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Sex-Differences in Reproductive Hormones during Mini-Puberty in Infants with Normal and Disordered Sex Development

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CONTEXT: The early activation of the hypothalamic-pituitary-gonadal axis during infancy can be used in the evaluation of infants suspected of disorders of sex development (DSD). However, few data exists on sex-specific reference ranges for these hormones during early life.

OBJECTIVE: To evaluate sex-differences in reproductive hormone concentrations in serum from healthy infants in order to define sex-specific cut-off values and to apply these in infants with DSD.

DESIGN: A cross-sectional study.

SETTING: A tertiary center for pediatric endocrinology at the University Hospital of Copenhagen.

PATIENTS OR OTHER PARTICIPANTS: 1,840 healthy infants and 27 DSD patients aged 2-5 months.

MAIN OUTCOME MEASURES: Serum concentrations of LH, FSH, testosterone, estradiol, SHBG, inhibin B, AMH, DHEA, DHEAS, 17-OHP, androstenedione, and LH/FSH-ratio.

RESULTS: LH and FSH concentrations showed overlap between sexes with LH being highest in boys and FSH being highest in girls. The LH/FSH-ratio separated infant boys from girls with minimal overlap at a cut-off value of 0.32. Inhibin B and AMH concentrations were markedly higher in boys compared to girls, with minimal or no overlap, respectively. In infants with Klinefelter syndrome, 45,X/46,XY mosaicism and male phenotype, and Turner syndrome, respectively, the LH/FSH-ratio matched the gender-of-rearing. However, infants with complete androgen insensitivity syndrome had LH/FSH-ratios within male range.

CONCLUSIONS: Reference ranges for reproductive hormones and LH/FSH-ratio during mini-puberty were established in this study. The classifiers that best separated sex in mini-puberty were AMH, LH/FSH-ratio and testosterone. Use of the LH/FSH-ratio may add valuable information in the work-up of infants suspected of DSD.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume103
Issue number8
Pages (from-to)3028-3037
ISSN0021-972X
DOIs
Publication statusPublished - 2018

ID: 54684680