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  • Title: Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development.
    Author: Johannsen TH, Main KM, Ljubicic ML, Jensen TK, Andersen HR, Andersen MS, Petersen JH, Andersson AM, Juul A.
    Journal: J Clin Endocrinol Metab; 2018 Aug 01; 103(8):3028-3037. PubMed ID: 29917083.
    Abstract:
    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 exist 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 to define sex-specific cutoff 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: Healthy infants (1840) and patients with DSD (27), aged 2 to 5 months. MAIN OUTCOME MEASURES: Serum concentrations of LH, FSH, testosterone (T), estradiol, sex hormone-binding globulin (SHBG), inhibin B, anti-Müllerian hormone (AMH), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17-hydroxyprogesterone (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 cutoff value of 0.32. Inhibin B and AMH concentrations were markedly higher in boys compared with girls, with minimal or no overlap. In infants with Klinefelter syndrome, 45,X/46,XY mosaicism and male phenotype, and Turner syndrome, the LH/FSH ratio matched the gender of rearing. However, infants with complete androgen insensitivity syndrome had LH/FSH ratios within the 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 T. Use of the LH/FSH ratio may add valuable information in the workup of infants suspected of DSD.
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