TESTOSTERONE TREATMENT ALTERS MELATONIN CONCENTRATIONS IN MALE-PATIENTS WITH GONADOTROPIN-RELEASING-HORMONE DEFICIENCY

Recently, we demonstrated that melatonin secretion is increased in unt reated male patients with GnRH deficiency. As testosterone (T) can be aromatized to estradiol (E(2)), and both T and E(2) increase during T enanthate treatment, we were interested in determining whether T treat ment (when T and E(2) levels were well matched with pubertal control v alues) has an effect on melatonin levels in these patients. We measure d nocturnal serum melatonin levels during the administration of 250 mg testosterone enantale/month for 4 months in 12 male patients with idi opathic hypogonadotropic hypogonadism (IGD; n = 6) and delayed puberty (DP; n = 6). Serum samples for melatonin and LH deteminations were ob tained every 15 min from 1900-0700 h in a controlled light-dark enviro nment. The results of melatonin profiles were compared with the pretre atment values in each group and with values obtained in six normal pub ertal male controls. After 4 months of testosterone treatment, all pat ients attained normal serum testosterone (19.5 +/- 3.7 in IGD vs. 20.8 +/- 4.1 nmol/L in DP) and E(2) levels (83 +/- 12 in IGD vs. 84 +/- 9 pmol/L in DP). Serum LH levels were suppressed in all patients during T treatment (0.12 +/- 0.1 in IGD vs. 0.12 +/- 0.2 IU/L in DP). Before T treatment, patient melatonin levels were greater than those in age-m atched pubertal controls. Melatonin levels were equal in patients and controls when T and E(2) levels were well matched. Mean (+/- SD) dark- time melatonin levels decreased from 286 +/- 23 to 157 +/- 36 pmol/L i n IGD and from 217 +/- 32 to 133 +/- 47 pmol/L in DP (vs. 183 +/- 64 p mol/L in controls). The integrated melatonin values decreased to norma l (from 184 +/- 16 to 102 +/- 21 in IGD and from 142 +/- 19 to 90 +/- 26 pmol/min . 1 x 10(3) in DP vs. 119 +/- 61 pmol/min . L x 10(3) in c ontrols). The intraindividual variations in melatonin levels ranged fr om 7.2-14.5%. These data indicate that male patients with GnRH deficie ncy have increased nocturnal melatonin secretion. T treatment decrease d melatonin secretion to normal levels. The results suggest that in Gn RH-deficient male patients, sex steroids, rather than LH, modulate pin eal melatonin in a reverse fashion.