Prospective study confirms oxandrolone-associated improvement in height in growth hormone-treated adolescent girls with Turner syndrome

Abstract

Background/aims: 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.

Trial registration: ClinicalTrials.gov NCT00029159.

Fig. 1

Enrollment, randomization and drop-outs from baseline to 2 years and from the beginning of the extension (in gray box) to 4 years.

Fig. 2

a Mean height SDS in GH/Ox and GH/Pl annually from baseline to year 4. b Delta height SDS in GH/Ox and GH/Pl from baseline to years 1–4. c Breast Tanner stage in GH/Ox and GH/Pl from baseline to year 4.

Fig. 3

a Breast development (Tanner stage) by visit in GH/Ox group. Box-and-whiskers plot: top and bottom of box represent 25% and 75%, dark line is median. b Breast development (Tanner stage) by visit in GH/Pl group. c Box-and-whisker plot of breast Tanner at final visit (visit 9) by karyotype and treatment group.