Postnatal Effects of Sex Hormones on Click-Evoked Otoacoustic Emissions: A Study of Adolescents with Gender Dysphoria

Abstract

Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds, generated by the inner ear in response to click-stimuli. A sex difference in emission strength is observed in neonates and adults, with weaker CEOAE amplitudes in males. These differences are assumed to originate from testosterone influences during prenatal male sexual differentiation and to remain stable throughout life. However, recent studies suggested activational, postnatal effects of sex hormones on CEOAEs. Adolescents diagnosed with gender dysphoria (GD) may receive gonadotropin-releasing hormone analogs (GnRHa) in order to suppress endogenous sex hormones and, therefore, pubertal maturation, followed by cross-sex hormone (CSH) treatment. Using a cross-sectional design, we examined whether hormonal interventions in adolescents diagnosed with GD (62 trans boys, assigned female at birth, self-identifying as male; 43 trans girls, assigned male at birth, self-identifying as female), affected their CEOAEs compared to age-and sex-matched controls (44 boys, 37 girls). Sex-typical differences in CEOAE amplitude were observed among cisgender controls and treatment-naïve trans boys but not in other groups with GD. Treatment-naïve trans girls tended to have more female-typical CEOAEs, suggesting hypomasculinized early sexual differentiation, in support of a prominent hypothesis on the etiology of GD. In line with the predicted suppressive effects of androgens, trans boys receiving CSH treatment, i.e., testosterone plus GnRHa, showed significantly weaker right-ear CEOAEs compared with control girls. A similar trend was seen in trans boys treated with GnRHa only. Unexpectedly, trans girls showed CEOAE masculinization with addition of estradiol. Our findings show that CEOAEs may not be used as an unequivocal measure of prenatal androgen exposure as they can be modulated postnatally by sex hormones, in the form of hormonal treatment.

Interventions to suppress puberty in adolescents experiencing gender dysphoria or incongruence: a systematic review

“…Studies were published from 2006 to 2022 with the majority published in 2020–2022 (n=29). Studies were conducted in the Netherlands (n=17),23–39 the US (n=15),40–54 the UK (n=6),55–60 Canada (n=4),61–64 three in Belgium65–67 and Israel68–70 and one in Brazil71 and Germany72 (online supplemental table S2).…”

“…The 50 studies included 11 cohorts comparing adolescents experiencing gender dysphoria/incongruence receiving puberty suppression with a comparator,35 39–42 45 49 50 52 56 72 8 cross-sectional with a comparator23 33 37 47 51 53 60 71 and 31 pre-post single group studies 24–32 34 36 38 43 44 46 48 54 55 57–59 61–70. More than half of studies (n=29) used retrospective chart review.…”

The effect of female hormone in otosclerosis. A comparative study and speculation about their effect on the ossicular chain based on the clinical results

“…Therefore women, who have more elastic ligaments, maintain this advantage also by aging. Moreover, the inner ear works better in females than in males thanks to the effect of female hormones since birth [ 28 ] ; this effect persists despite menopause, because there never is a complete inversion of the hormone rate (testosterone > estrogen/progesterone).…”

Sex vs Gender: A Biological Location for Gender, not Sex.

“…Response to one's infant cry and breastfeeding is associated with more significant fMRI activity in some cerebral regions (superior frontal cortex, thalamus, hypothalamus, and amygdala) (Lonstein et al, 2014). Newborn and adult females have greater hearing sensitivity and greater susceptibility to noise exposure at high frequencies (Burke et al, 2020;McFadden, 1998). Lactating mothers perceive noise differently (Lonstein et al, 2014).…”