Prospective study confirms oxandrolone-associated improvement in height in growth hormone-treated adolescent girls with Turner syndrome.
OBJECTIVE
Untreated girls with Turner syndrome (TS) have growth failure, and adult height is, on average, 20 cm less than predicted height. Treatment with growth hormone (GH) is now standard of care. The objective of this study was to investigate the benefit of adding oxandrolone (Ox) to GH in a long-term, randomized, placebo (Pl)-controlled prospective trial to near adult height in TS.


METHODS
prospective, randomized, Pl-controlled study: 76 girls with TS (ages 10-14.9 years) were randomized to receive Ox (0.06 mg/kg/day) or Pl in combination with GH (0.35 mg/kg/week, daily) over 2 years. Auxologic data, breast and pubic hair Tanner stages, and hormone and lipid levels were measured. Subjects who chose to continue were followed in a 2-year double-blind extension, also received estrogen therapy (years 3, 4), and had dual-energy X-ray absorptiometry evaluation of bone density (years 3, 4).


RESULTS
at year 4, the change in absolute height and height SDS was greater in the GH/Ox versus GH/Pl group [26.2 ± 6.7 vs. 22.2 ± 5.1 cm, analysis of covariance (ANCOVA) p < 0.001; 1.8 ± 0.9 vs. 1.2 ± 0.7 standard deviation scores, ANCOVA p < 0.001]. Bone mineral density (BMD) of the wrist (0.51 ± 0.17 vs. 0.54 ± 0.05 g/cm(2)) and spine (0.91 ± 0.34 vs. 0.96 ± 0.13 g/cm(2)) in the GH/Ox versus GH/Pl groups was similar after 4 years. Breast development was slower in the GH/Ox versus GH/Pl group [year 4: Tanner stage 2.9 ± 1.3 (Ox) vs. 4.1 ± 1.3 (Pl), p = 0.003], and menarche was approximately 1 year later.


CONCLUSIONS
the addition of Ox to GH at mean age 12.0 ± 1.7 year augmented height gain after 4 years of treatment, slowed breast development and did not affect BMD in girls with TS. Whether initiation of Ox prior to initiation of pubertal development would optimize height gain without impeding breast development will require further study.
Zeger
Martha P D
MP
Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pa. 19107, USA.
Shah
Kavita
K
Kowal
Karen
K
Cutler
Gordon B
GB
Kushner
Harvey
H
Ross
Judith L
JL
D000293:Adolescent; D041923:Adolescent Development / Q000187:drug effects*; D000728:Androgens / Q000009:adverse effects / Q000627:therapeutic use*; D001827:Body Height / Q000187:drug effects*; D015519:Bone Density / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008572:Menarche / Q000187:drug effects; D010074:Oxandrolone / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014424:Turner Syndrome / Q000188:drug therapy* / Q000235:genetics
D000728:Androgens; D004967:Estrogens; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D010074:Oxandrolone