SUMMARY

Melatonin, a hormone secreted by the pituitary gland of the brain, shows a regular daily pattern of beginning to increase in the late evening, peaking during the night, and declining in the early morning. It has been shown to promote sleep in human subjects. It is suppressed by light. Abnormal melatonin secretion has been observed in a variety of conditions associated with sleep disturbance, but has not yet been studied in Obstructive Sleep Apnea. That was the purpose of this study. The OSA patient group included nine men, ages 38 to 70 (average 55 yrs), mostly overweight (Body Mass Index from 25 to 36, average 31) with complaints of daytime sleepiness and moderate to severe OSA determined by more than ten oxygen desaturations per hour (range=10-63, ave=42) with a mean oxygen saturation nadir of 66% (range 50-80%). Control subjects included nine healthy men, ranging in age from 35 to 65 (average=51), in Body Mass Index rom 22-39 (average=28), which did not differe significantly from the patients. All denied snoring or excessive daytime sleepiness. The patients were tested just before starting CPAP and again after at least 4 weeks of continuous CPAP use. Controls were tested once. Testing took place between 8:00 p.m. and 8:00 a.m. At 11 p.m. the light was turned off until 7:00 a.m. the next morning. Blood levels of melatonin were measured every second hour between 8:00 p.m. and 8:00 a.m. Urine was collected between 10:00 p.m. and 7:00 a.m. for urinary melatonin assay. Meanwhile, monitoring of respiration and movements were done with a movement sensitive mattress; also measured were breathing sounds, oxygen saturation (with ear oximetry). Scoring of sleep time was estimated from the movement recording. Among the patients, CPAP reduced the oxygen desaturation index from 42.2 to 2.8 and increased the average oxygen saturation from 91 to 94 and the greatest desaturation from 66 to 86. Also, body movements during sleep were greatly reduced, from 37 to 5.6. CPAP treatment had no effect on any of various measures of blood and urine melatonin. The only differences-of marginal significance-between patients and controls were blood melatonin levels being higher in controls than in patients at 6:00 a.m. and 8:00 a.m. The authors were surprised not to find increased melatonin secretion in untreated OSA patients because there is considerably evidence of increased sympathetic autonomic activity in such patients during sleep which they hypothesized would increase melatonin secretion. Commendably, though they offered alternative explanations, they did not adhere to their original hypothesis. Nor did they yield to the temptation to over-interpret the two small significant differences they found between patients and controls among many comparisons made. They ended by suggesting that 24-hour studies be done.

COMMENTS

Negative findings never convey the excitement of positive findings, and in fact often go totally unreported in the published medical research literature, leading to a biassed impression about the total body of evidence on many topics. There is a legitimate basis to put less weight on negative findings, because of the truism in statistics that you cannot prove what they call the null hypothesis, that there is no difference. A difference might exist but go undetected because insufficient subjects or sensitivity of procedures left the test without enough power to detect differences below a certain magnitude. On the other hand, without compelling reason to believe that sleep apneics should have distinctive melatonin profiles, I am rather willing to accept the finding that there are none. Melatonin profiles may be more likely to be altered in sleep disorders which involve insomnia, or altered daily rhythms, like disorders of sleep phase, jet lag, or shift work. People with OSA do not usually have a lot of trouble staying asleep, so would probably not benefit much from the rather short-lived sleep-inducing effect of taking melatonin at bedtime. The effects of taking it later during the night, upon periodic awakenings resulting from apneic episodes, woulc be likely to result in undesirable shifting of the sleep-wake cycle, resulting in even later waking than is usual with sleep apneics. Where I see more interest for melatonin in OSA is in the typical naps of these patients. Normally, there is very little melatonin secretion during the day, but one wonders if some may occur during prolonged daytime napping, especially if done in a darkened room. I know of no data bearing on this point. If so, it might be of value to consider treatments which suppress melatonin, like bright light, at times of maximal drowsiness.





This page hosted by Get your own Free Home Page