Gender-related differences of hyaluronic acid distribution in the human vocal fold

Objective: To quantify the distribution of hyaluronic acid (HA) within the normal human vocal fold and evaluate gender- and age-related differences. Study Design: Prospective, cross-sectional study by age and gender groups using cadaveric vocal folds to study hyaluronic acid differences. Methods:Twenty-five vocal fold halves obtained at autopsy were evaluated from nine adult male (age range, 34-52 y), seven adult female (age range, 21-41 y), four geriatric male (age range, 65-77 y), and five geriatric female (age range 65-82 y) subjects, Midmembranous vocal fold sections were stained for HA using the Muller-Mowry colloidal iron (acid mucopolysaccharide) stain with and without hyaluronidase, Digital imaging software was used to quantify the distribution of HA across the lamina propria at the vocal fold edge from superficial (subepithelial) to deep (vocalis muscle). Results: A significant gender difference (P =.03) was noted in distribution when controlled for age. Combined, male subjects had a relatively constant distribution pattern throughout the depth of lamina propria, Female subjects showed relatively less HA in the first 15% of depth (most superficial) but showed more HA in the deeper 40% to 100% (toward vocalis muscle) than in male subjects. Conclusions: Important clinical implications may be extrapolated from our findings. First, relatively less HA in the most superficial area implies less protection from vibratory trauma and overuse and may explain in part why more female than male patients have phonotrauma to phonotraumatic lesions. Second, evaluating the distribution of HA in the normal human vocal fold allows more direction in our application of HA as a therapeutic lamina propria substitute in patients with voice disorders.