Testosterone treatment and sleep disorders
Testosterone therapy and obstructive sleep apnea: is there a real connection?
Hanafy HM. J Sex Med 2007;4(5):1241-1246.
Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnea: a randomized placebo-controlled trial.
Hoyos CM, Killick R, Yee BJ, Grunstein RR, Liu PY. Clin Endocrinol 2012;77(4):599-607.
Millions of men have received testosterone therapy over the past several decades, but only a few studies have addressed the possible link between testosterone treatment and obstructive sleep apnea (OSA). Despite the small number of patients studied, publications have generally cautioned clinicians about the possible cause or aggravation of OSA by testosterone therapy. A review of the literature by Hanafy in 2007 evaluated the scientific data behind these cautionary statements and found a lack of consistent findings from case studies and different patient groups and that the link between testosterone and OSA was weak. Further well designed studies in this area were recommended from this review.
To address this gap a recent randomized, placebo-controlled study evaluated the effect of testosterone therapy in obese men with severe OSA. Eligible subjects (recruited from sleep clinics in Sydney, Australia) were enrolled into an 18-week weight loss program and randomized to receive three intramuscular injections of either testosterone undecanoate 1,000 mg or placebo. Sleep and breathing parameters were measured (by nocturnal polysomnography) at 0, 7 and 18 weeks.
Compared with placebo treatment, testosterone mildly worsened the oxygen desaturation index (ODI, p=0.03) and nocturnal hypoxemia (sleep time with oxygen saturation <90%, SpO2T90%, p=0.01) at 7 weeks but not at 18 weeks. The time-dependent effects of testosterone treatment on ODI and SpO2T90% were not influenced by baseline testosterone concentrations.
What is known
OSA is a common disorder affecting up to 25% of middle-aged adult men3, many of whom are obese4,5. Biochemical androgen deficiency is also often observed in obese men and in men with OSA6,7 and the severity of this deficiency increases with greater hypoxemia in men with OSA8 and increasing adiposity in obese men9. Therefore, obese men with OSA are likely to be at greatest risk for androgen deficiency.
Blood testosterone levels in men with OSA or obesity can be increased by continuous positive airway pressure therapy (CPAP)8 and weight loss,10 ,11 respectively. Testosterone treatment to address androgen deficiency in obese men with OSA is attractive, but (despite the lack of systematic studies) concerns have been raised regarding the respiratory safety of testosterone therapy12. However, men who developed or worsened their sleep apnea received higher doses of testosterone and had other identifiable risk factors for sleep apnea13.
What this study adds
Results from the Hoyos study, in conjunction with earlier findings, suggest that near-conventional dose testosterone therapy mildly worsens sleep hypoxemia acutely, as shown by the two available measures of ODI and SPO2T90%. This effect may not be seen in the longer term1.
In this study, the first to purposefully treat men with severe OSA with testosterone, mild respiratory changes were observed for at least 7 weeks (and potentially up to 18 weeks). Larger and longer-term studies will be required to document the long-term morbidity and survival arising from these changes as well as the degree of inter-individual variability in testosterone response. Until such studies are conducted, patients requiring testosterone therapy should continue to be cautiously monitored and assessed on an individual basis. Nevertheless, lifestyle modification to achieve weight loss remains first-line therapy for all obese men with OSA.
Hoyos et al. chose to examine baseline total and free testosterone thresholds (validated for late onset hypogonadism9). They found no evidence, from post-hoc analysis and confirmed by correlational analyses, that the effect of testosterone therapy on sleep disordered breathing was influenced by baseline testosterone concentrations. However, they suggest larger, more intensive and longer-term studies be planned, particularly in men with the lowest blood testosterone concentrations in whom the overall risk-benefits of testosterone therapy may be more favorable.