Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration

J Clin Endocrinol Metab. 2015 Jun;100(6):2254-60. doi: 10.1210/jc.2015-1669. Epub 2015 Apr 15.


Objective: To determine dose-dependent effects of T administration on voice changes in women with low T levels.

Methods: Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3, 6.25, 12.5, or 25 mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics.

Results: Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P < .05); these changes in pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed.

Conclusion: Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice.

Trial registration: NCT00494208.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage
  • Estrogen Replacement Therapy
  • Female
  • Humans
  • Hysterectomy
  • Menopause / blood
  • Menopause / drug effects
  • Middle Aged
  • Ovariectomy
  • Sound Spectrography
  • Testosterone / administration & dosage*
  • Voice / drug effects*
  • Voice / physiology*
  • Voice Disorders / diagnosis
  • Voice Disorders / drug therapy


  • Testosterone
  • Estradiol

Associated data