64. Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study (lay summary)

Nguyen TV, Monnier P, Muckle G, Sathyanarayana S, Ouellet E, Velez MP, Dodds L, Arbuckle TE. Journal of Developmental Origins of Health and Disease.  2019 Mar 22:1-9. doi: 10.1017/S2040174419000059

Exposure of the fetus to sex hormones, such as androgens and estrogens, is critical for the future physical and mental development of a healthy child. However, obtaining accurate and reliable measurements of fetal exposure to these hormones is challenging. There are a range of physical characteristics that can be measured as potential indicators of fetal androgen exposure. These include: anogenital distance (AGD) (the distance from the anus to the genitals); the ratio of the lengths of the second and fourth fingers (2D:4D ratio); length and width of the penis; a measure of skin pigmentation in the genital and areolar (nipple) areas; and examining the maturity of vaginal cells (known as vaginal maturation index).

Using data from the MIREC-ID study, this research was designed to examine characteristics of the infants associated with these indicators. These measurements were taken either shortly after birth or around 6 months of age in 173 girls and 162 boys.  The study also measured the skinfold thickness of the infant’s triceps (muscle on back of upper arm), which is a measure of fat tissue.

This study observed a significant positive association between vaginal maturation index and triceps skinfold thickness. This finding suggests that the vaginal maturation index, a marker of estrogen exposure, may be sensitive to estrogen levels produced by fat tissue in girls. In addition, anogenital distance was associated with the level of areolar pigmentation in girls, thus supporting this distance as a marker of both androgen and estrogen exposure. In boys, AGD was associated with scrotal pigmentation and circumference of the infant’s right arm, supporting the notion that these markers may be used to indicate androgen exposure in boys.

In conclusion, the results of this study support the use of anogenital distances in boys and girls as potentially reliable markers of androgen exposure. The vaginal maturation index may be sensitive to levels of estrogens produced by fat cells in girls.  Finally, areolar pigmentation in girls appears to be a marker of both androgen and estrogen exposure.

This study recommends measurement of several physical markers in infants to convey a more a more complete understanding of fetal androgen and estrogen exposure.