title: Two-year results of treatment with depot leuprolide acetate for central precocious puberty.
abstract: We report results from 2 years of therapy with the long-acting form of the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate, which was previously reported in short-term trials to be efficacious in the treatment of central precocious puberty. Thirteen girls and two boys, aged 1.9 to 9.7 years, who satisfied clinical criteria including GnRH-stimulated luteinizing hormone (LH) greater than 10 IU/L (mean radioimmunoassay LH, 29.1 +/- 5.54 IU/L), received depot leuprolide, 6 to 15 mg intramuscularly every 4 weeks. Estradiol (or testosterone), insulin-like growth factor I, and GnRH-stimulated gonadotropins were obtained at baseline, at 2 months, and at 6-month intervals with bone age determinations. Pubertal progression ceased in all patients, and menses did not occur. Mean increase in height during therapy was 5.77 +/- 2.0 cm/yr. Predicted adult height increased over baseline by 5.52 +/- 1.16 cm at 18 months. Mean estradiol values in the girls declined from 3.3 +/- 0.6 to 0.60 +/- 0.03 ng/dl, with no overlap of baseline and treatment values. The mean basal LH value was unchanged by therapy; mean basal and peak LH values for all follow-up GnRH stimulation tests were 4.05 +/- 0.57 and 4.95 +/- 0.70 IU/L, respectively. Basal and peak follicle-stimulating hormone (FSH) values were suppressed from 4.10 +/- 0.62 and 10.06 +/- 1.34 IU/L, respectively, to generally undetectable levels (< 1). Comparison with untreated control patients suggested that basal LH did not completely return to prepubertal levels, whereas FSH levels were suppressed below prepubertal levels. Estradiol, FSH, and LH levels reached their nadir by 2 months; in contrast, mean serum levels of insulin-like growth factor I progressively declined from +0.57 +/- 0.19 SD score to -0.06 +/- 0.22 SD score at 24 months. Two girls were withdrawn from the study because of reactions at injection sites, with apparent sterile abscess formation in one patient. This study provides evidence that (1) long-term treatment with depot leuprolide is characterized by immediate and sustained laboratory and clinical suppression, (2) GnRH-stimulated LH and random FSH and estradiol concentrations are useful laboratory measures of efficacy, and (3) the progressive increase in predicted adult height is temporally associated with decreased serum levels of insulin-like growth factor I and striking deceleration of bone age advancement.
authors.affiliation: Department of Pediatrics, Stanford University Medical Center, California.
authors.forename: E K
authors.initials: EK
authors.lastname: Neely
authors.forename: R L
authors.initials: RL
authors.lastname: Hintz
authors.forename: B
authors.initials: B
authors.lastname: Parker
authors.forename: L K
authors.initials: LK
authors.lastname: Bachrach
authors.forename: P
authors.initials: P
authors.lastname: Cohen
authors.forename: R
authors.initials: R
authors.lastname: Olney
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
mesh_terms: D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D004341:Drug Evaluation; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood; D006128:Growth / Q000187:drug effects; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D016729:Leuprolide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011629:Puberty, Precocious / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D012739:Gonadal Steroid Hormones; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide