Stroke Is the Third Leading Cause of Death for Women, Yet They Remain Underrepresented in Clinical Trials
核心洞察
Stroke (搜索) kills 85,000 women annually in the U.S. and is the third leading cause of death for women, who face a two-year average delay in diagnosis across hundreds of conditions.
After menopause, declining estrogen levels elevate cardiovascular and cerebrovascular risks, with women more likely than men to experience severe strokes in every decade after 50.
Women who have had a stroke (搜索) are generally contraindicated for systemic hormone therapy, though non-hormonal options like fezolinetant and elinzanetant now offer alternatives for vasomotor symptoms.
Stroke (搜索) is the fifth leading cause of death in the overall U.S. population, but for women it ranks third, killing 85,000 each year. One in five women over the age of 55 will suffer a stroke, and stroke is also the leading cause of Alzheimer's disease (搜索) and dementia (搜索)—nearly two-thirds of those diagnosed are women. Yet as women live longer, often spending a third of their lives after menopause, researchers are only now beginning to understand how aging, hormones, and vascular disease interact to shape long-term brain health.
"In every decade after 50, women are more likely to experience stroke (搜索) compared to men, especially severe strokes. This significantly fuels the risk for cognitive impairment, and — eventually — dementia (搜索)," said Dr. Farida Sohrabji, head of the Department of Neuroscience at Texas A&M University and Experimental Therapeutics Director of Women's Health in the neuroscience program.
The Diagnostic Gap
Women experience an average two-year delay in diagnosis across hundreds of medical conditions, according to Dr. Liisa Galea, chair on women's mental health at the Centre for Addiction and Mental Health in Toronto and lead of the Women's Health Research Cluster. "A two-year delay in diagnosis is a huge problem. Earlier interventions are most important for effective outcomes," she said.
Galea noted that women who may have suffered a stroke (搜索) are often misdiagnosed. "We are still largely treating stroke as a male illness. You go to the emergency room and you're sent home. The doctor is saying: 'No, no, you're fine.' That's going to have more cascading issues for you."
Part of the challenge lies in symptom presentation. Most public health campaigns focus on classic stroke (搜索) symptoms such as facial drooping, slurred speech, and weakness on one side of the body. But women are more likely to experience symptoms that can be overlooked. "There are subsets of people, many of whom are women, who will report symptoms such as migraine, pain from the jaw radiating upward, confusion and anxiety," said Sohrabji. "Those symptoms will not get you diagnosed as an urgently stroke-needing individual."
Disparities in Risk
Black and Latina women suffer strokes at disproportionately higher rates than their white counterparts. The prevailing risk factor for Black women is hypertension (搜索), while the largest risk factor for Latina women is Type 2 diabetes (搜索), Sohrabji explained. After menopause, all of these factors increase, especially hypertension, irrespective of ethnicity. Black women experience stroke (搜索)-related death at higher rates than any other racial group, with socioeconomic factors—limited access to health care, delayed diagnoses, medication costs, and barriers to healthy nutrition—further compounding those risks.
Menopause and Cardiovascular Risk
More than 60 million women in the U.S., approximately 44%, are living with some form of heart disease. About one in five women will have a stroke (搜索) in their lifetime. "Age is probably the single strongest risk factor for heart disease and stroke," said Dr. Anum Minhas, a cardiologist and assistant professor of medicine at Johns Hopkins.
For women reaching midlife, the drop in estrogen compounds that increase in risk. "Prior to menopause, women have estrogen, which generally has cardio-protective effects," Minhas explained. But when estrogen levels drop, heart health risk factors like blood pressure and LDL cholesterol change. "A lot of women have fairly low blood pressure when they're younger, and then they hit menopause and it just starts going up," said Dr. Eliza Miller, a vascular neurologist and chief of women's neurology at the University of Pittsburgh Medical Center.
After the menopause transition, insulin resistance often increases, and "actual vessel function — the way our blood vessels work — can become impaired too," Minhas added. Disruptions to sleep, possibly due to night sweats and anxiety, also negatively impact heart health.
The Hormone Therapy Conundrum
For women who have experienced a stroke (搜索), the go-to hormone medications for common menopause symptoms can pose additional risks. "Hormone-based therapy is associated with a possible risk for clotting," Minhas explained, which can lead to strokes and heart attacks. "It's really contraindicated to use hormone therapy because we might be actually increasing their risk for another event," said Dr. Rajita Patil, an OB-GYN who leads UCLA Health's Comprehensive Menopause Care Program.
However, experts note that having risk factors is not the same as having had a stroke (搜索) or heart attack. "I would talk to the person and say, 'Let's do everything we can to lower your stroke risk in all the ways we know how to do,'" Miller said. Once a patient is on a blood thinner, has quit smoking, and adopted a healthy diet and exercise routine, "it may be that the small increased risk of a stroke related to taking hormones is outweighed by the benefit on your quality of life right now."
Vaginal hormone therapy may offer a safer alternative for local symptoms. "Vaginal hormone therapy is not systemically absorbed, so even for people who have contraindications, like history of stroke (搜索) or history of breast cancer, that is safe to use," said Rebecca Thurston, Ph.D., associate dean for women's health research at the University of Pittsburgh School of Medicine. Estrogen patches, while still systemic, do not get processed by the liver the same way a pill would and may be less likely to contribute to clotting.
Non-Hormonal Alternatives
For vasomotor symptoms such as hot flashes and night sweats, two recently approved non-hormonal medications—fezolinetant (Veozah) and elinzanetant (Lynkuet)—offer new options. These neurokinin (搜索) receptor antagonists target the same temperature-regulation system in the brain that estrogen therapies do but through a different mechanism. Temperature regulation is controlled by KNDy neurons in the hypothalamus; estrogen acts as a brake, while neurokinin acts as a gas pedal. These new drugs block neurokinin receptors, effectively blocking the gas pedal.
Other options include SSRIs and SNRIs used off-label, gabapentin for sleep issues, and oxybutynin for hot flashes, though Thurston noted that oxybutynin "can have cognitive side effects, so we don't use them as much." Cognitive behavioral therapy is recommended for insomnia, which Thurston described as "just as effective as medication" and "more durable."
The Clinical Trial Gap
In 1993, the National Institutes of Health mandated that women and minorities be included in clinical trials, requiring numbers proportionate to the prevalence of the condition under study. However, the NIH only funds about 15% of all clinical research, Galea noted. "Women's health research is severely undervalued and severely underfunded," she said.
"There was a long-standing assumption — and I think it's still true to this day — that women don't really differ from men. We're just smaller in general," Galea said. "But that ignores some very basic physiology. In every single cell in our body and every single organ that we have, there are XX, XY, or X0, XXY chromosomes."
Miller advocated for gender-specific clinical trial designs. "We have to power the trial to look at men and women separately. And we in the research community are recognizing and pushing the idea that sex is not a covariant. You can't adjust away someone's sex. Instead you have to stratify by sex."
In 2024, former President Joe Biden signed a memo requesting $12 billion in funding for research focused on women's health and established the White House Initiative on Women's Health Research. "Never before has there been such a comprehensive effort from the federal government to spur innovation in women's health research," said Carolyn Mazure, former chair of the initiative. The initiative initially faced funding cuts but was restored following public outcry.
The American Heart Association/American Stroke Association (搜索)'s Research Goes Red platform, the largest women's health registry, now includes more than 24,000 active participants, encouraging women to participate in clinical trials and informing them of their risk for stroke (搜索) and underlying conditions.
Time Is Brain
Because men experience strokes at a younger age, they are more at risk for having a second or even third stroke (搜索)—nearly one in four stroke survivors will have another. But women tend to suffer strokes later in life, after menopause, when naturally occurring estrogen levels decline. "There are so many more severe strokes in older women," Sohrabji said. "At that time, they might be living on their own. They may have outlived their spouses. Then when they have a stroke, there's nobody that they can call because they have lost function."
"The most common public service announcement is 'time is brain.' Because we lose neurons so quickly. And older women may suddenly find that they are not getting to care centers quickly enough," Sohrabji added.
Stroke (搜索) also acts as a seed for cognitive decline, fueling the buildup of amyloid or tau proteins often associated with dementia (搜索). Beyond memory issues, caregivers should watch for personality changes, depression, loss of social engagement, withdrawal from previously enjoyable activities, anxiety, and aggression. "Caregivers are in a very good position because they know what the baseline was, and they know what changes are occurring," Sohrabji said.
"Suffering is overrated," Thurston concluded. "If you're having a lot of menopausal symptoms and they are bothering you, you deserve treatment."