The effects of testosterone on ventilatory responses in men with obstructive sleep apnea: a randomised, placebo-controlled trial

We recently showed that testosterone therapy worsens sleep-disordered breathing at 67weeks, but not after 18weeks, 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, 12weeks) of either 1000mg 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 18weeks. Serum hormones levels were measured at every visit. A significant increase in blood testosterone levels (5.65nmol L1, 0.5110.8nmol L1, P=0.03) and lean muscle mass (2.36kg, 0.83.9kg, P=0.007) between the two groups was observed as expected. No significant differences were seen in ventilatory chemoreflexes between the two groups at 6weeks or at 18weeks. 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 67weeks, but not at 18weeks. Time-dependent alterations in ventilatory recruitment threshold may therefore mediate the time-dependent changes in sleep breathing observed with testosterone.