In women, the lower mean age at diagnosis demonstrate that the onset of OSAS occurs earlier in the female sex, given the high post-menopausal risk [
1]. In fact, with the onset of menopause, previous literature reported that the prevalence of OSA doubles [
12,
13] and that there is a reduction in respiratory drive and an increase in arousals and soft tissue collapsibility compared to premenopausal age [
14,
15]. The hypothesis highlighted in previous scientific studies asserts that estrogen and progesterone play a role in the control of ventilation and airway collapsibility during sleep [
16]. 17β-estradiol also protects women from the risk of developing OSAS through its antioxidant effects and through stimulation of upper respiratory tract musculature. Therefore, there is an increased susceptibility to OSAS with the onset of menopause and reduced serum levels of these hormones [
17]. This finding may suggest the introduction of screening for OSAS through dedicated questionnaires to women around menopausal period, to achieve early diagnosis and avoid long-term complications. The higher frequency of hypopneas compared to men is in agreement with data from previous scientific studies [
18] and could be related to the pathophysiological mechanism of low arousal threshold [
14,
19]. In fact, postmenopausal women, as reported in some previous scientific studies, have some typical polysomnographic predictors of low threshold arousal [
20]: AHI < 30 events per hour, nadir SpO2 > 82.5% and hypopnea frequency > 58.3%. These results were also seen in women in our study. In men, the supine AHI was significantly higher, in agreement with the literature [
21]. It is possible to assume that the supine position in men stimulates the tonic activity of the dilator muscles of the upper airways, while it reduces the phasic activity [
22]. Previous data in literature show that men develop an elliptically shaped airway in the supine position with the long axis oriented laterally [
23]. This anatomical change may generate altered pressure gradients in the velopharynx and therefore increase the propensity to collapse [
24]. This finding may suggest the use in men of positional devices that avoid supine position, especially when CPAP compliance is low. Furthermore, in men, the AHI and ODI were higher with increasing BMI and age, showing how obesity and senescence have a role in the pathophysiological mechanisms especially in the male sex. This is confirmed, for example, by AHI reduction after weight loss, both through bariatric surgery and/or intensive lifestyle intervention [
25,
26]. This finding may suggest the introduction of mass screening tests for OSAS in men with obesity, as well as the use of dietary interventions as first-line treatment in conjunction with CPAP therapy to reduce the severity of apneas. The low therapeutic CPAP adherence in men is a finding that can be explained at least in part by the higher average age and thus to an underestimation of long-term complications. In addition, also due to facial anatomical factors, men may have a more difficult adaptation to facial and/or nasal masks. This result, consequently, implies more attention to be paid to male patients both at the time of CPAP adaptation and during their follow-up. In addition, the implementation of telemedicine to follow-up these patients more intensively over time may be a right move to increase therapeutic adherence to CPAP [
27], as well as also the correct disclosure of OSAS severity and its complications, also working on the emotional-behavioral sphere [
28]. The ESS did not show significant specificity for the two sexes and its mean value was below the threshold of positivity in both sexes, underlining the limitations of these questionnaires regarding excessive daytime sleepiness (EDS). ESS sensitivity and specificity may increase with the support of patient's partner in the completion of the questionnaire and with physician supervision to avoid misunderstandings in the interpretation of the test. Moreover, the ESS is a test that assesses only a part of the patient's symptomatology; in fact, the literature reports that EDS is present in only 40% of patients with OSAS [
29]. In addition, literature reported that ESS is not strongly associated with EDS in the female sex; in fact, women often have an ESS score < 10, probably due to a different threshold for perceived sleepiness [
30].
The strength of the present study is that it has comprehensively investigated all the factors that may determine the gender differences found in clinical practice with OSAS patients. In fact, having collected data not only on polygraphic patterns but also on epidemiology and symptomatology (EDS), allowed us to identify several risk factors for OSAS that are more present in one sex than the other. In addition, we also investigated the follow-up behaviour of men and women, measuring therapeutic adherence to CPAP, so that we could also make a gender comparison on the consideration that these patients have for the pathology.
Possible limits of the present study lie in its retrospective and observational nature. As a pilot study, its small sample size could affect the generalisability of the results and the application of the findings in daily clinical practice. Furthermore, this study lacks measurements of anatomical factors (neck circumference, diameter of the oropharynx and neck fat on MRI), hormonal factors (serum dosage of female sex hormones such as luteinising hormone or follicle-stimulating hormone and male sex hormones such as testosterone or dehydroepiandrosterone) and oesophageal pressure to quantify the arousal threshold.
In conclusion, this study showed that, especially in women, BMI cannot be uniformly used as the main risk factor for OSAS severity. Moreover, in women, it is essential to suspect the syndrome in the period following the onset of menopause. The typical polysomnographic pattern in women has been that of a high hypopnea/apnea (HI/AI) ratio, while in men there is a high supine AHI and high ODI. In men, it is important to assess AHI in the supine position, given the possibility of using positional therapy along with or as an alternative to CPAP, considering the lower therapeutic adherence compared to women.