Estrogen deficiency and risk of hearing loss in pediatric Turner syndrome

BACKGROUNDEstrogen deficiency and progressive hearing loss (HL) are significant concerns in individuals with Turner syndrome (TS). However, whether childhood estrogen deficiency increases HL risk and whether estrogen replacement therapy (ERT) prevents hearing deterioration are still unclear.METHODSThis prospective cohort study recruited children with TS from a tertiary referral center between 2016 and 2024. All participants received standardized recombinant human growth hormone therapy. Longitudinal monitoring data of hormone levels, metabolic parameters, and annual audiological examinations were recorded. The primary analysis used a multivariate Cox model to estimate the adjusted hazard ratio (HR) of hearing loss between estrogen-deficient and estrogen-normal TS patients without prior exogenous estrogen exposure. The secondary analysis compared annual pure tone average (PTA) and its changes between the ERT and non-ERT groups in a substudy.RESULTSAmong 87 prepubertal pediatric patients with TS, 48 (55.2%) were estrogen deficient, and 38 HL events occurred over a 35-month median follow-up. The estrogen-deficient group had higher HL incidence (27 cases, 56.3%; 20.6 per 100 person-years [PY]) versus estrogen-normal (11 cases, 28.2%; 8.6 per 100 PY), with estrogen deficiency independently increasing HL risk (HR 2.93, 95% CI 1.21-7.12). Notably, estrogen deficiency also independently predicted abnormal distortion product otoacoustic emissions with an even higher effect size (HR 3.98, 95% CI 1.35-11.76). The substudy found that initiating ERT at the age of 12 significantly preserve auditory function, with the ERT group showing markedly lower PTA and slower hearing deterioration (-1.24 dB/year vs. 1.13 dB/year right ear; -1.85 dB/year vs. 1.04 dB/year left ear, P = 0.001).CONCLUSIONChildhood estrogen deficiency is a modifiable risk factor. Initiating ERT around early adolescence may help hearing preservation.TRIAL REGISTRATIONChinese Clinical Trial Registry: ChiCTR2300068063.FUNDINGNational Natural Science Foundation of China (grants 82173154 and 82471155), Fundamental Research Funds for the Central Universities Clinical Research 5010 Program (Sun Yat-sen University, no. 2024004).