TRACKING WOMEN'S HEALTH OVER TIME GIVES RESEARCHERS INSIGHTS INTO BETTER TREATMENTS, PREVENTION
Not long ago, little was known about how women experienced menopause and about how their health changed with age. The few studies that had been conducted involved relatively small numbers of only Caucasian women. In the 1990s, two landmark studies – the Women's Health Initiative (WHI) and the Study of Women's Health Across the Nation (SWAN) – changed that.
Thousands of Northern California women – and researchers at UC Davis – have played important roles in these two studies, which have led to changes in clinical practices as they continue to generate new findings.
More than 4,000 women in the Sacramento area have participated in WHI, which was established at 40 clinical centers across the nation to study cardiovascular disease, cancer and osteoporosis in postmenopausal women. Now, with 15 years of data from 162,000 women around the country, researchers can point to some valuable results.
"I think the most important thing we've learned is that the combination of estrogen and progesterone causes bad side effects – increased heart attacks, stroke, blood clots and breast cancer," says John Robbins, internal medicine professor and a principal investigator on the WHI study.
After the announcement of those findings in 2002, women's use of hormone replacement therapy dropped dramatically, followed by a drop in the incidence of breast cancer across the country. Robbins and others now hypothesize that estrogen may be a promoter of breast cancer.
As for cardiovascular disease, Robbins speculates that hormone replacement therapy can increase inflammation and the stickiness of platelets, causing blood vessels to become clogged. While some physicians previously prescribed female hormones to protect women from cardiovascular disease, guidelines now advise against that intervention.
A reservoir of data
WHI data still holds the potential for more answers. Because participating women provided DNA samples – and genome sequencing has become much more affordable – researchers are now searching for candidate genes that may be related to these common diseases.
In 2007, UC Davis was one of 12 institutions to receive a two-year contract to use the WHI data to study the genetic and biological markers of breast cancer, osteoporosis and cardiovascular disease. Robbins and his team have applied to renew the funding.
"We can look at 1,000 women with and without a disease and see where their genes differ," explains Robbins. "When we find a candidate gene, a [genetically engineered] mouse can be created to see what goes wrong and work backward to see what the gene does. It's mind-boggling – it will be absolutely fascinating to see what comes out of these studies."
Calculating hip-fracture risk
Robbins suspects that genes play a big role in women's risk of hip fracture. Women of African ancestry have higher bone-mineral density, a different hip architecture and a much lower incidence of hip fracture.
"Hopefully, we will discover that there's some kind of over- or underproduction of something that is related to ancestry, such as a bone protein. If we can figure out what that is, then we could change it, perhaps by giving women a supplement."
In the meantime, Robbins and his colleagues used the WHI data to develop a useful algorithm for predicting the five-year risk of hip fracture in postmenopausal women.
The Hip Fracture Risk Calculator, as it's called, is based on 11 factors: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of hip fracture over age 54, parental hip fracture, current smoking, current corticoid steroid use, and treated diabetes. This online survey tool is designed to help patients and clinicians make informed choices about lifestyle and use of medications. See http://hipcalculator.fhcrc.org/ for more information.
How women age
WHI isn't the only study devoted to finding practical solutions to women's health problems. The Study of Women's Health Across the Nation (SWAN) is investigating how midlife experiences affect women's health and quality of life during aging. "It's fundamentally a study about menopause," says Ellen Gold, professor and chair of UC Davis' Department of Public Health Sciences. "It's unique because it's a large multidisciplinary study of relatively healthy women over a long period of time, and it's looking at a racially and ethnically diverse sample of women."
In the mid-1990s, SWAN enrolled 3,300 women between 40 and 55 years old who were racially and ethnically diverse: 46 percent Caucasian, 28 percent African American, nine percent Hispanic, nine percent Japanese and eight percent Chinese. As one of seven clinical sites, UC Davis studied women in Northern California's East Bay area. At annual clinical visits, the researchers measured participants' hormone levels, lipid profiles and other markers of health, and also asked them questions about symptoms, illnesses, lifestyle and psychosocial health.
With 12 years of data that already has generated nearly 200 research articles, SWAN is yielding a treasure trove of information about menopause. Most importantly, the study finds that women from different racial and ethnic groups show significant differences.
"We see it in their physiological changes, symptomology, blood lipids and bone densities," says Gold. "People think of menopause as normal and natural and that all women experience it the same way – but it's just not true."
One surprise finding of the study has been that women with high body mass indexes (BMI) are more likely than leaner women to have hot flashes and night sweats – regardless of race or ethnicity.
"Why women who are heavier tend to have more hot flashes, we don't know."
Gold hypothesizes that the BMI effect is based on individual differences in physiology, perhaps on the kinds of estrogens a woman produces, or insulation or variations in perceptions of temperature.
Another little-known fact about menopause is that estrogen levels don't necessarily decline steadily – they can bounce up and down. Gold suggests that variability may be related to symptoms.
Keeping an even keel emotionally appears to be important, too.
"Women with high anxiety scores at baseline were at greater risk than women with lower scores of more menopausal symptoms later on."
Aging and menopause
SWAN has just been renewed for another five years, and Gold says many questions remain to be answered:
Researchers also hope to learn more about what's behind the racial and ethnic differences in symptoms – that is, how much of the divergence can be attributed to genetics, lifestyle or a woman's social environment.
Because most of the SWAN participants are now postmenopausal and are older, study researchers also can examine health changes related to aging. For instance, cognitive function will be evaluated using tests of their verbal and visual memory. The researchers hope to sort out which health changes are related to aging and which are related to the menopausal transition. For instance, increases in BMI appear to be more related to aging than to menopause, according to Gold.
Providing useful advice
From both WHI and SWAN, researchers should get a much better picture of what healthy aging looks like in women of diverse ethnicities. And that should translate into further advice for clinicians and women.
"Women enrolled in these studies participate because of altruism – they hope to help their daughters and other women," says Gold. "We have an obligation to translate the scientific findings to useful information for all women."