Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty

Abstract

The aim of this retrospective study was to analyze the factors which affected the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP) who had been treated with the same therapy protocol (Decapeptyl Depot, 60 mg/kg i.m. every 28 days) for at least 2 years (since 7.0 Ϯ 1.3 (S.D.) years of age) and followed until puberty was completed and FH was reached.During the entire treatment period we observed: (a) a decrease of height standard deviation scores (SDS) (from 1.5 Ϯ 1.7 to 0.9 Ϯ 1.3 SDS, P < 0.01); (b) a striking deceleration of bone age (BA), revealed by the subnormal DBA:Dchronological age (CA) ratio (0.2 Ϯ 0.1); (c) an increase of predicted adult height (from 155.6 Ϯ 7.0 to 160.7 Ϯ 6.7 cm, P < 0.0005). Treatment interruption was followed by an important catch-down growth, with an FH (158.4 Ϯ 5.8 cm) lower (P < 0.025) than that predicted at the end of therapy. However, FH fell within the population norm and the target range in respectively 87.3 and 90% of the patients. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a BA of 12.0-12.5 years. At stepwise regression analysis, FH in the whole study population was positively affected by the following independent factors: (a) height at the end of therapy (F = 45.45, P < 0.0001); (b) pretreatment height (F = 13.91, P < 0.0005); (c) treatment duration (F = 8.51, P < 0.005); (d) target height (TH) (F = 7.70, P < 0.01).We conclude that: (i) most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; (ii) the height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; (iii) the most favorable height prognosis with respect to TH is generally observed in the subjects with the tallest height at the end of treatment and the lowest BA2:CA2 ratio, due to the important deterioration of height prognosis which frequently follows therapy interruption; (iv) FH is also significantly conditioned by both TH and treatment duration; (v) in order to strengthen the weak therapeutic effect of GnRH agonists in CTPP this treatment should be started as early as possible and discontinued at a BA of 12.0-12.5 years.

MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty

“…The great majority of patients reached an adult height consistent with the TH (13,14,15,17,18,19,20,21,22,23,24,25), a minority of them did not reach the TH (19,26), and a very small portion of patients remained shorter than the predicted height before treatment (13,27). Discordant results were obtained when comparing the efficacy of treatment in females and males.…”

“…Elevated height (or height SDS) before (16,17,19,20,24,30) and at the withdrawal of treatment (12,16,17,19,20,25,30), as well as high TH (or TH-SDS) (17,20,21,23,30), has also been positively associated with adult height, supporting the primary influence of genetic factors in the determination of adult height even in patients treated with GnRHa (20).…”

“…Few studies (12,26) showed no correlation between HG and age at puberty onset or initiation of treatment, suggesting that girls with late onset CPP benefit from treatment similarly to girls with earlier pubertal onset (12). A longer treatment duration appears to be a positive outcome predictor in the majority (19,20,21,24,30), although not all (15,23), of the studies, together with a short interval between pubertal onset and the start of treatment (24,30), a great growth spurt after the end of treatment (12), low pre-treatment estradiol levels (30), and advanced BA at the start of treatment (14,18,19,20,21,25). The impact of advanced BA at the start of treatment on adult height was not documented in the study by Brito et al (30), whereas Carel et al (12) found a negative association between the BA/statural age ratio at the onset of treatment and adult height suggesting that treatment is not capable of restoring a full adult height potential if started after an irreversible advancement of BA.…”

“…5 years (15,22)) and of treatment (i.e. 6 years (18,20,21,23,24,25)) are associated with a taller adult stature. In a study by Klein et al (24) performed in 98 patients (F:MZ80:18) treated with histrelin or deslorelin, the average adult height and HG (14.5G9.9 cm vs 6.8G6.9 cm; P!0.001) were greater in girls with puberty onset !6 years of age than those with onset of puberty between 6 and 8 years of age.…”

“…Indeed, the tallest heights were achieved by patients who stopped treatment at a BA of 12-12.5 years (20) or even !11.5 years (27), whereas continuing treatment after a BA R13 years negatively impacted on statural growth (20).…”