Treatment of delayed male puberty: efficacy of aromatase inhibition.
We hypothesized that inhibition of estrogen synthesis would delay maturation of the growth plates and ultimately result in increased adult height in boys with delayed puberty. We conducted a randomized, double-blind, placebo-controlled study in which we treated boys with constitutional delay of puberty with testosterone plus placebo (testosterone-placebo) or with testosterone plus letrozole (testosterone-letrozole). Letrozole effectively inhibited estrogen synthesis: 17beta-estradiol concentrations increased in the testosterone-placebo group, but in the testosterone-letrozole group, no such increase was observed until letrozole treatment was discontinued. After 1.5 years, bone age had advanced by 1.7 +/- 0.3 years in the testosterone-placebo group, but by only 0.9 +/- 0.2 years in the testosterone-letrozole group (p = 0.02). Predicted adult height did not change significantly in the testosterone-placebo group, whereas in the testosterone-letrozole group the increase was 5.1 +/- 1.2 cm (p = 0.004). Our findings suggest that, if estrogen 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
L
L
University of Helsinki, Hospital for Children and Adolescents, Finland. leo.dunkel@hus.fi
Wickman
S
S
D000293:Adolescent; D047072:Aromatase Inhibitors; D001827:Body Height / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005544:Forecasting; D012739:Gonadal Steroid Hormones / Q000627:therapeutic use; D006128:Growth; D006728:Hormones / Q000097:blood; D006801:Humans; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D011628:Puberty, Delayed / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013737:Testis / Q000187:drug effects / Q000254:growth & development; D013739:Testosterone / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D012739:Gonadal Steroid Hormones; D006728:Hormones; D009570:Nitriles; D014230:Triazoles; D013739:Testosterone; D000077289:Letrozole