The Effect of Oxandrolone on Voice Frequency inآ Growth Hormone-Treated Girls With Turner Syndrome

Objectives/Hypothesis Oxandrolone (Ox) increases height gain but may also cause voice deepening in growth hormone (GH)-treated girls with Turner syndrome (TS). We assessed the effect of Ox on objective and subjective speaking voice frequency in GH-treated girls with TS. Study Design A multicenter, randomized, placebo (Pl)-controlled, double-blind study was conducted. Methods One hundred thirty-three patients were included and treated with GH (1.33آ mg/m2/d) from baseline, combined with Pl or Ox in a low (0.03آ mg/kg/d) or conventional (0.06آ mg/kg/d) dose from the age of 8 years and estrogens from the age of 12 years. Yearly from starting Ox/Pl until 6 months after discontinuing GHآ +آ Ox/Pl, voices were recorded and questionnaires were completed. Results At start, mean (آ±standard deviation [SD]) voice frequency SD score (SDS) was high for age (1.0آ آ±آ 1.2, Pآ <آ 0.001) but normal for height. Compared with GHآ +آ Pl, voices tended to lower on GHآ +آ Ox 0.03 (Pآ =آ 0.09) and significantly lowered on GHآ +آ Ox 0.06 (Pآ =آ 0.007). At the last measurement, voice frequency SDS was still relatively high in GHآ +آ Pl group (0.6آ آ±آ 0.7, Pآ =آ 0.002) but similar to healthy girls in both GHآ +آ Ox groups. Voice frequency became lower than −2 SDS in one patient (3%) on GHآ +آ Ox 0.03 and three patients (11%) on GHآ +آ Ox 0.06. The percentage of patients reporting subjective voice deepening was similar between the dosage groups. Conclusions Untreated girls with TS have relatively high-pitched voices. The addition of Ox to GH decreases voice frequency in a dose-dependent way. Although most voice frequencies remain within the normal range, they may occasionally become lower than −2 SDS, especially on GHآ +آ Ox 0.06آ mg/kg/d.