madman
Super Moderator
Introduction: There is persistent speculation that testosterone therapy (TTh) may induce the worsening of obstructive sleep apnea (OSA). As both the incidence of OSA and the use of TTh grow more prevalent, it is important to review the current evidence that supports or refutes this relationship.
Objectives: To review the current literature regarding the relationship between TTh and OSA. Methods: A literature search was conducted to identify relevant studies. Search terms included “obstructive sleep apnea” and “testosterone replacement therapy.” Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate.
Results: The association between TTh and OSA was initially described in a 1978 case report of an individual with worsened nighttime apneas during testosterone administration, a trend seen again in subsequent small case series. In the 1990s, large retrospective analysis and the first randomized controlled trial on the subject revealed no increased incidence of OSA in individuals on TTh. A randomized controlled trial conducted in 2012 provided a possible explanation for the previously reported discrepancies, describing a time-limited effect, wherein measures of OSA were elevated at seven weeks but were not significantly different at 18 weeks after initiation of TTh. A recent cohort study demonstrated an incidence of OSA in individuals on TTh of 16.5% compared with 12.7% in controls. TTh is thought to affect OSA in several ways. Theories that the anabolic effects of testosterone may decrease airway patency or that testosterone alters sleep architecture has been largely disproven. More likely, testosterone plays a role in altering neural response pathways to hypoxemia.
Conclusions: TTh likely plays a small role in exacerbating or inducing changes in OSA that may be time-limited in nature. Clinicians may choose to exercise caution in prescribing TTh to individuals suffering from severe OSA.
CONCLUSION
As TTh is increasingly used, it is important to understand its potential adverse effects. The idea that TTh may exacerbate OSA dates back more than 40 years. For several decades, the association was explored using only case studies or small uncontrolled case series, which suggested that TTh worsened OSA. As larger cohort studies and RCTs became available, this relationship has been questioned. The best current evidence suggests that short-term, high-dose testosterone administration mildly worsens OSA. Longer-term TTh in subjects undergoing concomitant weight loss was shown to mildly worsen OSA but only initially. By 18 weeks, patients demonstrated a return to baseline levels of OSA risk. These results suggest that TTh's role in exacerbating OSA is small and may be time-limited. However, it is also possible that weight loss acted as a confounding factor. Additional studies are needed to determine if men who are more obese at baseline have a higher risk of developing OSA with TTh than nonobese men. Why testosterone would have a time-dependent effect, however, remains unanswered. Regarding the mechanisms by which TTh may worsen OSA, anatomic TTh-induced airway changes and altered sleep stage architecture have been largely refuted. The mechanism of action is more likely related to altered hypoxic and hypercapnic ventilatory response with testosterone administration, though work is still needed to resolve inconsistencies in currently available studies. Until these questions are more fully understood, clinicians may choose to exercise caution in prescribing TTh to individuals with severe, untreated OSA.
Objectives: To review the current literature regarding the relationship between TTh and OSA. Methods: A literature search was conducted to identify relevant studies. Search terms included “obstructive sleep apnea” and “testosterone replacement therapy.” Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate.
Results: The association between TTh and OSA was initially described in a 1978 case report of an individual with worsened nighttime apneas during testosterone administration, a trend seen again in subsequent small case series. In the 1990s, large retrospective analysis and the first randomized controlled trial on the subject revealed no increased incidence of OSA in individuals on TTh. A randomized controlled trial conducted in 2012 provided a possible explanation for the previously reported discrepancies, describing a time-limited effect, wherein measures of OSA were elevated at seven weeks but were not significantly different at 18 weeks after initiation of TTh. A recent cohort study demonstrated an incidence of OSA in individuals on TTh of 16.5% compared with 12.7% in controls. TTh is thought to affect OSA in several ways. Theories that the anabolic effects of testosterone may decrease airway patency or that testosterone alters sleep architecture has been largely disproven. More likely, testosterone plays a role in altering neural response pathways to hypoxemia.
Conclusions: TTh likely plays a small role in exacerbating or inducing changes in OSA that may be time-limited in nature. Clinicians may choose to exercise caution in prescribing TTh to individuals suffering from severe OSA.
CONCLUSION
As TTh is increasingly used, it is important to understand its potential adverse effects. The idea that TTh may exacerbate OSA dates back more than 40 years. For several decades, the association was explored using only case studies or small uncontrolled case series, which suggested that TTh worsened OSA. As larger cohort studies and RCTs became available, this relationship has been questioned. The best current evidence suggests that short-term, high-dose testosterone administration mildly worsens OSA. Longer-term TTh in subjects undergoing concomitant weight loss was shown to mildly worsen OSA but only initially. By 18 weeks, patients demonstrated a return to baseline levels of OSA risk. These results suggest that TTh's role in exacerbating OSA is small and may be time-limited. However, it is also possible that weight loss acted as a confounding factor. Additional studies are needed to determine if men who are more obese at baseline have a higher risk of developing OSA with TTh than nonobese men. Why testosterone would have a time-dependent effect, however, remains unanswered. Regarding the mechanisms by which TTh may worsen OSA, anatomic TTh-induced airway changes and altered sleep stage architecture have been largely refuted. The mechanism of action is more likely related to altered hypoxic and hypercapnic ventilatory response with testosterone administration, though work is still needed to resolve inconsistencies in currently available studies. Until these questions are more fully understood, clinicians may choose to exercise caution in prescribing TTh to individuals with severe, untreated OSA.
