The effect of oxandrolone on voice frequency in growth hormone-treated girls with Turner syndrome.
OBJECTIVE
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.


METHODS
A multicenter, randomized, placebo (Pl)-controlled, double-blind study was conducted.


METHODS
One hundred thirty-three patients were included and treated with GH (1.33 mg/m2/d) from baseline, combined with Pl or Ox in a low (0.03 mg/kg/d) or conventional (0.06 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 GH+Ox/Pl, voices were recorded and questionnaires were completed.


RESULTS
At start, mean (±standard deviation [SD]) voice frequency SD score (SDS) was high for age (1.0±1.2, P<0.001) but normal for height. Compared with GH+Pl, voices tended to lower on GH+Ox 0.03 (P=0.09) and significantly lowered on GH+Ox 0.06 (P=0.007). At the last measurement, voice frequency SDS was still relatively high in GH+Pl group (0.6±0.7, P=0.002) but similar to healthy girls in both GH+Ox groups. Voice frequency became lower than -2 SDS in one patient (3%) on GH+Ox 0.03 and three patients (11%) on GH+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 GH+Ox 0.06 mg/kg/d.
Menke
Leonie A
LA
Dutch Growth Research Foundation, Rotterdam, The Netherlands. l.a.menke@lumc.nl
Sas
Theo C J
TC
van Koningsbrugge
Sophie H L
SH
de Ridder
Maria A J
MA
Zandwijken
Gladys R J
GR
Boersma
Bart
B
Dejonckere
Philippe H
PH
de Muinck Keizer-Schrama
Sabine M P F
SM
Otten
Barto J
BJ
Wit
Jan M
JM
D000293:Adolescent; D045930:Anabolic Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000188:drug therapy; D020249:Hormone Replacement Therapy / Q000379:methods; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D010074:Oxandrolone / Q000008:administration & dosage*; D014424:Turner Syndrome / Q000188:drug therapy*; D014833:Voice Quality / Q000187:drug effects*
D045930:Anabolic Agents; D004967:Estrogens; D019382:Human Growth Hormone; D010074:Oxandrolone