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 Women’s Health: News from the Front
The latest advances in diagnosis, treatment, and prevention for five major health threats
By Catherine Censor
Wouldn’t it be nice if your neighbor was a really prominent doctor? Let’s pretend for a moment. She’s not just on the leading edge of her field, but she’s also an approachable, chatty type of neighbor who will happily entertain all your questions and give you tons of free advice—not just the official “party line” that you usually get. She will share her inside hunch about where the research is heading. She’ll tell you what she’d do if you were her sister or best friend whose health and peace of mind were at issue.
Fortunately, we really do have neighbors like these. Our area’s hospitals and medical centers have the kind of expertise you only find in research centers like New York where the latest findings and technology are put into practice long before they’re on the radar of other institutions. People travel from all over the globe to see these doctors but we’re lucky enough to be able to see them over the backyard fence.
Although we didn’t stroll over to their homes armed with a plate of cookies, we did call some of the region’s leading medical experts to find out what’s new in the diagnosis, treatment, and prevention of women’s health issues. We asked them about heart disease (the leading cause of death for American women), osteoporosis, breast and ovarian cancer, and infertility.
“Most women don’t realize it, but heart disease is the single leading cause of death for American women,” says Dr. Dina Katz, attending cardiologist at Phelps Memorial Hospital in Sleepy Hollow. In fact, according to Donna Gaudioso-Zeale, R.N., and Dr. Robert Stark, a cardiologist and director of Greenwich Hospital’s Cardiovascular Prevention Program, heart disease accounts for 66 percent of all female deaths—twice as many deaths than from breast cancer and all cancers combined.
We tend to think of heart disease as primarily a man’s disease, but statistics show otherwise. “On average, women develop heart disease 10 years later than men, but we quickly catch up,” explains Katz. “After menopause, the risk of heart attack rises more than threefold,” adds Gaudioso-Zeale. And the image you’re probably forming in your head of a likely victim—an overweight, inactive smoker who lives on doughnuts and burgers—isn’t entirely accurate. “Even if you’re a thin marathon runner with normal cholesterol, you’re still at risk if you had a parent who had a cardiac event at 45,” says Stark. Stress is also a serious risk factor, especially if you’re a hard-driving, achievement-oriented woman in Westchester or Fairfield County. A healthy-looking appearance and an active lifestyle could mask early onset heart disease—what Dr. Stark dubs, “the Bill Clinton syndrome.”
Although women are at surprisingly high risk, they aren’t routinely screened for coronary artery disease (CAD). Why? Dr. Linda Cuomo, an interventional cardiologist at Cardiology Consultants of Westchester and an assistant professor of medicine at New York Medical College says women don’t always exhibit the classic symptoms that would trigger a workup for heart disease. “In most cases, physicians suspect CAD when there is chest pain or pressure which occurs when the heart does not get enough oxygenated blood to the heart muscle,” she explains. “However, many women do not get typical chest pain. Instead, more often women will complain that they just don’t feel right, they are tired, feel run down, or have stomach pain or nausea. A fair number of women will have no symptoms in the chest whatsoever.”
The good news is that if you suspect you might have CAD, advances have been made in diagnosis, treatment, and prevention. “I’ve been in practice for more than 20 years and my trips to the emergency room in the middle of the night have decreased dramatically because we’re treating with statins and aspirin,” says Katz. Stark concurs: “There are fewer heart attacks due to better preventative care and drug therapies.” In many instances, and especially when caught early, heart disease can be medically managed.
Diagnosis
“When to look depends on whether you’re high risk,” says Stark. “We look earlier in women who have risk factors like family history of heart disease, chronic stress from home or job, smoking, high blood pressure, high cholesterol, diabetes, or who are overweight.” Katz says she wants to see all women when they reach menopause and are therefore at enhanced risk. Like Stark, she wants to see women even earlier if they have additional risk factors. “If a woman has a first-degree relative (parent or sibling) who had heart disease at an early age— before age 55 for men, before age 65 for women—I want to see them early.”
Some standard tests for diagnosing heart disease in men aren’t as effective at diagnosing the disease in women. “Stress tests don’t work as well for women as they do for men,” says Stark. “Women’s coronaries are thinner and smaller so the test tends to generate more false positives.” For more accurate diagnosis, Stark favors doing an ultrasound of the carotid artery to check for abnormal thickening. “If it’s there, it’s a good indication that the same process is going on throughout the body. It’s like a canary in a coal mine.”
Doctors look for markers in the blood as well. “One newer test is for low vitamin D,” says Katz. “Women with cardiovascular disease tend to have lower amounts of vitamin D. We don’t know whether the deficiency is a marker for heart disease or whether it’s causal, but we do know that if a patient’s vitamin D level is less than 30 nanograms per milliliter, she should be seen by a cardiologist.” Although cholesterol level (particularly the ratio between “bad” LDL cholesterol and “good” HDL) is another such marker, Stark says, “We also look at cholesterol particle size, which is more predictive.” Additionally, doctors test for C-reactive protein, a blood test that measures inflammation in the arteries. “Eventually, we’ll be able to test DNA from a cheek swab and identify what patients are at risk for,” says Katz. “I want to see patients yearly because even if they don’t change, my field will.”
Treatment
Depending on the extent of the disease, treatment will include lifestyle changes (always), drug therapy (often), angioplasty with drug-soaked stents (sometimes) and bypass surgery (rarely). “The stents are the final last resort,” says Stark. “More good doctors are preventing the disease medically. Even when there’s 60 percent blockage, they’re drastically treating cholesterol so the blockage shrinks. You can sometimes reverse thickening of the coronary arteries with drugs and lifestyle.” In fact, the cardiologists we interviewed unanimously pointed to drug therapies as the most promising part of their practice. Doctors are particularly enthusiastic about statins, which not only lower cholesterol but also reduce the size of plaques. And they are increasingly less hesitant to prescribe them. “We’ve joked that statins should be in the water supply, like fluoride,” says Gaudioso-Zeale, “but people with lower-than-normal cholesterol have fewer heart attacks so what should the new standard be?” Statins are no longer reserved for patients with elevated cholesterol levels (where normal is defined as below 200). “Increasingly, if someone has normal cholesterol but abnormal particle sizes, they can be put on statins and helped,” says Stark. “We also put them on statins if they have other risk factors and we want cholesterol lower than normal.” The reason statins have become the most commonly prescribed drug in the U.S. is simple: They work where simple lifestyle changes don’t. “Approximately 80 percent of cholesterol comes from what you make, and 20 percent comes from what you eat,” explains Cuomo. “If you eat very badly, you might be able to bring it down by drastic lifestyle changes but if it’s very high, diet alone isn’t going to cut it.”
Statins, however, aren’t the only drugs in the pharmaceutical arsenal. “Besides statins, you have resins and niacin, which also raise HDL,” says Stark. “There’s also a class of drugs called fibric acid that lower cholesterol and triglycerides (fatty acids in the blood).” says Stark. What about aspirin? According to Cuomo, “Most of the studies looking at aspirin were done in men so it is difficult to apply the results to women. Usually low-dose aspirin is recommended for patients who have a high risk of developing CAD, for example those with a 10-year risk of greater than 10 percent. Once someone is diagnosed with CAD, they are treated with aspirin indefinitely.”
When drug therapy alone won’t clear arterial blockages, angioplasty is typically the treatment of choice followed by a drug-eluting stent. “We insert a balloon-tipped catheter in the coronary artery that squashes the cholesterol against the wall of the artery,” says Stark. “We insert the stent to keep the cholesterol from springing back. Stents are soaked in a drug that prevents re-growth of atherosclerosis.” The stents themselves are getting increasingly sophisticated. “Device companies are coming out with newer and better stents each year. We now have better stent options for patients with diabetes and patients with small arteries. The result is that the number of bypass surgeries has gone down but some patients will still need surgery.”
Prevention
Because the origins of coronary heart disease start early (arterial thickening has been found in kids as young as seven), experts like Gaudioso-Zeale believe in preaching the gospel of good nutrition and exercise early and often. “Ideally, they’d start in kindergarten, but between high school and college is when people really form habits. This has to be a way of life, not something we do when frightened enough to do it.” If that ship has long since sailed, Gaudioso-Zeale advises that you attend Greenwich Hospital’s Cardiovascular Prevention Program once you hit your early 30s. “It’s for people with a family history or other risk factors.”
While you already know that being at a healthy weight can help prevent heart disease, you might be surprised to learn that even modest weight loss can reap significant health benefits. “A loss of 10 percent of one’s weight has significant impact,” says Gaudioso-Zeale. “If you’re 250 lbs. and you lose 25, your blood pressure comes into range, your blood sugar comes in range—it’s the best treatment you can do for yourself.” When it comes to exercise, “The more you put in, the more you get out. You need to exercise for a half-hour, five days a week, at an intensity of 65 to 85 percent of your maximum heart rate (220-your age = maximum heart rate). But you don’t need to exercise for 30 minutes straight; it can be broken up into smaller bits throughout the day,” says Gaudioso-Zeale.
According to Dr. Elton Strauss, associate professor and chief of orthopedic trauma and adult reconstruction at Mount Sinai Medical Center in New York City, while both men and women suffer from osteoporosis, “Somewhere between 40 percent and 50 percent of 50-year-old females will have a fracture during the rest of her life related to osteoporosis.” And according to Dr. Steven Hindman, an orthopedic surgeon and partner of ONS Orthopaedic & Neurosurgery Specialists in Greenwich, CT, “Osteoporosis is painless, so you don’t know you have it until you break something.” To make matters just that more frightening, Hindman warns, “Once you’ve got it, it’s hard to fix it, and it may be impossible in lots of people. Bone builds up to age 30 and then it shifts to a negative balance for the rest of your life.” Oh, and it’s more common than ever: “We have an aging population and people are not as physically active because of more sedentary lifestyles,” says Hindman. “We’re therefore predisposed to osteoporosis. Some things that make it worse are being white, of small build, post-menopausal, drinking alcohol heavily, smoking, eating a poor diet, not getting enough exercise, living in the Northeast (where the lack of sun can create a vitamin D deficiency), and genetic predisposition.” Certain medications for other conditions can weaken bones and make osteoporosis even more likely. So, there’s nothing to do but put a deposit on one of those motorized scooters? Well, it’s bleak but it’s not quite that bleak.
Diagnosis
The first thing to understand about osteoporosis is that everyone eventually experiences bone density loss—men as well as women. “It runs on a spectrum of ‘normal’ to ‘osteopenia,’ which is an intermediate phase where you’re losing density, to finally, ‘osteoporosis’,” explains Hindman. Although osteopenia is a precursor to osteoporosis, not everyone who has osteopenia will develop osteoporosis. To measure the extent of your bone loss, doctors determine a ‘T-score’ based on bone mineral density (BMD) scans. Your T-score is essentially a predicted risk of fracture. The scans are important because the first places you’re likely to see fractures aren’t necessarily the places you’d expect to find them. Because the body isn’t building new bone at the rate it’s being depleted, the places where it’s getting turned over most frequently are where you’re most likely to see tiny fractures. “More people have problems in the spine as they age than in their long bones,” says Hindman. “As we all get older, we have insufficiency fractures—hairline fractures that take place in the spine and mostly in the pelvis—just from getting out of bed or up from a chair or while doing any twisting motion,” adds Strauss.
When should you get a BMD scan? Since almost every woman over 50 will show some evidence of osteopenia, available drugs aren’t without risk (more on this later), and a BMD scan can’t tell us much about bone quality (quantity, yes, but quality, no), that’s a matter of considerable debate. Women on certain medications or with other risk-elevating factors might be advised to get them and women who’ve had a fracture should strongly consider them. “Clearly if you’ve had a fracture, you need to be evaluated,” says Hindman. “Even if it was due to a fall, three to six months later, you need a bone density scan.”
To get a read on bone quality, doctors usually perform blood tests to determine a patient’s levels of calcium, phosphorus, and parathyroid hormones. “In osteoporosis, the calcium and phosphorus are usually normal, even in significant cases,” says Dr. Strauss. “What’s usually abnormal is vitamin D, which would be abnormally low, as well as the level of alkaline phosphatase (an enzyme that helps calcium deposit on bones), which might be elevated in some cases. Vitamin D is a major regulator of calcium metabolism and important in the development of osteoporosis.”
You might be surprised to learn that the doctor responsible for screening you for osteoporosis will probably be … your gynecologist? “Gynecologists have been put in charge of diagnosis and they do it by default because women see them once a year,” says Hindman.
Treatment
If your test results indicate a need for treatment, you’ll probably be referred to an … endocrinologist? “The real specialists have been endocrinologists because they manage metabolic bone disease,” explains Hindman. He or she can help slow down bone loss by resolving mineral deficiencies and abnormalities. An endocrinologist also sorts through the many drugs a patient could be taking— steroids, benzodiazepines, anti-depressants, etc. that can make bones more porous and prone to fracture. An orthopedist is the specialist of last resort. He or she deals with the fractures that are the consequence of osteoporosis. “By the time I see somebody, it’s too late,” says Hindman.
As you’ve probably noticed from the bevy of TV pharmaceutical ads, drugs like Boniva, Fosamax, and Actonel are often prescribed to treat osteopenia. “All of these drugs are bisphosphonates that slow down the rate of bone resorption (how quickly bone is broken down), but they don’t boost bone production,” explains Hindman. “Some are given weekly and some are given monthly or yearly but they’re all versions of the same drug.”
Recently, these medications have come in for serious scrutiny, especially when given long-term. “We like to think that these drugs are good but we have seen some incidence of fractures of sturdy bones, like the femur, that we think are induced by these meds,” says Strauss. “These medications are supposed to stiffen up bones and they do that. But when patients are taking them for seven or eight years, they have a higher risk of fractures because their bones are too stiff.” How risky are these medications? No one knows precisely. “We think they’re relatively rare. Let’s say there are a million patients taking the medication and you get six fractures, then that’s not a big deal—unless you’re one of those six,” says Strauss. “It’s a risk-benefit type of scenario that needs to be considered for each patient.”
Rather than just slowing bone loss, a promising new class of drug may increase bone production. “It’s called Prolia by Amgen and it’s just been approved by the FDA,” says Hindman. Given as an injection every six months, it’s currently prescribed for post-menopausal women with osteoporosis. “The only other drug that increases bone production is Forteo, a parathyroid hormone that’s injected daily for two years. It’s only used when other medications fail,” says Hindman. “It can only be used once in a lifetime because of a low incidence of bone sarcomas.”
“From an orthopedic point of view, patients who sustain a fracture aren’t facing as much of a doom and gloom scenario as it used to be,” says Strauss. “We have better implants and ways of stabilizing the fracture in bone that doesn’t have the best substance to it. However, some of us will replace a joint rather than trying to get osteoporotic bone to heal. Hip, knee, and shoulder replacements are better now and if you replace one of these at age 65, it should last for the rest of your life.”
Prevention
Hindman recommends calcium and vitamin D supplementation. “No one knows what the dosage should be for vitamin D, it’s a changing mark, but I’d say 1,200 to 1,500 units would help,” he says. “Calcium supplements need to be absorbable. If you put it in glass of vinegar and it’s not gone in 10 minutes, it’s worthless. Calcium carbonate, which is made from cow bones, may have trace elements like lead so it’s not an ideal source of calcium. Oyster shell supplements, like Oscal, are pretty clean so that might be a better choice.”
To these recommendations, Strauss adds, “Get more sun (use sunscreen on your face but let your arms absorb some vitamin D), eat more fish and eat more fish oils (vitamin D is predominant in salmon, mackerel, and sardines), milk, and orange juice fortified with vitamin D.” Both doctors heartily recommend exercise. “Exercise is the best treatment and prevention for osteoporosis,” says Strauss. “Bone loves motion. It’s quite flexible and the more you flex it, the less brittle it becomes.” But Hindman cautions that, “Weight-bearing exercise is helpful but not as helpful as people want it to be. Walking is not enough. You need high-impact exercise and weight-lifting, which provide healthful stress on the bones.”
Although one in eight women will get breast cancer in the course of her lifetime, the excellent news is that she’s increasingly more likely to become a breast cancer survivor than a breast cancer victim. “Treatment is unquestionably moving towards a less-is-more approach,” says Dr. Philip Bonanno, director of The Breast Institute at Northern Westchester Hospital in Mount Kisco. “Breast-conserving surgery, interoperative radiotherapy, and molecular evaluation of tumors are cumulatively giving women who develop breast cancer a better quality of life and a longer life.”
In fact, medical advances have changed the way doctors even talk about breast cancer. “The new buzz word is ‘survivorship,’ and it’s a good buzzword,” says Dr. Donna- Marie Manasseh, a breast surgeon and co-director of Stamford Hospital’s Women’s Breast Center. “Because so many women survive breast cancer, we are developing a program that addresses the needs of survivors coping with lingering effects of their treatments and psychological issues. The aim is no longer just helping these women fight breast cancer but also helping them get back to their new normal.”
Diagnosis
“No one knows how to prevent breast cancer, or cure advanced stage breast cancer, but we do know how to find it when it’s small, early, and very curable,” says Dr. Caren Greenstein, a radiologist and co-director of Stamford Hospital’s Women’s Breast Center. According to Dr. Howard Lee, a radiologist with Northeast Radiology (offices in Brewster, Mount Kisco, Danbury and other Connecticut locations), detection methods have gotten markedly better in the last five to 10 years. “Almost everyone has transitioned from film to digital mammograms,” he says. The advantages include no more missing images (film has a way of getting lost) and computer-aided detection. “The computer looks at the digital mammogram as a second set of eyes and highlights areas it thinks are of concern.” For women with dense breast tissue (usually younger women), Lee says the addition of ultrasound has yielded vastly improved detection. “The sensitivity of mammography to dense breast tissue is just 50 percent, which is like flipping a coin. When ultrasound is added, it’s over 90 percent.” But for the ultimate in accuracy, Lee and other physicians overwhelming prefer MRIs. “It’s the single best test for finding breast cancer because it’s not affected by breast density and it’s highly sensitive.” So why aren’t all women screened with MRIs? In short, because it’s expensive and insurance companies won’t routinely pay for it. “The American Cancer Society recommends that anyone with greater than a 20 percent lifetime risk get an annual MRI, and to make sure women who need MRIs get them, we help women calculate that risk,” says Lee.
The result of better screening is early detection. “Very often, we’re diagnosing in Stage 0 before it’s even penetrated the membrane of the duct in the breast,” says Manasseh. “At this stage, it’s 100 percent survivable and the patient often can avoid chemotherapy that more advanced cancers would need.” Despite recent controversy, physicians like Dr. Elisa Port, chief of breast surgery and co-director of The Dubin Breast Center at Mount Sinai Medical Center in New York City, firmly believe that mammograms for women between the ages of 40 and 49 save lives. “Currently about 25 percent of new cancer diagnoses are ductal carcinoma in situ (DCIS) or stage 0 and that’s solely related to mammographic screening,” she says. “Yes, there are false positives, so more isn’t always better, but there’s no question that mammograms save lives.”
So, when should you get your first mammogram and how often do you need one? “We screen BRCA mutation carriers or women who have had previous cancer or previous chest radiation at an early age and with different modalities but for other risk groups, there are no clearly defined protocols,” says Port. “I’ve stuck with the recommendation of mammograms beginning at age 40 unless there is a first-degree relative (i.e. parent or sibling) with breast cancer in which case, mammograms should start 10 years younger than when the youngest relative was diagnosed,” says Port.
Rather than testing everyone with the same degree of scrutiny, over-testing some women and under-testing others, doctors are getting better at parsing individual risk. “Every year, we make advances in methods to predict who is going to get breast cancer,” says Greenstein. “We have a large high-risk program, where women see a genetic counselor, get tested for known mutations, and even if they don’t carry the gene, they might be classified as high risk-based on family history. In high risk women, we screen more closely beginning at age 30. Of course, screening is important for everyone, regardless of risk profile. Seventy percent of breast cancer patients don’t have any family history.”
Treatment
“Breast cancer isn’t one disease,” explains Manasseh. “There are many types of cancer based on genetics and they behave very differently. Some cancers are aggressive and some are not; some cancers are receptive to estrogen and some aren’t; some patients will benefit from chemo but some won’t.” The recent advances in breast cancer treatment are, therefore, tailored to the individual patient.
“The ultimate goal is giving people what they need to cure their cancer without over- or under-treating it,” says Port. “Many women get chemotherapy as a precaution who would have been cured with surgery alone. The problem is that we’re not very good at figuring out who those women are. Oncotyping helps refine treatment for the individual. Some of this has to do with more targeted chemo agents and some has to do with treating patients with stage 2 or 3 cancers with chemo first, before surgery, so we can measure their response to treatment. When chemo is given after surgery, there’s no real way of knowing which agents work without waiting to see if the cancer recurs.”
For patients with invasive breast cancer who are having breast conservation therapy, The Breast Institute at Northern Westchester Hospital offers an exciting new development called interoperative radiotherapy (IORT), which is already in use in Europe. IORT delivers a concentrated beam of radiation to tumors as they are uncovered during surgery. “Traditional radiation therapy involves two parts: The entire breast is radiated externally and then the surgical site is further radiated,” says Bonanno. “The second part is called ‘the boost.’ This whole process can take six or seven weeks. The IORT that has been used up to now has been just for the boost (the patient still has external radiation prior to surgery). The newer approach that we and others are embracing is to have certain women with certain tumors be able to have their entire treatment in the form of that boost.” In other words, these patients will have a single radiation treatment while they’re still on the operating table and then their treatment is complete.
Surgical technique has also seen significant advances. “The primary advance is in breast conservation,” says Bonanno. “Good centers everywhere have a predominance of non-mastectomy management and non-open biopsies.”
If and when a mastectomy is required, some patients will be able to have nipple-sparing procedures and reconstruction options are more plentiful and more sophisticated than
ever before. Patients and their doctors can choose from methods that use the patient’s own fat and tissue (Deep Inferior Epigastric Perforator [DIEP] and other “flap” techniques) and novel improvements on procedures that use implants with or without expanders. “The choice of reconstruction method is one that’s influenced by other factors,” explains Bonanno. “The good news for women is that whatever reconstruction technique is performed, they’re getting pretty darned good results.” To help ensure those results, The Breast Institute takes advantage of another new technology, SPY interoperative imaging of breast skin using infrared technology. “Using an intravenous injection of material, we can make sure the skin has enough blood supply to support reconstruction,” says Bonanno.
Prevention
“Unfortunately, with breast cancer, the biggest risk factors— family history and age—can’t be controlled,” says Port. “The only non-surgical prevention option is Tamoxifen, which has been given for years to women with breast cancer to boost survival and prevent recurrence. It has been given to women at high risk and studies show that for this group, Tamoxifen can reduce risk by 40 to 50 percent. Many of these women are reluctant to take it, however, because side effects are serious. There’s a slight risk for uterine cancer, a slight risk for blood clots, and some women complain of menopausal symptoms.”
Another proven risk-reduction strategy is prophylactic bilateral mastectomy for women with high risk profiles. Surgical advances such as nipple-sparing mastectomies with scars hidden in the folds of the breast along with improved reconstruction techniques make this seemingly drastic measure an appealing alternative to a lifetime of high surveillance and constant worry.
“One big area of interest is vitamin D supplementation,” says Port. “A number of studies are showing that vitamin D deficiencies lead to increased cancer occurrence and risk of recurrence in women who have already had it.”
Ovarian cancer is a terrifying paradox. According to the Ovarian Cancer Network Alliance, it’s the ninth most common cancer among women, yet it’s our fifth leading cause of cancer-related death. A woman’s lifetime risk of being diagnosed with ovarian cancer is just one in 71, yet the five-year survival rate for women diagnosed with ovarian cancer is a dismal 46 percent (the five-year survival rate for breast cancer is 89 percent) and it hasn’t improved much in the 30 years since we collectively declared “war” on cancer.
Why is ovarian cancer so lethal and why has so little progress been made in treating it? The answer is frustratingly simple: “We have no validated test that provides accurate detection of early-stage cancer,” says Dr. David Fishman, professor of obstetrics, gynecology, and reproductive sciences and director of gynecologic oncology research at Mount Sinai Medical Center in New York City. “The goal of early detection is to find early, curable cancer. As it stands, most cases of ovarian cancer are discovered when they’re advanced, widespread, and difficult to treat. It’s easier to put out a campfire than it is to put out a wildfire that’s consuming half the state.” As far as treatments go, Dr. Joshua Raff, chief of hematology and oncology at White Plains Hospital says, “Baby steps are being made.” But as the survival rates indicate, there haven’t been any game-changing breakthroughs.
Some of the barriers to progress have to do with numbers— both the relatively small number of women who are diagnosed with ovarian cancer and the number of dollars allocated to fighting it. “The biggest issue is resources,” says Fishman. “Unfortunately, the ovary has not been a priority cancer.” Raff says that ovarian cancer isn’t on the public’s radar screen in the same way that breast cancer is. “Breast cancer has reached political awareness and there are many causes devoted to fighting it,” he says. “Ovarian cancer isn’t as common and it’s been somewhat overshadowed. Also, because ovarian cancer isn’t so common, robust research results from large clinical trials are harder to obtain.”
Against such a gloomy background, even modest gains are cause for celebration. And the field’s biggest goal, the development of an early detection test, has seen some interesting developments.
Diagnosis
Current screening methods are so poor that they don’t even qualify as screening methods. “There’s no accepted way to screen for ovarian cancer,” says Raff. Because the risk is relatively low for most women and the biggest portion of that risk is confined to women over age 45, most of the women who get tested for ovarian cancer are at elevated risk due to a genetic mutation such as BRCA or strong family history. “Some women have trans-vaginal ultrasounds and a blood test called CA-125 that measures inflammatory response, but there’s no evidence that these tests save lives.”
Unfortunately, CA-125 has a high rate of false positives. “CA-125 only tells us that your body is having an inflammatory response,” says Fishman. “But do you have a cold or do you have cancer? If you have cancer, where is it? What we want is something like a pap smear that picks up precancerous changes so that instead of treating late-stage cancer, we’re treating a non life-threatening disease.”
Fishman is one of many researchers looking for an earlystage test. The field is crowded with theories, beginning withwhether ovarian cancer is actually ovarian in origin. “There are questions as to whether ovarian cancer starts from the ovaries or from the fallopian tubes,” he says. “There’s been exciting progress but whether it’s clinically relevant has yet to be determined. We’ve identified hundreds of biomarkers for ovarian cancer but we don’t know if they’re relevant to early detection. For example, it’s been well known since 1900 that cancers have an abnormal blood supply. Theoretically, we should be able to look for abnormal vascularity. A blood test in combination with microvascular imaging might work. I want to get funding to try to validate this and if it works, we have an inexpensive test.”
One new blood test that’s currently on the market, OVA1 by Vermillion, Inc., uses an algorithm of several suspected markers for ovarian cancer to come up with a single score. It has been approved to help doctors determine whether a pelvic mass is likely to be malignant before exploratory surgery. Many hope that the use of this test might one day be expanded to early screening but again, it’s too early to say.
“The new frontier is validating proteins and lipids that appear to be part of the biology of cancer,” says Fishman. “The problem is that there are lots of ideas but we have to prove they’re real and lead to early detection.”
Treatment
At a recent conference of the American Society of Clinical Oncology, the news was about small advances rather than major breakthroughs. “One study showed that having really good debulking surgery may predict survival and lower recurrence rate,” reports Raff. “Also, after surgery, most women need six months of chemotherapy. A new drug called Avastin, which has only been used in advanced ovarian cancer, may lead to better survival rates when it’s given up-front and even after chemo.” Raff is particularly excited about a new class of molecular drugs called PARP inhibitors. “They work in a very elegant way by disrupting a tumor cell’s ability to repair itself and grow.” Fishman sees a bright future in biologics. “These are treatments based on the biology of cancer, drugs like Herceptin that affect the process by which cancer grows rather than simply killing all cells faster,” he explains. “Drugs that inhibit vascularization are also exciting because they decrease blood supply to the tumor. We want drugs that impact tumors but leave bones and hair alone.”
Prevention
There is no certain way to prevent ovarian cancer. Genetic testing helps identify women who are at heightened risk and, for them, state-of-the-art risk reduction consists of prophylactic oophorectomy—the surgical removal of presumptively healthy ovaries. “The problem we have is that we think we have ideas of what genes are associated with cancers of the breast, ovaries, and thyroid but these are only increased risks; they don’t tell us definitively who will get these cancers,” says Fishman. “As we become more sophisticated, we’ll know who really needs the surgery and who doesn’t.”
A healthful diet and plenty of exercise might offer some protection. “Some studies have suggested that people who exercise more may have lower incidences of cancer and lower incidences of recurrence,” says Raff. “Low amounts of animal fat and red meats, more whole grains than processed grains, and a rainbow of fruits and vegetables are also likely to be somewhat protective.” In addition, Raff recommends having vitamin D levels checked, then supplemented if low. “Low vitamin D has been associated with other malignancies, so it probably can’t hurt to take it under the supervision of a physician,” he says.
According to Dr. Elizabeth Fino a reproductive endocrinologist, attending physician at Greenwich Hospital and assistant professor at New York University School of Medicine, who splits her practice between the NYU Fertility Center and the Greenwich Fertility Center, one of the most common cause of infertility (which is defined as one year of trying well-timed intercourse without conception) is, not surprisingly, delayed child bearing. “Fertility is highly age dependent,” she explains. “In couples age 30 to 34, one in seven is infertile; in couples age 35 to 39, it’s one in five and in couples ages 40 to 45, it’s one in four.” Dr. Susan Malley of Westchester Health puts it bluntly: “It’s a lot easier to conceive at 30 than at 35 and if you’re trying to conceive at 42, you’re going to have to go straight to IVF [in vitro fertilization] and even then, success rates aren’t very good without donor eggs.”
Rather than revolutions in the way infertility is diagnosed and treated, refinements of technique, new applications of existing technology, and better predictive models are improving the odds for conception while diminishing some of the emotional stress. “Although the basic process of IVF hasn’t changed, it’s been refined,” says Dr. Kate Schoyer of The Ronald O Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College with offices in Mount Kisco.
Diagnosis
Because time is definitely not on your side, if you’re over age 35, Fino suggests going in for a work-up after six months of trying to conceive. “Besides age, there are other causes of infertility and they aren’t always on the female side of the equation,” says Fino. “Approximately one-third of the time, the problem is related to the female; one-third of the time, it’s with the male, and the other third of the time, the cause is unexplained.” A standard workup includes both partners and tests for each but for the purposes of this article we’ll look at the female side of the equation.
Malley, an obstetrician and gynecologist, says she often starts the work-up process while her patients are waiting for an appointment to see a specialist in reproductive medicine. She conducts a physical exam, asks about menstrual history (irregular or missed periods might indicate that a woman isn’t ovulating regularly or might not be ovulating at all), and runs blood tests for hormone levels that play a role in fertility including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin.
“An important component of the initial bloodwork is the evaluation of ovarian reserve which reflects the quantity, and to a lesser extent the quality of eggs remaining in theovaries,” says Fino. “A woman’s level of anti-mullerian hormone, which is produced in small ovarian follicles, reflects the size of the remaining egg supply. It’s thought to change earlier than FSH would so you can pick up the decline in ovarian reserve earlier. Women with a high level of antimullerian hormone tend to have a better response to ovarian stimulation for IVF and have more eggs retrieved than women with low levels.”
The last and final part of the work-up is a hysterosalpingogram (HSG), a radiology screening in which an injection of dye is observed as it flows through the cervix, fallopian tubes, and uterus. The test detects small lesions, blockages or other abnormalities that might prevent conception. “HSG also has a therapeutic benefit for some patients,” says Malley. “There’s increased pregnancy rate after the procedure because the tubes have been flushed out by the fluid that’s been pushed through them for the test.”
Treatment
Your treatment options depend on your diagnostic findings. “I do think a major area of improvement has been our ability to predict success with hormonal stimulation protocols,” says Schoyer. “We can provide more data about the likelihood of success with treatments because of our ability to measure ovarian reserve. ... If a patient is choosing between different options, it’s helpful to know right at the beginning what the odds are. For example, if a woman has tubal disease, you can offer laparoscopy or IVF; but if she’s older or has diminished ovarian reserve, hormonal stimulation, usually for IVF, is her best option.”
For women who aren’t good candidates for hormonal stimulation, the treatment of choice is IVF, in which her eggs are harvested and fertilized with sperm in a laboratory dish. The resulting embryo (typically more than one embryo) is then placed in her uterus. “We’ve gotten more successful with assisted reproductive technology,” reports Fino. “Success rates with IVF are tremendous. Of course, it’s age-dependent but at our center, in women who are less than 35, the pregnancy rate is 55 to 60 percent, in women age 35 to 37, it’s 42 to 45 percent, age 38 to 40, it’s 40 percent, and age 41 to 42, it’s between 25 and 30 percent.” One of the reasons success rates have improved is better-developed embryos. “More centers are carrying out embryo transfers on day 5 or 6, when they’re more developed, instead of on day 2 or 3,” says Schoyer.
To compare IVF outcomes at different clinics, Fino recommends that patients consult the Society for Assisted Reproduction Technology’s website, www.SART.org, which reports live birth rates and breaks down the information by patient age.
Other advances concern pre-implatnation genetic screening of the embryos. “We can diagnosis diseases before implantation,” explains Fino. “We can also test for chromosomal abnormalities such as Down’s Syndrome, and other common chromosomal causes of miscarriage in older women. We can now screen all 24 chromosomes of the embryo to detect aneuploidy.”
One consequence of IVF is that it often results in multiple births. “Because we as a center perform mostly day-five transfer, we can improve selection and replace fewer embryos and that has cut down on the rate of triplets dramatically,” says Fino. “It used to be very high but in our SART data of 2008 there were no triplets. There is still a significant chance of conceiving twins with IVF. We are working towards the goal of single embryo transfer in appropriate patients to alleviate this risk. In our center we typically transfer one to two embryos—again, it’s age dependent so sometimes we put back more than two—but patients under age 35 get, on average, get 1.5 embryos so many are getting a single embryo. Patients ages 40 to 42 get two or three.”
Prevention
If you’re staring down your biological clock or you’re facing cancer therapy that could destroy your fertility, IVF technology can be adapted to help preserve your ability to conceive. “We can’t stop your biological clock,” says Schoyer, “but we can buy you time.”
“Therapies for cancer can cause early or immediate menopause,” says Fino, “so the option to freeze your eggs or embryos before treatment is a tremendous advance. Despite the fact that we do not have abundant data on egg freezing, preliminary results are extremely promising.” According to Fino, “In a small group of patients at NYU we have demonstrated a 57 percent pregnancy rate with egg freezing which is comparable to our conventional in vitro fertilization using fresh oocytes. Today, more than 900 healthy babies have been born from oocyte freezing and thawing around the world. The incidence of birth defects in these babies does not appear to be increased as compared to natural conceptions.”
Malley notes that for cancer patients, there’s another option, ovarian transposition, in which an ovary is temporarily moved somewhere else in the body (like the arm) for the duration of therapy. “It has already yielded five live births,” she says. “GnRH agonist [a hormone] therapy can also help protect the ovaries during chemotherapy and offset some of the damage.”
For more garden-variety single-at-35 situations, freezing your eggs is an elective, albeit uncertain proposition. “It is available for single women in their 30s,” says Schoyer. “But egg-freezing is a newer technique and it should be done under the auspices of an institutional review board because it’s still considered experimental.” Freezing an embryo created with donor sperm may give you greater odds for conception but is obviously a complicated and often difficult decision.
The Best Defense
According to Dr. Woodson Merrell, the chairman of integrative medicine at the Continuum Center for Health and Healing (part of Beth Israel Medical Center) in New York City and Apogee Pilates and Wellness Centers’ integrative health advisor, “There are four fundamentals to optimal wellness: stress reduction, proper diet, proper and sufficient exercise, and sleep.” Here are his recommendations for incorporating these keys to better health.
Stress: The goal is to recognize what your stressors are and reduce your reactivity to those stresses by awareness and daily practice. Physical exercise can help. You also want some kind of relaxation practice on a daily basis, whether it’s yoga, meditation, or even just a few minutes of deep breathing in the morning. The goal is to recognize what your stressors are and reduce your reactivity to those stresses by awareness and daily practice.
Diet: For those facing any disease process, it’s helpful to be on diet that’s anti-inflammatory, like the Mediterranean diet (fruits, vegetables, healthy fats such as olive oil, complex carbohydtares (starches) and modest amounts of fish, poultry, and fat-free Dairy). Avoid trans-fats, saturated fats, charred meats, and preservatives: eat organic whenever possible. Have a plant-based diet with six or seven helpings of fruit per day, eat three or four times a day, and drink plenty of fluids. Look for foods in all colors of the rainbow. Each color has different phytonutrients and if you eat a colorful selection of fruits and vegetables—red, green, purple, blue—you’ll be getting a wide assortment. Finally, when you cook your food you take out some of the vitamins and destroy the enzymes. While you don’t have to eat a diet of raw foods, salads and juices retain all their enzymes and have anti-inflammatory properties.
Exercise: The literature is replete with reasons why everyone should exercise, even if it’s just going for a brisk, 30-minute walk three times a week. You can significantly increase longevity by taking two, 15-minute walks three times a week. In fact, people who are in the worst shape yield the biggest dividends by beginning to be more active. Don’t neglect flexibility. Staying flexible and supple, not just fit, helps preserve mobility. Pilates is a great way to enhance both flexibility and strength. It’s safe because it protects the back and it’s a great complement to aerobics.
Sleep: We all need eight hours a night. Before the invention of the electric light bulb, we slept just more than 10 hours, but today the average American gets less than seven. You can’t replenish your body without sleep. Exercise increases the quality of sleep and helps gets you to a deeper stage of sleep.
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