Novel treatment of delayed male puberty with aromatase inhibitors.
BACKGROUND
As the evidence for the role of oestrogens in epiphyseal closure appears unequivocal, we hypothesized that boys with constitutional delay of puberty would attain greater adult height if oestrogen action was suppressed.


METHODS
We conducted a randomized, double-blind, placebo-controlled study in which we treated boys with constitutional delay of puberty with testosterone plus placebo or testosterone plus a potent fourth-generation aromatase inhibitor, letrozole.


RESULTS
Letrozole effectively inhibited oestrogen synthesis. The 17beta-oestradiol concentrations increased in the untreated group and in the testosterone/placebo-treated group, but in the testosterone/letrozole-treated group no such increase was observed until letrozole treatment was discontinued. Testosterone concentrations were threefold higher in the testosterone/letrozole-treated group than in the other groups. Within 18 months, bone age had advanced by 1.1 +/- 0.3 years in the untreated group and by 1.7 +/- 0.3 years in the testosterone/placebo-treated group, but only by 0.9 +/- 0.2 years in the testosterone/letrozole-treated group (p = 0.02 between treatment groups). Predicted adult height did not change significantly in the untreated group and in the testosterone/placebo-treated group, whereas in the testosterone/letrozole-treated group the increase was 5.1 +/- 1.2 cm (p = 0.004).


CONCLUSIONS
Our findings suggest that, if oestrogen action is inhibited in growing adolescents, adult height will increase. This observation provides a rationale for studies aimed at delaying bone maturation in several growth disorders.
Dunkel
Leo
L
University of Helsinki, Hospital for Children and Adolescents, Finland. leo.dunkel@hus.fi
Wickman
Sanna
S
D000293:Adolescent; D000704:Analysis of Variance; D047072:Aromatase Inhibitors; D015415:Biomarkers / Q000097:blood; D001827:Body Height / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood; D006128:Growth / Q000187:drug effects; D006801:Humans; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011628:Puberty, Delayed / Q000188:drug therapy*; D013739:Testosterone / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D015415:Biomarkers; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D013739:Testosterone; D004958:Estradiol; D000077289:Letrozole