HYPOTHESIS AND THEORY ARTICLE Digit ratio (2D:4D): a biomarker for prenatal sex steroids and adult sex steroids in challenge situations (original) (raw)
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Frontiers in endocrinology, 2014
Digit ratio (2D:4D) denotes the relative length of the second and fourth digits. This ratio is considered to be a biomarker of the balance between fetal testosterone (T) and estrogen (E) in a narrow window of early ontogeny. Evidence for this assertion is derived from direct and indirect measures of prenatal hormonal exposure (in experimental animals, via amniotic fluid samples and in the study of sex-typical traits) in relation to 2D:4D. In contrast, the relationships between 2D:4D and levels of sex steroids in adults are less clear, as many correlational studies of 2D:4D and adult sex steroids have concluded that this association is statistically non-significant. Here, we suggest that in order to understand the link between 2D:4D and sex hormones, one must consider both fetal organizing and adult activating effects of T and E. In particular, we hypothesize that 2D:4D correlates with organizing effects on the endocrine system that moderate activating effects in adulthood. We argue ...
Early human development, 2015
Digit ratio (2D:4D) is a marker for prenatal sex steroids and a correlate of sporting performance. This association may exist because low 2D:4D is linked to high prenatal levels of testosterone (T) and low oestrogens (E). It was recently suggested that low 2D:4D, and particularly low right-left 2D:4D (or Dr-l), is a marker for T changes in response to physical and aggressive challenges. If correct, this link may in part explain the association between 2D:4D and sports performance. We tested this hypothesis in adults. Three experimental treatments were completed using a randomised, cross-over design; (i) cycle sprints plus an aggressive video (S+V), (ii) aggressive video plus cycle sprints (V+S), and (iii) a control session. 24 healthy adults (12 men and 12 women). Salivary T, oestradiol (E2) and cortisol (C) levels were measured on six occasions across each session and pooled for analysis. The S+V treatment was associated with a rise in T and C levels, and Dr-l was significantly and...
Journal of Developmental Origins of Health and Disease, 2021
The ratio of length between the second (index) and fourth (ring) fingers (digit ratio or 2D:4D) is frequently employed as a retrospective marker of prenatal sex hormone exposure. Lutchmaya et al. (2004) reported that the ratio of testosterone (T) to estradiol (E) present in second trimester amniotic fluid was negatively correlated with digit ratios for the right hand (but not the left hand) in a sample of 29 children at 2-year follow-up. This observation is frequently cited as evidence for the measure's validity but has not been replicated. We therefore present the findings of another study of amniotic T and E that did not find evidence for these effects at 4½-year follow-up. The confidence intervals were large, the direction of correlations observed was generally erratic, and the overall findings therefore question the premise that second trimester sex hormones affect the development of digit length ratios in humans.
The ratio of length between the second (index) and fourth (ring) fingers (digit ratio or 2D:4D) is frequently employed as a retrospective marker of prenatal sex hormone exposure. Lutchmaya et al. (2004) reported that the ratio of testosterone (T) to estradiol (E) present in second trimester amniotic fluid was negatively correlated with digit ratios for the right hand (but not the left hand) in a sample of 29 children at 2-year follow-up. This observation is frequently cited as evidence for the measure’s validity but has not been replicated. We therefore present the findings of another study of amniotic T and E that did not find evidence for these effects at 4½-year follow-up. The confidence intervals were large, the direction of correlations observed was generally erratic, and the overall findings therefore question the premise that second trimester sex hormones affect the development of digit length ratios in humans.
Human Biology Review, 2023
The second-to-fourth digit (2D:4D) ratio is a sexually dimorphic trait, with men having lower ratios than women, indicating relatively higher prenatal testosterone exposure compared to oestrogen. The 2D:4D ratio is fixed in intrauterine conditions that are affected by foetal sex steroids (testosterone and oestrogen) and an indirect method to determine intrauterine sex hormone levels that significantly correlate with somatic features, behavioural traits, fertility measures, reproductive characteristics, and predisposition to certain chronic diseases. Researchers discovered that a more masculine (low 2D<4D) digit ratio and a more feminine (high; 2D>4D) digit ratio are manifestations of increased prenatal testosterone and oestrogen exposure, respectively. Furthermore, digit ratio (2D:4D) values are widely used to predict reproductive capacity and success, fertility measures, natural menopause, and age at menarche, which varies between populations. The current review paper attempted to discuss sexual dimorphism in 2D:4D ratios, as well as its potential association and utility in evaluating certain reproductive characteristics and behavioural traits in populations. Methodological comparisons, benefits and drawbacks of determining the 2D:4D for studying the effect of prenatal sex steroids are also highlighted.
2nd to 4th digit ratios, foetal testosterone and estradiol
Background: The ratio of 2nd to 4th digit length (2D:4D) is sexually dimorphic (mean 2D:4D is lower in males than females) and is thought to be fixed early in development. 2D:4D has been reported to be related to fetal growth, hand preference, autism, Asperger's syndrome, sperm counts, family size, age at myocardial infarction in men and breast cancer in women. There is indirect evidence that 2D:4D is established in utero and is negatively related to prenatal testosterone and positively with prenatal estradiol. However, there are no studies which show direct relationships between fetal testosterone (FT), fetal estradiol (FE) and 2D:4D. Aims: To investigate the relationships between 2D:4D ratios and FT and FE from amniotic fluid. Study design: Cohort study. Subjects: 33 children. Outcome measures: Radioimmunoassays of FT and FE obtained from routine amniocentesis; 2D:4D ratios calculated from 2nd and 4th digit length of the right and left hands at age 2 years. Results: A significant negative association between right 2D:4D ratio and FT/FE ratio, which was independent of sex. Conclusions: These preliminary findings lend support to an association between low 2D:4D and high levels of FT relative to FE, and high 2D:4D with low FT relative to FE.
Sex Steroids at Birth: Genetic and Environmental Variation and Covariation
Three sex-steroids (estradiol, progesterone, & testosterone) were assayed from the umbilical cord blood of 58 same-sex twin pairs in an investigation of the effects of sex, as well as genetic and environmental factors, on neonatal hormone levels. Although significant mean differences were found between boys and girls for both testosterone and progesterone, sex appeared to account for very little of the total variation for any of the hormones. Results showed that genetic influences significantly affected within-sex variation in both estradiol and progesterone levels, while variations in the intrauterine (shared twin) environment accounted primarily for differences in levels of testosterone. Moderate correlations were also found among the three hormones. Multivariate biometrical analyses revealed these relationships to be explained by an underlying general factor of nonshared environmental influences affecting all three hormones. Genetic factors appeared to be specific to each hormone rather than correlated across hormones. These results suggest not only that genes are operating at this early age, but also that maternal and other prenatal factors (e.g., placental effects, uterine position) have a significant role in variations of sex-steroids and possibly on later behaviors.
Digit ratio (2D:4D) in newborns: Influences of prenatal testosterone and maternal environment
Early Human Development, 2013
Introduction: The 2D:4D digit ratio is sexually-dimorphic, probably due to testosterone action through the perinatal period. We characterize the 2D:4D ratio in newborn (NB) infants, in between the pre-and postnatal surges of testosterone, and relate it to the mother's 2D:4D and to testosterone levels in the amniotic fluid (AF). Subjects and methods: Testosterone was assayed in samples of maternal plasma and AF collected at amniocentesis. Shortly after birth, 106 NBs and their mothers were measured for 2D:4D ratio. Results: NB males had lower mean 2D:4D ratios than females but this dimorphism was significant only for the left hand (males: 0.927; females: 0.950; p =0.004). Mothers who had sons had lower 2D:4D ratios than those who had daughters and the mother's 2D:4D were higher than those of NBs regardless of sex. Both hands of NB females were negatively correlated with AF testosterone and positively correlated with the mother's 2D:4D, but males showed no significant associations. Maternal plasma testosterone also showed a negative weak correlation with NB's digit ratio in both sexes. Conclusions: Sexual dimorphism at birth was only significant for the left hand, in contrast with reports of greater right hand dimorphism, suggesting that postnatal testosterone is determinant for 2D:4D stabilization. The lower 2D:4D ratios in mothers who had sons support claims that hormone levels in parents are influential for determining their children's sex. NB female's digit ratio, but not males', was associated to the level of AF testosterone. The mother's 2D:4D ratios were positively correlated with their daughters' 2D:4D, but the same was not observed for male NBs, suggesting that prenatal testosterone levels in male fetus lead their 2D:4D ratios to stray from their mothers' with high individual variability.
2nd to 4th digit ratios, fetal testosterone and estradiol
Early Human Development, 2004
Background: The ratio of 2nd to 4th digit length (2D:4D) is sexually dimorphic (mean 2D:4D is lower in males than females) and is thought to be fixed early in development. 2D:4D has been reported to be related to fetal growth, hand preference, autism, Asperger's syndrome, sperm counts, family size, age at myocardial infarction in men and breast cancer in women. There is indirect evidence that 2D:4D is established in utero and is negatively related to prenatal testosterone and positively with prenatal estradiol. However, there are no studies which show direct relationships between fetal testosterone (FT), fetal estradiol (FE) and 2D:4D. Aims: To investigate the relationships between 2D:4D ratios and FT and FE from amniotic fluid. Study design: Cohort study. Subjects: 33 children. Outcome measures: Radioimmunoassays of FT and FE obtained from routine amniocentesis; 2D:4D ratios calculated from 2nd and 4th digit length of the right and left hands at age 2 years. Results: A significant negative association between right 2D:4D ratio and FT/FE ratio, which was independent of sex. Conclusions: These preliminary findings lend support to an association between low 2D:4D and high levels of FT relative to FE, and high 2D:4D with low FT relative to FE.