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Gender differences in OSA.

Seventy-five percent of sleep research has been conducted on men. 1 Early epidemiological studies of obstructive sleep apnea (OSA) performed during the 1970s and 1980s involved male subjects only, and based on clinical reports of that time, scientists estimated that the prevalence of OSA was 10 to 60 times greater in men than in women. As a result, OSA was considered primarily a "male" disease. Then in 1993, Terry Young and colleagues performed the first population-based epidemiological study on sleep-disordered breathing - 71 percent of the subjects were women. Young found that men were about three times more likely than women to have sleep-disordered breathing (e.g., snoring, hypopnea, obstructive sleep apnea). After this finding, scientists began to speculate that the great disparity in the male-to-female ratio in the earlier studies could mean either that OSA symptoms in women are not recognized, that the presentation of OSA symptoms may differ in women, or that women are being underdiagnosed--even when symptomatic. Some scientists now estimate that 90% of women with OSA may be undiagnosed.

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Sleep-disordered breathing involves impairments in the rhythmicity of respiration, depth of breathing, or ventilation. Obstructive sleep apnea (OSA) is an example of a sleep-disordered breathing disorder. OSA is the cessation of breathing (i.e., apnea) during sleep. Apnea occurs because upper airway muscles relax excessively during sleep, allowing the structures (e.g., tonsils, adenoids) supported by them to be drawn into the airway during inspirations. This partially or totally blocks the flow of air into the lungs and as a result the blood oxygen level falls. Once it falls to a certain level, the respiratory center in the brain becomes stimulated and the person arouses briefly to take some quick, deep breaths to restore the blood oxygen level. The arousal lasts for a few seconds and, on restoring the blood oxygen level, the person resumes sleep. However, once asleep, the process can recur. If a person has frequent OSA episodes during sleep, the consequence can be excessive daytime sleepiness due to frequent arousals from sleep. A person with OSA may report inexplicably arousing from sleep (i.e., insomnia), awakening with a sense of being choked, and bedpartners may complain that the person snores and/or stops breathing while asleep.

Studies that have compared the presentation of OSA symptoms in women and in men have found that women are more likely to complain of insomnia, restless legs, and depression, while men are more likely to complain of night sweats, difficulty falling asleep or restless sleep, lack of energy, and loud snoring. Polysomnographic studies investigating gender differences in OSA have found that, in comparison with men, women are more likely to have partial obstructions; have respiratory events of shorter durations; have a greater prevalence of mild apnea (as indicated by an apnea-hypopnea index [AHI] score of 5 to 14 respiratory events/hour); have more respiratory events during rapid eye movement (REM) sleep; and be more symptomatic (e.g., greater problems with fatigue, tiredness, lack of energy) at a lower disease severity.

Scientists are not sure why gender differences in OSA exist. Various studies have focused on gender differences in the ventilatory response; in body fat distribution; in upper airway collapsibility; and in the level of sex hormones (e.g., testosterone and estrogen). The findings of some studies are described below.

The end of an obstructive apnea is typically followed by hyperventilation (i.e., fast, deep breathing), which because of the sudden increase in oxygen, may produce a central apnea (i.e., the cessation of breathing due to the lack of a signal from the respiratory center) or produce a breathing pattern (e.g., hypopnea) that results in hypoventilation (i.e., reduced amount of air entering the lungs). In consideration of this, researcher Amy Jordan and colleagues investigated the ventilatory response occurring after an arousal in males and females with severe OSA who were treated with continuous positive airway pressure (CPAP) treatment. In CPAP treatment, pressurized air is blown through a person's nose or nose and mouth through a mask. The pressurized air forces the upper airway structures to remain open, thereby preventing episodes of apnea. In the study, the CPAP mask was attached to equipment that measured the frequency of breathing and the depth of breathing. The researchers measured changes occurring in ventilation after spontaneous arousals and after arousals the researchers had elicited with a tone. In both conditions they found that (he ventilatory response following an arousal from non-rapid eye movement (NREM) sleep was greater in men than in women.

Early studies focusing on the role of weight in OSA found that female OSA patients were heavier than their male counterparts (but the severity of symptoms was similar for both genders) and the prevalence of OSA in obese women was dramatically smaller than for obese men. This finding was surprising since obesity appeared to be a risk factor for OSA. In 1995, Richard Millman and colleagues suggested that the presence of excess body fat may not be the risk factor for OSA but how the body fat was distributed may be a risk factor. To test this hypothesis, they made anthropometric measurements of 25 women. The measured the women's body-mass index (the weight in kilograms divided by the height in meters squared), subcutaneous fat, neck skin fold thickness, and the waist-to-hip ratio, among other factors. They then compared the women's results with that of men whose measurements had been obtained earlier. The found that, although the men and women had a similar BMI, the men had a greater amount of upper body obesity, a greater waist-to-hip ratio, and a greater neck circumference. Millman noted a greater amount of fat around the pharynx in men and conjectured this may play a role in the greater prevalence of OSA in men.

Adam Whittle and colleagues focused on the role of pharyngeal fat in OSA and used magnetic resonance imaging (MRI) to measure pharyngeal soft tissue volume. On comparing the amount of neck fat to whole body fat, Whittle found that in men 22% of the total neck soft tissue was fat and 17% of the body mass was fat; by contrast, in women 29% of the total neck soft tissue was fat and 33% of the total body mass was fat. This demonstrated that men had a greater amount of neck fat, which Whittle believes may play a role in the greater prevalence of OSA in men.

Upper airway collapsibility may reflect the impaired function of upper airway dilator muscles such as the genioglossus muscle. However, scientists are unsure to what extent this is true since results of various studies have been conflicting. For example, one study found that the inspiratory and expiratory activity of the genioglossus muscle in women is significantly greater than in men, indicating that the airway in women is more stable (i.e., less collapsible), but other studies have found no gender differences in the activity of this muscle.

Other scientists have focused on the impact of pharyngeal size on the presence of OSA. In general, studies show that the airway of men is larger in diameter, which hypothetically means that women should have the greater prevalence of OSA. That they do not suggests that pharyngeal size is not a factor in airway collapsibility.

Another contributor to airway collapsibility may be related to difference in the growth of the larynx in males and female during puberty. During infancy in both genders, the larynx descends; but during puberty in males only, the larynx descends further. This elongates the oropharynx and reshapes the airway so that the front wall of the respiratory tract (e.g., the tongue) is more vulnerable to collapse. Therefore, it may be that the greater descent of the larynx in males may predispose them to OSA.

Hormones could be a factor in the difference in the prevalence of OSA in men and women (24 percent vs. 9 percent, respectively) and in the prevalence of OSA in premenopausal and postmenopausal women (0.6 percent vs. 1.9 percent, respectively). One way hormones may impact the prevalence of OSA in men and women is through their impact on body fat distribution. For example, as the level of sex hormones in a woman changes with age, the distribution of body fat can become more android (i.e., masculine) so that she has increased upper body fat and increased amounts of pharyngeal fat. As for men, this may increase an older woman's risk of developing OSA.

Some research has investigated whether sex hormones impact central respiratory control. The female sex hormone progesterone is known to have a stimulatory effect on respiration. Scientists initially believed that the greater amount of progesterone in premenopausal women and protected them from the upper airway collapse noted in postmenopausal women. However, studies later demonstrated that administering progesterone to postmenopausal women did not reduce their sleep-disordered breathing.

The increased levels of the female hormone estrogen appears to protect premenopausal women from upper airway collapsibility. How it does this is not fully clear. Nevertheless, studies show that administering estrogen alone to postmenopausal women can decrease the number respiratory events (e.g., apnea, hypopnea) during sleep and that administering progesterone with estrogen in women whose menopause was surgically induced can reduce the number of respiratory events.

More studies on women with polycystic ovary syndrome (PCOS) may some day shed some light on the role of testosterone in upper airway collapsibility. In women with PCOS, cysts on the ovaries produce increased amounts of male hormones (e.g., testosterone). Women with PCOS have more apneas and hypopneas, compared with women without the disorder. However, it is unclear whether testosterone alters central respiratory control.

There is some dispute to what extent a diagnosis of OSA may be missed in women. Some studies do not find that physicians miss diagnosing OSA more frequently in women because of their having "atypical" symptoms such as depression or insomnia. On the other hand, other studies find that women are more frequently assessed for a different problem. For example, an obese woman complaining of fatigue may first be assessed for hypothyroidism, whereas an obese male complaining of fatigue will more likely be initially assessed for a sleep disorder, and women with OSA or other types of sleep-disordered breathing (e.g., upper airway resistance syndrome [UARS]) are more likely than men to complain of depression and be prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants.

Witnessed apneas are less likely to be reported to a woman by others, especially if her symptoms are mild. A bed-partner, for example, may not consider her symptoms as disruptive or problematic and report symptoms; therefore she may not be aware of having OSA and may not seek out treatment. If she goes to a physician with "atypical" OSA complaints of depression or lack of energy, she may be assessed and treated for depression or other problem, while her OSA remains undiagnosed and untreated. Long-term untreated OSA has been associated with cardiovascular diseases such as hypertension, stroke, coronary heart disease, and dyslipidemia (i.e., improper levels of lipids such as cholesterol). Therefore, recognizing OSA symptoms--especially the "atypical" symptoms in women--and treating OSA early could potentially avoid the consequences of these cardiovascular diseases and other problems.

Regina Patrick is a Sleep Technologist at St. Vincent Mercy Sleep Center in Toledo, OH and appears regularly in Focus Journal.

by Regina Patrick RPSGT
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Title Annotation:SLEEP MEDICINE
Author:Patrick, Regina
Publication:FOCUS: Journal for Respiratory Care & Sleep Medicine
Date:Sep 1, 2010
Words:1890
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