Long-term GnRH-agonist treatment does not postpone central development of the GnRH pusle generator in girls with idiopathic precocious puberty

Author(s): Vanweissenbruch, M. M., Delemarrevandewaal, H. A.

Journal/Book: J Clin Endocrinol Metab. 1995; 80: 4350 East West Highway, Suite 500, Bethesda, MD 20814-4110. Endocrine Soc. 1696-1701.

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 dear 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) us. 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/Z) (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. Mean height standard deviation score for calender age decreased from 1.37 (range 0.44-2.46) at the end of therapy to 1.00 (0.05-1.96) 10 months after treatment (P < 0.01). The mean height was 159.1 cm (range 150.1-163.0 cm) at discontinuation of therapy and increased to 163.0 cm (range 158.0-167.5 cm) 10 months after treatment. In conclusion, in girls with central precocious puberty, 24-h LH measurements at diagnosis reveal pulsatile secretion patterns with a distinct wake-sleep difference in LH amplitude. After GnRH-agonist therapy in girls with central precocious puberty, the day-night rhythm disappears. The recovery of LH pulsatile secretion is characterized by an increase in LH pulse amplitude only, which is in contrast to normal puberty during which LH pulse frequency increases as well. LH, FSH, and estradiol levels soon reach a late pubertal state. On the basis of these data, we infer that maturation of the GnRH pulse generator progresses under GnRH-agonist treatment and will not be postponed.

Note: Article HA Delemarrevandewaal, Free Univ Amsterdam Hosp, Dept Pediat, POB 7057, 1007 MB Amsterdam, Netherlands

Keyword(s): HORMONE-RELEASING HORMONE; LUTEINIZING-HORMONE; SOMATIC GROWTH; ACTING ANALOG; LHRH AGONIST; ADULT HEIGHT; THERAPY; MATURATION; CHILDREN; WOMEN

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