Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy

We studied the effects of sleep apnea on neuroendocrine function in a cross-sectional study of 225 consecutive men undergoing sleep studies and in a longitudinal study of 43 men with severe obstructive sleep apnea before and after 3 months of successful treatment with nasal continuous positive airways pressure to eliminate upper airways obstruction. Blood samples were collected at 0600-0630 h on awakening for measurement of plasma insulin-like growth factor I (IGF-I), total and free testosterone, sex hormone-binding globulin (SHBG), LH, FSH, PRL, T4, T4-binding globulin, and cortisol. The plasma hormone levels were analyzed in relation to the severity of sleep apnea, as indicated by the desaturation index (the hourly rate of episodes of arterial oxygen desaturation greater than 4% of the stable baseline) and the mean minimal oxygen saturation during the desaturation episodes. In the cross-sectional study plasma IGF-I, free and total testosterone, and SHBG levels were significantly lower in relation to the severity of sleep apnea, whereas plasma LH, FSH, PRL, T4, T4-binding globulin, and cortisol were not. The decreases in plasma IGF-I and total and free testosterone were independent of the effects of aging and adiposity by covariance analysis. In the longitudinal study plasma IGF-I, total testosterone, and SHBG, but not free testosterone, significantly increased after 3 months of nasal continuous positive airways pressure treatment. We conclude that sleep apnea causes reversible neuroendocrine dysfunction in men, which is manifested by decreased plasma. IGF-I, testosterone, and SHBG levels. This neuroendocrine dysfunction is related to the severity of the sleep apnea, as indicated by the nadir levels of arterial oxygen desaturation and the rate of desaturation episodes. These hormonal measurements may provide biochemical markers for both the severity of sleep apnea and its response to therapeutic intervention. In addition, sleep apnea may be a previously unrecognized confounder of the neuroendocrine correlates of aging.