6-sulphatoxymelatonin Levels Research Articles

Elevated Nocturnal Melatonin Is a Consequence of Gonadotropin-Releasing Hormone Deficiency in Women with Hypothalamic Amenorrhea

Elevated nocturnal melatonin is found in women with idiopathic hypogonadotropic hypogonadism (IHH), but it is not known whether this is implicated in the etiology of their GnRH deficiency. It is unlikely that nocturnal melatonin can be implicated in the etiology of the GnRH deficiency of Kallmann’s syndrome (KS), because this condition is caused by defective neuronal migration in embryonic life. We therefore measured nocturnal melatonin in women with IHH and KS to determine whether it was elevated in one or both conditions and thereby to determine whether it was implicated as cause or consequence of GnRH deficiency. Four women with IHH, 3 women with KS, and 7 individually matched (age and body size) controls were recruited. Frequent day- and nighttime samples were taken for LH pulsatility studies. All patients showed absent or diminished LH pulsatility, compared with their respective controls. Samples were also taken over 24 h for melatonin and 6-sulphatoxymelatonin (the principle metabolite of melatonin and an independent marker of its secretion). Melatonin and 6-sulphatoxymelatonin levels were elevated in 6 of 7 patients (compared with their matched controls) and were significantly elevated in the KS group (compared with their controls). The finding of elevated nocturnal melatonin (and its metabolite) in GnRH-deficient women with KS (as well as IHH) suggests that nocturnal melatonin is elevated as a consequence of GnRH deficiency, irrespective of its etiology.

Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea.

Elevated nocturnal melatonin is found in women with idiopathic hypogonadotropic hypogonadism (IHH), but it is not known whether this is implicated in the etiology of their GnRH deficiency. It is unlikely that nocturnal melatonin can be implicated in the etiology of the GnRH deficiency of Kallmann's syndrome (KS), because this condition is caused by defective neuronal migration in embryonic life. We therefore measured nocturnal melatonin in women with IHH and KS to determine whether it was elevated in one or both conditions and thereby to determine whether it was implicated as cause or consequence of GnRH deficiency. Four women with IHH, 3 women with KS, and 7 individually matched (age and body size) controls were recruited. Frequent day- and nighttime samples were taken for LH pulsatility studies. All patients showed absent or diminished LH pulsatility, compared with their respective controls. Samples were also taken over 24 h for melatonin and 6-sulphatoxymelatonin (the principle metabolite of melatonin and an independent marker of its secretion). Melatonin and 6-sulphatoxymelatonin levels were elevated in 6 of 7 patients (compared with their matched controls) and were significantly elevated in the KS group (compared with their controls). The finding of elevated nocturnal melatonin (and its metabolite) in GnRH-deficient women with KS (as well as IHH) suggests that nocturnal melatonin is elevated as a consequence of GnRH deficiency, irrespective of its etiology.

60 Hz magnetic field exposure and urinary 6-sulphatoxymelatonin levels in the rat

Four separate experiments were carried out to investigate the effect of extremely low frequency magnetic field (MF) exposure (60 Hz, 1 mT rms) on urinary 6-sulphatoxymelatonin (aMT6s) levels in Sprague-Dawley rats. In the first experiment, immature male rats maintained under a regular 12 h daily photoperiod (white fluorescent light) were exposed to a 20 h daily MF exposure for 6 weeks. The second experiment was similar to the first, except that the MF exposure was limited to 10 days. In the third experiment, adult male rats acclimated to a combination of continuous dim red light and regular 12 h daily photoperiod (white fluorescent) were subjected to a single 1 h exposure to intermittent MF (1 min on and 1 min off cycles), 2 h before fluorescent lights went off. The fourth experiment was similar to the third, except that the animals received 2 consecutive days of 20 h daily exposure to intermittent MF, beginning 1 h before the fluorescent lights went off each day. In all four experiments, the circadian profile of urinary aMT6s was examined before, during, and after the MF exposure. No significant effect of 1 mT MF on indoleamine metabolism was observed in any of the above experiments. However, in one of the experiments (no. 4), both the control and the MF groups showed a lower aMT6s level during the exposure days, when compared with that of pre- and post-exposure days, suggesting that the existence of possible effects with lower field strengths at the range of stray field cannot be ruled out.

Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral melatonin: a case report

A 43 year old woman had suffered from insomnia for the past 11 years and was being treated with benzodiazepines. All attempts to stop benzodiazepine treatment resulted in withdrawal symptoms and a renewal of the insomnia. Treatment with 1 mg of controlled release melatonin enabled the patient to completely cease any benzodiazepine use within two days, with an improvement in sleep quality and no side effects. Examination of urinary 6-sulphatoxymelatonin levels before the melatonin treatment indicated that the levels were very low and lacked the typical circadian rhythm of excretion. Reexamination of 6-sulphatoxymelatonin levels during melatonin treatment revealed the existence of a normal circadian rhythm of excretion. This case may suggest that some of the people suffering from insomnia and addicted to benzodiazepines may successfully undergo withdrawal from these drugs and improve their sleep by means of treatment with melatonin. The results of this single case study warrant further investigation of a larger population by means of a double- blind placebo-drug study.

Nocturnal melatonin and 24-hour 6-sulphatoxymelatonin levels in various phases of bipolar affective disorder

Nine bipolar patients (2 men and 7 women) and 12 healthy control subjects completed overnight sampling for serum melatonin (MT) and urinary 6-sulphatoxymelatonin (aMT6s). The patients were investigated during manic, depressed, and/or euthymic states. Although serum MT levels did not differ significantly across the bipolar groups, in all cases serum MT levels were significantly lower than in control subjects. Differences in MT levels were also present between bipolar patients who were in a depressed phase and control subjects. There were no statistically significant differences in urinary aMT6s levels among the patients and control subjects, although in all cases nocturnal aMT6s levels were significantly higher than daytime levels. This study provides tentative evidence for decreased serum MT as a trait but not a state marker in bipolar affective disorder.

Primary early onset dysthymia, biochemical correlates of the therapeutic response to fluoxetine: II. Urinary metabolites of serotonin, norepinephrine, epinephrine and melatonin

The present study investigated pre- and post-treatment 24-h urinary metabolites of monoamines and melatonin as a function of response to treatment in primary early onset dysthymic patients. The main finding was that treatment responders had lower urinary 5-hydroxyindolacetic acid (5-HIAA) levels prior to treatment. Following treatment, urinary 5-HIAA tended to be decreased in nonresponders and increased in responders. As well, metanephrine levels were lower and 6-sulphatoxymelatonin levels were higher in responders prior to treatment. These data support the view that there is a biological substrate for certain subgroups of dysthymia, part of which may involve serotonergic systems.