Why Men and Women React Differently to Stress and a High-Fat Diet

It’s more difficult to study women than men — women have monthly hormonal cycles, and depending on where they are in their cycle, these hormones can affect the outcome of studies. To get around this, many researchers exclusively study males. The assumption, until recently, was that non-reproductive data gathered about men would also apply to women.

As cases such as the new Ambien dosage guidelines indicate, this lack of data on female patients can be dangerous. Women were found to be taking up to twice as much of the sleeping drug as was safe, based on data from men.

The bottom line is that men and women have many physiological differences. In order to address these, the National Institutes of Health (NIH) have issued mandates requiring that human studies include women and that preclinical animal studies include female animals.

Now, two new studies explore differences in the way men’s and women’s brains respond to stress and a high-fat diet.

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Don't Overlook Stress in Heart Disease Risk

Researchers from Duke University Medical Center were already conducting a study on the effects of mental stress on the heart when they decided to take a look at the specific effects of gender, in research published in the Journal of the American College of Cardiology.

The researchers gathered 56 women and 254 men from the parent study. The subjects were asked to perform three tasks that were mentally stressful: a mental math test, a mirror tracing test, and an anger recall test. To compare the effects of mental stress to exercise, the volunteers also completed a treadmill test. At each step in the process, the scientists measured the participants’ heart activity and took blood samples.

The men in the group showed larger increases in blood pressure and heart rate in response to mental stress compared to the women. The women, however, experienced fewer positive emotions and more negative emotions. They also had increased platelet aggregation (which leads to the formation of blood clots), and more frequent signs of cardiac ischemia, or reduced blood flow to the heart.

“Psychosocial stress affects men and women differently; the fact that women had more platelet clumping and cardiac ischemia suggests women may have different mechanisms of low blood flow to the heart,” said Dr. Zainab Samad, an assistant professor of medicine at Duke and the lead author of the study, in an interview with Healthline.

Read More: 10 Ways to Reduce Stress and Protect Your Heart »

Samad believes that mental stress shouldn’t be overlooked when evaluating a patient’s heart disease risk.

“Psychosocial stress is not routinely evaluated when working up patients for heart disease; clearly this is important and needs to be recognized,” she said. “Unlike physical stress, psychosocial stress patients experience is not predictable or controllable. But we can teach patients to be more mindful about being ‘stressed out’ and how to cope with psychosocial stress in healthier ways.”

High-Fat Foods on the Brain

Another research team looked at gender differences in the way a high-fat diet contributes to heart disease, obesity, and type 2 diabetes. Their results were published in Cell Reports.

The team already knew that heart disease rates are higher among men and postmenopausal women than among premenopausal women. They were also aware that estrogen protects against inflammation, which contributes to these chronic diseases.

The fact that males and females differ as much as they do really tells us how important sex-based research is. Men and women are not the same, and the more we pay attention to this, the better and more efficacious healthcare can become.
Deborah Clegg, Cedars-Sinai Medical Center

The researchers examined the role of palmitic acid in mice. Palmitic acid is a fatty acid that is commonly found in Americans’ diet (and in their bloodstreams).

A diet rich in palmitic acid caused levels of the fatty acid to rise in the brains of male mice, but not in female mice. The high levels of palmitic acid decreased the levels of a compound called PGC-1a, which normally gives a boost to estrogen receptors.

With reduced PGC-1a, the number of estrogen receptors in the male mice decreased. This took away the protective effects of estrogen in the males and increased their inflammation levels.

Specifically, the inflammation occurred in the brain’s hypothalamus, which regulates hunger and metabolism. Inflammation of the hypothalamus is associated with overeating, and also causes insulin resistance, which leads to diabetes.

To confirm this finding, the team manipulated the brains of the male rats to have extra estrogen receptors, thereby making up for the ones lost by the high-fat diet. With the receptors restored, the male rats were protected against brain inflammation once again.

“These data are novel and exciting, and again, remind us that there is so much more we need to learn about,” said Deborah Clegg, a research scientist with the Diabetes and Obesity Research Institute at Cedars-Sinai Medical Center and senior author of the paper, in an interview with Healthline.

“The fact that males and females differ as much as they do really tells us how important sex-based research is. Men and women are not the same, and the more we pay attention to this, the better and more efficacious healthcare can become,” Clegg added.

Samad agrees. “Our knowledge regarding how gender, race, environment, and genes interact to cause disease is evolving currently,” she said. “One day we may be able to fine tune and offer more tailored therapy for individuals. We are not there yet.”

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