ESPE Abstracts

Objective: The influence of androgens and estrogens on growth is complex, and understanding their relative roles is important for optimizing the treatment of children with various disorders of growth and puberty.

Design: We examined the proportional roles of androgens and estrogens in the regulation of pubertal growth in boys with constitutional delay of growth and puberty (CDGP). The study compared 6-month low-dose intramuscular testosterone (T) treatment (1 mg/kg/month) (n = 14) with peroral letrozole (Lz) treatment (2.5 mg/day) (n = 14) which inhibits conversion of androgens to estrogen.

Patients: Boys with CDGP were recruited to a randomized, controlled, open-label trial between 2013 and 2017 (NCT01797718)¹.

Measurements: The patients were evaluated at 0-, 3-, and 6-month visits, and morning blood samples were drawn. Linear regression models were used for data analyses.

Results: In the T-group, serum testosterone concentration correlated with serum estradiol concentration at the beginning of the study and at 3 months, whereas in the Lz-group the sex steroids correlated only at baseline. Association between serum T level and growth velocity differed between the T- and Lz-groups, as each nmol/l increase in serum T increased growth velocity 2.6 times more in the former group. Serum T was the best predictor of growth velocity in both treatment groups. In the Lz-group, adding serum estradiol to the model significantly improved the growth estimate. Only the boys with serum estradiol above 10 pmol/l had a growth velocity above 8 cm/year.

Conclusions: During puberty promoting treatment with T or aromatase inhibitor Lz, growth response is tightly correlated with serum T level. A threshold level of estrogen appears to be needed for optimal growth rate that corresponds to normal male peak height velocity of puberty. Serum T one week after the injection and serum T and estradiol 3 months after aromatase inhibitor treatment onset can be used as biomarkers for treatment response in terms of growth.

1. Data on primary endpoints, i.e. changes in testicular volume and hormonal markers of puberty have been published before. Varimo T, Huopio H, Kariola L, et al. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: A randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019;3(2): 109-120. doi: S2352-4642(18)30377-8