madman
Super Moderator
Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, which are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is per se linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency, and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy(TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS.TRT might in fact worsen OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythemia and TRT might exacerbate polycythemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalized way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas long-term lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH, and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography.
Introduction
Obstructive sleep apnoea syndrome
Obstructive sleep apnoea syndrome (OSAS) represents a common and often underrecognized and under-diagnosed medical disease that is characterized by sleep-dependent pauses and reductions in airflow (1, 2). In particular, the sleep-dependent pauses may be complete (apnoeas) or partial (hypopnoeas), further resulting, among other consequences of OSAS, in hypoxemia and sleep fragmentation (3). OSAS has a prevalence of about 15% in men and 5% in women in the adult age (4). Other data show that about 34% and 17% of middle-aged men and women, respectively, are affected by OSAS (3), whose prevalence has been increasing during the past decades (5). The prevalence of OSAS is higher in patients with systemic diseases, such as hypertension, heart failure, coronary artery disease, metabolic alterations, and stroke (2–4, 6). On the other hand, OSAS is associated with an increased risk of hypertension, atrial fibrillation, myocardial infarction, insulin resistance, and stroke (2).
The main risk factors for OSAS are male sex, older age, and obesity (3). In particular, regarding the association between obesity and OSAS, the risk of OSAS correlates with the body mass index (BMI), and obesity is probably the most relevant risk factor for OSAS (3). Epidemiological data show that about 50% of obese patients are affected by OSAS (3). The clinical symptoms of OSAS include, among others, snoring, nocturnal polyuria, daytime sleepiness, morning headache, neurocognitive deficits, reduced libido, irritability, and depressive symptoms (2, 4–6). In addition, excessive daytime sleepiness may cause motor vehicle and work-related accidents(7). Clinical categorization of OSAS is based upon apnoea hypopnoea index (AHI), obtained by the polysomnography, which represents the ratio between the number of apnoeas and hypopnoea per hour which identifies mild OSAS (5–15), moderate OSAS (15–30) and severe OSAS (>30). Moreover, an AHI > 15 per hour in the absence of symptoms may be diagnostic of OSAS (3).
The treatment of choice for OSAS is the application of continuous positive air pressure (cPAP) (3, 8, 9). Furthermore, it is mandatory to treat the underlying pathophysiological factors, such as obesity, in order to improve the symptoms and the severity of OSAS (8). Other approaches include, among others, mandibular advancement devices, maxillofacial surgery, bariatric surgery in case of morbid obesity, and hypoglossal nerve stimulation(3, 8). In addition, an interesting future pharmacological approach might be based on histamine 3-receptor antagonist/inverse agonists (10).
*OSAS and male hypogonadism
Perspectives and Clinical Messages
This manuscript underlines the need for an active collaboration between different specialists, including endocrinologists, general physicians, obesity physicians, otolaryngologists, pneumologistand sleep specialists. Furthermore, in light of the evidence that OSAS represents a complex clinical condition—and not just a sleep disorder—and that nowadays multidisciplinary groups are created in order to offer better care for complex patients, multidisciplinary evaluation for patients with OSAS might be evaluated and even become mandatory in patients with OSA and other complex diseases. Regarding the gonadal evaluation in patients with OSAS, albeit sleep disorders are not considered to be the main signs/symptoms of hypogonadism (13), we would like to share the interplay between signs/symptoms that might be associated with both OSAS and MH, such as sexual dysfunction, low BMD, low motivation and vitality, poor concentration and memory, and even fatigue. Therefore, albeit for further studies are needed, a complete endocrine and metabolic evaluation in patients with OSAS might be suggested, in order to (i) evaluate endocrine-metabolic alterations caused by OSAS itself and (ii) evaluate possible endocrine-metabolic underlying disorders that might be even the cause of OSAS.
Conclusion
In this review, we described the relationship between OSAS and MH, which are two under-recognized and inter-connected medical disorders, with particular attention to TRT and OSAS. The analysis of the literature highlights the general lack of well-done studies and therefore the evidence is of low quality. We cannot confirm or reject the guidelines that suggest avoidingTRT in the presence of untreated or severe OSAS, as this appears reasonable clinical practice. Indeed, some evidence suggests that short-time high-dose TRT might indeed worsen OSAS, whereas chronic low-dose TRT might improve OSAS. Notwithstanding, the therapy of OSAS might benefit the gonadal status and sexual functions. In light of the few and sometimes inconclusive studies in this field, and therefore of the limited evidence and large grey areas, we wish for further studies and more active collaboration between endocrinologists and otolaryngologists.
Introduction
Obstructive sleep apnoea syndrome
Obstructive sleep apnoea syndrome (OSAS) represents a common and often underrecognized and under-diagnosed medical disease that is characterized by sleep-dependent pauses and reductions in airflow (1, 2). In particular, the sleep-dependent pauses may be complete (apnoeas) or partial (hypopnoeas), further resulting, among other consequences of OSAS, in hypoxemia and sleep fragmentation (3). OSAS has a prevalence of about 15% in men and 5% in women in the adult age (4). Other data show that about 34% and 17% of middle-aged men and women, respectively, are affected by OSAS (3), whose prevalence has been increasing during the past decades (5). The prevalence of OSAS is higher in patients with systemic diseases, such as hypertension, heart failure, coronary artery disease, metabolic alterations, and stroke (2–4, 6). On the other hand, OSAS is associated with an increased risk of hypertension, atrial fibrillation, myocardial infarction, insulin resistance, and stroke (2).
The main risk factors for OSAS are male sex, older age, and obesity (3). In particular, regarding the association between obesity and OSAS, the risk of OSAS correlates with the body mass index (BMI), and obesity is probably the most relevant risk factor for OSAS (3). Epidemiological data show that about 50% of obese patients are affected by OSAS (3). The clinical symptoms of OSAS include, among others, snoring, nocturnal polyuria, daytime sleepiness, morning headache, neurocognitive deficits, reduced libido, irritability, and depressive symptoms (2, 4–6). In addition, excessive daytime sleepiness may cause motor vehicle and work-related accidents(7). Clinical categorization of OSAS is based upon apnoea hypopnoea index (AHI), obtained by the polysomnography, which represents the ratio between the number of apnoeas and hypopnoea per hour which identifies mild OSAS (5–15), moderate OSAS (15–30) and severe OSAS (>30). Moreover, an AHI > 15 per hour in the absence of symptoms may be diagnostic of OSAS (3).
The treatment of choice for OSAS is the application of continuous positive air pressure (cPAP) (3, 8, 9). Furthermore, it is mandatory to treat the underlying pathophysiological factors, such as obesity, in order to improve the symptoms and the severity of OSAS (8). Other approaches include, among others, mandibular advancement devices, maxillofacial surgery, bariatric surgery in case of morbid obesity, and hypoglossal nerve stimulation(3, 8). In addition, an interesting future pharmacological approach might be based on histamine 3-receptor antagonist/inverse agonists (10).
*OSAS and male hypogonadism
Perspectives and Clinical Messages
This manuscript underlines the need for an active collaboration between different specialists, including endocrinologists, general physicians, obesity physicians, otolaryngologists, pneumologistand sleep specialists. Furthermore, in light of the evidence that OSAS represents a complex clinical condition—and not just a sleep disorder—and that nowadays multidisciplinary groups are created in order to offer better care for complex patients, multidisciplinary evaluation for patients with OSAS might be evaluated and even become mandatory in patients with OSA and other complex diseases. Regarding the gonadal evaluation in patients with OSAS, albeit sleep disorders are not considered to be the main signs/symptoms of hypogonadism (13), we would like to share the interplay between signs/symptoms that might be associated with both OSAS and MH, such as sexual dysfunction, low BMD, low motivation and vitality, poor concentration and memory, and even fatigue. Therefore, albeit for further studies are needed, a complete endocrine and metabolic evaluation in patients with OSAS might be suggested, in order to (i) evaluate endocrine-metabolic alterations caused by OSAS itself and (ii) evaluate possible endocrine-metabolic underlying disorders that might be even the cause of OSAS.
Conclusion
In this review, we described the relationship between OSAS and MH, which are two under-recognized and inter-connected medical disorders, with particular attention to TRT and OSAS. The analysis of the literature highlights the general lack of well-done studies and therefore the evidence is of low quality. We cannot confirm or reject the guidelines that suggest avoidingTRT in the presence of untreated or severe OSAS, as this appears reasonable clinical practice. Indeed, some evidence suggests that short-time high-dose TRT might indeed worsen OSAS, whereas chronic low-dose TRT might improve OSAS. Notwithstanding, the therapy of OSAS might benefit the gonadal status and sexual functions. In light of the few and sometimes inconclusive studies in this field, and therefore of the limited evidence and large grey areas, we wish for further studies and more active collaboration between endocrinologists and otolaryngologists.
