Females sleep less, wake up more often and get less restorative sleep than males, according to a new animal study by CU Boulder researchers.
The findings, published in the journal , shed 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 primarily on males.
鈥淚n humans, men and women exhibit distinct sleep patterns, often attributed to lifestyle factors and caregiving roles,鈥� said senior author Rachel Rowe, assistant professor of integrative physiology. 鈥淥ur results suggest that biological factors may play a more substantial role in driving these sleep differences than previously recognized.鈥�
Sleep research has exploded in recent years, with thousands of animal studies exploring how insufficient sleep impacts risk of diseases like diabetes, obesity, Alzheimer鈥檚 and immune disorders鈥攁nd how such diseases impact sleep. Meanwhile, mice have often been the first to be tested to see whether new drugs, including medications for sleep, work and what the side effects are.
But many of those results may have been skewed due to a lack of female representation, the study suggests.
鈥淓ssentially, we found that the most commonly used mouse strain in biomedical research has sex-specific sleep behavior and that a failure to properly account for these sex differences can easily lead to flawed interpretations of data,鈥� said first author Grant Mannino, who graduated with degrees in psychology and neuroscience and was named outstanding undergraduate of the College of Arts and Sciences in May.
Rachel Rowe
How mice sleep
For the non-invasive study, the authors used specialized cages lined with ultrasensitive movement sensors to assess the sleep patterns of 267 鈥淐57BL/6J鈥� mice.
Males slept about 670 minutes total per 24-hour period, about an hour more than female mice. That extra sleep was non-Rapid Eye Movement (NREM) sleep鈥攖he restorative sleep when the body works to repair itself.
Mice are nocturnal and are 鈥減olyphasic sleepers鈥濃�攏apping for a few minutes before arousing briefly to survey their environment and then resuming their slumber. Females, the study found, have even shorter bouts of sleep鈥攅ssentially, their sleep is more fragmented.
Similar sex differences have been seen in other animals, including fruit flies, rats, zebrafish and birds. Evolutionarily, it makes sense.
鈥淔rom a biological standpoint, it could be that females are designed to be more sensitive to their environment and be aroused when they need to be because they are typically the one who is caring for the young,鈥� Rowe said. 鈥淚f we slept as hard as males sleep, we would not move forward as a species, right?鈥�
Stress hormones like cortisol (which promotes wakefulness) and sex hormones likely play a role. For instance, women tend to report worse sleep during the time in their menstrual cycle when estrogen and progesterone are at their lowest.
Some have hypothesized that females inherently require less sleep.
鈥淔or me, the question is: Are we creating too much stress for ourselves because we don鈥檛 sleep as much as our husband or partner and think our sleep is poor when actually that is a normal sleep profile for ourselves?鈥� said Rowe.
The authors hope their findings inspire more research into underlying biological differences. More importantly, they hope the study prompts scientists to re-evaluate how they do research.
Progress made but more work to be done
In 2016, the National Institutes of Health began requiring scientists applying for funding for animal studies to consider 鈥渟ex as a biological variable.鈥� 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 females, they found that it was accurately reflected only if the sample size was made up evenly of males and females.
Bottom line: If females are underrepresented, drugs that work best for them may seem ineffective, or side effects that hit hardest may go unnoticed.
鈥淭he pipeline from bench to bedside is decades-long and often things that work in animals fail when they get to clinical trials. Is it taking so long because sex isn鈥檛 being considered enough?鈥� said Rowe.
The authors encourage researchers to include both sexes equally when possible, analyze data for males and females separately, and re-evaluate past studies that underrepresented females.
鈥淭he most surprising finding here isn鈥檛 that male and female mice sleep differently. It鈥檚 that no one has thoroughly shown this until now,鈥� said Rowe. 鈥淲e should have known this long before 2024.鈥�
