Digit ratio (2D:4D) in newborns: Influences of prenatal testosterone and maternal environment (original) (raw)
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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.
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.
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.
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.
Journal of Developmental Origins of Health and Disease, 2018
Foetal sex hormones can have powerful and far-reaching effects on later phenotype. However, obtaining accurate measurements is difficult for ethical reasons, and researchers often employ proxy variables to examine their effects. The relative length of the second and fourth fingers (digit ratio or 2D:4D) is frequently used for this purpose, as it is hypothesized to index variance in prenatal androgen and oestrogen exposure. Most studies employing this method examine digit ratio for the right hand (R2D:4D) and/or left hand (L2D:4D), though the mean value (M2D:4D) (i.e., the average of R2D:4D and L2D:4D) and directional asymmetry (D[R–L]) (i.e., R2D:4D minus L2D:4D) are also commonly used. As no published studies have examined M2D:4D or D[R-L] in relation to testosterone measured from amniotic fluid, we conducted a secondary analysis of data published by Ventura et al. The sample comprises 106 mothers from Portugal who underwent amniocentesis during the second trimester and their neona...
Digit ratio (2D:4D) and maternal testosterone-to-estradiol ratio measured in early pregnancy
Scientific Reports
The ratio of index to ring finger (2D:4D) has been hypothesised to indicate prenatal androgen exposure, yet evidence for its validity is lacking. We report the first pre-registered study to investigate mothers’ early pregnancy sex hormone concentrations in relation to their children’s digit ratios measured at 18–22-month follow-up. Although the testosterone (T) to estradiol (E) ratio correlated negatively with right hand digit ratio (R2D:4D) and directional asymmetry (right-minus-left) in digit ratio (D[R−L]), neither effect remained statistically significant once demographic and obstetric covariates were controlled for. Nevertheless, the multivariate level of analysis did reveal that T correlated positively with left hand digit ratio (L2D:4D) and negatively with D[R−L]. However, the first of these effects is in the opposite direction to that predicted by theory. Taken together, the results of our study suggest research with larger samples is required to determine whether digit rati...
Maternal 2nd to 4th digit ratio does not predict lifetime offspring sex ratio at birth
American Journal of Human Biology, 2008
The low ratio of second-to-fourth digit length (2D:4D) of parents, a putative indicator of high prenatal and even adult testosterone levels, has been suggested to predict a male-biased secondary offspring sex ratio. We investigated this question in 244 contemporary postreproductive Finnish women. Information on the lifetime offspring birth sex ratio of women was collected by questionnaires and the 2D:4D of both their hands were measured from scanned photographs. We found no evidence that the right hand 2D:4D, the left hand 2D:4D, the mean of the right and the left hand 2D:4D, or the difference between the right and the left hand 2D:4D was related to offspring sex ratio at birth among these women. Our results thus do not support the suggestion that offspring birth sex ratio is related to 2D:4D in women. Am.
Sexual dimorphism in the prenatal digit ratio (2D:4D).
The second to fourth digit ratio (2D:4D) is smaller in human males than in females and hence this trait is sexually dimorphic. The digit ratio is thought to be established during early prenatal development under the influence of prenatal sex hormones. However, the general assumption of early establishment has hardly been studied. In our study, we analyzed the 2D:4D ratio in 327 deceased human fetuses. We measured digit lengths in 169 male and 158 female fetuses ranging from 14 to 42 weeks old. Our results showed a slight, but significant, sexual dimorphism in the expected direction, i.e., females had, on average, a ratio of 0.924 and males a ratio of 0.916. There was no significant relationship with the presence or absence of minor and major or single and multiple congenital abnormalities. There was a minimal, but significant difference between digit ratios based on digit lengths including and excluding the non-bony fingertip with the values being strongly correlated (r = .98). The prenatal 2D:4D ratio was lower than has thus far been reported for children and adults both for males and females. The extent of the sexual dimorphism in fetuses was similar to that found for children, but lower than for adults. The 2D:4D ratio, thus, seems to increase after birth in both men and women, with the second digit growing faster than the fourth digit (positive allometric growth of digit two) and perhaps more so in women than in men. Therefore, the sexual dimorphism is probably determined by prenatal as well as by postnatal developmental processes.
Are there any “direct” human studies of digit ratio (2D:4D) and measures of prenatal sex hormones?
Early Human Development, 2017
Are there any "direct" human studies of digit ratio (2D:4D) and measures of prenatal sex hormones? Richards [1] has reviewed evidence for an association between digit ratio (2D:4D) and direct measures of prenatal sex hormones in humans. He reports that there are only six such papers, two concerning hormonal measures obtained from amniocentesis [2,3] and four that report hormone assays obtained from cord blood [4-7]. He concludes that in humans, support for an association between 2D:4D and prenatal sex hormones is stronger for amniotic than cord-blood studies. However, Richards argues that overall the link is tenuous and applies only to females. Further, he suggests that more amniotic studies are indicated to validate (or invalidate) 2D:4D as a tool for examining hormonal effects in the human foetal environment. These are important issues and it is appropriate that they are debated. However, we have disagreement with regard to Richards' review of the literature and with regard to the way forward to resolve the issues that he raises. Firstly, there are six (not four) studies concerning 2D:4D and sex hormones in human cord blood. The two additional reports are from the Hokkaido Study on Environment and Child Health. Mitsui and colleagues investigated relationships between a number of cord-blood hormones and 2D:4D in school-aged children (n = 117, 45 males). The sex hormones included adrenal androgens with a focus on dehydroepiandrosterone (DHEA) [8] and testicular hormones with a focus on testosterone and Insulin-like 3 (INSL3) [9]. With regard to adrenal androgens, there was a significant negative association between mean 2D:4D and DHEA in males but not in females. With regard to the testicular hormones, it was reported that mean 2D:4D correlated negatively but not significantly with testosterone and significantly negatively with INSL3 in boys but not girls. INSL3 is secreted along with testosterone by the Leydig cells of the testis. It is produced in large amounts by male foetuses and by boys during puberty. Deficits in INSL3 production are associated with male sterility and cryptorchidism. Follow-ups of this cohort showed significant negative correlations between 2D:4D in masculine-typical activities in boys, but no significant effect for 2D:4D and feminine-typical behaviours in girls [10]. Therefore, the relationships between 2D:4D and sex hormones in cord blood are stronger than indicated by Richards and they do include significant effects for males. Secondly, it is doubtful whether amniotic studies are the best way forward to consider links with 2D:4D. There is evidence that 2D:4D is sexually dimorphic by the end of the 1st trimester, and it may well contain information regarding sex hormone effects from week 8 to 12 [11,12]. Amniocentesis is typically performed in the 2nd trimester (weeks 14 to 16) and cord-blood yields perinatal hormones. Both are likely to include echoes of hormonal levels from the 1st trimester but they do not provide "direct" evidence for links between foetal sex hormones and 2D:4D. This is the reason why there has been significant effort devoted to animal models for 2D:4D and prenatal sex hormones [13]. In conclusion, we do not think the links between human 2D:4D and foetal sex hormones are tenuous. The available evidence is consistent with a real association for both males and females. However, we cannot "directly" measure 1st trimester foetal hormones, because the risk to the foetus would be too great. One alternative is to consider human maternal hormones. Two studies have shown that testosterone in the mother's serum, assayed during the 2nd trimester, correlates negatively with the child's 2D:4D [3,14]. This suggests that the maternal/foetal barrier is not as strong as previously thought [14]. In contrast to amniocentesis samples, maternal serum assays are possible to collect during the 1st trimester of pregnancy. They may provide a more reliable method to assess 2D:4D as a tool for examining hormonal effects in the very early human foetal environment.
Objectives: The 2nd to 4th digit ratio (2D:4D) is thought to reflect exposure to androgens during foetal development. This study examined the relationship between low (more masculine) and high (more feminine) 2D:4D and body size at different stages of the life course, adult testosterone levels and number of children among males. Methods: Five hundred and fifty-eight men from rural Poland at the Mogielica Human Ecology Study Site participated in this study. Life history data and anthropometric measurements were collected. Salivary morning and evening testosterone levels among 110 men from the same population were measured. Results: Low 2D:4D was related to higher birth weight (p ¼ 0.04), higher birth length (p ¼ 0.01), higher body mass during childhood and adolescence (p ¼ 0.01), higher BMI (borderline significance, p ¼ 0.06), higher number of children among fathers (p ¼ 0.04) and higher testosterone levels during adulthood (p ¼ 0.04). Conclusions: This study shows, for the first time in a single population, that digit ratio is related to sub-adult body size at different stages of the life course, adult testosterone levels and number of children. The observed results suggest that digit ratio might be a valuable predictor of male body size and reproductive characteristics.