Androgen Therapy in Constitutional Delay of Growth

Abstract

Background/Aims: Two modalities of androgen therapy prevail in the treatment of constitutional delay of growth (CDG): monthly injections of testosterone or daily tablets of the non-aromatizable oxandrolone. The present study was undertaken to prospectively compare both compounds and dose. Methods: Thirty patients with CDG were the subjects of this study. The protocol required that they all be at age 12–14 years with a bone age delay of more than 2 ‘years’, height less than –2 SDS and growth velocity less than –0.5 SDS. The subjects were at a Tanner stage 1 or 2 and testicular volume were no larger than 4 ml. They were randomly assigned into 3 treatment groups: group 1 patients received monthly injections of 25 mg testosterone propionate-enanthate; group 2 patients received monthly injections of 50 mg testosterone propionate-enanthate; group 3 patients received oral oxandrolone at a weekly dose of 0.7 mg/kg. Treatment was given for a period of 6 months and follow-up commenced 6 months later and yearly thereafter for 2 years. Results: Height velocity and height increased significantly only in groups 2 and 3. Bone age advanced most in group 2. Puberty progressed faster in that group as compared with group 3. The predicted adult height before and 2 years after completion of treatment remained unchanged in the two testosterone groups. It increased significantly in the oxandrolone group from a mean 169.8 cm before therapy to a mean 177.5 cm 2 years after completion of therapy. Peak GH levels were significantly higher on both testosterone 50 mg and oxandrolone, as compared to pretreatment levels. The increment was significantly greater in group 2 as was the increment in serum IGF-1 and IGFBP3. Conclusions: These results imply that 6 months of testosterone injections at a dose of 50 mg, but not 25 mg, is an effective and safe treatment for patients with CDG, with no considerable impact on final height prediction. On the other hand, daily oxandrolone treatment, starting at age 12–14 years, may increase the predicted final adult height.

A Double-Blind, Placebo-Controlled Comparison of Letrozole to Oxandrolone Effects upon Growth and Puberty of Children with Constitutional Delay of Puberty and Idiopathic Short Stature

“…Therefore as a consequence, it caused an insignificant change in PAH, similar to that of placebo. These results are in agreement with some reports [6,7], but not with the claims that oxandrolone increases PAH [4,5]. …”

“…The usual treatment is with physiologic doses of androgen, which accelerate linear growth and onset of pubertal changes [1,2,3]. However, they do not improve predicted adult height (PAH) [2,3,4], which is a problem for those with coincidental predicted short stature. Some studies suggest that oxandrolone, an anabolic non-aromatizable androgen, increases PAH [4,5], while others do not [6,7].…”

“…However, they do not improve predicted adult height (PAH) [2,3,4], which is a problem for those with coincidental predicted short stature. Some studies suggest that oxandrolone, an anabolic non-aromatizable androgen, increases PAH [4,5], while others do not [6,7]. Recently, the combination of testosterone and letrozole, an aromatase inhibitor, has been reported to increase PAH [8,9,10,11,12] and ultimately near-final height [11] in CDGP by interfering with estrogen action on epiphyseal maturation and fusion [13].…”

Androgen Receptor Modulation Does Not Affect Longitudinal Growth of Cultured Fetal Rat Metatarsal Bones

“…It has been used clinically to treat boys with constitutional delay of growth and puberty [4] and girls with Turner syndrome [5]. Many studies have confirmed that oxandrolone induces a short-term increase in growth rate in boys with constitutional delay of growth and puberty [6,7,8,9]; an increase that is sustained even after the treatment has been completed [8]. More controversial is the effect of oxandrolone on adult height in these boys.…”

“…More controversial is the effect of oxandrolone on adult height in these boys. Some studies show no effect on adult height [8], while others suggest that there might be a positive effect also on adult height in boys who start the treatment before puberty [6, 9]. In girls with Turner syndrome, oxandrolone has been used in combination with growth hormone (GH) therapy and has been shown to increase both growth rate and adult height when given alone or in combination with GH [5].…”