Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

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.)

So, the Low-Fat Diet is Kaput, Now What?

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Last week, researchers conducting a long-awaited study on the effectiveness of low-fat diets dropped a bombshell: Eating a low-fat diet does not appear to reduce the risk of getting breast cancer, colorectal cancer, or cardiovascular disease.

The $415 million study, part of the Women’s Health Initiative, followed nearly 49,000 women aged 50 to 70 over eight years. It was the largest, longest, and best-designed study ever to test the merits of a low-fat diet.

To help sort out what to make of the new research, Globe columnist Judy Foreman and staff writer Carey Goldberg posed questions about the study to five leading experts on diet, heart disease, cancer, metabolism, and preventive medicine.

They all agreed on one thing: Although the study failed to prove a strong link between low-fat diet and better health, “it’s not really license to head for the butter,” as Dr. Michael Thun, chief epidemiologist for the American Cancer Society, put it.

They all pointed to other research though often less definitive than the new study suggesting that the most heart-protective diet includes lots of fruits, vegetables, whole grains, fish, and “good” fats like omega 3 fatty acids and olive oil.

The new study “is probably the final nail in the coffin for low-fat diets,” said Dr. Walter Willett, chairman of the department of nutrition at Harvard School of Public Health. “But people should not conclude that diet is not important. The right dietary choices can make a huge difference in long-term well-being. . . . It’s just this particular diet that doesn’t matter.”

Other excerpts from their responses:

Q: After considering the new data, what diet would you tell your patients to follow?

Trick or Treatment?

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A spate of recent studies reinforces the idea that what we think about our
medical care really can affect our health.

The new research into the power of placebos is giving scientists new
insights into how patients’ expectations their beliefs about whether an
inactive, sham treatment will work can have an actual, observable effect on
their well-being.

In one small study, volunteers with jaw pain were repeatedly injected with
what they were told was a pain drug but in reality was nothing but salt
water, yet PET scans showed that after every injection, their brains
produced endorphins natural, opiate-like painkillers.

The men’s beliefs about the treatment caused changes in the brains and
reduced their perception of pain, said Dr. Jon-Kar Zubieta, the study
leader and associate professor of psychiatry and radiology at the
University of Michigan Medical School.

The placebo effect can work in reverse, too, through its evil twin, the
“nocebo” effect. At least 25 percent of the time, when people take an
inactive placebo they report experiencing side effects like headache,
insomnia, and fatigue, said Dr. Arthur Barsky, a psychiatrist at Brigham
and Women’s Hospital. In other words, telling patients about potential side
effects can make it more likely that they’ll occur.

And last week, Harvard researchers reported that sham acupuncture provides
more pain relief than a sugar pill that comes with a promise of relief. The
conclusion to draw from the study, said researcher Ted Kaptchuk, is that
medical ritual “may be a critical component” of treatment.

The work on placebos will help researchers determine precisely what their
drugs are doing and what the contribution of the placebo effect is for
healing though it’s still unclear precisely how best to harness the placebo
effect to make patients feel better.

“The whole point of all this is, how do we capitalize on the placebo
response,” said Dr. Helen Mayberg, a professor of psychiatry and neurology
at Emory University School of Medicine.

The research shows that it’s not possible to “psych yourself” into making a
drug work. But not trusting your care whether it’s popping a pill handed to
you by a doctor or undergoing 30 minutes of treatment from an alternative
medicine practitioner is likely to undermine any benefits.

“This is not about the power of positive thinking, it’s about positive
expectations,” Mayberg said. “I can’t think myself well, but if you go in
with a new treatment and say, `This is not going to work,’ it probably
won’t help you.”

In general, from 30 to 60 percent of patients with everything from
arthritis to depression report an improvement in symptoms after receiving a
placebo. One-third of depressed people feel better after taking placebos,
while 50 to 60 percent of those taking antidepressants do, said Dr. Andrew
Leuchter, vice chairman of the department of psychiatry at the University
of California, Los Angeles.

“The placebo effect is the summation of all the things we do in treatment
that help people get better that are not part of a known specific
treatment,” he said.

“I define it that broadly because when we interact with someone in a
positive way, when we give them encouragement and support, and also when
they become part of the healthcare system no longer sitting at home ill,
but in a milieu where they are getting treatment we tap into positive
expectations.”

The effects of placebos wear off with time, but real drugs keep on working.

Because of this and medical ethics no one is suggesting that doctors
prescribe their patients sugar pills or sham treatments.

But combining real medicines with the “placebo effect” does more than
either can alone.

“The take-home message is that when you get an active drug, you get the
effect of the drug itself and the placebo effect,” said Michigan’s Zubieta.

The newest research, much of it based on brain imaging techniques, provides
direct evidence of how the placebo effect works. The research will help
scientists determine more precisely the contributions of the “placebo
response” to the effectiveness of medications.

Some other recent findings:

Columbia University researcher Tor Wager has used brain scans to map where
in the brain the placebo response occurs. It turns out that those areas
including the thalamus, the insula, and the anterior cingulate cortex are
also among the areas activated when a person is in pain.

The placebo effect can even kick in when there’s no placebo, according to
Dr. Fabrizio Benedetti, a professor at the University of Turin.

In one study, Benedetti hooked pain patients to a computerized injection
device. In some cases, the computer administered morphine without the
patients knowing it, and in others, a doctor gave the drug in full view.
The hidden therapy was much less effective than the open one, showing that
to get the most from a treatment, you have to know you’re getting it.

Similarly, Parkinson’s patients improved more when they were told doctors
were activating a stimulator in their brains than when the stimulator was
turned on without their knowing it, Benedetti showed.

In Alzheimer’s patients, however, the Italian team found the expectation of
pain relief did not reduce the perception of pain, suggesting that a mostly
healthy brain is required for the placebo effect to work.

Though all this makes for compelling research, it’s still unclear what it
means to patients and their doctors. “That’s the new frontier,” Harvard’s
Kaptchuk said.

What is clear is that having a reasonably positive attitude that a new
treatment will work can at least stack the odds in your favor, and not
focusing on all the possible side effects makes sense, too.

It’s also essential to pick a healthcare provider you trust so that his or
her words of encouragement about a treatment can boost the chance it will
work for you.

The Competitive Edge? It’s a Zen Thing

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In a few weeks, millions of us will be glued to our TV sets, watching the best athletes in the world ski, skate and slide their way into Olympic history in Turin, Italy.

We will certainly be dazzled, as always, by the sheer physical skill of these folks who have pushed their bodies so hard for so many hours a day, year after year.

But just as important as physical training, say those who study elite athletes, is the mental training that goes into a peak performance. If two athletes are equally fit, the edge often goes to the one with the better emotional skills — not a do-or-die focus on winning, but a set of habits that all of us can learn, including positive “self talk,” maintaining an energy level that is neither too excited nor too relaxed and, perhaps most important, a Buddhist-like ability to focus totally on the moment at hand, on this particular breath, stroke, turn.

So useful are these techniques that sport psychologists say their coaching is increasingly being sought by surgeons, trial lawyers, musicians, public speakers, business people and others who need to perform at their best in high stress situations. Partly because of this increasing demand, the Association for the Advancement of Applied Sport Psychology, the major professional organization in the field, has grown from a few hundred 20 years ago to 1,300 today, said the group’s president, Craig Wrisberg, a sport psychology professor and mental training consultant at the University of Tennessee.

Nowhere has the teaching of mental skills become a finer art than at West Point, where Nate Zinsser, director of the performance enhancement program, runs a sophisticated lab that is the envy of sports teams around the country. He’s building better athletes (Army must beat Navy) and also better soldiers, who have imagined every possible thing that might go wrong with a military operation. “You don’t want to experience anything for the first time in combat.”

Among other things, Zinsser has what he described as “very cool”  ergonomically designed chairs in which cadets sit and, through biofeedback techniques like monitoring heart rate, learn to relax and ignore potential distractions — such as crowd noise — piped in through speakers.

 “The process of training and learning to compete competently is a much more valuable lifetime lesson than simply the accomplishment of having won something on a given day,” said Zinsser. The key, for Olympic athletes as well as weekend warriors, is to learn to juggle two contrasting disciplines. “You have to be almost an obsessive-compulsive workaholic to get yourself ready to be good. But then you have to be this relaxed, Buddha-like Zen master, which allows all the stuff you have been training to come out.”

In other words, you train your body, especially your nervous system, so that you can automatically do your best on every step, jump, start or landing. Then you get your mind and its anxious chatter out of the way, go on “autopilot” and let your body “fly itself,” said Jim Bauman, a sport psychologist for the US Olympic Committee who has been working this year with the men’s alpine ski team.

Naturally, you can’t will yourself into the zone. But you can set the stage for it, in an athletic event, public speaking or any potentially stressful performance. Here’s how:

Some comfort for the grieving: There’s no wrong way to do it

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Grieving used to be seen as a very straightforward process: You cried at the funeral, were sad for a few months, then you had some “closure,” and got on with your life.

Psychologists — both pop and professional — thought that anyone who didn’t cry at the funeral or were still crying a year later was either heartless or overly emotional.

But, mercifully, the emerging view among mental health experts is that grieving for a lost loved one is really a disorderly, highly idiosyncratic process — that there are no set stages to go through and no “normal” or “right” way to do it.

For Lynn Osborn, 48, who lost her husband to Lou Gehrig’s disease four years ago after a slow, awful decline, the grieving process “has been very personal, and it’s still not over yet,” she said. “Fortunately, it never occurred to me that there was a “right” way to grieve.”

Osborn, a vivacious woman with a passion for rowing and ballet who is the mother of two sets of twins, now aged 8 and 11, has become something of an expert on grief. She lost her father suddenly to a car crash 16 years ago (“I had had breakfast with him that morning. I came home to a phone call saying he had been killed.”).

Though she had much more time to prepare herself for her husband’s death, it was no less terrible when it actually came than her father’s had been, she said.

As the disease slowly robbed her husband Charley, also a rower, of his ability to pick up his children, feed himself, talk and, toward the end, even blink and smile, Lynn spoke with a psychiatrist at Mass General. “I told him I felt there was a freight train coming. He said, ‘There IS a freight train coming. And there is nothing you can do to prepare for it.'”

Osborn said that insight proved liberating — and very different from the kind of counseling someone in her position might have received in the past.

In the old days, following (or perhaps twisting) the advice of Dr. Sigmund Freud, there was a virtual commandment for people to “process” their grief intensely, then “let go” and, as soon as possible, “move on,” experts said.

But newer research has shown that there is no right way to grieve.

Some people get depressed when a loved one dies. Some don’t. Some move on reasonably quickly. Others maintain a relationship with the deceased that — new research shows — is healthy, not depressing.

“The idea that grief is necessarily a debilitating experience is not true. We cope much better than our social expectations say we will,” said psychologist George Bonanno of Columbia University Teachers College, who has shown that among a group of “normal, everyday people,” only about half will get depressed at any point during their grieving process.

Maintaining a “continuing bond” with the person who has died is also normal. That doesn’t mean living in the past, but honoring the ways in which the relationship, in a sense, still goes on, said Phyllis R. Silverman, an associate in the department of psychiatry at Massachusetts General Hospital and author of the 2004 book “Widow to Widow.” The relationship with the dead person “is a part of who we are. So, much of our life is still connected to that person.”

It’s also very common — and not crazy — for bereaved people to talk to the person they have lost, said Roxane Cohen Silver of the University of California, Irvine: “There is no sign that is unhealthy.”

It is also normal to feel distressed when you realize you are moving on, said Silver, citing the case of a patient who had lost a child. “One of the worst days of her life was when she realized she had gone 15 minutes without thinking about her baby. She realized she was feeling better, but that also got her upset.”

Although there’s no way to fully prepare emotionally for the expected death of a loved one and no “right” way to grieve afterward, there are a few things that can help, said Dr. John Rolland, a psychiatrist and co-director of the Center for Family Health at the University of Chicago.

In a couple, if the husband has a potentially fatal disease and the couple has had traditional gender roles, it may help to begin to “re-organize” these roles while the husband is relatively healthy. The wife may want to look for a job, said Rolland. If she doesn’t know how to balance the checkbook, he could teach her. “You can’t wait until the person is lowered into the ground.”

It also helps, he said, to do some “re-prioritizing so that life goals are focused on the here and now, rather than 30 years later.”

Researchers used to think that grieving before a loved one’s death necessarily made things easier later. But many people are still “shocked by how intense the grief is because they figured they had already done this,” said behavioral scientist Kathleen R. Gilbert at Indiana University in Bloomington.

Osborn has some suggestions, too.

  • One is to “record your loved one’s voice. I didn’t figure that out with Charley. But I will do that for my children.”

  • The other is to treasure the time you do — and did — have with the person you love.

“I don’t mean to be a Pollyanna, but I had 20 wonderful years with that man,” she said. “There are people who don’t have one day as happy as I had.

“It took me six months after Charley died to realize that that feeling will never go away. It’s like the Grand Canyon. There’s this big hole, and it hurts like hell, but it’s beautiful.”

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

Saliva May Replace Blood as Test for Disease

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Within two years, you may be able to go for a regular dental visit, spit into a cup and, before your appointment is over, find out from an analysis of your saliva whether you’re at risk for oral cancer. Currently, dentists have to do a thorough mouth exam to probe for oral cancer, which will strike more than 28,000 Americans and kill more than 7,000.Within a few more years, you may be able, with a fancier spit test, to find out if you’re at risk for a number of other diseases as well, including breast cancer, Type 2 diabetes, ovarian cancer, Alzheimer’s disease and rheumatoid arthritis.

If you’re among the avante garde, you might even have a tiny chip implanted in your cheek to monitor proteins in saliva such as CRP, a protein that is often linked to an increased risk of heart disease. With constant monitoring, the chip could sound an alarm – maybe a beep, maybe an electronic message to your doctor – whenever levels of a particular protein drift too high or too low.

Until a few years ago, the technology to analyze minute quantities of genetic material and proteins in saliva was simply not good enough for many of the tests doctors want to do or tests consumers could do in the privacy of their own homes, said Dr. David Wong,, associate dean of research at the UCLA School of Dentistry and co-director of head and neck cancer research program at the Jonsson  Cancer Center at UCLA.

In the brave new world of genomics and proteomics – the study of genes and the proteins they make – the best body fluid to analyze disease risk may soon be saliva, not blood. Saliva, the slippery fluid that helps moisten and digest food, is a medical goldmine because it is almost identical to the clear part of blood, but with everything, including infectious organisms, present in weaker concentrations.

Saliva testing is less invasive, less painful, less likely to cause infection and potentially cheaper than blood testing because there’s no need for a phlebotomist to draw blood. And because it’s so easy to test saliva repeatedly during the day, doctors believe they will be able to use saliva-based tests to keep track of real-time physiological changes such as how an infection is responding to antibiotics.

The idea of using saliva for detection is not new. Among ancient peoples, legend has it that saliva was used as a primitive lie detector test. A person accused of wrongdoing would be given a handful of rice and told to swallow it; if he couldn’t, it meant he was dry-mouth, nervous and guilty.

Medically, researchers have long been fascinated by what can be studied in saliva, and there are already saliva-based tests on the market to detect the presence of the AIDS virus, alcohol, illicit drugs, the influenza virus, hormones that signal premature labor or