Obstructive sleep apnea (OSA) has historically been regarded as a male disease. However, there are a number of significant gender-related differences in the symptoms, diagnosis, and consequences of OSA, which seems to be more severe in male than in female patients, although this sex difference decreases with increasing age. Female patients with OSA tend to present nonspecific symptoms, such as insomnia, depressive symptoms, fatigue, morning headache, and nightmares, often resulting in underdiagnosis and undertreatment compared to male patients. Understanding these differences in women is essential for early identification and referral of patients for diagnosis and treatment of OSA.

Highlights of the Study

  • Female patients with obstructive sleep apnea are more likely underdiagnosed and present atypical symptoms, such as insomnia and depressive symptoms, leading to suboptimal treatment.

  • The association of obstructive sleep apnea with several adverse outcomes, such as hypertension, diabetes mellitus, thyroid disease, and asthma, may be more pronounced in female patients.

  • Healthcare professionals should be aware of obstructive sleep apnea in women.

Obstructive sleep apnea (OSA) is a frequent chronic disorder that requires lifelong care [1]. It is characterized by recurrent episodes of decreased or absent airflow in the upper airway due to partial or complete collapse, respectively, during sleep [2]. Undiagnosed and untreated OSA is a significant burden on the healthcare system, highlighting the importance of early identification and accurate diagnosis of this common disorder [3]. Potential consequences and adverse clinical outcomes of OSA include excessive daytime sleepiness, which may lead to traffic or work-related accidents, impaired daytime function, metabolic dysfunction, increased risk of cardiovascular disease, and mortality [4].

OSA has historically been considered as a male disease. This is not surprising as it has been estimated to have a male-to-female ratio ranging from 3:1 to 5:1 in the general population and between 8:1 and 10:1 in subjects recruited from sleep laboratories [5-7]. However, recent studies suggest that globally nearly 1 billion adults aged 30–69 years worldwide have OSA [8] with a mean OSA prevalence of 27.3% in men and 22.5% in women, resulting in a less pronounced difference in male-to-female patient ratio of about 1.5:1 [9-11]. Moreover, female patients now represent up to 40–50% of presentations at sleep clinics [12]. Therefore, OSA in female patients is not as rare as was originally believed, probably because female patients are being diagnosed and treated for OSA less frequently than male patients.

In light of these recent data, there is now considerable concern about the characteristics of gender-specific OSA and long-term health consequences of OSA in female patients. The limited data available suggest that although the prevalence of OSA may be lower in female than in male patients, untreated severe OSA has been independently and significantly associated with cardiovascular death in female patients [13], as well as worse health status, and higher healthcare costs compared with male patients [14, 15]. Therefore, there is an urgent need to recognize the increasing burden of OSA in female patients, early identification, and referral for evaluation in order to facilitate improvements in disease management. The aim of our review was to update on female aspects of OSA.

This is a narrative review of the literature on the specific topic of female gender and OSA with the aim to review key data and provide suggestions for better identification of this disease in female patients in primary care. A systematic database search of medical literature (PubMed, January 1995 onward) was performed by using various combinations of the terms “obstructive sleep apnea,” “OSA,” “obstructive sleep apnea syndrome,” “sleep disordered breathing,” “gender,” “sex,” “women,” and “female”; this search was followed by a manual screening, based on expert opinion, of the results for articles of interest. In addition, we reviewed relevant cross-referenced articles of relevance identified by the original search criteria. The main inclusion and exclusion criteria were studies published in English; data on human subjects; studies investigating prevalence, clinical, and polysomnographic characteristics of OSA in women and the impact of OSA on morbidity and mortality in female and/or male patients; and adult patients aged >18 years. All abstracts of articles identified by the bibliographic search were read by the authors who determined whether the studies met the inclusion criteria. More than 3,700 publications were retrieved, manually screened for articles of interest, and after review, 286 studies met the inclusion criteria; we did not include the ones that did not reveal any new findings or contribute to the main topic of this review. Finally, a total of 76 relevant articles were used as references in this review (shown in Fig. 1).

Fig. 1.

Flowchart of selection process for studies included in this article.

Fig. 1.

Flowchart of selection process for studies included in this article.

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Why Are Female Patients Less Often Diagnosed with OSA

It has been suggested that the higher prevalence of OSA in male patients may result from the differences in symptoms between male and female patients, along with the reluctance of women to acknowledge symptoms of OSA and seek medical help [16]. Sex differences in aging, hormones, upper airway anatomy, fat distribution, and respiratory stability in OSA may also play a role [17]. The upper airways in female patients are less collapsible and more stable during sleep than in male patients, as a result of various complex mechanisms, including the modulating effects of sex hormones [18]. Another potential explanation for gender differences is the fat distribution between the sexes. For the same body mass index (BMI), male patients tend to have higher upper airway fat distribution, which is important in the pathogenesis of OSA [19]. Furthermore, the general characteristics and the clinical guidelines for evaluation and diagnosis of OSA are based primarily on studies conducted in male patients.

Characteristics and Presentation of OSA in Women

At present, the typical population in need of evaluation is quite different from the classical picture of the male, obese, and sleepy patient, suggesting that different clinical faces of OSA exist. Furthermore, female patients with sleep apnea tend to present differently from male patients and are harder to diagnose [20-22]. Whereas female patients with OSA predominantly present nonspecific symptoms such as insomnia, depressive symptoms, fatigue, morning headache, and nightmares [22-24], discordant results exist regarding the reporting of snoring, apneas, and excessive daytime sleepiness [25-28]. In a recent study, severe daytime sleepiness (Epworth Sleepiness Scale [ESS] ≥16) [29], which seems more likely to be associated with objective sleepiness and driving problems, was associated with male gender [30]. Another study showed that female gender was an independent predictive factor of frequent awakenings, restless leg syndrome, and nocturia [31]. Due to this “atypical” clinical presentation, female patients may be misdiagnosed and treated for other diseases, such as depression, insomnia, and hypothyroidism [24], and are diagnosed with OSA later, when they are older and have higher BMI than male patients [32, 33]. Knowledge of these gender-related differences in clinical presentation of OSA and especially searching for features of insomnia, poor sleep quality, and headache on awakening in female patients may contribute to an increased awareness of this condition among primary care providers and improved screening of OSA and referrals for diagnosis.

Polysomnographic Characteristics of OSA in Women

Compared to male patients, female patients seem to have less severe OSA with lower overall Apnea-Hypopnea Index (AHI) in all ages, shorter apneic episodes, less severe oxygen desaturations, lower proportion of supine OSA, and more clustering of apneas during rapid eye movement sleep despite being older and more obese [30, 32, 34, 35]. However, it is important to point out that despite less severe OSA in terms of AHI, female patients are not less symptomatic compared to males and report sleepiness at relatively low levels of AHI [36]. Furthermore, severity of OSA increases in both genders with age, but the difference in AHI between female and male patients decreases after the age of 60–62 years [30, 37].

Sleep architecture also differs between genders. Women seem to take longer to fall asleep than men and normally, once asleep, have fewer awakenings and slower wave sleep [30, 38, 39].

The Role of Menopause

Sex differences in the severity of OSA seem to be attenuated in the postmenopausal years, as there is a significant increase in the incidence of OSA in female patients after menopause [40]. The mechanisms through which menopause may influence the development of OSA are not yet fully understood. Moreover, it is difficult to distinguish whether menopause itself with the effect of sex hormones after controlling for confounding factors such as age and BMI is associated with greater risk of OSA. It is also worth noting that according to the Italian Association of Sleep Medicine position statement and guideline on the treatment of menopausal sleep disorders, menopausal status in female patients needs to be taken into account during clinical evaluation for OSA risk, as well as in the diagnosis and treatment of OSA [41].

Comorbidities

Compared with men with a similar OSA severity, women were found to be using more healthcare resources for atypical symptoms associated with OSA, prior to OSA diagnosis [42]. It is well known that OSA is associated with several cardiovascular consequences, such as hypertension, stroke, and arrhythmias, and data suggest an increased incidence of these cardiovascular outcomes in female patients suffering from severe disease [37, 43-45]. Apart from hypertension, diabetes mellitus, thyroid disease, and asthma are reported to be more common in female patients as are insomnia and depression [23, 37, 46]. The positive association of OSA with hypertension, diabetes, and metabolic syndrome seems to be present only for higher AHI levels [47]. Although Basoglu et al. [48] found no gender preference in gastroesophageal reflux disease, another study by Hesselbacher et al. [49] found a significant increase in female patients with OSA, necessitating further investigation. Moreover, it has been reported that the severity of certain OSA-associated comorbidities, such as cardiovascular disease, diabetes, and gastroesophageal reflux disease, seems to be more likely or worse in female than in male patients upon initial OSA diagnosis [20, 50].

It is noteworthy that female patients with moderate OSA are reported to have more severe endothelial dysfunction than male patients, suggesting that women might be more vulnerable to the effect of OSA on the cardiovascular system [51]. Female patients with normal to moderate OSA had higher levels of the pro-inflammatory cytokines IL-6 than in male patients [52]. Previous studies have also shown that OSA was associated with endothelial dysfunction as well as with subclinical myocardial injury, incident heart failure, death, and left ventricular hypertrophy only in female patients [51-54]. Nevertheless, further research is needed to identify measurable biomarkers that predict higher cardiovascular risk in female patients than in male OSA patients. Furthermore, there are limited and conflicting data in the literature regarding the impact of OSA on all-cause and cardiovascular mortality as well as the impact of PAP therapy in both genders and do not provide a definitive answer as to whether there exist sex differences in susceptibility [55].

Quality of Life and Sleep

Quality of life (QoL) in the female OSA population has been another issue of concern and demands further investigation. Recent data suggest that female patients suffering from OSA have greater impairment in QoL than male patients [50, 56-58]. It has been shown that poorer QoL in OSA female patients was associated with insomnia or sleepiness, but not with indices of OSA severity such as AHI [58]. Moreover, in a more recent study, using instruments to assess sleep, fatigue, depression, and anxiety, female patients with OSA scored significantly worse on all clinical scales compared to male patients [59]. These differences were particularly pronounced for fatigue (i.e., physical and mental rest propensity) and for anxiety symptoms.

Prediction of OSA in Females

Although several screening tools have been evaluated for the identification of OSA [60], these tools are not gender-specific and use variables and OSA symptoms derived from initial studies of predominantly male patients. One recent study showed that only BMI, neck circumference (NC), and a high ESS score were independently predictive of moderate to severe OSA in male patients, whereas age, NC, and morning headaches were independently predictive in female patients [61]. Furthermore, the gender-specific predictive value of anthropometric measures differs also according to OSA severity [62]. It seems that the predictive performance of questionnaires, such as the STOP-BANG questionnaire, is better if we use alternative scoring systems applying gender-specific cutoffs separately for male and female patients [63]. Pataka et al. [44] also found that there were gender differences in the predictive values of different questionnaires, such as the ESS, STOP, STOP-BANG, Berlin Questionnaire, Athens Insomnia Scale, and Fatigue Scale; they concluded that gender-specific considerations should be incorporated into the application, analysis, and interpretation of OSA screening questionnaires.

Response to Treatment

Research on gender differences regarding the effect of OSA treatment appears limited. Although improvement in clinical symptoms and functional status seems to not vary by gender [20], studies have demonstrated that PAP and Mandibular Advancement Device reversed cardiovascular risk, especially blood pressure, in female patients with adequate compliance compared to male patients [45, 64]. On the other hand, the reduction in enhanced cardiac sympathetic nerve activity after PAP therapy in OSA patients was more pronounced in male patients [65]. Furthermore, no significant effect was found on all-cause mortality of PAP treatment in female OSA patients [66]. CPAP therapy, however, seems to reverse elevated markers of systemic inflammation more rapidly in male than in female patients, which may indicate gender differences in effects of PAP affects cardiovascular risk factors [67].

Studies have also highlighted gender differences in the level of PAP pressure required to stabilize the upper airway and treat OSA, showing that female patients require significantly lower levels of PAP than male patients [68, 69]. Adherence to therapy should also be considered, but there is conflicting evidence as to whether there are gender-related differences in PAP usage [70, 71]. Moreover, it is unclear whether female patients respond differently compared to male patients in terms of realization of OSA treatment benefit, mask fit, and effect on intimate relationships. Future studies addressing several endpoints with significant numbers of women and men with similar OSA severity are needed to clarify the role of gender in outcomes of PAP treatment [72].

Interactions between Females with OSA and Healthcare Providers

In the primary care setting, evaluation of OSA and its symptoms should begin with early recognition, mainly based on patient reports or physician’s questions about symptoms, risk factors, and associated comorbidities. Female patients being diagnosed with OSA are more likely than male patients to have the classical clinical features of the syndrome (obesity, loud snoring, daytime sleepiness). In contrast, male patients may be referred for investigation and diagnosed with OSA as part of secondary prevention of CVD. However, general practitioners (GPs) also need to be aware that many patients may have minimal or no symptoms. These findings may reflect different elements in the investigative and diagnostic processes according to gender. Given the need for stratification to determine patients who urgently require evaluation by a sleep specialist, it would clearly be beneficial if GPs use screening questionnaires.

Female patients who do not present with the classical clinical picture of the syndrome might not get referred by GPs for screening for OSA. Female patients also might be more reluctant to report snoring owing to a lack of awareness from their bed partner or an opinion of it being a male symptom [73]. Furthermore, female patients come to clinical interviews alone more frequently than male patients, possibly leading to underreporting of sleep sounds [74], and even if bed partners participate in the interview, they do not complain of snoring or observed apneic episodes [75]. On the other hand, even if women do report classic OSA symptoms, such as snoring and EDS, a failure of medical professionals to respond to OSA symptoms in women is noted as female patients are significantly underdiagnosed and less frequently treated for sleep apnea [41, 42].

A recent study used a recruitment approach, in which middle-aged and older patients from family medicine clinics were offered sleep assessment and agreed to spend a night in a sleep laboratory; similar numbers of men (85%) and women (75%) had diagnosed with OSA of similar severity [76]. These data suggest that sleep should be included when managing health-related lifestyle risks, such as smoking, exercise, and hypertension. Moreover, a higher index of clinical suspicion of sleep apnea is required particularly in women who may not be inclined to report snoring and daytime sleepiness but who have other potential sleep symptoms.

OSA has traditionally been assumed to be a male disease with the stereotype of an overweight, snoring, middle-aged, sleepy man. Furthermore, the incidence of OSA in female patients may not have been accurately reported in the literature, leading to delays in identification from primary care professionals and even lack of a diagnosis. Although over the past 2 decades, this deficit in knowledge is slowly being filled with research found in sleep medicine publications, this area remains underrepresented [20].

It is now evident that there are notable differences in the frequency and severity of sleep apnea by gender (shown in Fig. 2). Although the prevalence in women seems to be lower than men, the consequences of the disease are similar if not worse. Without an awareness of these differences in presentation of the disease state, women can remain unrecognized and undiagnosed in primary care. Ultimately, the recognition of gender differences in symptoms and associated comorbidities could improve screening, referrals, and early diagnosis, potentially resulting in the development of female-specific screening questionnaires.

Fig. 2.

The impact of female gender on OSA. OSA, obstructive sleep apnea; QoL, quality of life.

Fig. 2.

The impact of female gender on OSA. OSA, obstructive sleep apnea; QoL, quality of life.

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Importantly, there are major challenges so to achieve better clinical care and a cost-effective policy to address OSA in women. The first challenge is to objectively determine the prevalence of OSA in women. The second challenge is to correctly identify within the community women at risk of OSA-related sequelae and thus require referral for diagnosis and treatment with a possible focus on presentation of atypical symptoms. Women with OSA are at risk of accidents, reduced productivity at work, and social functioning, as well as reductions in QoL. Therefore, novel screening strategies are required to identify, prevent, and reduce OSA-related disparities in health in women. Furthermore, primary care professionals should be aware of OSA in women and the use of different OSA screening questionnaires with specific cutoffs.

The authors have no conflicts of interest to declare.

The authors received no financial support for the review article, authorship, and/or publication of this article.

I.B. and I.T. conceived of the presented idea. S.S. provided critical feedback and supervised the review. All authors discussed the results and contributed to the final manuscript.

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