ABNORMAL MELATONIN SECRETION IN HYPOGONADAL MEN - THE EFFECT OF TESTOSTERONE TREATMENT

OBJECTIVE We have recently demonstrated that GnRH deficient male patie nts have increased nocturnal melatonin secretion, whereas hypergonadot rophic hypogonadal males have decreased melatonin revels. We were inte rested in determining whether testosterone (T) treatment (when T lever s were well matched with pubertal control values) has an effect on mel atonin secretory profiles in these patients. DESIGN Prospective, contr olled. SUBJECTS Six male patients with idiopathic hypogonadotrophic hy pogonadism (IGD), six males with hypergonadotrophic hypogonadism due t o Klinefelter's syndrome (KS) and seven controls. Patients were examin ed before and during the administration of 250 mg testosterone enantha te/month for four months. MEASUREMENTS Serum samples for melatonin lev els were obtained every 15 minutes from 1900 to 0700 h in a controlled light-dark environment. The results of FSH, LH, T and oestradiol (E-2 ) (determined at hourly intervals) and melatonin profiles, were compar ed with the pre-treatment values in each group, and with values obtain ed in the control group. RESULTS All 12 patients had row pre-treatment T levels (1.4 +/- 0.7 in Ion and 2.0 +/- 0.4 in KS vs. 19.8 +/- 2.3 n mol/l in controls) and attained normal levels after four months of T t reatment (19.5 +/- 7 in Ion and 22.7 +/- 3.8 nmol/l in KS). Serum LH, FSH and E-2 levels (11+/-4 IU/l, 24+/-10 IU/l and 113+/-12 pmol/l, res pectively) were still elevated in KS during T treatment as compared wi th values in controls (2 +/- 1 IU/l, 2 +/- 1 IU/l and 67+/-4 pmol/l, r espectively). In Ion, serum LH (0.12 +/- 0.1 IU/l) and FSH (0.16 +/- 0 .2 IU/l) levels during T treatment were suppressed. Pretreatment melat onin levels in ion were greater than those in age-matched pubertal con trols while in KS, melatonin levels were lower than values in controls . Melatonin levels were equal in all 12 hypogonadal patients and contr ols when T levels were well matched. Mean (+/-SD) dark time melatonin levels decreased from 286+/-18 to 157 +/- 26 pmol/l in Ion and increas ed from 92 +/- 19 to 183 +/- 48 pmol/l in KS (vs 178 +/- 59 pmol/l in controls). The integrated melatonin values decreased in Ion (from 184 +/- 14 to 102 +/- 21 pmol/min.lx10(3)) and increased in KS (from 64 +/ - 13 to 123 +/- 40, vs. 116 +/- 39 pmol/min. I x 10(3) in controls). N o correlations were found between melatonin and LH, FSH or E-2 levels. CONCLUSIONS These data indicate that male patients with GnRH deficien cy have increased nocturnal melatonin secretion while in hypergonadotr ophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Take n together, the results suggest that GnRH, gonadotrophins and steroids modulate pineal melatonin in gonadal steroids modulate pineal melaton in in humans.