Females sleep less, wake more often and sleep less restoratively than males, according to a new animal study by CU Boulder researchers.
The findings were published in the journal Scientific Reportsshed new light on what may underlie sleep differences in men and women and could have broad implications for biomedical research, which for decades has focused mostly on men.
In humans, men and women exhibit distinct sleep patterns, often attributed to lifestyle factors and caregiving roles. Our results suggest that biological factors may play a more substantial role in causing these sleep differences than previously recognized.”
Rachel Rowe, senior author, assistant professor of integrative physiology, CU Boulder
Sleep research has exploded in recent years, with thousands of animal studies investigating how insufficient sleep affects the risk of diseases such as diabetes, obesity, Alzheimer’s and immune disorders—and how such diseases affect sleep. Meanwhile, mice have often been the first to be tested to see if new drugs, including sleep drugs, work and what the side effects are.
However, many of these results may have been skewed by a lack of female representation, the study suggests.
“Essentially, we found that the most commonly used mouse strain in biomedical research has sex-specific sleep behavior, and that failure to properly account for these gender differences can easily lead to misinterpretations of the data,” said first author Grant Mannino. , who graduated. with degrees in psychology and neuroscience and was named the College of Arts and Sciences’ outstanding undergraduate in May.
How mice sleep
For the non-invasive study, the authors used specialized cages lined with hypersensitive motion sensors to assess the sleep patterns of 267 “C57BL/6J” mice.
Males slept a total of about 670 minutes per 24-hour period, about an hour more than female mice. This extra sleep was non-rapid eye movement (NREM) sleep – the restorative sleep when the body works to repair itself.
Mice are nocturnal and are ‘polyphasic sleepers’ – they sleep for a few minutes before waking up briefly to survey their surroundings and then resuming their sleep. Women, according to the study, have even shorter sleep periods – essentially, their sleep is more fragmented.
Similar sex differences have been observed in other animals, including fruit flies, rats, zebrafish and birds. Evolutionarily, it makes sense.
“Biologically, it could be that females are designed to be more sensitive to their environment and to be stimulated when needed because they are usually the ones taking care of the young,” Rowe said. “If we slept as hard as the males do, we wouldn’t progress as a species, would we?”
Stress hormones such as cortisol (which promotes alertness) and sex hormones likely play a role. For example, women tend to report worse sleep during their menstrual cycle when estrogen and progesterone are at their lowest.
Some have hypothesized that females inherently require less sleep.
“For me, the question is: Are we putting a lot of stress on ourselves because we’re not getting as much sleep as our spouse or partner and thinking we’re getting poor sleep, when in fact that’s a normal sleep profile for us?” Rowe said.
The authors hope their findings will inspire more research into the underlying biological differences. More importantly, they hope the study will prompt scientists to reevaluate the way they do research.
Progress has been made, but more work needs to be done
In 2016, the National Institutes of Health began requiring scientists applying for funding for animal studies to consider “sex as a biological variable.” Progress has been made, but research has shown that sex bias still exists. And it can have real consequences, the authors found.
When they simulated a sleep treatment that worked best in women, they found that it was only accurately reflected if the sample size consisted equally of men and women.
Bottom line: If women are underrepresented, the drugs that work best for them may appear ineffective, or the side effects that affect them the most may go unnoticed.
“The pipeline from bench to bedside takes decades, and often things that work in animals fail when they get to clinical trials. Does it take so long because sex isn’t considered enough?” Rowe said.
The authors encourage researchers to include both sexes equally when possible, to analyze data for men and women separately, and to re-evaluate previous studies that underrepresented women.
“The most surprising finding here is not that male and female mice sleep differently. It’s that no one has thoroughly shown this until now,” Rowe said. “We should know well before 2024.”
Source:
Journal Reference:
Mannino, GS, et al. (2024). The importance of including both genders in preclinical studies and sleep analyses. Scientific Reports. doi.org/10.1038/s41598-024-70996-1.