TY - JOUR

T1 - Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development

AU - Johannsen, Trine Holm

AU - Main, Katharina Maria

AU - Ljubicic, Marie Lindhardt

AU - Jensen, Tina Kold

AU - Andersen, Helle Raun

AU - Andersen, Marianne Skovsager

AU - Petersen, Jørgen Holm

AU - Andersson, Anna-Maria

AU - Juul, Anders

PY - 2018

Y1 - 2018

N2 - ContextThe 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.ObjectiveTo 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.DesignA cross-sectional study.SettingA tertiary center for pediatric endocrinology at the University Hospital of Copenhagen.Patients or Other ParticipantsHealthy infants (1840) and patients with DSD (27), aged 2 to 5 months.Main Outcome MeasuresSerum 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.ResultsLH 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.ConclusionsReference 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.

AB - ContextThe 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.ObjectiveTo 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.DesignA cross-sectional study.SettingA tertiary center for pediatric endocrinology at the University Hospital of Copenhagen.Patients or Other ParticipantsHealthy infants (1840) and patients with DSD (27), aged 2 to 5 months.Main Outcome MeasuresSerum 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.ResultsLH 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.ConclusionsReference 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.

U2 - 10.1210/jc.2018-00482

DO - 10.1210/jc.2018-00482

M3 - Journal article

C2 - 29917083

VL - 103

SP - 3028

EP - 3037

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 8

ER -