Abstract
BackgroundStudies investigating the influence of perinatal hormone exposure on sexually differentiated traits would greatly benefit from biomarkers of these early hormone actions. Click-evoked otoacoustic emissions show sex differences that are thought to reflect differences in early androgen exposure. Women with complete androgen insensitivity syndrome (CAIS), who lack androgen action in the presence of XY-chromosomes, enabled us to study the effect of complete androgen inaction. The main goal was to investigate a possible link between click-evoked otoacoustic emissions and effective androgen exposure and, thus, whether this can be used as a biomarker. In addition, we aimed to replicate the only previous 2nd vs 4th digit-ratio study in women with CAIS, because despite the widely expressed criticisms of the validity of this measure as a biomarker for prenatal androgen exposure, it still is used for this purpose.MethodsClick-evoked otoacoustic emissions and digit ratios from women with CAIS were compared to those from control men and women.ResultsThe typical sex differences in click-evoked otoacoustic emissions and digit ratios were replicated in the control groups. Women with CAIS showed a tendency towards feminine, i.e., larger, click-evoked otoacoustic emission amplitudes in the right ear, and a significant female-typical, i.e., larger, digit ratio in the right hand. Although these results are consistent with androgen-dependent development of male-typical click-evoked otoacoustic emission amplitude and 2nd to 4th digit ratios, the within-group variability of these two measures was not reduced in women with CAIS compared with control women.ConclusionsIn line with previous studies, our findings in CAIS women suggest that additional, non-androgenic, factors mediate male-typical sexual differentiation of digit ratios and click-evoked otoacoustic emissions. Consequently, use of these measures in adults as retrospective markers of early androgen exposure is not recommended.
Highlights
Studies investigating the influence of perinatal hormone exposure on sexually differentiated traits would greatly benefit from biomarkers of these early hormone actions
The present observation that mean right ear Click-evoked otoacoustic emission (CEOAE) amplitudes as well as mean right hand 2D:4D digit ratios in complete androgen insensitivity syndrome (CAIS) women resembled values obtained in control women as opposed to control men point to a possible contribution of fetal androgen action to male-typical development of these two variables
Our finding that the variability in both measures was similar across all three groups argues against the notion that differences in CEOAE amplitudes and digit ratios solely reflect differences in fetal androgen exposure, or in androgen exposure later in life
Summary
Studies investigating the influence of perinatal hormone exposure on sexually differentiated traits would greatly benefit from biomarkers of these early hormone actions. I.e., organizational, effects of prenatal androgen exposure in humans, a prospective study design including direct measurements of fetal testosterone levels, preferably at several gestational time points, would be ideal. This type of study design is expensive, time consuming and, above all, incurs fetal risks and is unethical. Previous studies showed that women had more and stronger SOAEs and larger CEOAE amplitudes than men ([6, 7]; for review see [2]) These sex differences were present in adults and were found in neonates and appeared to remain reasonably constant throughout life [8,9,10,11,12]
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