The buzz is growing around sleep apnea right now, thanks to a potential “sleep apnea pill” and other promising new treatments on the horizon. Yet experts say the next real breakthrough won’t come from new treatments alone — it will come from a better understanding of how the disorder differs in women.

Sleep experts have long known that women experience sleep apnea differently from men and are less likely to be diagnosed. Now scientists are finally starting to understand the mechanisms, symptoms, and outcomes driving that gender gap, and what they’re learning could soon change the way clinicians diagnose and treat the disorder.

“We are at this inflection point now, where there is a great deal of data about the heterogeneity of the condition,” said Susan Redline, MD, MPH, senior sleep physician at Brigham and Women’s Hospital in Boston.

That data span more than three decades of research. In 1993, a major longitudinal study of more than 1500 people — known as the Wisconsin Sleep Cohort Study — helped shed light on sleep apnea underdiagnosis in women, plus the disorder’s cardiovascular and menopause-related risks. Research in the mid-2000s hinted at female-specific impacts, such as lower quality of life, higher healthcare costs, and longer-term risk of missing work, compared to male-specific ones.

More recent research shows that women tend to have less dramatic oxygen drops during sleep, potentially preventing diagnosis, but they may experience as much sleepiness as men and may be at a higher risk for major adverse cardiovascular events and early death.

“In my viewpoint, sleep apnea is likely several different diseases,” said Redline, who’s leading a National Institutes of Health-funded effort to better define how sleep apnea differs between sexes and other groups. “That’s not how current clinical care is managed.”

She and other scientists are optimistic that’s about to change.

The Emerging Science Behind Sleep Apnea in Women

Sleep apnea’s physiologic sex differences are well established, said Robson Capasso, MD, a professor of otolaryngology at Stanford University, Stanford, California. Men experience more pronounced pauses in breathing (apneas) and deeper oxygen drops, while women tend to have less severe apneas and more frequent awakenings (hypopneas with arousals).

New research is changing perspectives on how these differences should be weighed. 

The diagnostic threshold for the drop in blood oxygen level varies, ranging from 3% to 4% depending on the clinic. A study published in March found that the lower threshold increases the chances of spotting sleep-disordered breathing in women. But many insurers use stricter criteria, which widens disparities, according to sleep specialists at Rush and Northwestern Universities in Chicago.

Shorter breathing pauses could also be more dangerous for women than for men. Redline’s research has found a link between even brief pauses in breathing in women and mortality risk. In addition, mild drops in oxygen levels with breathing pauses were more common among younger, Black, and female patients. Her team’s preliminary data suggest that even mild drops in oxygen are associated with an increased cardiovascular risk, especially in Black female patients.

Women with less severe disruptions in breathing are often diagnosed with upper airway resistance syndrome, said Safia S. Khan, MD, an associate professor of family medicine and neurology at UT Southwestern Medical Center in Dallas. Many insurers don’t cover continuous positive airway pressure (CPAP) treatment for this condition despite its impact on quality of life, and women often “dismiss” it or go untreated, Khan said.

“Treating upper airway resistance syndrome helps improve mood, quality of sleep, [and] energy during the day,” Khan said. “And when you’re improving sleep, you’re also reducing risk for a lot of other disorders, like heart disease, high blood pressure, and diabetes.”

Cardiovascular risks specific to women with sleep apnea are also under investigation. Previous research by Redline revealed higher levels of galectin-3 — a biomarker associated with cardiovascular diseases — in female patients with moderate-to-severe sleep apnea than in those with mild or no sleep apnea. Researchers found no such differences among male patients. A 2021 study found a stronger association between high hypoxic burden and major adverse cardiovascular events in women with sleep apnea than in men.

Menstrual Cycles, Menopause, and How Women Perceive Symptoms

Women’s vulnerability to sleep apnea ticks up during perimenopause, and researchers are starting to untangle why, Redline said. Potential mechanisms include loss of firmness in throat muscles/tissues, changes in how the brain controls breathing, weight gain, and hormonal shifts.

One of those hormones is progesterone, which protects against airway collapse. Lower levels may worsen symptoms, while higher levels can hide them, Khan said. This matters for premenopausal patients, too — women may not display symptoms when progesterone levels peak, between days 14 and 28 of the menstrual cycle, leading to missed diagnoses, Khan said. Yet clinicians rarely address this when scheduling sleep studies. “We’re just randomly picking a day, whatever is right, comfortable, feasible for patients,” Khan said. “We don’t ask, ‘Hey, what day of your menstrual cycle will you be on?’”

Symptoms of perimenopause and menopause — such as disrupted sleep and night sweats — can also mimic sleep apnea, said Anita Shelgikar, MD, the American Academy of Sleep Medicine’s board president and a professor of neurology at the University of Michigan Medical School, Ann Arbor, Michigan. “Trying to tease that apart really requires a thorough discussion and evaluation,” Shelgikar said. “Could [your patient] have both menopausal symptoms and obstructive sleep apnea? Because one does not preclude the other.”

Language can offer clues too because men and women may describe symptoms differently. “Some people may clearly articulate daytime sleepiness, where others may use the word ‘fatigue’ or ‘fogginess’ or ‘tiredness,’” Shelgikar said.

Many women blame symptoms on stress, Khan said. “Women will usually present with fatigue, and a lot of times they self-attribute the fatigue to all the house chores that they’re doing, all the work outside the house that they’re doing, taking care of the kids.... They attribute symptoms to these stressors, and they don’t think of their sleep as the cause.”

What’s Next, and What to Do Now

Emerging treatments could be especially impactful for women, who tend to have lower CPAP adherence rates than men. Women’s tendency to wake up more easily (low arousal threshold) means they may experience more fragmented sleep from apnea events and may also find it harder to adapt to CPAP use, Redline said.

The sleep apnea pill, which stimulates the muscles that keep the airway open, demonstrated success in a large clinical trial this year, helping prevent apneas and shallow breathing in over half of the participants. It also reduced breathing disruptions to fewer than five per hour for 22% of participants. FDA approval is expected as early as next year.

Another “promising” therapy is upper airway stimulation, Capasso said. It uses a pacemaker implanted around the hypoglossal nerve in the back of the throat to tone muscle, helping prevent airway collapse. A 2019 analysis of about 1000 patients (26% women) found that low BMI and female sex were correlated with better outcomes 1 year after getting the implant. “Once we have a bit more adoption in [women], I would love to see the results,” Capasso said.

In the meantime, physicians can take steps to help their female patients, starting with a few key questions for sleep apnea assessment:

• Are you experiencing persistent fatigue, brain fog, or mood changes? (These symptoms may be more relevant for female patients than classic signs such as snoring.)
• Do your symptoms change throughout your menstrual cycle? (Consider progesterone’s protective effect.)
• Are you in perimenopause or menopause, and if so, do you have sleep disruptions intensified?
• Do you notice awakenings or restless sleep more than daytime sleepiness?
• Have you been told you have insomnia, anxiety, or depression? (These can mask a sleep disorder.)

For female patients prescribed CPAP, consider offering phone check-ins to help keep them on track and encourage cognitive-behavioral therapy for insomnia, which can limit CPAP adherence, Capasso said. Be sure female patients are fitted with CPAP masks designed for their facial anatomy, and educate them on options for adjusting airway pressure as women tend to require lower pressure settings than men for effective therapy.