But new research at the University of Michigan Health System may counter the conventional wisdom that menopause is an unavoidable "rite of passage" for middle-aged women, and suggests that medical advances may make it possible to ease its symptoms, delay its onset, or even "cure" it.

U-M researchers, led by Nancy Reame, M.S.N, Ph.D., the Rhetaugh Graves Dumas professor in the U-M School of Nursing, are in their fourth year of a trial to test the theory that menopause doesn't start in the ovaries, as is commonly understood, but with a disruption of circadian rhythms in the brain. Although the study, funded by the National Institutes of Health's Institute on Aging, is not completed, preliminary findings are already showing promise.

"If we can understand the causes of the very early, initial changes that may be happening in the brain to bring on menopause, we will probably then have a way of intervening much earlier than at the time of menopause," Reame says.

She explains that finding the physiological origins of menopause could have numerous advantages, such as delaying menopause for women who want to have children in their 40s and 50s, or easing the effects of hot flashes and other symptoms.

Researchers may even be able to use this information to find ways to decrease women's risks of heart disease, heart attacks and osteoporosis -- three medical conditions for which women in menopause are more susceptible. But first, the U-M team and their peers must continue their research.

For decades, it has been commonly accepted that menopause starts when a woman runs out of eggs in her ovaries as she ages.

"The importance of the loss of eggs over time is that the egg is the source of estrogen that we need to protect our bones and our heart," Reame says. "It's also important in the regulation of the menstrual cycle. So, as the number of eggs declines with age, we also gradually lose the estrogen and by the time menopause comes around, the levels of estrogen are much, much lower than they are in a young woman."

At birth, female babies have about 5 million eggs. By about age 35, that number has declined to about 25,000 eggs. After age 35, egg loss accelerates.

Recently, though, there has been a shift in researchers' thinking away from crediting the loss of eggs for the start of menopause. Reame and other researchers are now suggesting that changes in a woman's brain due to aging might be the initial trigger for menopause.

"Obviously, you can't go in and look at women's brains to see the changes to the hypothalamus, which is the part of the brain that regulates the menstrual cycle and ovulation," Reame says. "Instead, we at U-M are studying a particular brain function that we know plays an important role in the menstrual cycle regulation, and that is the production of the hormone GnRH."

In particular, Reame says she is measuring how the production of GnRH - gonadotropin releasing hormone -- changes both through a woman's life and throughout a 24-hour period -- especially during sleep. GnRH is released from the brain and interacts with the pituitary gland to secrete hormones in a special rhythm that signals the ovary to stimulate growth of a new egg each month.

"Because GnRH is the conductor of the reproductive cycle, any changes in the brain that start early on could conceivably be the preemptive cause for this change in ovarian function and perhaps, may be part of early changes associated with menstrual cycle irregularity," Reame says. "We are speculating that in older women there is a different, or disordered, signal from the brain in terms of the stimulation of the ovary to accelerate egg loss."

When young women sleep, the frequency of the release of GnRH decreases significantly, but the size of the pulses of hormone that come from the brain are much larger. There's an important slowing-down, but magnifying, of each message from the brain to the ovaries at night in young women, Reame says. In older women, the rhythm appears to be altered.

To measure the exact changes in the levels of hormones in each pulse, researchers bring study participants to a sleep lab at the U-M General Clinical Research Center and take blood samples through an IV every 10 minutes around the clock. That allows them to analyze the day and night differences in GnRH being released by the brain.

In addition to younger women with regular cycles, older women who are still having normal menstrual cycles and postmenopausal women were studied in the same fashion "to see whether the same change in GnRH levels occurs in the brains of older women," Reame says.

"We're in our fourth year of our research study right now and, although still preliminary, we're seeing some exciting results," Reame says. "We certainly are now able to see some differences between the young cycling women and the older cycling women in relation to this sleep entrained change and brain function."

Other findings have revealed the ovaries produce more hormones than was initially thought. "Besides estrogen, there are a number of other hormones produced by the ovaries that we think play an important role in fine tuning menstrual cycle regularity and maintaining fertility," Reame says. "We now know that these fine-tuning hormones are also lost over time, well before estrogen levels drop."

Reame hopes that finding the origins of menopause may lead to relief for women who suffer from its symptoms, and bring hope to women who want children in mid-life.

"One in 100 women will undergo menopause before age 40, and that can be devastating if they are still planning to have more children," Reame says. "These women with early menopause may also have a significant risk of increased cardiovascular disease and heart attack. The loss of estrogen also carries with it a significant risk of osteoporosis for these younger women."

Reame's work and that of other researchers in the field could ultimately lead to a voluntary absence of menopause. "We may have a cure for menopause, if we really want to do that," Reame says.

"The downside to this would be a much higher incidence of breast cancer," Reame says. "It's well known that there's a direct correlation between the length of exposure to estrogen and risk of breast cancer. The greater the number of menstrual cycles, the higher the risk."

If you are between the ages of 20 and 30, or 40 and 50, a non-smoker of average weight with no sleep problems, and want to see if you're eligible to participate in the study, check out this website. - By Valerie Gliem

Facts about menopause:

· Menopause is the time in a woman's life after she ceases to menstruate.

· Most women will experience menopause by age 50, but it can occur earlier or later, depending on individual hormone patterns. Some of the signs of menopause include hot flashes, sweating, heart palpitations, anxiety, and depression. Hormone replacement therapy or other medications may be taken to ease these symptoms.

· Women after menopause have a higher risk of heart disease, osteoporosis, breast cancer and other diseases.

Related websites:

U-M Health Topics A to Z: Menopause

U-M Health Topics A to Z: Aging and Your Body

National Institutes of Health: Menopause

American Heart Association

North American Menopause Society

[Contact: Valerie Bliem, Kara Gavin]

12-Mar-2001