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

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

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.

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.

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.