Aromatase inhibitors (AIs), blockers of estrogen biosynthesis, delay bone maturation and therefore are used increasingly to promote growth in children and adolescents with growth disorders. The effects of treatment on skeletal health are largely unknown. Since estrogen deficiency is associated with various detrimental skeletal effects, we evaluated in this cross-sectional posttreatment study vertebral body morphology, dimensions and endplates, and intervertebral disks by the use of magnetic resonance imaging (MRI) in two cohorts of males previously treated with the AI letrozole or placebo. Males with idiopathic short stature received treatment with letrozole or placebo for 2 years during prepuberty or early puberty; males with constitutional delay of puberty received letrozole or placebo in combination with low-dose testosterone for 1 year during early or midpuberty. In males with idiopathic short stature, mild vertebral body deformities were found in 5 of 11 (45%) letrozole-treated subjects, whereas in the placebo group no deformities were detected ( p ¼ .01). In the cohort of males with constitutional delay of puberty, a high prevalence of endplate and intervertebral disk abnormalities was observed in both the letrozole-and the placebo-treated groups. We conclude that AI therapy during prepuberty or early puberty may predispose to vertebral deformities, which probably reflect impaired vertebral body growth rather than impaired bone quality and compression fractures. If AIs are used in growth indications, follow-up of vertebral morphology is indicated. ß
Testosterone (T)-substitution therapy is widely used in adult patients with Klinefelter syndrome (KS) to prevent symptoms and sequels of androgen deficiency, but it is currently unknown if adolescent boys with KS benefit from early T therapy. To evaluate the optimal age to start T substitution, we searched for signs of androgen deficiency in pubertal boys with KS. 14 nonmosaic 47,XXY boys, aged 10 -13.9 y, were followed up for 4 -37 mo with staging of puberty and frequent reproductive hormone measurements. Furthermore, indices reflecting androgen action (serum SHBG, leptin, and prostate-specific antigen (PSA) levels) were studied. Both onset and progression of puberty according to Tanner stages were normal in boys with KS. Consistently, serum T concentrations increased as expected and remained normal throughout follow-up. Changes in the indices of androgen action (decreases in serum SHBG and leptin, and increase in serum PSA concentrations) occurred normally, except that average leptin levels were higher in the boys with KS (KS boys 11.8 Ϯ 7.0 g/L; controls 7.6 Ϯ 4.7 g/L; p ϭ 0.033). Despite normal T concentrations, the KS boys displayed from the age of 13 y elevated serum FSH and LH levels, and exaggerated gonadotropin responses to gonadotropin-releasing hormone. These data do not demonstrate an unequivocal androgen deficiency in adolescent boys with KS that would necessitate androgen supplementation therapy during early puberty.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.