Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

Egg Freezing

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Doctors have been freezing sperm for 60 years and embryos (fertilized eggs) for 30. The first pregnancy that resulted from a frozen egg occurred in 1986.

But it’s been only in the past few years that fertility specialists have begun freezing eggs with any regularity – so short a time that two major professional groups, the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine still consider egg freezing experimental. They caution that a request to freeze eggs should be reviewed by an institutional review board before being granted.

Freezing eggs for non-medical reasons — a healthy woman choosing to harvest and preserve her eggs for conceiving a baby sometime in the future — is new enough that there are few reliable statistics on how successful the procedure is. “Success” in such cases means a take-home baby, not just an egg that is frozen without damage, or thawed safely, or even fertilized to yield a genetically normal, healthy embryo.

“So few women who have frozen eggs have come back to use them [that it’s impossible] to quote a clear pregnancy rate on it,” says Dr. Elizabeth Ginsburg, medical director of assisted reproductive technologies at Brigham and Women’s Hospital. There hasn’t been time to collect enough data, since women usually plan to freeze eggs for many months or years before retrieving them for conception.

But the idea is clearly catching on. Nationwide, roughly half of 282 US fertility centers surveyed offer egg freezing, according to researchers at the University of Southern California, who conducted the study and published findings last month(june) in Fertility and Sterility, a journal of the American Society for Reproductive Medicine. There’s a total of about 400 fertility centers in the US.

Egg freezing, not usually covered by insurance, can cost $10,000 or more per procedure. Beyond the initial expense, there are annual fees, often hundreds of dollars, to maintain the eggs. At Boston IVF, a leading fertility center in the US and one of the oldest as well, typical fees are $6000 for the harvesting and freezing of eggs, which does not cover the cost of hormones and medications, subsequent fertilization, or transfer of eggs to the uterus. The center has begun offering seminars on the process to young women, many of who are just outof college or grad school and heading into the work force.

At BostonIVF, egg retrieval is performed under general anesthesia, though other centers may use IV sedation plus pain-killing drugs.

Two-thirds of the clinics in the USC survey reported that they made the service available to women for elective reasons. Traditionally, egg freezing “has been used in women with cancer who face imminent loss of ovarian function. But recently, the technology has advanced to the point where it is worth using for women who want to preserve their oocytes for social reasons,” says Dr. Briana Rudick, a reproductive endocrinologist at the University of Southern California and the lead author of the survey.

There are no reliable numbers for how many women have chosen to have their eggs frozen so far. About 60 women have done so at BostonIVF, most of them as a hedge against their advancing age, says Dr. Kim Thornton (cq), clinical director of the center’s egg-freezing program. So far, none has returned for the next step, she said.

Worldwide, more than 900 babies have been born from frozen eggs, according to a 2009 study conducted by researchers at the New York University Fertility Center, and published last year in Reproductive BioMedicine Online.

Of course, there are no guarantees that freezing eggs will preserve fertility, just as there are no guarantees – at any age – that a woman can get pregnant naturally. In both cases, the odds get worse as egg quality declines with age.

“Humans are the poorest of all mammalian species in terms of chromosomal integrity,” says Dr. Geoffrey Sher, founder of the Sher Institutes for Reproductive Medicine in Las Vegas, N.M. “With humans, even when they’re young, there’s only a 2 in 5 chance that an egg is normal. By the time a woman is 45, approximately one in 15 is normal.”

“Pregnancy rates at age 40 are pretty low even with fresh eggs,” says Ginsburg , at Brigham and Women’s. “You can chop that by two-thirds if it’s frozen eggs.”

Still, several advances are nudging the use of egg-freezing forward. One is “vitrification,” in which eggs are frozen within 15 minutes. Typically, eggs have been frozen slowly, over several hours, using programmable freezers that drop temperatures step by step. While many fertility clinics still use this method, ice crystals can form, making egg survival only about 60 percent, says Michael Tucker, scientific director at Georgia Reproductive Specialists in Atlanta. The claim with vitrification is that the egg survival rate may rise to 80 percent or even higher.

Testing the genetic viability of both eggs and embryos has also boosted interest in freezing. Several methods are available, including CGH, or comparative genomic hybridization, which checks eggs or embryos to be sure they have the correct number of chromosomes. Some embryos appear look normal under the microscope but have the wrong number of chromosomes, meaning they are not viable, says Sher of Las Vegas. Bottom line, a woman who wants to conceive a child at some point in the future should carefully consider the options — the risks, costs, and unknowns.

Regarding the use of egg freezing, a more recently available choice, Ginsburg advises, “If you want to have a child and it’s feasible socially, do it. … I get infertile patients, married for five years, who couldn’t imagine having a baby in [their] small apartment. That’s a bad reason to wait until age 35. It’s really sad, and I see it a lot.” 

Book on fertility and diet stirs buzz, skepticism

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Researchers at the Harvard School of Public Health have created a buzz with their new – and controversial – book, “The Fertility Diet.”

The book doesn’t actually come right out and claim that the new Harvard diet is a cure for infertility. But that’s the message desperate couples could be forgiven for getting, given its title, some of the authors’ public statements, the intense media hype, and, of course, the clout of almost anything with the Harvard imprimatur. That’s why some critics are upset.

The book, by epidemiologists Drs. Walter Willett and Jorge Chavarro and writer Patrick J. Skerrett, is based on the authors’ research, published in the November issue of “Obstetrics and Gynecology.”

In that paper, the authors reported on 17,544 women participating in the Nurses’ Health Study who recorded their diets and their quests to get pregnant in biennial questionnaires.

The study found that women had a lower risk of infertility due to anovulation – the failure to produce a viable egg every month – if they ate a diet that emphasized monounsaturated fats like olive oil over trans fats often found in baked goods; vegetable proteins such as in beans and nuts rather than animal sources such as red meat; whole grains instead of refined carbohydrates that cause too rapid a rise of blood sugar and insulin; some whole milk, a little ice cream or other high-fat dairy products daily; multivitamins containing folic acid; and iron from plants and supplements.

The study is groundbreaking because it “is one of the first times that anyone has shown that what you eat and drink can impact the reproductive system,” said Alice Domar, a psychologist who heads the Domar Center for Mind/Body Health at Boston IVF, one of the country’s largest infertility centers.

But it’s a huge leap to go from a statistical correlation to actually giving advice. The authors veer toward prescription when they say in their book, “We have discovered 10 simple changes that offer a powerful boost in fertility for women with ovulation-related infertility.” Ditto, in a cover story they wrote for the Dec. 10 issue of Newsweek, when they said their recommendations are aimed at preventing and “reversing” infertility – a conclusion Willett defended in an interview.

Observational studies like the Nurses’ Health Study do not prove that a behavior causes or prevents a health problem, only that it might do so. To prove that diet affects fertility, researchers would have to take a group of women with diagnosed infertility and randomly put half on a special diet and half on a regular diet and compare conception rates.

This would be an interventional study, which would have come closer to the “gold standard” of medical research and would have provided the solid ground to offer advice. Such a study could also show how long a woman would need to eat this way to affect her fertility.

Dr. Guy Ringler, a fertility specialist at California Fertility Partners and a board member of the American Fertility Association, cautioned in an e-mail that the new findings are interesting but “not sufficient to conclude that a modified diet in an infertile population would improve fertility. There need to be randomized, prospective studies comparing the different diets before such claims could be made.”

So where’s the harm in a little hype? Since the diet is basically a healthy one, except for the controversial suggestion to eat more high fat dairy, including ice cream, it is unlikely to cause direct harm. But a woman who follows the diet and still doesn’t get pregnant may blame herself, even though the diet isn’t proven effective.

Worse yet, a woman may follow the diet and postpone seeing a doctor. “If you’re 22 and you follow this diet for six months, that’s no big deal. But if you’re 42, you can’t afford to postpone seeing a doctor and try this diet in the meantime,” said Domar.

Dr. Gil Wilshire, a reproductive endocrinologist at Boone Hospital Center in Columbia, Mo., put it even more strongly: “This book is blatantly irresponsible. I am going to be cleaning up the damage from this book for years to come. I will be having women who wasted one, two, three years of their lives with imprecise, ineffective treatment. Those are precious years you can’t get back.”

But the book has obvious market appeal. Infertility is a source of heartache for more than 6 million American couples, although infertility due to problems with ovulation only account for about one-quarter of these cases. The diet won’t help if male biology – such as inadequate production of viable sperm – is the problem, as the authors themselves note. Or if the woman has blocked fallopian tubes or fibroids that impair the lining of the uterus.

All this said, the observations make biological sense, particularly the idea that certain foods may influence levels of hormones involved in ovulation and conception.

For instance, a diet high in refined carbohydrates is detrimental to ovulation because it sends blood sugar and insulin, the hormone that escorts sugar into cells, skyrocketing, Willett said in a telephone interview. Too much insulin makes the ovaries overproduce testosterone, the male hormone. Meanwhile, insulin reduces production by the liver of a protein called SHBG (sex hormone binding globulin), which captures testosterone. The net result of these processes is too much testosterone in the bloodstream, which can impede ovulation.

The ice cream recommendation is surprising, Willett acknowledged, and a bit tricky to explain. But his research suggested that “higher fat dairy products were related to better fertility and lower fat dairy was related to lower fertility. The reason? We’re only speculating, but it may well be that the relatively modest amounts of estrogen and progesterone that are present in the fatty part of whole milk can have a positive effect on fertility,” he said.

The Harvard team is not recommending a switch to high-fat dairy for a whole lifetime – if consumed long-term, high fat dairy products can increase the build-up of fatty plaques in artery walls, contributing to heart attacks.

The take-home message? If you’re having trouble getting pregnant, see your doctor before you hit the bookstore.

The balance between life and disease

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Like many other Americans lately, I’ve found myself thinking hard about – and personally identifying with – the dilemma faced by Elizabeth Edwards and her husband, John, the former senator and would-be president.

His career, her health. Not an easy balancing act. Who should sacrifice for whom? How much? Nobody wants to be – or live with – a martyr. But nobody wants to deal with – or watch a loved one deal with – cancer unsupported, either. Ultimately, everybody’s mental health counts – the sick partner’s, the healthy one’s, and the kids’.

For 11 years, my husband, Tom, and I grappled with these dilemmas, first because of his lymphoma, and for the last five or six years, because of his prostate cancer as well. We knew, of course, that there were millions of other couples in similar situations, but that didn’t help much. We had to juggle each other’s needs – and each make sense of our own – with every up and down of the cancer roller coaster.

He had a need, which was sometimes tough for me, to minimize things, and to remain fiercely independent. I was more emotional.

He wanted to go through his first chemotherapy infusions alone, reading his physics journals and his newspapers. I wanted to be there. That’s what “good” wives did. But this particular man felt my particular presence would overly-dramatize things. He could do better, he felt, pretending that he was just sitting there reading, as usual, even while powerful drugs dripped into his arm.

So I let him — I developed a kind of rule; we worked as a team, but he was the patient, so on big decisions, he got two votes and I got one. Once, though, because he had seemed more anxious than usual before an infusion, I showed up at the hospital uninvited. That time, we were both glad I did.

Like Elizabeth Edwards, Tom, who died last year, was amazingly generous in encouraging me to keep up my own life, almost to the very end, when I did drop everything. So, for year after uncertain year, he would tell me to keep working, keep swimming, keep singing with my singing group, keep going to my book group, keep going to see my grandkids. All of which I did, with some guilt, but also, to be honest, with considerable relief. Unlike Tom, I had the luxury of getting away from cancer once in a while, and I like to think it helped us both that I did.

Still, I asked him over and over how, given his situation, he could be so generous. I didn’t think I would be. But Tom didn’t seem to see it as generosity. He saw it as protecting his best asset – me – from despair and burnout.

I never did burn out, but I did despair. We spent hours and hours over the years talking, and crying, about Tom’s fears and sadness and my dread of losing him. I always felt selfish and weak when he sympathized with my fear of life without him. But he kept telling me that, precisely because of that, I had the tougher job. I’m not sure if that’s correct, but his acknowledgement of how tough it was for me helped.

When I first read of the Edwards’ decision to stay in the presidential race, I was horrified. I thought he was being utterly selfish, that they were painting an overly optimistic view of her prognosis and that he should drop out now and focus on being her husband.

But then I thought about her, and Tom. From Tom’s example, I could believe that, from the bottom of her soul, she would not want him to give up his (and their) dream, would not want to take on the “sick role” any sooner than necessary, would not want to be a burden. I think she is absolutely right to urge him to keep running. I’m less sure whether he’s right to agree.

Unlike Tom and me, the Edwards’ case involves the rest of the country, or could. If he wins and she’s dying, how could he possibly balance her needs against the world’s ? But they’re not there yet. Cancer is a chronic disease until it becomes a fatal one, and, as we discovered, it’s quite possible to have many good, relatively disease-free times for many years.

On the other hand, cancer is a crapshoot. You never quite know how pessimistic or optimistic to be. You never quite know which doctors are giving it to you straight, or who’s right about the statistics and the studies and the chances.

So, you do your best, individually and together. And you never really know if you did it “right.”

How to cope with shock of cancer diagnosis

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Late last fall, Dartmouth Medical School researchers reported in the journal Cancer that all newly diagnosed breast cancer patients in their study experienced at least some level of distress, and nearly half met the criteria for a significant psychiatric disorder such as major depression or post-traumatic stress disorder.

Well, duh!

Is it really news that a serious medical diagnosis can shake a person to the core? The only surprise to me is that a study like this is necessary. While some medical schools are adding classes in things like “how to deliver bad news,” the medical establishment as a whole still isn’t as good as it could be at helping people who go in a heartbeat from merely having a medical appointment to wondering how long they have to live.

Sure, cancer specialists are busy, as Mark T. Hegel , the clinical psychologist who headed the Dartmouth study, put it. ” They have short visits. They are very focused on treating the cancer. They are not well trained to look at the psychological issues.”

But we’re talking major life-altering event here. And while there are books, groups, and therapists galore to help with the long haul — clarifying the diagnosis, bearing up under treatment, then living the rest of your life as best you can — there’s much less to help with the first days and weeks after your life has been turned upside down.

Unfortunately, I’m speaking from personal experience. My husband’s two cancer diagnoses over the past 11 years were devastating to both of us. Dealing with everything that came later, including his death last summer, has also been difficult, to put it mildly. But for sheer, soul-shattering shock, the first hearing of the bad news was in a class by itself.

I learned — the only way, the hard way — how to muddle through the early days of a terrible diagnosis. Eat. Sleep, with sleeping pills if necessary. Breathe. Talk to a few close people. Don’t, as I did, tell everybody every single medical bulletin — you’ll spend all day and evening on the phone. Triage your life: Cancel what you can, but not the fun things — in my case, exercise and singing.

Do cruise the Internet for information about the disease if that helps control your anxiety, but log off immediately if it upsets you too much. You have doctors. You don’t have to become the molecular biologist or brain surgeon who will fix everything. Despite my decades as a medical journalist, I found that truly understanding a complex diagnosis is a daunting intellectual and emotional task.

A life-altering diagnosis, in other words, moves you abruptly from a normal existence into a parallel universe of fear and disease, though illness, of course, is part of life, too.

Social psychologist Jessie Gruman puts it this way in her wonderful, forthcoming book, “AfterShock : What to do When the Doctor Gives You — or Someone You Love — a Devastating Diagnosis,” for which she interviewed more than 250 people.

“Every time I have received bad health news,” she writes, “I have felt like a healthy person who has been accidentally drop-kicked into a foreign country: I don’t know the language, the culture is unfamiliar, I have no idea what is expected of me, I have no map, and I desperately want to find my way home.”

Gruman, 53, who is president of the Center for the Advancement of Health, a nonprofit patient education group based in Washington, D.C., has been drop-kicked into this foreign world four times, each unexpectedly.

The first was Hodgkins’ disease, a type of cancer, at age 20. “I was a total wreck,” she recalled recently. Then cervical cancer, picked up by routine screening when she was 30. “I had a successive series of operations that ultimately left me without a uterus.” Then, at 47, a terrifying case of viral pericarditis — an infection in the sac around the heart that landed her in the intensive care unit for eight days. Then, at 50, colon cancer, another surprise picked up by a routine colonoscopy.

She’s fine now, and armed with hard-won wisdom. A bad diagnosis “is a crisis. Treat it like one. Don’t try to go on as though nothing is happening to you. Don’t go to work for at least 48 hours, and cancel your social engagements until you get your feet back under you.”

You have to put yourself first. “You owe no explanations to anyone right now,” she writes. “Talk if you want to talk, cry if you feel like it. There is no particular benefit or harm in either. You are not responsible for taking care of others who are distraught at your news.” What you do have to do is make sure to set up your next doctor’s appointment and remember that “you will not always feel like this.”

Hester Hill Schnipper , chief of oncology social work at Beth Israel Deaconess Medical Center, has gotten bad medical news twice in the last 12 years, both times a diagnosis of breast cancer. “The very beginning, psychologically, is the worst time,” said Hill, author of “After Breast Cancer: A Common-sense Guide to Life After Treatment.” Things “always get better than the first couple of days,” she said. “Everybody copes, because what is your choice?”

If you have an inkling that your doctor visit may yield bad news, take someone with you, said Nicholas Covino , a clinical psychologist who heads the Massachusetts School of Professional Psychology. People often hear bad news alone, he said, “then have to find their way home by themselves.”

Lastly, don’t be surprised if, on top of your other troubles, your self-esteem takes a nose dive, said Dr. John Wynn , medical director of PsychoOncology at the Swedish Medical Center in Seattle. “The feeling is often one of shame, of punishment,” said Wynn. It’s irrational, but people often feel, “I am bad because I am sick.”

In truth, you are not bad because you are sick, or vice versa. You are in crisis.

So if you have just gotten bad medical news, take Jessie Gruman’s words to heart: “You will not always feel like this.”

Endometriosis Can Afflict Young Women, Too

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Christina Shimek, a senior at St. Bernard’s High School in Fitchburg, is only 17, but she has already had more pain than many adults have in a lifetime.

A year ago, Shimek, who lives with her parents in Leominster, said she woke up one morning “in excruciating pain in my lower back and pelvic area. I was in tears.” Frantic, her parents took her to the hospital, where doctors assumed the trouble was her appendix and took it out. But it turned out to be normal.

The pain persisted. She missed school for four months, had to repeat chemistry and missed an important rite of passage, her “junior ring ceremony” in which students get their class rings. She went to two doctors, who “were both baffled,” she said. Finally, a nurse suggested endometriosis, a diagnosis confirmed by surgery.

Historically, endometriosis — in which tissue from the lining of the uterus, called the endometrium, escapes and lodges in other areas – has been thought of as a problem of adult women.

According to the National Institutes of Health, 5.5 million women in North America have endometriosis; there is no cure, but pregnancy can sometimes trigger a lasting remission and the disease often gets better at menopause. The disease causes infertility in 30 percent to 40 percent of women who have it.

Two-thirds of adults with endometriosis began getting symptoms before age 20, and endometriosis is increasingly being found in young women as well.

It’s hard enough for any woman, adult or teenager, to get a correct diagnosis of endometriosis because there are so many other causes of abdominal pain, including appendicitis, bowel disease and pelvic inflammatory disease. In fact, it takes an average of 9 years for most adult women to get a correct diagnosis, according to a review paper published last year by the American College of Obstetricians and Gynecologists.

But while adult women typically have two to three doctor visits before they get diagnosed, it takes more than four visits on average for teens whose symptoms began before age 15, partly because endometriosis in young women is still not on the radar screen for many doctors.

And teenagers themselves often put off seeing a doctor for fear they will get a pelvic exam, in which the doctor inserts a finger or metal instrument into the vagina to feel the cervix and ovaries.

“Some kids are so afraid of a pelvic exam they won’t even get out of the car,” said Dr. Marc Laufer, chief of gynecology at Children’s Hospital Boston and lead author of the review paper. Doctors sometimes use ultrasounds on girls uncomfortable with pelvic exams.

Nobody knows why endometriosis occurs in the first place — it may be from menstrual blood flowing backwards and into the abdomen, from endometrial cells migrating to the wrong place during fetal development, from normal cells in the pelvis turning into endometrial cells, or for some other genetic, immunologic or environmental reason. This aberrant tissue then causes painful scarring and bleeding, because it responds to the same monthly hormones as the uterine lining itself. (In rare cases, endometrial tissue even winds up in the nose, triggering monthly nosebleeds.)

Slowly, doctors are getting a better handle on how to treat endometriosis in young women, though the treatments don’t always work. The first line of attack is continuous use of birth control pills containing the hormones estrogen and progestin to shut down ovulation and stop periods, said Dr. Meredith Loveless, who runs the pediatric and adolescent gynecology service at Johns Hopkins University. Non-steroidal anti-inflammatory medications like Motrin or Advil can help control the pain.

If this approach doesn’t help, laparoscopic surgery — in which doctors insert instruments through tiny incisions — is the next step. The endometriosis lesions, or areas, are then cut out or destroyed.

To make sure they don’t grow back, doctors prescribe more hormones, either birth control pills or a drug called Lupron, which shuts down ovulation. Because Lupron triggers hot flashes, mood swings and interferes with the formation of bones at the time of peak bone growth, doctors don’t use it for girls under 16. For older teens, they give Lupron with “add-back” hormones — small doses of estrogen and progestin to prevent these side effects.

“The hope is that by treating young women with endometriosis earlier, we can get better outcomes in terms of both pain and fertility,” said Dr. Claire Templeman, an assistant professor of obstetrics, gynecology and surgery at the University of Southern California. “But so far, there’s no data on long-term outcomes.”

And even with aggressive treatment, the pain doesn’t always go away. Anna George, 20, a junior at Hamilton College who comes from West Roxbury, said surgery and Lupron did get her endometriosis under control, enabling her to return to her volleyball team, which she had to quit last year.

But things have not worked out so well for Shimek: “Now I know what I have, but the pain is still there,” she said. Despite surgery and Lupron, there are still “days I just can’t go to school because it hurts too much.” And she’s still haunted by the threat of infertility. “I want children. That’s the most important thing. I would be devastated if I couldn’t.”

Reading the Signs:

Endometriosis, in which tissue from the lining of the uterus escapes to the rest of the body, can be hard to diagnose. But, according to the National Institutes of Health, there are often telltale signs, among them:

Extremely painful menstrual cramps that may get worse over time

Chronic pelvic pain (including in the lower back)

Pain during or after sex

Intestinal pain

Painful bowel movements or painful urination during menstrual periods

Heavy menstrual periods

Premenstrual spotting or bleeding between periods

Infertility

Complicating matters is the fact that symptoms of endometriosis can mimic those of some bowel diseases.

Getting Warmer in Bid to Kill Tumors

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A year ago, when Gayle Driscoll’s, breast cancer recurred on her skin, the 63-year-old retired teacher from Barnstable tried an experimental treatment that gave her radiation therapy some extra oomph . Every time she lay down for radiation treatment on her chest, her tumors were also heated with a special device that emitted radio frequency waves. After six weeks, the skin tumors were gone.

The heat therapy called hyperthermia was meant only as a local treatment — and the cancer ultimately spread to her bones — but it was “psychologically important” to her to see the tumors in her skin disappear, she said.

Hyperthermia, in which microwaves are used to raise the temperature of a tumor or the patient’s whole body to 104 to 106 degrees Fahrenheit, is a new twist on an old treatment idea that has gained new currency recently thanks to some successful studies.

Hypothermia significantly boosts the killing power of chemotherapy and radiation. It is generally used to help prevent local recurrences, but some doctors speculate that may improve overall survival as well. . At least eight studies in recent years have shown that adding hyperthermia to chemotherapy or radiation can improve local control of cancers of the esophagus, cervix, head and neck, brain, melanoma and breast cancers that have spread to the chest wall, said Dr. Mark Dewhirst, director of the hyperthermia program at Duke University Medical Center in Durham, N.C.

Scientists who have observed first hand the effects of hyperthermia are impressed. “I’m amazed at some of the tumors that just melt away with the combination of radiation and heat,” said Dr. David Wazer, radiation oncologist in chief at New England Medical Center.

At Long Beach Memorial Medical Center in California, Dr. Nisar Syed, director of radiation oncology, has treated more than 3,000 patients with hyperthermia plus radiation over the years. In many cases, “we saw rapid regression of the tumor,” he said, and in some cases, improved survival as well.”

In the future, hyperthermia could turn out to be among the most powerful anti-cancer weapons yet. Consider this idea, now being studied at

Duke: Researchers have created a tiny bubble, or liposome, with water on the inside and a ring of fat on the outside. Mixed in with the water is a chemotherapy drug, doxorubicin. The liposome is designed to be stable at body temperature but to burst when heated. By using hyperthermia to explode the liposomes, Dewhirst has shown in mice that doctors can deliver 30 times more chemotherapy than would otherwise be possible.

Scientists think hyperthermia probably fights cancer in several ways.

“When you combine heat and radiation, the cell-killing of cancer cells is better,” said Dr. Jay Harris , chairman of radiation oncology at both Dana-Farber and Brigham and Women’s Hospital.

Radiation works by damaging DNA. But there must be enough oxygen nearby for this damage to occur. Parts of tumors are tough to kill because they have a poor blood supply and thus, low oxygen levels. Raising the temperature of a tumor brings more blood, hence more oxygen, to the tumor.

With chemotherapy, drugs get in through small channels on the cell surface. “The heat opens these channels so that chemotherapy drugs can more easily enter in,” said Wazer of New England Medical Center.

Hyperthermia also seems to “jump-start the immune response,” at least in mice, said Elizabeth Repasky, an immunology professor at the Roswell Park Cancer Institute in Buffalo, N.Y., who is now looking at the effects in humans. Just as a fever with the flu may boost immune response, so may hyperthermia, a kind of artificial fever.

The idea of using heat to treat cancer started more than 100 years ago when an American surgeon, Dr. William B. Coley, noticed that some cancer patients who also had high fevers from bacterial infections had their tumors shrink. He began inducing fevers on purpose in cancer patients by infecting them with bacteria.

Several decades ago, a number of medical centers, including Dana-Farber and Johns Hopkins Medical Institute, began pursuing the idea — with disappointing results. Insurance payments for the procedures were low and a major study about 15 years ago showed no benefit to hyperthermia, though the study was highly flawed.

“So the technique was by and large abandoned,” said Wazer of NEMC.

The good news is that today, reimbursement rates are rising and the instruments that can deliver microwaves even to tumors deep into the body are more precise. In the last few years, new , better-designed studies “have rekindled interest” in the idea, said Harris. Moreover, the National Cancer Institute recently opted to grant $19 million to Duke to continue its hypothermia research.

Among the studies turning the tide for hyperthermia is one published last year by Dr. Ellen L. Jones, a Duke radiation oncologist. Writing in the Journal of Clinical Oncology, her team reported that, compared to patients getting radiation but not hyperthermia, those who got both had a significantly reduced the risk of recurrence of”superficial” tumors, chiefly breast cancers that had spread to the chest wall.

“I really trust the data coming out of this Duke group,” because the team was so meticulous, said Harris, who was not involved in the study.

In another study of 68 women with cervical cancer in the US, Norway and the Netherlands, also published last year, Jones and colleagues showed that a triple combination — hyperthermia, radiation and chemotherapy — was highly effective at lowering the risk of recurrence. A larger study comparing this triple treatment with standard treatment is now underway.

Dr. Joan M.C. Bull , director of thermal therapy research at the University of Texas Medical School at Houston is even pursuing whole-body hyperthermia for some kinds of cancers, including metastatic pancreatic cancer. Bull places patients, head and all, inside a radiant heat machine that brings body temperature to that of a high fever, about 104 F. It’s very safe, she said, though patients are monitored carefully. Some patients get “cranky” during the treatment, she said, as they might with a fever.

Working with rats, Bull has heated the body for about six hours, and found that chemotherapy can be given before, during and after heat treatment. Her early, still-unpublished, results “appear promising,” she said, particularly for cancers that have spread beyond a local area.

Clearly, more research is needed. But many regions now have at least one center. In Boston, it’s New England Medical Center; in Providence, a center is about to open at Rhode Island Hospital.

So if you or a loved one is getting treated for cancer, it’s worth asking a doctor if hyperthermia might help.

Hormones: Does Timing Make a Difference

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After years of frightening findings on hormone therapy, there is finally some reassuring news for women who start taking hormones close to menopause.

The new results suggest that there is a “window of opportunity” near menopause during which estrogen therapy may actually reduce heart disease risk, not raise it, as starting hormones a decade or so later seems to do. And this makes good biological sense.

“Estrogen slows the early stages of arterial disease,” said Dr. Jacques Rossouw, project officer for the Women’s Health Initiative, a study of 27,000 women aged 50 to 79 run by the National Heart, Lung and Blood Institute and published in a series of articles beginning in 2002.

But starting hormones later, say in a woman’s mid-60s, when arteries inevitably become more clogged with plaque, may be dangerous. “We know now from trials and angiographic studies [of blood vessel walls] that women who already have arterial disease, if you give them hormones, you do them no good and may increase the risk” of heart disease, he said.

“We have come full circle on this,” said Dr. Hunter Champion , a cardiologist at the Johns Hopkins School of Medicine. “It’s not one size fits all” with hormone therapy.

It’s increasingly clear that “a woman’s age, or more specifically, the time since menopause, is an important factor in terms of heart outcomes on hormone therapy,” said Dr. JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital.

The idea that starting hormones early can be beneficial was bolstered by two new studies, one published last week in the Archives of Internal Medicine and the other published several weeks ago in the Journal of Women’s Health. Two more studies – one called KEEPS by the Kronos Longevity Research Institute and the other, ELITE (Early versus Late Intervention with Estradiol) sponsored by the National Institute on Aging – are now enrolling women close to the age of menopause to further explore the issue.

In last week’s study, researchers focused on the youngest women (aged 50 to 59) in the part of the WHI involving women with hysterectomies who took estrogen alone, without progestin, the hormone needed to protect the uterus in women who still have one. Even in the original analysis of this group in 2004, these women had no increased cardiac risk. The new study last week goes further, showing a clear benefit in these women.

In this group, there was a 45 percent lower rate of cardiac bypass surgery or angioplasty (a technique for opening clogged arteries) in those on estrogen versus those on placebo, and a 34 percent lower rate of fatal or nonfatal heart attack, bypass or angioplasty.

(For the record, it was in the other part of the 2002 WHI study – on nearly 17,000 women aged 50 to 79 taking both estrogen and progestin – that researchers found the hormone therapy linked to a modest increase in heart disease, as well as breast cancer, stroke and blood clots. That study panicked millions of women into giving up their hormones, even though the increased cardiac risk was principally in the first year of combined hormone use, and the risk tapered off with time.)

The other new study involved a different group of women, those participating in the Nurses’ Health Study. This study showed that women who started taking hormones within four years of menopause had a 30 percent lower risk of heart disease than women who never used hormones. This was true whether a woman took estrogen alone or with progestin, said Manson, an author on both studies.

“It all relates to the underlying stage of atherosclerosis,” said Manson. Estrogen slows development of atherosclerosis in several ways. It decreases “bad” (LDL) cholesterol and raises “good” (HDL). It makes blood vessels more elastic, allowing them to dilate better, which increases blood flow. But in older women who already have plaques on artery walls, estrogen can increase the likelihood of blood clots or plaque ruptures that can trigger heart attacks and strokes.

Estrogen also assists in the secretion of nitric oxide from the cells that line arteries, said Dr. Alan Altman, a menopause specialist in private practice in Brookline. Nitric oxide helps dilate arteries. But when there is a lot of plaque, as there is in older women, the plaque blocks the access of estrogen to its receptors on artery walls, thus reducing the output of nitric oxide and making it harder for vessels to dilate.

In addition, estrogen stimulates production of a protein called MMP9, an enzyme that breaks down tissue, including plaque on artery walls, said Dr. Howard N. Hodis , chairman of cardiology at the University of Southern California Keck School of Medicine. That means that “estrogen may facilitate the rupture” of plaques in older women.

Of course, defining exactly when menopause is and thus, when to start taking hormones, is “very tricky,” said Dr. Rowan Chlebowski , a medical oncologist at LABioMed, a nonprofit research institute at Harbor-UCLA. The time around menopause, called peri-menopause, can last four or five years. It is only when a woman has not had a period for a year – which can only be determined retrospectively – that she is defined as menopausal.

Another unresolved issue is how long to continue taking estrogen if you do start within a few years of menopause. Should it become a lifetime treatment? “We can’t say that yet,” said Altman of Brookline. “That’s what I say to my patients, but I don’t think the data is obviously supportive of that yet.”

“We don’t have good evidence for either taking estrogen therapy forever or for taking for a short time only, when you look at benefits and risks for heart disease,” said Hodis of California.

Others shudder at the mere idea that a woman might be wedded to her estrogen until death do them part. The mainstream party line is still that a woman should start estrogen at menopause not for its heart benefits, but to combat symptoms like hot flashes, and that she should stay on it for a short time.

Nobody knows, said Rossouw of the WHI, “if estrogen will prevent heart disease into the future,” as a woman ages.

As for breast cancer risk, the two new studies did not address that issue. The original WHI study showed a slight increase in risk on combined hormone therapy after four years of use, but no increase on estrogen alone during seven years of treatment. For stroke, WHI data showed a slight increased risk for both oral estrogen alone and with progestin.

And so it goes. The studies pile up. The data get refined. The nuances get clearer. Some questions get answered, but we’re still stuck with an ever-growing mass of new ones.

For more information on the ELITE trial: 1 866 240 1489. For more information on the KEEPS study, visit www.keepstudy.org. (In the Boston area, call 617-732- 9870.)

Hormones Given Through the Skin are Worth a Look

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True confession time again: Just when I thought I had made peace with the Great Post-Menopausal Hormone Decision — in my case, sticking with very low dose oral hormones, despite the risks revealed in a 2002 study — I have plunged into the murk again.

This time, my curiosity and my game plan are focused on ”bioidentical hormones,” which are synthesized from soy and yams. They are made to be very similar to the hormones your body already produces — much more similar, for instance, than the hormones post-menopausal woman swallowed in pills like Prempro and Premarin.
Proponents argue that such similarity means bioidentical hormones won’t have the side effects of oral hormones, like Prempro, which the 2002 study found to modestly increase the risk of breast cancer, heart disease, stroke, and, blood clots.

But some mainstream researchers are leery. Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital, called the research on bioidentical hormones ”very, very sparse,” and warned that women should not flock to them.

”We need to be cautious about not repeating the debacle that occurred with conventional hormone therapy,” said Manson, a leader in the 2002 research on standard hormone replacement therapy. In a September newsletter, doctors from the Mayo Clinic similarly warned that ”hormones aren’t safer or better just because they’re labeled natural or bioidentical.”

So why am I even considering replacing oral hormones with something ”bioidentical”?

Because I like the way they’re delivered. The only way to get a ”bioidentical” substance — that is, an exact chemical match to something the body already makes — into the system is non-orally, chiefly through the skin, via patches, creams, lotions, or gels. Medicines taken orally don’t enter the bloodstream in the same form that you take them because they pass first through the liver, where their chemical structure is altered. Medicines taken transdermally do not pass through the liver en route to the bloodstream, and hence are not altered.

When a woman takes oral estradiol, the hormone that declines precipitously at menopause, it is converted in the liver to estrone, a weaker hormone, said Dr. Alan Altman, a menopause specialist in private practice in Brookline. By contrast, when estradiol is taken transdermally, it gets right into the bloodstream — as estradiol.

The transdermal form appears not to increase certain cardiovascular risk factors, such as blood clotting proteins, triglycerides, and C-reactive protein, as oral estradiol does, hormone specialists say. And, there may also be another advantage to taking transdermal estradiol. Research suggests that oral estradiol reduces the amount of available testosterone and therefore sex drive, while the transdermal form does not.

For the moment, at least, ”non-oral is the way to go,” said Dr. Carolyn Shaak , medical director of WomanWell in Needham and a longtime proponent of bioidentical hormones. ”If you want to duplicate the function of the ovary, you want to use a non-oral delivery system.”

Bioidentical hormones can either be made by drug companies or — as proponents prefer — on a patient-by-patient basis by a ”compounding” pharmacist, who follows a doctor’s prescription to deliver a precise dose. The compounded versions, because they’re more similar to the body’s own hormones, are safer and more effective than the hormone pills cooked up by Big Pharma, proponents insist.

Dr. Steven F. Hotze, who owns a compounding pharmacy in Houston and has treated thousands of patients with bioidentical hormones, has no doubts about the superiority of these products. His patients, he said, ”come in on Premarin and [don’t feel well]. We put them on bioidentical hormones and they get well. Hello? Come talk to my patients!”

Compelling words, to be sure. But there’s no hard proof that compounded hormones, which are not approved by the US Food and Drug Administration, are safe and effective.

In late October, a review committee of the American College of Obstetricians and Gynecologists found that ”there is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies.” The group cited a government analysis of 29 product samples (not all of them hormones) from 12 compounding pharmacies; it found that one-third of the products flunked quality tests, with many not even containing the proper amount of the active ingredients.

You don’t have to go to a compounding pharmacy to get many of these products. There have long been FDA-approved estradiol patches on the market. And in the last year or so, one FDA-approved cream (Estrasorb) and an FDA-approved gel (Estrogel) have also become available.

There are also FDA-approved vaginal rings that deliver estradiol, one called Estring which only combats vaginal dryness; and another called Femring, which addresses more menopausal symptoms.

For progesterone, which women who still have a uterus must take to offset the risk of uterine cancer from estrogen, a good solution is a type of progesterone sold as Prometrium — which, studies suggest, may carry less cardiovascular risk than the synthetic progesterone sold as Provera.

Needless to say, the growing popularity of non-oral approaches to hormone replacement is not lost on big drug companies, some of which make patches and creams.

Wyeth Pharmaceuticals, which makes the pill Premarin, went so far as to file a citizens’ petition to the FDA in October to address what a company spokeswoman called ”the growing and unlawful manufacture and marketing of so-called bioidentical hormone replacement therapy.”

The reaction to that in the bioidentical world is also no surprise. As Hotze put it: ”They’re putting pressure on the FDA to drive us little guys out of business. It’s a big monopoly push.”

As for me, my path through the murk is getting clearer. I’m switching from Premarin to an estrogen patch to keep feeling good. I could have switched to a compounded cream, but I feel safer with an FDA-approved product.

But, as we all know by now, hormone therapy is a moving target. So stay tuned!

Judy Foreman is a freelance columnist who can be contacted at foreman@globe.com.

You’re Getting Sleepy; Could that Stop Cancer?

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Melatonin, long known to insomniac Americans as an over-the-counter sleep aid, is now being studied as a way to prevent and treat breast and other cancers.

Dubbed the “hormone of darkness,” melatonin is a hormone that is made by the brain’s pineal gland at nighttime. This summer, researchers at Brigham and Women’s Hospital led by pidemiologist Dr. Eva Schernhammer showed that women who produced the lowest levels of melatonin had a 70 percent higher chance of getting breast cancer than those with the highest levels.

Schernhammer’s group had previously shown that women who work at night are at higher risk of both breast and colon cancer. Light at night can shut off melatonin production.

A Finnish study to be published this fall explores whether women who sleep 9 hours or more a night — and hence produce more melatonin — are at lower than average risk of breast cancer.

A co-author of that study, cancer epidemiologist Richard Stevens of the UConn Health Center in Farmington, Conn., said that breast cancer rates are much higher in industrialized countries, where, among other things, people use artificial light at night, which suppresses melatonin production.

“We can’t say yet, but the evidence is accumulating that light-at-night, and the consequent decrease in melatonin, may be a major driver of breast cancer,” Stevens said. From an evolutionary point of view, melatonin may have developed as a signal to tell animals when to breed. In sheep, melatonin levels rise in the fall as the nights get longer, and ewes become fertile — perhaps as nature’s way of insuring that when they give birth four months later, the weather will be balmier.

Melatonin is also an important regulator of the circadian clock in the brain, which keeps the body on a regular cycle of day and night. Light, whether from the sun or electric lights, suppresses melatonin production.

But when light disappears, and darkness falls, there’s a cascade of nerve signals from the eye to the pineal gland, which then starts making melatonin.

That’s why melatonin has been popularized as a sleep aid. But a government study in 2004 found the melatonin pills on the market had limited effectiveness. A more recent study from MIT suggests that the problem may simply be dosing: The pills that are currently sold in healthfood stores are many times too strong. A dose of only .3 milligrams helps people fall asleep faster, according to a study led by Richard Wurtman, director of MIT’s Clinical Research Center.

Frustrated by the high rates of breast cancer in industrialized countries, Stevens of UConn hypothesized back in the late 1980s that light-at-night might drive cancer and that melatonin might protect against it.

“We know that if you take out the pineal gland in animals, that removes all melatonin, and then if you inject cancer cells, the cancer growth rate increases,” said Steven Lockley, a neuroscientist at Brigham and Women’s, who is now studying blind women to see if they have higher than normal levels of melatonin, and whether they get less breast cancer. “We know that when you put an animal in constant light, that also stops all melatonin production, and you get a similar response. And if you then treat an animal with melatonin, you can slow down the cancer rate.” Researchers are just now starting to look at the treatment potential for melatonin.

At the Bassett Research Institute in Cooperstown, NY, Dr. David Blask, a senior research scientist, reported at a cancer meeting this summer that melatonin can “put cancer cells to sleep” by blocking their ability to soak up linoleic acid, which makes cancer cells grow rapidly. In animal studies, Blask said he has found that cancer cell growth is slower at night, when melatonin is highest, and faster during the day. He also found that adding melatonin to human breast cancer cells grown in rats can slow the cancer’s growth.

In other animal studies, Steven Hill, vice chairman of structural and cellular biology at Tulane University in New Orleans, has found that melatonin binds to receptors on both normal and breast cancer cells. Once it lands on a receptor, he said, it acts on chemical signals inside the cell to suppress estrogen, which drives many breast tumors. “We can prevent 85 percent of mammary tumors in our rats with a combination of melatonin and retinoid [vitamin A],” he said.

In Europe, studies of people with cancer who are given melatonin are also promising, though preliminary. Melatonin appears able to not only slow cancer progression and improve survival in advanced cancer patients, but to protect healthy cells from the side effects of chemotherapy and radiation, said Dr. Fade Mahmoud, a clinical instructor at the University of South Dakota School of Medicine who published a review of the studies this summer.

Spanish researchers have shown that melatonin acts in human breast cancer cells much like drugs called aromatase inhibitors, such as Arimidex, Aromasin and Femara. This means it can prevent the body from converting the hormone testosterone into estrogen.

Italian researchers, in a long series of human studies, have shown that melatonin, which appears to have little toxicity, can boost survival at least modestly in some people with melanoma and cancers of the lung, breast, kidney and other organs.

These studies “sound intriguing,” said Dr. Mark Pegram, director of the Women’s Cancer Program at the Jonsson Comprehensive Cancer Center at UCLA. “But obviously more experimental studies are needed to evaluate whether or not melatonin may play a role in breast cancer growth regulation.”

Spurred by the positive results, American researchers are starting to pay attention to melatonin. With colleagues at a cancer research center in Zion, Ill., Dr. William Hrushesky, a senior clinician-investigator at the Dorn VA Medical Center in Columbia, S.C., is doing a randomized, double-blind study with melatonin plus chemotherapy to see if melatonin helps lung cancer patients.

While it’s too soon to rush out and buy over-the-counter melatonin to fight cancer, it is a good idea to “live a melatonin-friendly lifestyle,” said Stevens of UConn.

That means going to bed earlier if you’re a night owl, making sure the bedroom is dark and keeping the light dim in the bathroom if you make nightly trips there.

If you’re a shift worker, ask your employer to explore changing the room lighting, more closely simulating normal night.

“The longer you stay in the dark,” Stevens said, “the more melatonin you’re putting out.”

A Diagnosis Of Cancer Is Trying For Any Marriage

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Cancer can be very tough on a marriage just ask Sandro Segalini, 64, of Falmouth.

His first wife died of breast cancer 14 years ago. His second wife, Marcia Woltjer, 59, left him earlier this year, three years after her own diagnosis with breast cancer. Segalini, a retired businessman, had been totally willing to take control of things and help Woltjer the way he had helped his first wife to be, as he put it, “chief cook, bottle washer, bandage changer, and jester.”

But Woltjer, a registered nurse who has since moved to Michigan, wanted someone who didn’t feel he had to be in charge all the time.

Obviously, when cancer strikes, there’s no easy role in any marriage, whether you’re the patient or the spouse. What makes some marriages fall apart under the strain of cancer and others get stronger? That’s a tough one, but researchers are finding some clues.

When it’s the man who has the cancer, the sheer fact of having a partner regardless of the quality of the relationship is linked to better survival and quality of life, according to a recent study of men with prostate cancer, by Dr. Mark Litwin, a professor of urology and public health at the Jonsson Cancer Center at UCLA.

But when it’s the woman who has cancer and that’s the scenario most frequently studied the quality of the relationship may matter more, perhaps because of the challenges to traditional gender and care-taking roles, said Laurel Northouse , a professor of nursing at the University of Michigan School of Nursing.

What many women both with and without cancer want, Northouse said, is not so much for the husband to be in charge, but for him to understand her feelings and to talk about his own.

For many couples, this means that when the wife gets cancer, both partners have to adapt, said Northouse. Men may have to listen, and express, feelings more, and women may have to turn to friends and supporters when the husband is maxed out on listening.

Researchers who studied 73 Israeli couples in which the wife had breast cancer found that if husbands were emotionally or behaviorally disengaged or unable to express their feelings in a constructive way, the wives were more distressed.

Other studies published in the 1990s also show that venting feelings in an uncontrolled way does not help, nor does criticizing each other’s emotional styles or withdrawing emotionally. Empathizing with each other’s feelings does help.

It’s also important, when the woman is the patient, for men to give up the desire to “fix” things, said Marc Silver, an editor at US News & World Report and author of the 2004 book “Breast Cancer Husband,” which he described as a “guide for clueless guys.”

“Every guy I interviewed said he had an urge to `fix it,’ ” said Silver, whose wife had breast cancer. Guys have “an inability to sit there with things not fixed. They want to get in there and make it better. But what guys really need to do is shut up and listen.”

Marc Heyison, founder of a Maryland-based group called Men Against Breast Cancer, which has a $1.1 million grant from the federal Centers of Disease Control and Prevention to help African-American, Latino, and Native American men support their wives with breast cancer, put it even more bluntly: “Be honest, men. You have to give up the remote control.”

Giving up control can be hard, especially when there’s disagreement about treatment. Silver recalled one wife with breast cancer who wanted holistic treatment. Her husband was appalled. But instead of taking charge, he just gently asked if there was any evidence for the holistic