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Serum Androgen Bioactivity in Adolescence: A Longitudinal Study of Boys with Constitutional Delay of Puberty

Biomedicum Helsinki, Institute of Biomedicine/Physiology (T.R., O.A.J.), and Department of Clinical Chemistry (O.A.J.), University of Helsinki, FIN-00014 Helsinki, Finland; and Hospital for Children and Adolescents (T.R., L.D., S.W.), University of Helsinki and Helsinki University Central Hospital, FIN-00029 Helsinki, Finland

Address all correspondence and requests for reprints to: Taneli Raivio, M.D., Ph.D., Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 Helsinki, Finland. E-mail: taneli.raivio{at}helsinki.fi.

We have examined the relationship between serum androgen bioactivity, as measured with a recombinant cell bioassay, and progression of puberty in 14 boys with constitutional delay of puberty. Six boys were followed up without treatment (control group), and eight boys received low-dose (1 mg/kg) testosterone enanthate im for 0–6 months together with an aromatase inhibitor, letrozole, 2.5 mg orally once a day for 0–12 months (treatment group). In the control group, serum androgen bioactivity increased during the course of puberty (P < 0.001). During 0–12 months of the study, the boys in the treatment group had higher androgen bioactivity levels (P < 0.05) and faster rate of pubic hair growth than the control boys (P < 0.05). Overall, the average serum androgen bioactivity during 12 months of follow-up correlated strongly with the concomitant changes in Tanner genital (r_S = 0.89; n = 13; P < 0.005) and pubic hair stages (r_S = 0.79; n = 13; P < 0.01). In conclusion, our results suggest that circulating androgen bioactivity mediates the tempo of pubertal maturation and that the combination of testosterone and letrozole given to boys with constitutional delay of puberty accelerates puberty.

This work was supported by grants from the Medical Research Council (Academy of Finland), National Technology Agency (TEKES), Helsinki University Central Hospital, and Foundation for Pediatric Research, Helsinki, Finland.

Abbreviations: AR, Androgen receptor; DHT, 5-dihydrotestosterone; G, Tanner genital; LBD, ligand-binding domain; P, Tanner pubic hair.

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