Does exogenous testosterone (testosterone replacement therapy) increase the risk of sleep apnea?

From the Guidelines

Exogenous testosterone can increase the risk of sleep apnea, particularly in individuals with predisposing factors such as obesity, advanced age, or anatomical airway issues. The mechanism appears to be related to testosterone's effects on upper airway muscle tone and ventilatory control, as suggested by a study published in the British Journal of Pharmacology in 2017 1. When men receive testosterone replacement therapy (TRT), the hormone can alter respiratory drive and potentially reduce upper airway muscle activity during sleep, leading to increased airway collapsibility.

Key Considerations

• The risk of sleep apnea associated with TRT appears to be dose-dependent, with higher doses potentially carrying greater risk, as noted in a study published in the New England Journal of Medicine in 2004 1.
• Patients starting TRT should be monitored for sleep apnea symptoms, including excessive daytime sleepiness, loud snoring, witnessed breathing pauses during sleep, morning headaches, and irritability.
• Those with existing risk factors for sleep apnea should consider sleep testing before starting therapy or during early treatment.
• If sleep apnea develops or worsens during TRT, treatment options include CPAP therapy, dose adjustment of testosterone, or in some cases, discontinuation of therapy if symptoms are severe.

Monitoring and Management

• Regular monitoring of patients on TRT for signs and symptoms of sleep apnea is crucial, as the condition can have significant impacts on morbidity, mortality, and quality of life.
• Healthcare providers should be aware of the potential risks associated with TRT and take steps to mitigate them, including educating patients about the signs and symptoms of sleep apnea and the importance of reporting any concerns promptly.

From the Research

Exogenous Testosterone and Sleep Apnea

• The relationship between exogenous testosterone, also known as testosterone replacement therapy (TRT), and sleep apnea has been studied in several research papers 2, 3, 4, 5, 6.
• A 2007 study found that cautionary statements about TRT and obstructive sleep apnea (OSA) appear frequently in the literature, despite a lack of convincing evidence that TRT causes and/or aggravates OSA 2.
• A 2021 review of the current literature regarding the relationship between testosterone therapy (TTh) and OSA found that TTh likely plays a small role in exacerbating or inducing changes in OSA that may be time-limited in nature 3.
• Another study published in 2019 suggested that TRT may exacerbate OSA in some patients, and patients should be asked about OSA symptoms before and after starting TRT 4.
• The association between serum testosterone levels and sleep characteristics was examined in a 2008 cohort study, which found that low total testosterone levels were associated with less healthy sleep in older men, including lower sleep efficiency and more sleep time with O2 saturation levels below 90% 5.
• A 2015 study investigated the relationship between fatigue and serum testosterone in adult obese males affected by OSA, and found that OSA-related fatigue was strongly associated with serum testosterone, together with OSA severity 6.

Key Findings

• The current evidence suggests that the link between TRT and OSA is weak, based on methodological issues in many of the studies, and most studies involved small numbers of men 2.
• TRT may play a role in altering neural response pathways to hypoxemia, which could contribute to the development or exacerbation of OSA 3.
• Clinicians may choose to exercise caution in prescribing TTh to individuals suffering from severe OSA 3.
• Further studies are needed to fully understand the relationship between exogenous testosterone and sleep apnea 2, 3, 4, 5, 6.