Abnormal melatonin secretion in hypogonadal men: The effect of testosterone treatment

Abstract

OBJECTIVE: We have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion, whereas hypergonadotrophic hypogonadal males have decreased melatonin levels. We were interested in determining whether testosterone (T) treatment (when T levels were well matched with pubertal control values) has an effect on melatonin secretory profiles in these patients. DESIGN: Prospective, controlled. SUBJECTS: Six male patients with idiopathic hypogonadotrophic hypogonadism (IGD), six males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS) and seven controls. Patients were examined before and during the administration of 250 mg testosterone enanthate/month for four months. MEASUREMENTS: Serum samples for melatonin levels were obtained every 15 minutes from 1900 to 0700h in a controlled light-dark environment. The results of FSH, LH, T and oestradiol (E2) (determined at hourly intervals) and melatonin profiles, were compared with the pre-treatment values in each group, and with values obtained in the control group. RESULTS: All 12 patients had low pre-treatment T levels (1.4 ± 0.7 in IGD and 2.8 ± 0.4 in KS vs. 19.8 ± 2.3 nmol/l in controls) and attained normal levels after four months of T treatment (19.5 ± 7 in IGD and 22.7 ± 3.8 nmol/l in KS). Serum LH, FSH and E2 levels (11 ± 4IU/l, 24 ± 10IU/l and 113 ± 12pmol/l, respectively) were still elevated in KS during T treatment as compared with values in controls (2 ± 1 IU/l, 2 ± 1 IU/l and 67 ± 4pmol/l, respectively). In IGD, serum LH (0.12 ± 0.1 IU/l) and FSH (0.16 ± 0.2 IU/l) levels during T treatment were suppressed. Pretreatment melatonin levels in IGD were greater than those in age-matched pubertal controls while in KS, melatonin levels were lower than values in controls. Melatonin levels were equal in all 12 hypogonadal patients and controls when T levels were well matched. Mean (±SD) dark-time melatonin levels decreased from 286 ± 18 to 157 ± 26 pmol/l in IGD and increased from 92 ± 19 to 183 ± 48pmol/l in KS (vs 178 ± 59pmol/l in controls). The integrated melatonin values decreased in IGD (from 184 ± 14 to 102 ± 21 pmol/min. 1x103) and increased in KS (from 64 ± 13 to 123 ± 40, vs. 116 ± 39 pmol/min. I x 163 in controls). No correlations were found between melatonin and LH, FSH or E2 levels. CONCLUSIONS: These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion while in hypergonadotrophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Taken together, the results suggest that GnRH, gonadotrophins and gonadal steroids modulate pineal melatonin in humans.