Solving the Mysteries of Aging

What happens to a woman’s body at age 40 or 45 or 50? We know, only too well, that things start to look different on the outside. But, surprisingly, this time period represents a big unknown in women’s health research.

The ‘90s decade has been a rich one in understanding diseases such as breast cancer, osteoporosis and heart disease, generally ailments of old age. But how do women end up with those diseases?

What does it mean to your long-term health to have a baby at 41?

What is the significance of having hot flashes throughout your 40s?

Why do women tend to gain weight in this period of the 40s and early 50s called midlife?

By the turn of the century, those questions won’t hold as much mystery, say the leaders of a transformative new study, the first large-scale look at women’s experiences at midlife.

The investigators expect that the Study of Women’s Health Across the Nation (SWAN) may confirm their hunch that what women do in the decade before menopause is just as important as what they do afterward.

“Women in this age period have been under-studied,” says Sherry Sherman, who is directing the project, launched last year, at the National Institute on Aging. “There is almost nothing [in medical literature] with respect to their physiology. And it’s pivotal. The question is: How does a healthy, vigorous woman end up as a frail, older woman?”

Sponsored by the NIA, the $17.5-million study will follow 2,500 women, between ages 42 and 52 who are still having menstrual periods, for at least four years. In a novel twist to the study, each of the seven research sites will focus on the following ethnic groups: women of Japanese descent, Chinese descent, African American, Hispanic Puerto Rican descent, Hispanic Mexican descent and Caucasian.

At UCLA, for example--one of two California study sites--researchers will follow 250 Japanese women and 200 Caucasian women. The women will undergo periodic physical exams and tests as well as answer questions about their lifestyles, attitudes and experiences at midlife.

Exhaustive in scope, the study will examine smoking and alcohol consumption, exercise, premenstrual syndrome, commitment to work, attitudes about aging, reproductive health, environmental exposures, genetics and many other facets of health, says Dr. Gail Greendale, director of research at the Iris Cantor-UCLA Women’s Health Center.

“As we worked with women 50 and older, we began to realize that these health issues developed more in the midlife,” says Greendale, the principal investigator for UCLA’s arm of the study. “Thinking in terms of ‘pre-menopausal’ or ‘post-menopausal’ isn’t the way to do it.”

Both women and their doctors, however, tend to think of the transition to menopause as an abrupt event.

But, Greendale says, “It’s not as if a light bulb goes off. It’s more realistic to think of all these changes occurring over a long period of time.”

The study had its roots in an eye-opening meeting that Sherman convened a few years ago to explore what was known about women at midlife.

“The bottom line from this brainstorming session was ‘not much,’ ” Greendale says. “But what the NIA realized is that what happens to women all along the life span impacts them in old age. And the major transition is going on at midlife.”

It’s unfortunate that women and their doctors often don’t begin considering the diseases of old age until menopause occurs, Greendale says.

“Saying, ‘I want to exercise at 60 to protect my bones’ is admirable. But better is to exercise your whole life. Women at midlife will start to realize they have to pay more attention to their health.”

Many women are eager to do just that, says Miriam Schocken, the SWAN project director at UCLA.

“Women have a sense that they need to do more,” she says.

Vicki Cohen, 43, a Redondo Beach mother of three who is participating in the study, says she sometimes feels unsettled by the mysteries of aging.

“There are so many changes occurring in myself,” she says. “My hair is turning gray, my face is aging. Everything is changing. It’s not the same anymore. It’s scary. I’m feeling older.”

Like Cohen, many of the women contacted to participate in the study have responded with enthusiasm.

As part of their effort to enroll 450 women in the study, UCLA researchers have conducted hundreds of random telephone surveys with women ages 40 to 55. So far, more than 80% of the women contacted have agreed to participate in the 15-minute interview--a very high response rate for cold calling, Schocken says.

The women who participate won’t be disappointed with the outcome of the study, Sherman says. “Our findings should help change the way women view this time in their lives and change the way health care providers approach both the physical and emotional issues women face.”

In general, the study will look at the biological, emotional, environmental and behavioral changes that alter a woman’s risk factors for disease. By giving equal attention to emotions and lifestyle, the researchers hope to learn which changes at midlife are attributable to biology and which are more influenced by lifestyle.

Each study site will explore dozens of specific questions. For example, UCLA researchers will study a hypothesis that hormone levels fluctuate wildly in the years preceding menopause. To examine this, a group of women will collect a urine sample each day for one month. The routine will be repeated each of the four years. The urine samples provide information on hormone levels.

Moreover, the women will keep daily diaries about their moods and feelings. Their entries will be matched to their daily hormone levels to explore whether hormone changes trigger mood changes.

“This will help us try to figure out what is biological and what is not biological,” Greendale says. “We can then learn which problems may be amenable to biological remedies and which are not.”

UCLA will also study hot flashes in women to see if they are markers for significant hormonal changes. Some women will even stay overnight for one weekend at the UCLA clinic for hourly monitoring that will record their hot flashes and hormone levels.

“The current theory is that hot flashes are just a nuisance,” Greendale says. “This [experiment] might tell us why hot flashes occur, how they affect women and do they have any other biological meaning?”

One theory is that hot flashes might correlate with an increased risk of bone loss.

UCLA researchers have already discovered that hot flashes seem to be an issue only among their Caucasian study group. Women of Japanese descent rarely complain about hot flashes. Though they are often petite, they tend to have a much lower rate of hip fractures, which is indicative of bone loss, than Caucasian women. The study will explore factors that may account for these differences.

“One of the great opportunities in working with Japanese American women is that their diet is so different,” says Greendale, who will compare women who eat traditional Japanese diets with those who don’t. “One thing that has been postulated is that the Japanese diet is protective because it blocks hot flashes. We don’t know that, but it’s an interesting theory.”

Japanese diets are often rich in soy products, which contain a substance called phytoestrogens.

“Phytoestrogens are a mixture of estrogens. Some of them may have cancer prevention effects, heart disease prevention effects, bone loss prevention effects and even prevent some of the symptoms of menopause,” Greendale says.

The other study sites will also explore specific questions about midlife.

A team at Massachusetts General Hospital in Boston will evaluate whether blood tests for a material called Mullerian inhibitory substance can predict the onset of menopause before other symptoms appear.

Researchers at the University of California, Davis, will examine alternative therapies used to deal with premenstrual and menopausal symptoms.

A University of Michigan team will study African American and Caucasian women and their risk factors for obesity, osteoporosis, hypertension and arthritis.

A University of Pittsburgh group will look at rates of clinical depression and anxiety during midlife.

And a New Jersey group will use ultrasound examinations to study how fibroids change in midlife.

“We have no good data on what happens with uterine fibroids at midlife and why some women bleed so badly,” Greendale says of the study at the University of Medicine and Dentistry of New Jersey. “Why do fibroids tend to grow at midlife? What are the risk factors for fibroids?”

In the final analysis, the study results might take a little anxiety out of that monumental 40th birthday.

Study participant Midori Sato says she often wonders if changes in her body are normal or signal illness.

“I want to learn more about konenki shogai,” which is the Japanese term for problems in midlife, says Sato, a native of Nagasaki who lives in Rancho Palos Verdes. “I started wondering how the changes in my body would affect my mind. . . . I do not understand if certain physical and psychological symptoms are abnormal or due to illnesses.”

Says Greendale: “Part of the goal is preventing disease. But part of the goal is to help women understand their bodies better.”