Final Height in Girls With Central Idiopathic Precocious Puberty Treated With Gonadotropin-Releasing Hormone Analog and Oxandrolone

Abstract

Central precocious puberty (CPP), the onset of sexual development before age 8 in girls, reflects early activation of the hypothalamic-pituitary-gonadal axis and currently is treated with a gonadotropin-releasing hormone analog (GnRHa). One of the goals of such treatment is to slow bone maturation and thereby increase final adult height. Some patients, however, grow at a less than optimal rate and become short-statured as a result. This open-label study was carried out in 20 girls with CPP who experienced marked growth deceleration (height velocity below the 25th centile for age) during GnRHa treatment. All of them continued to receive 3.75 mg Leuprorelina intramuscularly at monthly intervals. Ten girls (group 1) also received, by mouth, 0.06 mg/kg daily of the androgen oxandrolone (Ox). The remaining 10 girls (group 2) continued to receive only the GnRHa. The groups were matched for chronologic age, bone age, the duration of GnRH analog treatment (averaging 5 years), and the degree of growth deceleration. In both groups, plasma concentrations of luteinizing hormone and follicle-stimulating hormone remained suppressed, rising to appropriate levels within 18 months of the time that GnRHa treatment stopped. Menarche occurred an average of 16 and 18 months after treatment stopped in groups 1 and 2, respectively. Bone age progressed regularly in both groups. When GnRHa treatment began, predicted adult height (PAH) in patients in group 1 did not differ significantly from that recorded at the time Ox was added. At the end of combined treatment, PAH was significantly higher than at the time of diagnosis and at the start of GnRHa therapy. Final height significantly exceeded target height in patients in group 1, was similar to the PAH at the end of treatment, and was significantly higher than when GnRHa treatment began. In patients in group 2, PAH at the start of treatment did not differ significantly from that at the time GnRHA therapy ended. Their final height was similar to the PAH at both the beginning of treatment and its end. Target height was not reached and it significantly exceeded final height. The gap between pretreatment PAH and final height in patients in group 1 differed significantly from that in patients in group 2 (7.8 vs -3.8 cm). The same was the case for the difference between final height and target height (4.6 vs -4.2 cm). No adverse effects were noted in either treatment group. Treatment did not alter circulating levels of insulin-like growth factor I. Adding oxandrolone to GnRHa treatment in girls with idiopathic CPP whose growth has markedly decelerated improves final height without causing significant side effects. In the present study, combined treatment permitted the girls to reach a final height greater than the target height. This was not the case for girls who continued to receive only GnRHa whose final height was lower than target height.