Estradiol as a potential adjunctive marker for congenital hypogonadotropic hypogonadism in infants and toddlers

Congenital hypogonadotropic hypogonadism, leads to gonadal insufficiency and external genital abnormalities. In this case-control study, we investigated the early diagnosis of congenital hypogonadotropic hypogonadism-induced gonadal dysfunction in male infants/toddlers using hormone-level analysis. We included 25 male infants and toddlers with congenital hypogonadotropic hypogonadism, hospitalized between January 1, 2018, and December 31, 2019, and divided them into two groups: ≤0.5 years and 0.5–3 years. Healthy controls were matched using a 1:4 ratio. We compared physical examination results, biochemical indices, sex hormone levels, anti-Müllerian hormones, and inhibin B between the groups. Anti-Müllerian hormone, inhibin B, and estradiol levels were identified as factors associated with CHH. Estradiol had the strongest diagnostic efficacy for congenital hypogonadotropic hypogonadism in the ≤ 0.5-year and 0.5–3-year groups (areas under the curve: 0.951 and 0.939; cutoff: 9.79 and 5.55 pg/mL, respectively). No significant differences in diagnostic efficacy were observed for luteinizing hormone, follicle-stimulating hormone, estradiol, inhibin B, and anti-Müllerian hormone levels. The presence of low anti-Müllerian hormone and inhibin B levels, combined with estradiol cutoff values of 9.79 pg/mL (mini-puberty) and 5.55 pg/mL (0.5–3 years), significantly improved early detection of congenital hypogonadotropic hypogonadism. Estradiol may serve as a useful adjunctive marker in the differential diagnosis of congenital hypogonadotropic hypogonadism, particularly when combined with other indicators.