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An About Face
In the middle of the trial, disaster hit. Researchers discovered that Prempro–the HRT drug used in the study–was increasing, not decreasing, a woman's risk of heart attacks, blood clots, and stroke. Add to this the previously discovered breast cancer downside, and the verdict appeared clear–HRT was no longer the panacea it had been touted to be. In July 2002, WHI investigators cut short the trial and alerted physicians to begin weaning their patients off hormone replacement therapies.

"On the morning of July 9…physicians and the 30 million U.S. patients taking estrogen products woke up to discover that the world, after all, was flat," Seaman wrote in her book.

A Body of Change

Menopause can be defined as the moment when menstruation has stopped for a year. Yet, the transition unfolds over several years in a phase called perimenopause. Before its onset, a woman ovulates each month because a small knot of tissue at the base of the brain, the hypothalamus, signals another structure directly under the brain, the pituitary gland, to produce hormones that course through the body.

Michael Loose, associate professor of neuroscience at Oberlin, now studies this brain-hormone link. His lab and others have shown that a relay system of neural and hormonal signals cause the ovary to release an egg and also produce estrogen and progesterone in a well-timed cycle. (The latter readies and maintains the uterus for an embryo).

But in women between the ages of 45 and 55, the pituitary and ovaries fall out of sync. Simply, the ovaries slacken their production of hormones. The pituitary senses this and tries to push the ovaries harder with a gush of chemical stimulants. This plays out as erratic fluctuations–too much estrogen revs the body, followed by too much progesterone, which puts on the brakes.

Meanwhile, the hypothalamus, which also controls temperature regulation, gets thrown off. It signals the pituitary, which dilates blood vessels near the skin to create a hot flash. Almost two-thirds of 25 million women going through perimenopause experience this. It's an intense buildup of heat, often followed by sweating and chills.

Other common symptoms include anxiety and irritability, insomnia and fatigue, depression and mood swings, memory lapses, and an erratic menstrual cycle.

Few women experience all of these symptoms. In general, perimenopausal women fall into three categories: an estimated quarter of perimenopausal women report almost no disruption to their daily lives, 55 to 65 percent experience some mild problems, and an unlucky 10 to 20 percent suffer severe, often debilitating symptoms, according to Dr. Nancy Lonsdorf, author of Women's Best Medicine for Menopause.

"I ask why the variance is so wide," says Lonsdorf, who has been practicing Ayurvedic medicine, a 5,000 year-old holistic approach to healing, for 17 years.

Thus far, no one can give the reason. If Western science were to focus on that question instead of oversimplifying menopause as a lack of estrogen, then medicine might be able to offer women better answers.

It was a really big switch," says oncologist Chlebowski, who was a coinvestigator at the WHI. The results of the HRT study stunned many medical professionals. Some say it was because physicians had listened to years of drug company-selected messages instead of researching all the evidence themselves.

"Doctors are so busy most of the time that they don't have time to read every journal article," says Dr. Nancy Lonsdorf, a practitioner of Ayurvedic medicine and author of Women's Best Medicine for Menopause.

Seaman puts it this way: "Medical policy on estrogens has been to shoot first and apologize later–to prescribe the drugs for a certain health problem and then see if there is a positive result," she writes in her book.

In other words, she says, pharmaceutical companies, through doctors, have used women as guinea pigs in a huge, profit-driven experiment. In this case, the experiment went bad.

How Bad Is It, Really?
To make matters worse, says Seaman, estrogen fell short in yet another area: Alzheimer's prevention. Researchers examined a subset of the WHI women–4,532 volunteers aged 65 and older–for signs of dementia and memory loss. The results were revealed in May 2003: Hormones not only failed to halt dementia, they doubled the risk of it. They also impaired overall memory and increased the risk of stroke. More disconcerting still, heightened dementia could show up as early as a year after taking the drugs, suggesting that the drugs were speeding up the onset of the disease.

In short, "the hoped-for benefits never materialized, at least not for women who have passed through menopause," says Dr. JoAnn Mansonone, one of the investigators in the WHI at Brigham and Women's Hospital in Boston.

To be fair, the WHI results did reveal some positive effects. The hormone supplements did lower the risk of colon cancer and bone fractures–a plus for osteoporosis-prone women. Considering, however, that other osteoporosis medications exist without the "multiple dangers" of cancer or heart-related side effects, Seaman suggests that women make other choices.

Meanwhile, the research continues. Investigators are focusing on whether different kinds of hormones, especially plant-based estrogens, might perform better than FDA-approved HRT. Also, the previous studies involved women between the ages of 50 to 79 years. Might younger, premenopausal women still take hormones for shorter periods of time (less than four or five years) to combat severe hot flashes and insomnia?

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