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

Trine Holm Johannsen1,2, Katharina Maria Main1,2, Marie Lindhardt Ljubicic1,2

  • 1Department of Growth and Reproduction, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

The Journal of Clinical Endocrinology and Metabolism
|June 20, 2018
PubMed

Insights

Establishing sex-specific hormone reference ranges in infants is crucial for diagnosing disorders of sex development (DSD). This study defined these ranges, finding the LH/FSH ratio, AMH, and testosterone best differentiate sex in newborns.

Area of Science:

  • Pediatric Endocrinology
  • Reproductive Biology
  • Neonatal Medicine

Background:

  • Early activation of the hypothalamic-pituitary-gonadal axis occurs in infancy, impacting the evaluation of infants with disorders of sex development (DSD).
  • Limited sex-specific reference ranges for reproductive hormones in early life hinder accurate DSD diagnosis.

Purpose of the Study:

  • To establish sex-specific reference ranges for reproductive hormones in healthy infants.
  • To define cutoff values for these hormones to aid in DSD diagnosis.
  • To investigate sex differences in hormone concentrations during early development.

Main Methods:

  • Cross-sectional study conducted at a tertiary pediatric endocrinology center.
  • Serum hormone concentrations (LH, FSH, T, estradiol, SHBG, inhibin B, AMH, DHEA, DHEAS, 17-OHP, androstenedione, LH/FSH ratio) were measured in 1840 healthy infants and 27 infants with DSD (aged 2-5 months).

Main Results:

  • LH and FSH concentrations showed some overlap between sexes; LH was higher in boys and FSH in girls.
  • The LH/FSH ratio effectively separated infant boys from girls (cutoff 0.32) with minimal overlap.
  • Inhibin B and anti-Müllerian hormone (AMH) were significantly higher in boys than girls, with little overlap.
  • In DSD cases, the LH/FSH ratio generally aligned with the gender of rearing, except in complete androgen insensitivity syndrome.

Conclusions:

  • Sex-specific reference ranges for reproductive hormones and the LH/FSH ratio during mini-puberty were established.
  • Anti-Müllerian hormone (AMH), LH/FSH ratio, and testosterone (T) were identified as key classifiers for sex differentiation in infants.
  • The LH/FSH ratio can provide valuable diagnostic information for infants suspected of having DSD.
Abstract

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