UNIVERSITY PARK, Pa. — In endometriosis, cells similar to uterine tissue grow outside the uterus. According to researchers in the Penn State Department of Kinesiology who study the disease, endometriosis is often treated as a purely gynecological condition. In a new study, however, they demonstrated how the condition, which affects 10% of women around the world, alters how the body responds to feedback.
In a new study published in the journal Hypertension, the research team revealed that endometriosis alters how the autonomic nervous system functions — which regulates aspects of the body that are not typically managed through conscious thought, including blood pressure, digestion, breathing and heart rate.
When exposed to exercise or submerging their hand in cold water, women with endometriosis experienced a lower blood pressure response compared to women without the condition. This finding — opposite of what the researchers expected — may have significant implications for both the diagnosis and management of endometriosis, the researchers said.
“In this study, almost every prediction we made was wrong, but we were wrong in the most interesting and impactful ways possible,” said Auni Williams, postdoctoral fellow in kinesiology at Penn State. “Medical science understands very little about endometriosis, so in order to diagnose and treat the disease effectively, we need to grasp the full scope of the disease and what it is doing to women throughout their bodies.”
Understanding and treating endometriosis
During the menstrual cycle, uterine tissue thickens and sheds in response to fluctuating hormones. In endometriosis, tissue similar to the uterine lining develops outside of the uterus throughout the pelvic region. When this tissue grows where it doesn’t belong, it can form lesions and cause systemic inflammation and scarring, leading to severe chronic pain, infertility or heavy bleeding.
One of the most common treatments for endometriosis is surgery to remove the lesions. Surgery is effective at providing pain relief, but it does not address other symptoms of endometriosis like the decreased blood pressure response identified in this study, according to the researchers.
Blood pressure differences in response to stress
To assess the blood pressure responses of women with endometriosis under mild stress, the researchers conducted two experiments on 21 participants — 12 women with endometriosis and nine without the condition. After two weeks, all women participated in both experiments a second time.
In one experiment, the researchers measured heart rate and blood pressure before the experiment started and then when participants placed their right hand in cold water — between 4 and 8 degrees Celsius — for three minutes. Once the women removed their hands from the water, the researchers monitored their heart rate and blood pressure for an additional 15 minutes.
The other experiment also involved continuously monitoring blood pressure and heart rate, but this time, women began by squeezing a tool that measures grip strength as hard as they could. Once their maximum force was established, the women rested to allow their blood pressure and heart rate to recover. The women then squeezed with 30 percent of their maximum hand strength for two minutes. Just before the two minutes expired, the researchers inflated a blood pressure cuff around the women’s squeezing arm for three minutes. After the cuff deflated, blood pressure was measured for another five minutes.
When a person experiences stress, like the water or exercise in the experiments, it increases blood pressure in response, like a reflex. The researchers expected that women with endometriosis would experience higher increases in blood pressure. Prior research has shown that endometriosis is also associated with higher risk of artery disease, diabetes and high cholesterol, and people with these conditions typically display higher blood pressure responses to things like physical activity.
In both experiments in this study, however, the researchers found the opposite. When women with endometriosis stuck their hands in cold water or squeezed the grip strength device, their blood pressure increased a lower amount compared to women without the condition when exposed to the same stressors.
A whole-body condition?
The decreased blood pressure response among women with endometriosis suggests a reduced neurological response to the stress and may be the cause of lightheadedness, which has been previously reported as a symptom of endometriosis, the researchers explained.
“Compared to the crippling pain that endometriosis can cause, the lightheadedness associated with a decreased blood-pressure response is trivial,” said Williams, who conducted this research as part of her doctoral studies at Penn State. “What matters here is the evidence that the autonomic nervous system functions differently in women with endometriosis. Most of the women with endometriosis in our study had undergone surgery to remove lesions. While the gynecological issues had been addressed, the changes to their nervous systems were still present, so they demonstrated lower blood pressure increases than women without endometriosis.”
The findings are an example of how endometriosis can lead to symptoms outside of the reproductive system. In addition to lightheadedness, Lacy Alexander, professor of kinesiology at Penn State and coauthor of this study, and others have previously demonstrated that the cardiovascular system function is impaired by endometriosis. The combination of these findings demonstrates that endometriosis needs to be treated systemically, the researchers said.
“Any time women experience a symptom of any kind, they should tell their endometriosis-care provider. A side effect like lightheadedness may not seem related to a gynecological condition, but this study demonstrated that it very well could be,” said Alexander, who was Williams’s doctoral adviser and is currently her postdoctoral mentor.
To address low blood pressure, women with endometriosis should drink more water and potentially increase their salt intake, in consultation with their doctor, the researchers said. Doing so may help prevent lightheadedness, especially during exertion.
A less invasive way to diagnose endometriosis
It can take over six and a half years — and visits to three different medical specialists — for a woman to receive a diagnosis for endometriosis, according to the researchers. Currently, ultrasounds and MRIs can help doctors identify endometriosis lesions, but the only approved way to diagnose the condition is with surgery.
“These results may point to less invasive methods for diagnosing endometriosis,” Alexander said. “If — as this study shows — women with endometriosis have predictably lower blood-pressure increases in response to mild stressors, then there may be less invasive tests that would allow women to be diagnosed sooner. Tests like these could be conducted during a routine office visit and potentially prevent years of unnecessary suffering.”
The value of federal research support
Alexander said this project underscored the importance of federal research support. The project began when Williams came to Alexander’s office, expressing an interest in the potential effects of endometriosis on blood pressure responses. Together, they decided that Williams would apply for a research-training grant from the National Institutes of Health.
“This funding was intended to train Auni to conduct research at the intersection of gynecology and cardiovascular disease,” Alexander said. “It did that, but it also provided insights that might someday improve the lives of the millions of women who live with endometriosis in the United States. None of that would have been possible without federal funding.”
The National Heart, Lung and Blood Institute funded this research.
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