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The question of why men develop obstructive sleep apnea more frequently than women has scientists scratching their polysomnography equipment. Middle-aged men are affected by sleep apnea at triple the rate of middle-aged women, and several theories for this have been proposed.

Anatomy
The first theory suggests that anatomical differences may be responsible. Robert Fogel, MD, an instructor in the Division of Sleep Medicine at Brigham and Women's Hospital and Harvard Medical School in Boston, says that men tend to have a different pattern of fat deposition compared with women. For example, men tend to have more upper body obesity and bigger necks, while women usually have larger hips and buttocks.

"So it may be that men, at any level of obesity, have a slightly different pattern of obesity that may predispose them to sleep apnea," he explains.

Atul Malhotra, MD, also of Brigham and Women's Hospital and Harvard Medical School, found that men have a much longer airway than women, even when corrected for body height. He documented this trend using magnetic resonance imaging studies. This is important, Fogel explains, because "if you take any collapsible tube and make it longer, it's more likely to collapse."

Other investigators have also concluded that women have less collapsible airways.

"If you move the jaw backward, which usually is the common occurrence in sleep, men narrow their airway significantly - but not so in women," says Vahid Mohsenin, MD, associate professor of medicine and director of the Yale Center for Sleep Medicine in New Haven, Conn. "Women maintain their airway caliber, indicating that there are some anatomic reasons or protections from developing obstructive sleep apnea in women. This is not related to any respiratory muscle control or the upper airway muscle control."

However, several studies by James A. Rowley, MD, an associate professor of medicine at Wayne State University in Detroit, dispute the importance of anatomic features.

His research examined upper airway mechanics in three ways: upper airway resistance, collapsibility and critical closing pressure, and upper airway compliance. His team only found a variation between men and women in upper airway compliance - how much the airway changes for a given alteration in pressure. However, the disparity quickly vanished when they corrected for neck circumference differences between men and women.

"We think part of the gender difference is anatomy in the sense that men in general have larger neck circumferences than women," Rowley says. "But beyond that, we don't think there's a true gender difference in the upper airway."

Hormones
The other main set of theories about how OSA develops centers around the effects of hormones. Research primarily has focused on whether testosterone is adversely related to OSA and whether estrogen and progesterone play a protective role. The results have been mixed.

In one study cited by Fogel, men who had below-average levels of testosterone displayed an increase in OSA after receiving testosterone treatment. Another study examined women with polycystic ovary syndrome. These women typically have higher than normal levels of testosterone, and when compared with controls, women with the disease had a greater incidence of OSA.

"The severity of sleep apnea was related to how much testosterone they had," Fogel explains. However, another study examining this same relationship didn't find a similar connection, he notes.

Future research should examine whether OSA in women with polycystic ovary syndrome improves if the testosterone is blocked - and whether this hormone leads to different areas of fat distribution or differences in ventilation control, Fogel suggests.

New studies should look at the hormonal effects of menopause on women as well, Mohsenin adds. "Several recent studies have shown that menopausal women actually have a significantly increased risk of sleep apnea compared with premenopausal women," he says. "But it's not totally clear if the hormonal deficiency of menopause is responsible for this because it does take time for menopausal women to develop sleep apnea." Perimenopausal women don't exhibit sleep apnea at the same rate as men, he points out.

Other studies have not supported the theory that estrogen and progesterone influence OSA incidence. When researchers gave progesterone to men with OSA, it didn't have a significant effect, Fogel says. Also, hormone replacement therapy for a postmenopausal woman who already has OSA does not improve OSA symptoms.

However, Fogel says the Sleep Heart Health Study provides some important findings supporting a link to female hormones. "Women who were on estrogen replacement since they crossed into menopause were much less likely to get obstructive sleep apnea than women who hadn't been. So, it may be that if you have estrogen and progesterone, and it's there for a long time, it is protective. Why it's protective is not 100% clear."

He notes that investigators don't need to narrow themselves to one area of research in this gender conundrum. The answer may be somewhere in between.

"There are a number of theories out there, and my guess is that it's going to be a little bit of each one of those things," he says. "It's not going to be all estrogen and progesterone. It's not going to be all testosterone. It's not going to be all pure upper airway anatomy."

Presentation
While the reason for OSA prevalence in men is still unclear, researchers know for sure that women and men with the disorder present differently in sleep labs. Men tend to have a much higher apnea-hypopnea index during NREM (non-rapid eye movement) sleep than women, though it appears that the apnea-hypopnea index is similar between the genders during REM (rapid eye movement) sleep, Rowley says.

Also, women tend to report different symptoms, such as fatigue and depression. "These aren't necessarily red flags for sleep apnea," Fogel explains. "Men tend to present with classic sleepiness and more reports of snoring."

Because OSA in women may be hiding under the covers, providers need to ask them about sleep problems as often as they do men.

"[Providers] have to pursue it a little bit," Rowley explains. "If a woman says she doesn't snore, ask her: Do you wake up choking? Do you wake up gasping? Do you just wake up a lot at night for no apparent reason? You have to make sure you ask all the other questions about sleep apnea because that might be what gives you the clue."

Mike Bederka is on staff at ADVANCE. Reach him at mbederka@merion.com.




     

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