Impact of early postnatal androgen exposure on voice development

PLoS One. 2012;7(12):e50242. doi: 10.1371/journal.pone.0050242. Epub 2012 Dec 19.

Abstract

Background: The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood.

Methods: The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels.

Results: Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz.

Conclusions: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms / drug therapy
  • Adrenal Cortex Neoplasms / physiopathology
  • Adult
  • Androgens / pharmacology*
  • Androgens / therapeutic use
  • Dose-Response Relationship, Drug
  • Environmental Exposure*
  • Female
  • Humans
  • Time Factors
  • Voice / drug effects*
  • Voice / physiology
  • Young Adult

Substances

  • Androgens

Grants and funding

This project was funded by grants from the Brazilian State of Paraná Secretary of Science, Technology and Higher Education (SETI, 2008), the Brazilian National Council for Research and Development (CNPq, 2009), (Curitiba, Brazil), the Raul Carneiro Hospital Association for Childhood Protection (AHPIRC), and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SETI funded equipments and transportation of all participants; AHPIRC funded all laryngological exams; CNPq and ALSAC provided additional support for the ACT project (materials, statistical analysis and scholarship).