Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Abstract

Objective: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. Design and methods: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixtyeight women (Pl, nZ23; Ox 0.03, nZ27; and Ox 0.06, nZ18) participated in the double-blind followup study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. Results: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2 G4.9 cm, Ox 0.06 9.7G4.4 cm vs Pl 8.0G4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. Conclusion: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe.European Journal of Endocrinology 168 91-99

Safety and Efficacy of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome: Evidence from Recent Studies and Recommendations for Use

“…Three girls who had received Ox still had objective clitoromegaly. In addition, the dose-dependent effect of Ox on lowering voice frequency, which was reported in the pediatric Dutch study [10], was also seen in the follow-up study [11]. However, only a few [7 of the 43 (16%) Ox-treated versus 2 of the 23 (9%) Pl-treated] patients had developed a voice frequency <-2 SDS; in most instances the voice frequency remained within the normal range.…”

“…This follow-up study showed that even after an average period of 8.7 years, the number of girls who still subjectively experienced virilization was higher in the group that had received Ox compared to Pl [11]. There was also a trend towards a higher Ferriman-Gallwey hirsutism score with Ox (though the score was subclinical for most girls).…”

“…However, only a few [7 of the 43 (16%) Ox-treated versus 2 of the 23 (9%) Pl-treated] patients had developed a voice frequency <-2 SDS; in most instances the voice frequency remained within the normal range. The percentage of patients reporting subjective voice deepening was similar between the GH+Ox and GH+Pl groups [11]. …”

“…In the Dutch follow-up study, about 50% of the women had experienced their breast development as delayed, while in 24% the delay of breast development was accompanied by negative emotions or unhappy feelings [11]. In line with expectations based on previous observations [13], Ox therapy was associated with delayed breast development in the US study as well as in the Dutch studies [7,4] while this parameter was not monitored in the UK study [8].…”

“…However, the Dutch follow-up study showed no difference in the subjective experience of delay in breast development during puberty and adolescence between the treatment groups. In addition, the effect of Ox on breast development was transient since final breast size, measured as subtraction of the smallest chest circumference (under the breasts) from the widest chest circumference (at the level of the nipples) with the patient in supine position and Tanner breast stage, was similar in the Ox and Pl groups [11]. …”