Led by UC Davis Health System endocrinologist and epidemiologist Jennifer Lee, the study, which is the first to look specifically at endogenous estrogen in older women and stroke, also found that women with the highest levels of naturally occurring estrogen had larger waist sizes.
Lee conducted the research to find out why menopausal women taking hormone therapy did not experience cardiovascular benefits and, in fact, had more strokes. She noticed this trend as an investigator in the Women’s Health Initiative (WHI), a national study that has dramatically changed clinical practice. Millions of women have stopped taking estrogen therapy due to WHI outcomes showing fewer advantages and more harms than expected, according to Lee.
“Prior to WHI, most health-care providers advised women that estrogen therapy would provide some cardiovascular protection when they lost most of their naturally occurring estrogen during menopause,” said Lee. “Post-WHI, we realized we needed to reassess this guidance. We wanted to know if naturally occurring estrogen levels prior to the start of estrogen therapy could affect stroke risks.”
Lee is among the few researchers examining the relationship between estrogen and stroke, which is the third leading cause of death and a significant cause of adult disability in the United States. These cerebrovascular events occur when blood flow to the brain is interrupted either by a blood clot or when a blood vessel breaks, causing brain cells to die.
“Over 40 million women face menopause for about a third of their lives, so this research aims to improve their quality of life and promote healthy cardiovascular aging,” said Lee, an assistant professor of internal medicine whose research focuses on determining the effects of hormones and metabolism on disease risks across women’s life spans.
To conduct the study, Lee and her team assessed medical histories and blood samples from 9,704 generally healthy postmenopausal Caucasian women who were recruited from four U.S. communities for an osteoporosis study in the late 1980s. All participants received annual questionnaires for health updates, including confirmed stroke events. Levels of estradiol, the most potent naturally occurring estrogen, were measured in banked blood collected when participants began the osteoporosis study. Women on hormone therapy were excluded from the UC Davis study.
During eight years of follow-up, 247 of the study participants experienced a first stroke. The investigators compared those women with 243 participants who did not have a stroke. After dividing the participants into four groups based on estradiol levels, the researchers found that those in the highest quarter were 2.3 times more likely to experience a stroke than those in the lowest quarter.
“Higher naturally occurring estrogen indicated a twofold greater stroke risk,” Lee said. “These results raise the possibility that estradiol levels might be a decision-making tool for health-care providers and their female patients when discussing stroke and weighing the option of estrogen therapy.”
Lee and her team also found that higher naturally occurring estradiol and increased stroke risk were more pronounced for women with waist measurements greater than 34 inches, which is a known risk factor for cardiovascular disease.
“In women with waist girths greater than 34 inches, high estradiol levels conferred a sixfold greater stroke risk over low levels,” said Lee. “This might be because fat around the midsection is a source of naturally occurring estrogen. Reducing waist size would be a good defense against future stroke.”
Before making this recommendation, Lee will further clarify the relationship between estrogen, midsection size and stroke in upcoming studies. She is also determining whether naturally occurring estradiol levels in postmenopausal women on hormone therapy affect their risks of coronary heart disease, blood clots, fractures, cognition changes and cancers of the breast, endometrium and colon.
“Our goal is to give more certain and specific health advice to postmenopausal women based on their particular health scenarios,” said Lee.
The UC Davis study and Lee were funded by a grant from the National Center for Research Resources to the UC Davis Clinical and Translational Science Center. Support for the Study of Osteoporotic Fractures and the Women’s Health Initiative was provided by the National Institutes of Health.
In addition to Lee, the study authors were Kristine Yaffe of UC San Francisco; Warren Browner, Steven Cummings and Li-Yung Lui of California Pacific Medical Center Research Institute; Jane Cauley of the University of Pittsburgh; and Brent Taylor of the University of Minnesota.
UC Davis Health System is an integrated, academic health system encompassing UC Davis School of Medicine, the 613-bed acute-care hospital and clinical services of UC Davis Medical Center, the 800-member physician group known as UC Davis Medical Group, and the Betty Irene Moore School of Nursing.