Major Sleep Disorders Among Women

(Women's Health Series)

Sadeka Tamanna, MD, MPH; Stephen A. Geraci, MD

Disclosures

South Med J. 2013;106(8):470-478. 

In This Article

OSA

OSA is a common disorder characterized by repetitive upper-airway collapse during sleep. The diagnosis is made by nocturnal polysomnography, which measures the total number of apneic and hypopneic episodes per hour of sleep (the Apnea-Hypopnea Index [AHI]). The American Academy of Sleep Medicine has defined OSA as mild (AHI 5–15), moderate (AHI 15–30), or severe (AHI >30) based on the frequency of these events.[18]

The disorder is associated with conditions that contribute to excess mortality in adults, including cardiovascular disease, stroke, neurocognitive dysfunction, and motor vehicle crashes.[19] The estimated prevalence of OSA is 9% in women (vs 24% in men).[20,21] The Wisconsin Sleep Cohort Study estimated that sleep apnea was undiagnosed in >90% of women with moderate to severe sleep apnea[21] and suggested that underdiagnosis related to atypical symptomatology may explain much of the perceived disparity.[22]

Loud snoring, breathing pauses during sleep, and excessive daytime sleepiness are classic symptoms seen in most men with OSA, whereas atypical symptoms such as insomnia, morning headache, fatigue, tiredness, depression, and anxiety are more common presentations in women. Women are two to three times less likely than men to report classic OSA symptoms,[23] with approximately 20% of women presenting primarily with complaints of insomnia, supporting the position of frequently missed diagnoses. As such, women are more likely to be treated inappropriately for depression, anxiety, or hypothyroidism than are men with the same severity of OSA.[24]

In women at risk for OSA, other less typical symptoms, including memory loss, poor concentration, decreased libido, irritability, worsening unexplained fatigue, and tiredness, should be appraised using a comprehensive sleep evaluation. A large neck size (>16 in.), a body mass index (BMI) >30 kg/m2, and the presence of structural abnormalities (oropharyngeal narrowing, retrognathia, macroglossia, uvula elongation, high arched hard palate, nasal septal deviation) should be sought during physical examination; each anatomic finding increases the probability of OSA.[25]

Obesity may be the most important risk factor for OSA. Women with OSA are more likely to be obese than are men with OSA of similar severity.[26] In a study of women with BMI >30 kg/m,[2] one-third of asymptomatic women were found to have OSA by polysomnographic criteria, and a significant correlation was identified between AHI and BMI in this cohort.[27]

Hormonal status also contributes to sleep abnormalities in women. A study in a general population evaluated the effects of menopause and hormone therapy (HT) on polysomnographic findings in women and compared the female cohorts to the male cohorts.[28] The study found that women slept objectively better than men and that sleep in young women is more resistant to external stressors. Menopause showed a negative effect on sleep: Postmenopausal women had longer sleep latency, less slow-wave sleep, and less deep sleep as compared with premenopausal subjects. Postmenopausal women not receiving HT had longer sleep latency than did those on treatment, suggesting that estrogens may exert a protective effect on sleep integrity. Bixler et al found a low prevalence of OSA (0.6%) among premenopausal women and postmenopausal women receiving HT (0.5%) compared with postmenopausal women not receiving HT (2.7%).[29]

Vasomotor symptoms (VMS), particularly hot flashes, correlate strongly with subjective sleep complaints.[30] Declining estradiol levels during the climacterium demonstrates an association with increased VMS, trouble sleeping, and diminished sexual response.[31] Worse mood associates with poorer sleep and concurrent VMS, explaining in part the increased anxiety, depression, and mental health issues seen in some postmenopausal women. In a prospective crossover study, postmenopausal women with OSA were treated with estrogen alone, and with an estrogen-progestin combination.[32] Polysomnography was performed at baseline and repeated after 3 to 4 weeks of each regimen. Both treatment strategies reduced OSA, with a 50% reduction of AHI following estrogen-progesterone treatment and a 25% reduction following estrogen-only therapy.[32] Estrogen effects were further studied in two groups of postmenopausal women (one receiving HT and the other untreated); treated women had lower free cortisol levels and better polysomnographic sleep parameters than untreated subjects.[33]

Despite these data, HT is not a recommended treatment for perimenopausal OSA at this time.[32,33] Women with established cardiovascular disease experience more coronary and thromboembolic events and greater mortality when prescribed HT,[34] and with the higher incidence of major cardiovascular risk determinants in OSA patients overall, the potential for harm is significant. Further long-term outcomes studies are needed to evaluate the net effect of HT on postmenopausal women with OSA.

Cardiovascular complications associated with untreated OSA include hypertension, myocardial infarction, congestive heart failure, atrial fibrillation, and stroke.[35] Upper airway collapse during sleep results in intrathoracic pressure swings, which cause myocardial transmural pressure gradients, stretching thin atrial walls. Over time, this combined with secondary pulmonary hypertension from hypoxic vasoconstriction may result in atrial enlargement, impaired intraatrial conduction, enhanced atrial automaticity, and subsequent atrial fibrillation.[36,37] Repetitive intermittent hypoxia from OSA also produces oxidative stress and inflammation (with release of cytokines, interleukins, and tumor necrosis factor) and promotes fibrosis and endothelial dysfunction, which results in pathologic vasoconstriction and an increased incidence of atherosclerosis.[38]

In a prospective study of 1116 women for 88 months, the hazard ratio for cardiovascular mortality in patients with untreated severe OSA was 3.50 (95% confidence interval 1.23–9.98); adequate continuous positive airway pressure (CPAP) therapy reduced the relative risk to 0.55 (95% confidence interval 0.17–1.74) after controlling for age, BMI, previous cardiovascular history, hypertension, and diabetes. These data strongly suggest that severe OSA independently associates with cardiovascular mortality and that CPAP therapy may reduce cardiovascular death in these patients.[39]

Many metabolic conditions also demonstrate an association with OSA. Impaired glucose metabolism, demonstrated by elevated HbA1C concentrations, correlates with increasing AHI among patients with OSA.[40] Diabetics have a high prevalence of OSA, and CPAP improves glucose control in these patients.[41] Women with a history of witnessed OSA have a threefold increased risk of diabetes.[42] Insulin-resistant women with polycystic ovary syndrome are at high risk for OSA, early-onset diabetes, and cardiovascular disease; CPAP treatment improves insulin sensitivity, decreases sympathetic nervous system outflow, and decreases diastolic blood pressure in these patients.[43] Secretion of growth hormone and prolactin are regulated by processes occurring during stage 3 and rapid-eye-movement sleep; when these sleep components are disturbed by OSA, hormone concentrations fall and symptomatic deficiency states develop.[44]

Neurocognitive dysfunction, including dementia, memory loss, depression, and anxiety, also can result from untreated OSA. There is a strong association between depression and OSA, although it is unclear whether depression is triggered by sleep deprivation and subsequent sleepiness or whether OSA itself causes this mood disorder.[43]

OSA should be approached as a chronic disease requiring long-term, multidisciplinary management. Medical, behavioral, and surgical treatment options are available and patients should be active participants in the treatment decision process. Positive airway pressure therapy (PAP), the treatment of choice for all degrees of OSA, provides pneumatic splinting of the upper airway and is effective in reducing AHI.[48] It may be delivered in CPAP, bilevel PAP, or autotitrating PAP modes. Full-night, provider-observed polysomnography performed in a sleep laboratory is the preferred approach to titrate to optimal PAP parameters.[44] Compliance is a major challenge. Ye[56] found that CPAP improved functional status and OSA symptoms in both sexes, but CPAP compliance was not different between women and men. Nino-Murcia[45] confirmed that CPAP compliance rates (65%–83%) were similar between the sexes, whereas a population-based prospective study found that female patients used CPAP more frequently than their male counterparts.[46]

Behavioral therapy, including sleep hygiene (Fig. 1), weight reduction, exercise, alcohol avoidance, and bedtime sedatives are important adjuncts to PAP. Oral appliances (mandibular repositioning or tongue retaining devices) may improve upper airway patency.[47] Surgical therapy is site directed and patient based. Nasal (septoplasty, turbinate reduction, nasal polypectomy), oropharyngeal (uvulopalatoplasty, tonsillectomy, adenoidectomy), and global (maxilla-mandibular advancement) airway procedures can be considered based upon patient anatomy in individuals who fail less-invasive treatment. Bariatric surgery may be needed for patients with refractory obesity.[25]

To date, most treatment trials have been conducted in male patients and few trials have included enough women to define differences in the efficacy of various modalities in female patients.[48,49] Selected clinical studies including female patients are presented in Table 2.

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