Should Skeletal Maturation Be Manipulated for Extra Height Gain?

Abstract

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported.

Gonadotropin-releasing hormone analogue and recombinant human growth hormone treatment for idiopathic central precocious puberty in girls

“…Long-acting GnRHa analogs make the gonadotrophs non-responsive since they require pulsatile stimulation by native GnRH in order to release LH and FSH. Treatment delays skeletal maturation by inhibiting sexual development to allow height catch-up and efficacy has been demonstrated in several studies ( 8 , 15 – 17 ). However, a proportion of children with CPP did not show substantial improvement in final height or experienced growth deceleration that affected adult height outcomes after GnRHa treatment ( 9 , 11 , 18 ).…”

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height

“…The level of evidence of many of these studies, however, was limited due to either small numbers of patients, the lack of a control group or a short follow-up time (32). Furthermore, most studies did not consider the limited accuracy of height prediction in this group of patients.…”

Longitudinal Analysis of Latvian Child Growth: Anthropometric Parameters Dynamics from Birth to Adolescence

“…At this age, boys can grow more than 11 cm per year, and girls can grow more than 9 cm per year. Age at onset and peak of growth spurts are useful reference points for studying the timing and duration of spurts in children [23]. After reaching a peak, the growth rate declines rapidly, indicating the end of the growth cycle near the end of growth, which occurs at about 16-17 years for girls and about 18-19 years for boys in Western countries [23].…”

“…Age at onset and peak of growth spurts are useful reference points for studying the timing and duration of spurts in children [23]. After reaching a peak, the growth rate declines rapidly, indicating the end of the growth cycle near the end of growth, which occurs at about 16-17 years for girls and about 18-19 years for boys in Western countries [23]. Age growth can continue up to twenty years, but height growth will be small (below 1 cm per year) [23].…”

“…After reaching a peak, the growth rate declines rapidly, indicating the end of the growth cycle near the end of growth, which occurs at about 16-17 years for girls and about 18-19 years for boys in Western countries [23]. Age growth can continue up to twenty years, but height growth will be small (below 1 cm per year) [23]. There are large differences between nations, between individuals, and between both sexes in terms of the height reached at each age, the time of accelerated growth, and the age at which the growth ceases [23].…”