RELIABLE ANALYSIS OF INDIVIDUAL HUMAN MELATONIN PROFILES BY COMPLEX COSINOR ANALYSIS

The analysis of diurnal secretion patterns of the pineal hormone melat onin should provide information about magnitude of peak concentration, time of peak (acrophase), and duration of elevated hormone levels. We report here on a method for analysis of human melatonin secretory rhy thms which fulfills these requirements with considerable precision. Bl ood samples were obtained from 10 healthy male volunteers at 30 min in tervals throughout a 24 hr period, three times (the initial blood samp ling was repeated after 2 weeks and 3 months). These sets of 48 plasma samples per volunteer were analyzed for melatonin by radioimmunoassay . The mean intra-assay variation was 10.3%, and inter-assay variations were 15.8% at 21 pg/ml, 11% at 28 pg/ml, and 9.4% at 48.6 pg/ml. Data were subjected to single cosinor analysis (SCA) or analyzed by a comp lex cosinor analysis (CCA) with the fundamental and the first harmonic as parameters. Both methods provided essentially the same information about the acrophases, whereas the CCA had a clear advantage in terms of better regression coefficients between the original data points and the calculated curve (CCA: 0.952 +/- 0.018; SCA: r = 0.867 +/- 0.039 [means +/- SD]; P < 0.001). As a consequence, maximum and minimum valu es and the times of onset and cessation of melatonin production could be estimated easily and reliably without the need for rough and/or sub jective measures. By comparing the three sampling sessions, the secret ory rhythm of each individual was clearly reproducible (mean coefficie nt of variation 8.4%), thus confirming earlier work. Interindividual d ifferences, however, were quite pronounced, especially with respect to amplitudes (more than 25% coefficient of variation). The present meth od for describing the secretory pattern of melatonin may also be usefu l for other study protocols since it requires only slightly more effor t than the commonly used single cosinor analysis.