Induction of puberty in boys with delayed adolescence by methandrostenolone.

Abstract

Methandrostenolone administration at a daily dose of 0.03 mg/kg for 3 months was successful in inducing puberty in 9 boys (aged 14 6/12±6/12 years, m±SD) with delayed puberty and studied in the prepubertal stage. One year after initiation of treatment they reached a mid-pubertal stage (testicular volume m±SD 6±2 ml and pubic hair development Tanner stage 3–4). At the same time growth velocity accelerated from 5.3±1.5 to 8.5±3.4 cm/yr and bone age advanced from 10 9/12±9/12 to 13±6/12 years (m±SD). During treatment there was suppression of basal plasma LH and FSH (m±SD) from 1.3±0.3 to 0.5±0.2 mIU/ml (P<0.001) and from 1.4±0.8 to 0.8±0.3 mIU/ml (P<0.05) respectively, and of the LH response to LRH (50 mcg/m2, i.v.) from 5.2±1.0 to 1.9±0.6 mIU/ml (P<0.001). After discontinuation of methandrostenolone there was a significant and prolonged elevation of the basal plasma LH (2.0±0.4 mIU/ml) and testosterone levels (from 24±7.7 to 175.6±67.5 ng/dl, P<0.01) and an enhanced LH response to LRH (8.3±2.4 mIU/ml, P<0.05), compared to the pre-treatment levels. Eleven prepubertal boys with constitutional short stature (aged 9 3/12±9/12 years, m±SD) maintained their prepubertal state one year following the same therapeutic regime with methandrostenolone. No significant changes in the basal plasma testosterone and gonadotropin levels, or the responses to LRH, were noted in this group. During treatment a significant increase in growth velocity was noted (from 4.1±1.7 to 9.7±3.0 cm/year, P<0.02), with a subsequent decrease to 5.4±2.9 cm/year (m±SD) which was not significantly different to the pre-treatment value. Bone age advanced from 6 3/12±1 before treatment to 8±1 6/12 years 12 months following methandrostenolone administration. It is concluded that methandrostenolone can induce puberty in boys with delayed puberty if administered in the prepubertal stage, but not in younger prepubertal boys with short stature. The concomitant changes in the basal plasma testosterone and gonadotropin levels, and their response to LRH stimulation, which were found in the boys with delayed puberty indicate that a certain degree of maturation of the hypothalamic pituitary gonadal axis is probably needed to permit induction of puberty by methandrostenolone. The effect of this drug is due in part to its androgenic potency and probably also to its modulation of negative feedback in the hypothalamic-pituitary-gonadal axis, causing a rebound phenomenon following brief suppression.