Feb. 25, Unigene completed testing of the clinical supplies of oral calcitonin that will be used by Warner-Lambert in its upcoming Phase I/II human study. Unigene received a $1 million payment from Warner-Lambert for this milestone.
— Melissa R. Mac

dm09.jpg (8471 bytes)Women less likely to receive cholesterol-lowering drugs
Although many men with heart disease are not taking cholesterol-lowering medication, even though the drugs are proven to prevent heart attacks, women in particular may be missing out on the benefits of cholesterol-lowering medication.
A study in the Feb. 14 Archives of Internal Medicine, reported that men and women with heart disease appear to be undertreated at major medical centers in the United States and Canada. Doctors have the wherewithal to fight heart disease, they just have to do it more effectively, according study author Michael Miller, M.D., of the University of Baltimore Medical Center in Baltimore.
   In recent years, several studies have shown that taking cholesterol-lowering drugs can reduce high levels of LDL (bad) cholesterol and dramatically reduce the risk of heart attacks. However, many individuals who might benefit from the drugs are not getting the prescriptions.
   In the study, Miller and his colleagues looked at 825 men and women who were enrolled in a clinical trial at 16 hospitals in the United States and Canada between 1994 and 1997. Originally, the study was designed to examine the effects of a common blood pressure drug on heart disease.
   Approximately 42 percent of men and 38 percent of women with the highest LDL levels were taking cholesterol-lowering drugs at the start of the study. After a 1994 study found that the drugs could reduce the risk of heart attack, a letter was sent to physicians in the study recommending that participants start taking cholesterol-lowering drugs.
   However, three years later, the researchers found that only 55 percent of the men and 35 percent of women with the highest LDL were taking the drugs. During the study, the rate of men with high LDL levels dropped from 50 percent to 29 percent, but there was little change in women. Forty-eight percent of women still had high LDL levels, compared with 51 percent at the start. The reason for the gender gap could be that physicians think women are less likely to benefit from the drugs, or that heart disease progresses more slowly in women, according to Miller. The researchers called for increased efforts to ensure that all patients with coronary heart disease receive appropriate medications. Pfizer Pharmaceuticals Inc. of New York funded the study.
— Melissa R. Mac

Link between clotting factors and estrogen
The levels of two blood factors associated with heart disease risk go up and down over the course of a woman’s menstrual cycle, according to research from this year’s American College of Cardiology meeting. This finding could contribute to understanding heart disease risk in pre-menopausal women and the cardiovascular effects of estrogen supplementation after menopause, according to Elsa-Grace Giardina, M.D., professor of clinical medicine at Columbia University College of Physicians & Surgeons.
   Giardina’s research investigates levels of plasminogen activator inhibitor (PAI-1), fibrin D-dimer, and von Willebrand Factor (vWF) in pre-menopausal women. PAI-1 enhances the breakup of blood clots, while vWF promotes clotting. Clot formation in the blood vessels can lead to heart attack or stroke.
   Giardina and her colleagues at the Columbia Presbyterian Center for Women’s Health, where Giardina is also medical director, used an enzyme-linked immuno-absorbent assay to check levels of the three factors in 19 women at days two, nine, 16 and 23 of their menstrual cycles. During a normal menstrual cycle, estrogen levels increase steadily. The Columbia team found that levels of PAI-1 decreased steadily as the cycle progressed, while levels of vWF peaked at days two and 23 of the cycle. Giardina said that while the increase in vWF may not be good for premenstrual women, “it may be disastrous for post-menopausal women,” who are at greater risk for heart attacks.
   Giardina believes two inferences can be made from the research. First, young women who have heart attacks may have abnormally high levels of PAI-1 and vWF. Second, it may be helpful to monitor levels of these factors in postmenopausal women, just as estrogen levels are monitored, to gauge heart disease risk.