Testosterone Replacement in Hypogonadal Men: Effects on Obstructive Sleep Apnoea, Respiratory Drives, and Sleep

Abstract

The obstructive sleep apnoea syndrome occurs predominantly in men. To determine the effect of testosterone on ventilatory function and whether testosterone may play a role in the development of obstructive apnoea, we performed waking ventilatory drive studies and sleep studies in five hypogonadal men. These androgen-deficient subjects were studied both while receiving no treatment and after six weeks of testosterone replacement therapy (testosterone oenanthate 200 mg i.m. every 2 weeks). Hypoxic ventilatory drive decreased significantly, from 158 +/- 39 (mean +/- SEM) off testosterone to 88 +/- 19 on testosterone therapy (P less than 0.05). Hypercapnoeic ventilatory drive did not change significantly on testosterone. Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 +/- 3% to 22 +/- 2% when the men were receiving testosterone (P less than 0.01), but the episodes of sleep apnoea tended to occur during non-REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiology of Adult Obstructive Sleep Apnea

“…Hormonal differences between men and women have long been proposed to contribute to the increased male prevalence in OSA and to the propensity for women to develop OSA after menopause (109,110). Indeed, testosterone administration in hypogonadal men has been shown to induce sleep-disordered breathing in some patients (111)(112)(113). However, thus far, attempts to manipulate OSA severity on the basis of hormone-targeted approaches have revealed little benefit (114,115).…”

Sex differences in sleep: impact of biological sex and sex steroids

“…Conversely, high-dose testosterone replacement in older men and the use of anabolic androgenic steroids in healthy young men are associated with a reduction in sleep efficiency and total sleep time [71,72]. A number of studies suggest that testosterone is linked to a worsening of obstructive sleep apnoea in men [71,[73][74][75]; however, blocking androgen action, via flutamide administration, does not affect sleep architecture or breathing parameters in men with sleep apnoea [76]. Interestingly, androgen deprivation therapy (ADT) for prostate cancer is highly associated with insomnia, potentially as a consequence of an increased occurrence of hot flushes and night sweats [77,78].…”

The benefits and risks of testosterone replacement therapy: a review

“…312,313 The effect of testosterone is not on the dimensions of the upper airway, but it most likely contributes to sleep disorder breathing by central mechanisms. 314 The development of signs and symptoms of obstructive sleep apnea during testosterone therapy warrants a formal sleep study and treatment with continuous positive airway pressure (CPAP) if necessary. If the patient is unresponsive or cannot tolerate CPAP, the testosterone must be reduced or discontinued.…”