title: Long-term GnRH-agonist treatment does not postpone central development of the GnRH pule generator in girls with idiopathic precocious puberty.
abstract: Gonadotropin and estradiol secretion were studied in two groups of female patients with idiopathic central precocious puberty, at diagnosis (group 1, age 4.8-8.7 yr) and during recovery after long-term treatment with a GnRH agonist (group 2, age 6.5-9.4 yr). The protocol included 24-h sampling of blood at 10-min intervals just before GnRH-agonist treatment (group 1, n = 7), and at 4 and 10 months after discontinuation of treatment (group 2, n = 8). LH was estimated at 10-min intervals, and FSH and estradiol were estimated at 1-h intervals for 6-h periods during the day (wake) and during the night (sleep). In group 2, height was measured in the follow-up at 4 and at 10 months. In group 1, all the girls showed a pulsatile LH secretion with a clear wake-sleep difference in mean LH and LH pulse amplitude: mean LH daytime levels were 1.33 IU/L (range 0.57-7.34 IU/L) vs. nighttime levels of 3.12 IU/L (range 2.35-5.19 IU/L) (P < 0.05). Mean LH pulse amplitudes were 1.39 IU/L (range 0.35-1.76 IU/L) at daytime and 3.85 IU/L (range 1.10-12.37 IU/L) at night (P < 0.05). In group 2, all girls showed pulsatile LH patterns after 4 months as well as after 10 months. At both sampling periods, no wake sleep differences in LH pulse frequency, mean LH levels, or LH pulse amplitude were observed. Mean daytime LH levels increased from 1.66 IU/L (range 0.67-3.29 IU/L) at 4 months to 3.04 IU/L (range 0.73-5.59 IU/L) at 10 months, after therapy (P < 0.05). The number of LH pulses were not different at 4 and at 10 months. The mean LH pulse amplitude increased from 1.68 IU/L (range 0.54-2.04 IU/L) to 2.79 IU/L (range 1.01-3.41 IU/L), comparing 4 months with 10 months (P < 0.05) at daytime. The mean FSH level increased from 1.0 IU/L (range 0.5-2.1 IU/L) at discontinuation of treatment to 4.29 IU/L (range 3.15-5.12 IU/L) at 4 months (P < 0.01) and to 4.49 IU/L (range 2.72-6.50 IU/L) at 10 months (daytime = NS). The estradiol levels increased from less than 37-51 pmol/L at the end of treatment to 77.5 pmol/L (range < 37.0-102.4 pmol/L) and 96.8 pmol/L (range 61.8-169.8 pmol/L) (daytime) at 4 and 10 months, respectively (P < 0.05). Menarche occurred in five of the eight girls within 13 months after treatment. No pubertal growth spurt was observed after treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Schroor
authors.forename: M M
authors.initials: MM
authors.lastname: Van Weissenbruch
authors.forename: H A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
mesh_terms: D001827:Body Height / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000096:biosynthesis*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008572:Menarche / Q000187:drug effects; D010053:Ovary / Q000000981:diagnostic imaging; D010060:Ovulation / Q000187:drug effects; D011627:Puberty / Q000187:drug effects; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D011673:Pulsatile Flow; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone