NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
J Sleep Res. 2013 Jun;22(3):331-6. doi: 10.1111/jsr.12027. Epub 2013 Jan 19.
We recently showed that testosterone therapy worsens sleep-disordered breathing at 6-7 weeks, but not after 18 weeks, in men with obstructive sleep apnea. Changes in ventilatory chemoreflexes may be responsible. The effect of testosterone on ventilatory chemoreflexes in men with obstructive sleep apnea has not been systematically studied before. Twenty-one obese men with obstructive sleep apnea, a subgroup of our recent report, were randomised in an 18-week, randomised, double-blind, placebo-controlled, parallel group trial to three intramuscular injections (0, 6, 12 weeks) of either 1000 mg testosterone undecanoate (n = 10) or placebo (n = 11). Awake ventilatory chemoreflex testing was performed before (week 0), during (week 6) and at the end of treatment (week 18) to determine the ventilatory carbon dioxide recruitment threshold and chemosensitivity. Sleep and breathing was assessed by overnight polysomnography at 0, 7 and 18 weeks. Serum hormones levels were measured at every visit. A significant increase in blood testosterone levels (5.65 nmol L(-1) , 0.51-10.8 nmol L(-1) , P = 0.03) and lean muscle mass (2.36 kg, 0.8-3.9 kg, P = 0.007) between the two groups was observed as expected. No significant differences were seen in ventilatory chemoreflexes between the two groups at 6 weeks or at 18 weeks. However, positive correlations were observed between changes in serum testosterone and hyperoxic ventilatory recruitment threshold (r = 0.55, P = 0.03), and between changes in hyperoxic ventilatory recruitment threshold and time spent with oxygen saturations during sleep <90% (r = 0.57, P = 0.03) at 6-7 weeks, but not at 18 weeks. Time-dependent alterations in ventilatory recruitment threshold may therefore mediate the time-dependent changes in sleep breathing observed with testosterone.
我们最近的研究表明，在患有阻塞性睡眠呼吸暂停的男性中，睾丸激素治疗在 6-7 周时会加重睡眠呼吸障碍，但在 18 周后不会加重。通气化学感受器的变化可能是导致这种情况的原因。以前尚未系统研究睾丸激素对患有阻塞性睡眠呼吸暂停的男性通气化学感受器的影响。我们最近的报告中的一个亚组，21 名肥胖的阻塞性睡眠呼吸暂停男性被随机分配到一项 18 周、随机、双盲、安慰剂对照、平行组试验中，接受三组肌肉内注射（0、6、12 周），分别为 1000mg 十一酸睾酮（n=10）或安慰剂（n=11）。在治疗前（第 0 周）、治疗期间（第 6 周）和治疗结束时（第 18 周）进行清醒通气化学感受器测试，以确定通气二氧化碳募集阈值和化学敏感性。在 0、7 和 18 周时通过整夜多导睡眠图评估睡眠和呼吸。在每次就诊时测量血清激素水平。正如预期的那样，两组之间的血液睾丸激素水平（5.65nmol/L，0.51-10.8nmol/L，P=0.03）和瘦肌肉量（2.36kg，0.8-3.9kg，P=0.007）显著增加。在 6 周或 18 周时，两组之间的通气化学感受器没有明显差异。然而，在 6-7 周时，血清睾丸激素变化与高氧通气募集阈值之间存在正相关（r=0.55，P=0.03），高氧通气募集阈值变化与睡眠期间血氧饱和度低于 90%的时间之间存在正相关（r=0.57，P=0.03），但在 18 周时没有。因此，通气募集阈值的时间依赖性改变可能介导了与睾丸激素相关的睡眠呼吸的时间依赖性变化。
