Gonadotropin-Suppressive Therapy in Girls with Early and Fast Puberty Affects the Pace of Puberty but Not Total Pubertal Growth or Final Height

Abstract

Early and fast puberty (EFP) in girls, defined as pubertal onset at age 8-9 yr, with an accelerated course, may cause compromised final height (FHt) and psychosocial distress. Treatment with a gonadotropin-suppressive agent is controversial, because the improvement in FHt is equivocal and there may be risk of obesity. We analyzed the data of 126 girls with EFP: 63 treated with GnRH analog (GnRHA) since Tanner stage 3, for 2-4 yr; and 63 untreated. Age at onset of puberty; accelerated time of transition from Tanner stage 2 to 3 (<1.3 yr); and clinical, hormonal and sonographic findings were similar in the 2 groups. The girls given GnRHA treatment had a significantly prolonged pubertal course, compared with the accelerated course in the untreated girls (4.7 +/- 0.4 vs. 2.45 +/- 0.4 yr, P < 0.001). After therapy, they reached Tanner stages 4 and 5 and FHt at a significantly older age than the untreated group (P < 0.001), and their menarche was delayed (12.8 +/- 0.6 vs. 10.8 +/- 0.5 yr, P < 0.001). However, the different pace of puberty in the 2 groups did not change the total pubertal growth and the bone maturation rate. The Ht gain from Tanner stage 3 to 4 (10.4 +/- 2.7 vs. 11.2 +/- 3.1 cm) and from Tanner stage 4 to FHt (8.2 +/- 2.7 vs. 8.8 +/- 3.6 cm) was similar in the treated and untreated girls, as were absolute Ht and bone age at each pubertal stage. The weight gain of the treated girls was more pronounced during treatment (P = 0.0016), but it was arrested after discontinuation of therapy; and by the time FHt was reached, the body mass index was similar in the 2 groups. The treated and untreated girls achieved a similar mean FHt, which was not significantly different from their respective mean target Ht (THt). Individual analysis revealed that 70% of the treated girls and 67% of the untreated girls attained their THt range (THt +/- 0.5 SD) or surpassed it. In conclusion, treatment with GnRHA affected only the pace of EFP. The similar Ht gain and bone maturation rate at each pubertal stage in the treated and untreated girls may suggest that the total pubertal growth is not dependent on pubertal duration and pace and is probably determined already at the onset of the normal pubertal development. The treatment did not compromise the FHt and did not cause long-lasting obesity. Therefore, GnRHA therapy may be suggested for use in girls who have psychosocial difficulties in coping with EFP.

Central precocious puberty: revisiting the diagnosis and therapeutic management

“…Conversely, CPP diagnosed after the age of 6 yr had reduced post treatment height gain and compromised final height, probably due to pre treatment intrinsic changes in the growth plate according Lazar and cols. (24,47). In a Brazilian study involving 45 girls, we found no significant association between chronological age at the start of therapy and posttreatment linear growth (42).…”

“…In fact, the main factors determining normal final height in girls with CPP treated with depot GnRHa were shorter interval between the onset of puberty and onset of therapy, higher height SDS at the onset and end of therapy, and target height (42). Finally, no benefits on final height was demonstrated in those girls with early or fast puberty, although benefits on psychosocial profile and in delay menarche should be considered (24,44,47). Transitional changes in body composition and bone mass may occur without consequences in adulthood (44,47,59).…”

“…ment of secondary sexual characteristics between the ages of 8 and 9 years in girls and 9 and 10 years in boys) (23,24). In boys, testicular development is often indicative of activation of the HPG axis, whereas in peripheral puberty, penile growth occurs without concomitant testicular development, or the size of the testis is disproportional to the virilization of the genitalia.…”

“…There is no consensus about the recommendation of pubertal arrest exclusively for psychosocial reasons (behavioral disorders, emotional immaturity, mental retardation, seizures) (44). In early and fast puberty, pubertal arrest may be beneficial (24,47).…”

Can we increase adolescent growth?

“…In addition, other studies in children with 'premature' or 'early' puberty and decreased predicted height have made similar observations, i.e. that short treatments with GnRH agonists led to no or clinically insignificant adult height gains (19,22,23). This is reminiscent of the increased adult height of patients with hypogonadism, only if untreated to the age of 20 years (24).…”