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.

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.

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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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