By Julie Steenhuysen
Reuters

CHICAGO -- The latest data from a long-running study of hormone therapy suggests women who started taking hormone replacements within five years of menopause were 30 percent less likely to develop Alzheimer's disease than women who started years later.

The findings, reported on Wednesday in the journal Neurology, add to evidence suggesting that taking hormone treatments around the time of menopause may be doing more than just helping women cope with hot flashes and night sweats.

"Our results suggest that there may be a critical window near menopause where hormone therapy may possibly be beneficial," Peter Zandi of Johns Hopkins University in Baltimore, one of the study leaders, said in a statement.

The findings come as menopausal women and their doctors continue to parse out the risks and benefits of hormone replacement therapy.

Most researchers agree that hormone replacements do not protect women from diseases of aging, and taking these drugs for long periods of time are associated with significant risks, including breast cancer, heart disease and gall bladder disease.

Earlier this week, the U.S. Preventive Services Task Force reaffirmed its 2005 guidelines recommending against the treatment as a way to prevent chronic disease.

But the influential advisory panel did not weigh in on the use of hormones to treat symptoms of menopause, a practice many professional societies endorse as long as the drugs are prescribed at the lowest possible dose for the shortest period of time.

The most definitive study on hormone replacement therapy to date comes from the Women's Health Initiative study, a large, randomized trial that was stopped early in 2002 when it became clear that women who were taking a combination of estrogen and progestin for five years had higher rates of ovarian cancer, breast cancer, strokes and other health problems.

A related study known as the Women's Health Initiative Memory Study also showed an increased risk of Alzheimer's disease in women who took hormone therapy.

The findings came as a shock to many doctors and their patients, who thought the study would show a protective benefit. Prescriptions of hormone treatments plummeted, with sales of Wyeth's combination estrogen and progestin pill Prempro cut in half since 2001 to around $1 billion a year. Wyeth is now owned by Pfizer.

Because the average age of women in the Women's Health Initiative study was 63, several years past menopause, questions remain about whether the findings apply to younger women.

30 percent lower risk
Zandi and colleagues decided to investigate whether the timing of starting hormone replacement therapy had any effect.

Their findings come from the Cache County Study on Memory, Health, and Aging, a study backed by the National Institute on Aging that has been following nearly all of the residents of Cache County, Utah, over age 65 since the study began in 1995.

Earlier results of the Cache County study published in 2004 had suggested that hormone treatments might help reduce the risk of Alzheimer's disease.

So, the team turned back to this population, looking specifically at the timing of when women started taking hormone therapy and their risk of Alzheimer's disease.

Zandi's team followed 1,768 women ages 65 and older for 11 years. A total of 1,105 women had used hormone therapy, which consisted of estrogen alone or estrogen in combination with progestin. During the study, 176 women developed Alzheimer's disease, including 87 of the 1,105 women who had taken hormone therapy compared to 89 of the 663 others.

The study found that women who began hormone therapy within five years of menopause had a 30 percent lower risk of Alzheimer's dementia than those who had not used hormone therapy.

There was no change in the risk among other hormone users who had begun treatment more than five years after menopause, but they did find a higher risk of dementia among women who started combined estrogen and progestin at age 65 or older.

Zandi said the study findings support the so-called timing hypothesis - that earlier treatment with hormones may be beneficial while later treatment may be harmful.

"It doesn't prove the hypothesis, " Zandi said. "But it does suggest there might be something to that merits further investigation."

Given that there are no treatments that can alter the course of Alzheimer's disease, Zandi said a 30 percent reduction would be meaningful, if it proves to be real.

For now, however, the results should not be used to make treatment decisions, said Dr. Victor Henderson of Stanford University, who wrote an editorial on the study.

"The consideration of whether or not to use hormone therapy in midlife shouldn't be driven by concerns for Alzheimer's disease risk," Henderson said in a telephone interview.

But, he said, as women seeking treatment for menopausal symptoms weigh the other benefits and risks that go along with the decision, the Cache County study may offer evidence of another potential benefit, rather than an added risk.

Most professional societies advise against hormone therapy for chronic disease prevention, including the American Heart Association, the American Congress of Obstetricians and Gynecologists and the American Academy of Family Physicians.

A new study may reassure some women considering short-term use of hormones to relieve hot flashes and other menopause symptoms. Starting low-dose treatment early in menopause made women feel better and did not seem to raise heart risks during the four-year study.

However, the research didn't address the risk of breast cancer, perhaps the biggest fear women have about hormones since a landmark study a decade ago. The new one was too small and too short for that.

Still, it is the first fresh research in many years on the sometimes-confusing effects of hormones on women's health. The advice remains the same: Use hormones only for severe symptoms — not to prevent bone loss or aging-related problems — at the lowest dose for the shortest time possible.

"The benefits outweigh the risks when hormone therapy is used for symptom management with relatively short-term treatment," said Dr. JoAnn Manson, preventive medicine chief at Brigham and Women's Hospital in Boston. She was a study leader and discussed results Wednesday at a conference of the North American Menopause Society in Orlando, Fla.

Two study participants found they helped. "My mood leveled out. I found that I was just generally calmer" on the estrogen patch, said Kathy Smerko, 60, a nurse practitioner from Phoenix. 

Dianne Fraser, 56, an accountant from suburban Boston, said the patch eliminated the drenching sweats that woke her in the night. She was able to quit treatment after five years and seldom has problems now. 

"It was enough to get me through that crazy period" right after menopause began, she said.

For decades, doctors believed hormone pills helped prevent heart problems and were good for bones and minds. That changed in 2002, when a big federal study was stopped because women taking estrogen-progestin pills had higher rates of heart disease and cancer.

Critics pounced on the study's limitations. Participants were well past menopause — 63 on average — and most were not seeking symptom relief. Many were overweight and smokers, and at higher risk of heart disease to start with. Only one type of pill in one dose was tested.

Women who could take estrogen alone — those who had had hysterectomies — did not have the risks that women on the combination hormone pills did. In fact, they had lower rates of breast cancer.  These factors led many experts to think some hormones might help certain women, and that the type and dose might matter. The new study tested that.

It enrolled about 700 healthy women ages 42 to 58 within three years of menopause. They were given either low-dose estrogen pills (Premarin, made by Wyeth, now part of Pfizer Inc.), a low-dose estrogen skin patch (Climara, made by Bayer), or a placebo. Women on estrogen also received Prometrium, a progesterone that more closely mimics what the body makes.

All women received a patch and two types of pills, but some of those were fake treatments and neither they nor their doctors knew who had the real medicine versus placebos until the study ended. That is standard study design to test who is really helped by a medication.

The main goal was seeing whether hormones made a difference in hardening of the arteries, a precursor to heart disease, as seen on imaging tests. Other health measures also were tracked. After four years, doctors found:

—No effect on blood pressure or artery hardening.

—Both types of estrogen reduced hot flashes and improved bone density, mood and sexual health.

—Estrogen pills raised good cholesterol and lowered the bad form, but also caused triglycerides (another type of fat in the bloodstream) to rise.

—Estrogen patches did not affect cholesterol but improved blood sugar levels and insulin sensitivity, possibly making them a better choice for overweight women at risk of diabetes.

Patches and pills have different effects, said Dr. S. Mitchell Harman, an endocrinologist and director of the Kronos Longevity Research Institute, a Phoenix-based group with no industry ties that paid for the study. Oral estrogen goes straight to the liver, resulting in higher concentrations than when it's absorbed through the skin. That raises blood-clotting factors that might be especially harmful to smokers. But higher estrogen levels also cause the liver to make more HDL, or good cholesterol. So estrogen can have good and bad effects depending on the form, he said.

Skin patches account for just 2 percent of hormone use, some studies estimate. Besides Climara, at least one other is on the market — Vivelle-Dot, sold by Novartis and Noven Pharmaceuticals Inc. A generic version is expected in about a year.

Dr. Sanjay Asthana, a geriatrician at the University of Wisconsin-Madison, led a separate analysis that found estrogen pills and patches improved depression and anxiety but had no effect on cognition or memory. The National Institute on Aging paid for that study.

Women need to realize the new study is much less definitive than the big federal one that found more lung and breast cancer deaths among women on estrogen-progestin pills, said one researcher involved in the earlier work, Dr. Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. It would be unwise to try to prevent certain health problems by using a treatment "that increased the two leading causes of cancer deaths in women," he said.

Manson agreed that hormones should be used only for severe symptoms.

Hormone study still worries women

Study offers hope for menopause pudge

Courtesy of Robin Herman

Robin Herman, 60, says it's harder to keep weight off after menopause. But some simple, subtle changes may help.

Robin Herman has always been slender. She eats right, exercises regularly and keeps an eye on her weight. But middle age and menopause have hit her right in the waistband, and she’s frustrated.

“What is this? I used to be able to look straight down at my feet and now there’s this rounded tummy in the way,” Herman says. While she’s still not overweight, Herman, 60, has gained 11 pounds that she just can’t seem to shake. Her problem illustrates what many women are finding in mid-life -- they are putting on pounds despite their best efforts.

“At first I cut back about a quarter of what I was eating. And then I was just eating about half of what I had been eating. Now I don’t take seconds. I don’t eat a lot of bread. I don’t eat potatoes. I don’t eat empty calories. I don’t drink sodas,” said Herman, who recently retired from the Harvard School of Public Health in Boston.

She joined Weight Watchers, a program that’s been clinically proven to work in helping people lose weight. “I kept a food diary. You could eat as many fruits and vegetables as you wanted. I put in a little more exercise,” she says.

“I got nowhere. It just wasn’t doing anything. And it was making me crazy about following every spoonful I ate.”

Herman sounds like thousands of women across the country who are slowly tipping over the point from being normal weight to overweight, or from being overweight to obese. A study published on Tuesday sheds a little light on what may work and why some approaches that help women shed a few pounds in the short term aren’t helping them keep the weight off long-term.

Bethany Barone Gibbs of the University of Pittsburgh Medical Center and colleagues analyzed data from a study of more than 500 overweight women in their 50s and 60s to see what made a difference. They had been randomly assigned to either intensive nutritional and exercise counseling, or to a more general, less weight-loss-focused program. The woman also reported what and where they ate, for four years.

As expected, more of the women who got specific diet and nutrition counseling lost weight. But Gibbs and colleagues wanted to know what worked for any of the women who managed to lose weight, regardless of which group they were in.

Early on, some of the more obvious diet strategies worked -- eating less fried food, staying away from restaurants, avoiding sweets and eating more fish. But these approaches didn’t work for the women in the long term, Gibbs reported in the Journal of the Academy of Nutrition and Dietetics.

 “What we found at four years is that the women who changed their eating behaviors to eat more fruits and vegetables, who ate less desserts, less sugar-sweetened beverages and less meats and cheeses were more likely to have greater weight loss or less weight gain long term,” says Gibbs, an assistant professor in the Department of Health and Physical Activity.

“But on the other hand, something like eating more fruits and vegetables did not predict weight change at six months but was one of the most important predictors for long-term weight change.”

Avoiding restaurants didn’t seem to make a difference long-term, either, she said. Gibbs said the key to keeping weight off long-term may be a little counter-intuitive. “Short term, people are still motivated when they start a weight loss program,” she said. “They are never going to eat another French fry, eat another piece of pie, so you see the pounds coming off.”

But hardly anyone can keep this kind of abstinent behavior up forever. The women who added fruits and vegetable to their diets, using them to replace higher-calorie meats and cheeses, lost more weight over the long-term. “That small change can give you a big, long-term result,” Gibbs said.

How could something so subtle work better than going for the big effect? In part, it’s because weight gain is often subtle and sneaky, too, says Katherine Tallmadge, a personalized nutrition counselor and speaker and immediate past president of the DC Metro Area Dietetic Association. “When people gain weight, it’s usually a pound or a pound and a half a year,” she says. “It is a very small and creeping kind of weight gain.”

The study also illustrates what many middle-aged women complain about. “I recall at age 25 if I wanted to lose five pounds I could do it in a week.  Now, it takes far longer to lose weight,” says Karen Giblin, president of menopause support organization Red Hot Mamas North America, Inc.   

This doesn’t surprise Dr . Domenica Rubino, an endocrinologist who runs the Washington Center for Weight Management and Research. “As we age, the average person has a tendency to gain weight and to gain more fat than muscle,” Rubino says. On top of this, women are undergoing hormonal changes that can disrupt sleep, stress them out and make them tired, three things also associated with weight gain. “Women are getting early morning awakening  and even though they are exhausted, they are not getting back to sleep,” she says.

Giblin can vouch for what happens next. “My willpower goes down the tube when I'm stressed and I will not do all the good things I should do be doing like eating properly and exercising,” Giblin says.

It all can add up to the muffin top effect: that shift of weight to the abdomen that makes clothes fit poorly, if at all, and that stresses out a woman every time she gets dressed.

“It’s so hard counting calories and keeping food diaries for years and years and years,” Gibbs agreed. “We have a population-sized problem here.” With two-thirds of Americans overweight or obese, she says, people need some simple solutions.  

“I've had to make exercise a lifestyle choice,” says Giblin, who co-authored "Eat to Defeat Menopause" with Dr. Mache Seibel last year. “Never skip a meal,” she advises. “And if you are prone to snacking, grab a piece of fruit or six  to eight almonds.”

Rubino says hormone replacement therapy can help, too, if it helps cut hot flashes and anxiety. “You are sleeping better and not having the hot flashes and your mood is better,” she says.

STOP Obesity Alliance Director Dr. Scott Kahan says managing stress can really help people control weight. “If things are very stressful, things are going on in your life, often stress management techniques can help,” he says.

Kahan and others admit this can be easier said than done. “I think we live in a very difficult time, a toxically busy world,” Tallmadge says. “What really upsets me is when people call themselves lazy or undisciplined when in fact they are running themselves ragged.”

But it’s not exercise.  Many women are busy getting their families ready for the day and then commuting during the very morning hours when they would have been otherwise most likely to exercise.

“It’s a real balancing act.”

Related stories:

• Weight worries after 50
• How to lose that matronly look after menopause
• Stroke rates triple among middle-aged women

Only one in 10 middle-aged women thinks hormone replacement therapy is a good thing, but doctors who treat them think it could help many women – if only they’d get up the nerve to ask.

A survey released this week by the Endocrine Society shows 90 percent of doctors would be happy to talk to their patients about menopause, and 73 percent think hormone replacement therapy can be a good thing. But 71 percent of them say they are prescribing hormone replacement therapy (HRT) less often than they were 10 years ago. The reason: a landmark study called the Women’s Health Initiative that showed HRT raises the risk of heart attacks, stroke and breast cancer.

The study, released 10 years ago this week, caused women to drop HRT wholesale -- even though it might help some of them. Women say they are still doubtful about it and the Endocrine Society says a separate survey it commissioned in April confirms this.

 “Nearly every physician participating in the survey said menopausal symptoms have a negative impact on quality of life,” Dr. William Young, president of The Endocrine Society, said in a statement. “It’s important for a woman to know what hormonal and non-hormonal treatment options may be best for them to provide symptom relief,” Young added.

The group, which educates doctors specializing in hormonal conditions from obesity to menopause, asked pollsters Lake Research Partners to survey 424 internal medicine, family practice and OB/GYN specialist doctors. In April the group surveyed 810 women aged 45 to 60.

The doctors who were surveyed said they believe women are uncomfortable: 88 percent of the doctors said patients are unwilling to even consider HRT because of the risks, and 57 percent of OB/GYNs said their patients were confused. And just 11 percent of the women surveyed said they had a favorable view of HRT.

The Endocrine Society, North American Menopause Society and the American Society for Reproductive Medicine issued a joint statement on Monday outlining the risks and benefits of HRT.  “Hormone therapy is an acceptable option for the relatively young (up to age 59 or within 10 years of menopause) and healthy women who are bothered by moderate to severe menopausal symptoms,” it says. “Individualization is key in the decision to use hormone therapy. Consideration should be given to the woman's quality of life priorities as well as her personal risk factors such as age, time since menopause, and her risk of blood clots, heart disease, stroke, and breast cancer.

Related stories:

Hormone study still worries women

Questions and answers about menopause and hormone study

Video: Handling hormone fluctuations

Denny Henry / for msnbc.com

Ingrid Gorman, a 48-year-old senior vice president at Discovery Communications, said she never discussed menopause with her mother, but wants to now that she's approaching that age. "I don't even remember discussing menstruation with her when I was little," she said.

By Maggie Fox

When her aunt died of breast cancer, Mari-Anne Pisarri had no doubts about what caused it. She was certain it was estrogen pills. “So when the Women’s Health Initiative released their findings, I thought, ‘Well, of course, Aunt Betty could have told them that years ago’,” said Pisarri, a 56-year-old partner at a Washington, D.C. law firm.

Pisarri is one of tens of millions of U.S women who have no intention of taking hormone replacement therapy to ease the symptoms of menopause. “I am just not willing to take the risk,” she said.

Like so many women in the 1970s, 1980s and 1990s, Pisarri’s aunt got estrogen as a matter of course when she entered menopause. Doctors routinely prescribed hormones in the belief that HRT prevented heart disease, cancer and the bone-thinning disease osteoporosis.

The federal government decided to check out these assumptions, and commissioned the Women’s Health Initiative – a giant study of 161,000 women. In 2002, regulators stopped the study when it became startlingly clear that HRT did not lower the risk of heart disease or cancer in the women taking part in the study. In fact, it raised the risk of stroke, heart attacks and breast cancer, they reported in a paper published 10 years ago Monday in the Journal of the American Medical Association.

Women stopped taking the pills in droves. While as many as 17 million women used HRT in 2001, by 2009 just about 8 million did. A decade after the Women’s Health Initiative report was released, women are still confused and so are many doctors.

It would be impossible to say for sure that Pisarri’s aunt got cancer because she took HRT. But the giant drug company Pfizer said last month it has paid $896 million so far to settle lawsuits alleging the pills made women sick without warning them of the risks. Pfizer owns Wyeth, the company that made the most popular HRT drugs Premarin and Prempro.

Swinging pendulum
Dr. JoAnn Manson, a professor at Harvard Medical School and Brigham and Women’s Hospital in Boston who helped conduct the study, says people overreacted to its findings. “The pendulum has swung from ‘hormone therapy is good for all women’ to ‘hormone therapy is bad for all women’ after the Women’s Health Initiative,” Manson said in a telephone interview. “What the WHI showed us is that hormone therapy is appropriate for some, but not all, women.”

The problem was that doctors were in the habit of prescribing HRT to protect women’s health, instead of treating it as any other drug that should be used only when the benefits outweigh the risks. “At the time the WHI began in the early 1990s it was becoming an increasingly common practice for hormone therapy to be prescribed for women who were in their 70s and 80s and women at very high risk of cardiovascular disease,” Manson says. The study made it clear just how misguided this was. “Those practices came to a screeching halt,” Manson said.

But the younger women who could more safely take HRT became afraid to ask for it and, often, their doctors were afraid to prescribe it. This has made for a perfect storm for women in their 40s and 50s who are often approaching the peak of their careers and have more flexibility since their children are grown. Then menopause hits, with no easy answer to managing the symptoms.

“I do have trouble sleeping,” says Bev, a 54-year-old neuroscientist living in Silver Spring, Maryland, who asked for her last name to be withheld because she was discussing personal health. “But I don’t really know what to do about that. I tried exercising more to try and wear myself out. I don’t even know if it’s actually a sign of menopause or perimenopause."

Bev says her hands also ache worse lately -– she fears arthritis is setting in -- but is not sure if menopause or the lack of sleep is a factor. “I’ve had some symptoms, like mainly hot flashes, but they’ve been minimal,” Bev says. "If I was having more severe symptoms I would probably be checking into it more.”

While Bev doesn’t fear discrimination at work, she, like many women, cringe at the thought of describing their symptoms publicly – and sometimes even with their own doctors. As a result, they may miss the chance to be educated. “I feel pretty ill-informed now about the whole issue,” Bev admits.

Part of this lack of information is because drugmakers have, for obvious reasons, stopped advertising HRT. But menopause is itself often a taboo subject that involves not only women’s reproductive health but also another subject that U.S. society finds embarrassing – aging.

Stultifying silence
Ingrid Gorman, a senior vice president at Discovery Communications, wonders if women fear a return to the arguments that they are untrustworthy in the workplace because they are ruled by their hormones. Remember premenstrual syndrome?

“It used to be when I was growing up … PMS (was) talked about all the time. You would blame a lot of women’s moods on that,” says Gorman, 48.

“I don’t really hear it talked about any more,” she added. “I wonder if it’s because these are different generations, or if as a group we really didn’t want that to be something that people could use against us. … We just don’t want to call that out about ourselves.”

Rachel Pentlarge, a 48-year university grant manager in Washington, D.C., says a little wishful thinking may be going on. "We are all hoping that menopause will never hit us, or that no one will notice,” she says.

"There is so much discomfort with women's health issues and also with aging -- and the way that sexism and age discrimination come together on this. The silence is stultifying."

Pisarri is more hopeful about why menopause isn’t a big point of discussion. “It’s a benefit of being in the baby boomer generation. There are just too many menopausal women. Have there ever been this many hot flashes going on at the same time?” she asked. “When there are so many of us doing the same thing … I don’t think it is something that is quite unusual.”

But now, thanks to the publicity surrounding the WHI, women often think they must tough it out, even as they joke about hot flashes with friends and even with colleagues.

Hormone therapy study: Confusion, mistakes and fear

 “About 15 to 20 percent of women have significant symptoms that interfere with sleep and can impair quality of life and that certainly can have adverse effects in the workplace as well,” Manson says. These include problems sleeping, hot flashes and vaginal dryness. For these women, the benefits of HRT can outweigh the risks.

There are new formulations of HRT as well, which give far lower doses of hormones than the pills used in the WHI study. Women can use ultra-low-dose skin patches and creams and they can use targeted delivery systems such as vaginal inserts to address their particular symptoms.

Other studies done since the WHI have also shed more light on who might be harmed by HRT. Manson worked on one that showed if women take HRT when they first begin menopause, they significantly lower their risk of heart disease.  And Manson points out that even doubling a very small risk, such as the risk of stroke, still leaves a woman with a very small risk.

The answer, as with so many health issues, is for women to talk to their doctors.

Doctors often determine whether a woman is going through menopause based on symptoms, such as whether she’s stopped having a menstrual period, but in some cases, may do blood tests to measure hormone levels. Some of the women interviewed for this story said they were still taking birth control pills and weren’t sure if that was masking other symptoms.

Physicians need to be more open to talking about menopause with women, said Manson, who is president of the North American Menopause Society. “Not just gynecologists but internal medicine (specialists) and family practice (physicians) often have to be discussing these issues with women,” she said. “I think it has been confusing for clinicians and, unfortunately, many clinicians have stopped prescribing hormone therapy. It is a very, very difficult situation for women who have menopausal symptoms and are trying to find a clinician who can help them make an informed decision.”

NAMS has a website at www.menopause.org that can help, Manson says.

When the time comes, Pentlarge says, she trusts her gynecologist to help her make the right decision. "So much unnecessary and totally avoidable anxiety is attached to menopause that if you can figure out a way to feel positive about yourself, it could be a much less traumatic experience,” she says.

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