Wednesday, September 28, 2016

2D:4D digit ratio corresponds with fetal testosterone (and other hormones)

Correlation between 2D:4D digit ratio and testosterone

"Several studies now provide indirect support for the utility of 2D:4D ratio as an index of prenatal androgen concentrations. 
First, men and women with congenital adrenal hyperplasia (CAH), a condition leading to hyper-secretion of testosterone, have decreased 2D:4D ratios (Brown et al., 2002; Buck et al., 2003; Ökten et al., 2002; Rivas et al., 2014). Second, men with Klinefelter’s syndrome, a chromosomal abnormality associated with low androgen levels, have higher (i.e., feminized) 2D:4D ratio relative to healthy men (Manning et al., 2013). Third, there is some evidence indicating that 2D:4D ratio is masculinized in women with a male twin relative to women with a female twin, suggesting that hormone transfer from the male co-twin is masculinizing (Hiraishi et al., 2012; van Anders et al., 2006). Additionally, some studies indicate that testosterone concentrations from amniotic fluid is negatively correlated with 2D:4D ratio (Lutchmaya et al., 2004; Ventura et al., 2013). 
Perhaps the most compelling evidence for the validity of 2D:4D ratio as a marker of prenatal androgen exposure comes from work in rodents demonstrating that prenatal manipulations of testosterone as well as steroid hormone receptors modulate the development of 2D:4D ratio (Auger et al., 2013; Zheng and Cohn, 2011). Specifically, administration of anti-androgenic compounds results in feminized digit ratios (Auger et al., 2013). Additionally, inactivation of the androgen receptor during prenatal development decreases growth of the 4th digit, leading to a higher (i.e., feminized) 2D:4D ratio, whereas inactivation of the estrogen receptor α increases growth of the 4th digit, leading to a lower (i.e., masculinized) 2D:4D ratio. Similarly, testosterone administration during the prenatal period leads to a lower 2D:4D ratio, while estrogen administration leads to a higher 2D:4D ratio (Zheng and Cohn, 2011). For the purpose of the analyses conducted here we conceptualize 2D:4D ratio as a marker of prenatal androgen exposure. However, it should be noted that 2D:4D ratio can be influenced by multiple factors, including exposure to estradiol (Zheng and Cohn, 2011)."
"​Digit ratio—the relative length of index (2D) to ring (4D) finger—is a sexually dimorphic trait, with males typically having lower values of 2D:4D than females. The sex difference in 2D:4D is determined early in ontogeny, presumably by the end of the first trimester (...), and remains virtually unchanged through childhood and puberty (...). Although the sex difference is small, there is substantial variation in 2D:4D within each sex; this variation is associated with variations in fetal exposure to testosterone and estrogen, with testosterone increasing the relative size of the fourth digit and estrogen shortening it (...). Subsequent experimental studies of mice (...) and rats (...) have supported this model. Likewise, 2D:4D has been shown to deviate from human norms in the expected directions in such conditions as elevated testosterone (congenital adrenal hyperplasia [...]), androgen insensitivity (...), and low prenatal testosterone (...)."
(source: Digit Ratio (2D:4D) and Gender Inequalities Across Nations, Evolutionary Psychology, www.epjournal.net – 2014. 12(4): 757-768, John T. Manning, Department of Psychology, Northumbria University, Newcastle-upon-Tyne, UK, Bernhard Fink, Institute of Psychology and Courant Research Center Evolution of Social Behavior, University of Göttingen, Germany, Robert Trivers, Graduate Program in Ecology and Evolution, Rutgers University, New Brunswick, USA, retrieved 27/7/2016)

"A significant negative association between right 2D:4D ratio and FT (fetal testosterone)/FE (fetal estradiol) ratio [was found], which was independent of sex. 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."
(source: 2nd To 4Th digit ratios, fetal testosterone and estradiol, in Early Human Development 77(1-2):23-8 · May 2004 , Svetlana Lutchmaya, Simon Baron-Cohen, Peter Raggatt, John T Manning)


"Studies on levels of testosterone (T) and oestrogen (O) in amniotic fluid following amniocentesis (...) have shown that, for the right hand only, there is a inverse relationship between the 2D:4D ratio and the T:O ratio which is independent of sex. Thus, individuals with higher 2D:4D ratios tended to show lower testosterone levels relative to oestrogen levels. No such relationship was observed for the left hand. Other investigations on females have noted positive correlations between 2D:4D ratios and levels of [luteinizing hormone] LH (right and left hands), oestrogen (right hand only) but not [follicle-stimulating hormone] FSH (...). These observations have led authors to suggest that the 2D:4D ratio in the right hand may be more sensitive to hormone ratios and this notion is supported by more recent studies showing that 2D:4D ratio is correlated with salivary oestradiol levels (...)."


"The ratio of the second digit (index finger) to the fourth digit (ring finger), herein referred to as 2D:4D, has been shown in infants to reflect their mothers’ amniotic ratios of testosterone to estradiol (Lutchmaya et al. 2004), which makes it a useful albeit noisy proxy for retrospectively measuring prenatal androgen exposure in humans (Cohen-Bendahan et al. 2005, Wong and Hines 2016). Though this biomarker cannot be ethically validated in humans experimentally, it has been shown that experimental manipulation of prenatal testosterone in rat fetuses results in a smaller 2D:4D claw-length ratio after the rats are born (Talarovičová et al. 2009). The effect is more pronounced on the right hand for both rodents (Talarovičová et al. 2009) and humans (Cohen-Bendahan et al. 2005), and right-hand 2D:4D has been shown to predict a level of conformity to aspects of stereotypical gender roles within a single-sex cohort (Atkinson et al. 2017, Brown et al. 2002)."
(Hejná, M., Ackerman, L., & Wallenberg, J. C. (2020). Attention to People Like You: a proposal regarding neuroendocrine effects on linguistic variation. Journal of Biolinguistics.)


Prenatal androgens may have greater effect on right hand digit ratio then on left hand digit ratio, postnatal androgens the opposite

"these data confirm the predominantly right-sided influence of androgens on digit length"
(Benderlioglu, Zeynep, and Randy J. Nelson. "Digit length ratios predict reactive aggression in women, but not in men." Hormones and behavior 46.5 (2004): 558-564.) 
Directional asymmetry of 2D:4D (left hand 2D:4D minus right hand 2D:4D) may be a better measure of prenatal testosterone than simply the right-hand 2D:4D.
"One possible explanation of this pattern, rather speculative indeed, could be that the right hand 2D:4D ratio reflects more the prenatal testosterone levels, while the left hand 2D:4D ratio is rather linked to postnatal testosterone levels (and thus is more prone to be influenced by environmental  factors (...))."
(Hodková, Hana, et al. "Higher perceived dominance in Toxoplasma infected men--a new evidence for role of increased level of testosterone in toxoplasmosis-associated changes in human behavior." Neuroendocrinology Letters 28.2 (2007): 110-114.)

"The sex difference in 2D:4D is larger in the right hand than in the left. (...) Right-hand 2D:4D might be a better indicator of prenatal androgenisation than left-hand 2D:4D."
(Hönekopp, Johannes, and Steven Watson. "Meta‐analysis of digit ratio 2D: 4D shows greater sex difference in the right hand." American Journal of Human Biology 22.5 (2010): 619-630.)

"These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences"
(Flegr, Jaroslav, Jitka Lindová, Věra Pivoñková, and Jan Havlíček. "Brief Communication: latent toxoplasmosis and salivary testosterone concentration—important confounding factors in second to fourth digit ratio studies." American Journal of Physical Anthropology: The Official Publication of the American Association of Physical Anthropologists 137, no. 4 (2008): 479-484.)


2D:4D ratio reflects prenatal balance of androgen (tesosterone) to estrogen to be precise, not exactly prenatal tesosterone as such

"Here we report that the 2D:4D ratio in mice is controlled by the balance of androgen to estrogen signaling during a narrow window of digit development. Androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas inactivation of ER-α increases growth of digit 4, which leads to a lower 2D:4D ratio. We also show that addition of androgen has the same effect as inactivation of ER and that addition of estrogen mimics the reduction of AR."
(Zheng, Zhengui, and Martin J. Cohn. "Developmental basis of sexually dimorphic digit ratios." Proceedings of the National Academy of Sciences 108.39 (2011): 16289-16294.)


Correlation between 2D:4D ratio and other hormones


Right-hand (not left-hand) 2D:4D ratio positively associated with estradiol (but not progesterone) levels in women's saliva

"We tested the association between the index-to-ring finger length ratio (2D:4D) and ovarian steroid hormone concentrations measured over the course of a menstrual cycle in the saliva of 38 young women. Estradiol levels were positively associated with right-hand, but not left-hand, 2D:4D, and also with the difference between right- and left-hand 2D:4D. None of these measures predicted progesterone level."
(McIntyre, Matthew H., et al. "Index‐to‐ring finger length ratio (2D: 4D) predicts levels of salivary estradiol, but not progesterone, over the menstrual cycle." American Journal of Human Biology 19.3 (2007): 434-436.).


Ghrelin appears to be a further biochemical parameter in addition to the sex steroids which correlated with different digit-length ratios at least in boys

"The aim of this study was to investigate possible relationships between different right-hand finger-length ratios and different fasting hormone concentrations in young swimmers. Fifty-five young swimmers participated in this study (26 boys and 29 girls, aged 10–17 years). [...]
The following finger-length ratios were calculated: 1D:2D, 1D:3D, 1D:4D, 1D:5D, 2D:3D, 2D:4D, 2D:5D, 3D:4D, 3D:5D, and 4D:5D. All finger-length ratios were significantly higher in girls compared with boys. Ghrelin, leptin, testosterone in boys, estradiol in girls, insulin-like growth-factor I (IGF-I), IGFBP-3, and insulin were analyzed. Leptin and insulin concentrations were lower in boys compared with girls.[...]
In girls, estradiol correlated negatively with 2D:3D (r = −0.51) and 2D:4D (r = −0.49) finger ratios. In boys, ghrelin concentration correlated with most of the finger-length ratios (r = 0.37–0.40). In girls, the relationship of ghrelin with the 2D:3D (r = 0.45) and 2D:4D (r = 0.48) finger ratios was significant. In boys, but not in girls, IGF-I (r = 0.42) and IGFBP-3 (r = 0.44) correlated only with the 2D:4D finger ratio. Leptin and insulin did not correlate with the finger-length ratios. In boys, the most important hormone to characterize several finger-length ratios was ghrelin (13.7–15.6% variance accounted for). Ghrelin and testosterone together accounted for 20.3% (R 2 × 100) of the variance in the 2D:4D ratio. In girls, estradiol was correlated with the 2D:3D ratio (25.7%) and estradiol in combination with ghrelin with the 2D:4D ratio (30.0%). In conclusion, ghrelin appears to be a further biochemical parameter in addition to the sex steroids which correlated with different digit-length ratios at least in boys."
(Jürimäe, T., et al. "Relationships between finger-length ratios, ghrelin, leptin, IGF axis, and sex steroids in young male and female swimmers." European journal of applied physiology 104.3 (2008): 523-529.)

"Ghrelin [...] increase[s] body weight and fat mass [...].
[...]
In addition to its function in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic reward link in inputs to the ventral tegmental area and in the mesolimbic pathway, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food and addictive drugs such as ethanol. [...] Ghrelin has been linked to inducing appetite and feeding behaviors. [...] [G]hrelin does not increase meal size, only meal number. Ghrelin injections also increase an animal's motivation to seek out food, behaviors including increased sniffing, foraging for food, and hoarding food."

(source: Wikipedia article on ghrelin, retrieved 5/8/2016)


One study calls for caution in relating prenatal testosterone to 2D:4D ratio

"Our results show the subtlety of androgen effects on digit ratio, and thus both confirm and refute claims about the value of 2D:4D. On the one hand, the higher mean ratios in individuals with CAIS (complete androgen insensitivity syndrome) than in typical men support the claim that digit ratio is influenced by androgen exposure. On the other hand, the modest size of the difference and the considerable within-group variability challenge the claim that digit ratio serves as a marker of individual differences in prenatal androgen exposure that can be related to other physical and psychological characteristics."
(Berenbaum, Sheri A., et al. "Fingers as a marker of prenatal androgen exposure." Endocrinology 150.11 (2009): 5119-5124.)


Assymetry in 2D:4D digit ratio correlates with circulating oestradiol in women

"Asymmetry in digit ratio [right 2D:4D ratio minus left 2D:4D ratio] correlated positively with oestradiol at each [menstrual] phase, as well as with average levels across the cycle. (...) No other significant correlations were observed between digit ratio variables [2D:4D and 2D:4Dr - 2D:4Dl] and circulating hormone levels [(progestrone and testosterone)]. Our results might suggest that low exposure to androgens and/or high exposure to oestrogens during gestation is a predictor of high oestradiol levels in naturally cycling females of reproductive age. However, considering that it was asymmetry in digit ratio, and not either right or left 2D:4D, that was a significant predictor, it is also possible that these effects reflect more general associations between bilateral asymmetry and circulating oestradiol levels."
(Richards, Gareth, et al. "Digit ratio (2D: 4D) and circulating testosterone, oestradiol, and progesterone levels across the menstrual cycle." Early Human Development 117 (2018): 68-73.)



2D:4D ratio may correspond to prenatal testosterone/estrogen ratio, but does not reflect current testosterone levels


"Consistent with meta-analytic conclusions (Honekopp et al., 2007), digit ratio and [baseline current] testosterone [measured from saliva sample] did not covary among males."
(Mead, Nicole L., et al. "Power Increases the Socially Toxic Component of Narcissism Among Individuals with High Baseline Testosterone.")



No correlation between testosterone in amniotic fluid or maternal plasma and mean 2D:4D (average of right-hand and left-hand 2D:4D) or D[R–L] (right-hand 2D:4D minus left-hand 2D:4D)

"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 neonates. Newborn M2D:4D was negatively correlated with amniotic testosterone in females (P<0.05) but not in males; no significant association was observed between amniotic testosterone and D[R–L] in either sex. In addition, we examined testosterone measured from maternal circulation during the second trimester, and found that it was not a significant predictor of M2D:4D or D[R–L] in male or female infants. Further research should aim to measure the ratio of testosterone to oestradiol present in amniotic fluid and maternal plasma, to examine whether either is a predictor of digit ratio variables at different stages of postnatal development."
(Richards, G., M. Gomes, and T. Ventura. "Testosterone measured from amniotic fluid and maternal plasma shows no significant association with directional asymmetry in newborn digit ratio (2D: 4D)." Journal of developmental origins of health and disease (2018): 1-6.)




Association between right-hand 2D:4D and estrogen recpetor polymporphism in school-aged boys

"The ratio of the lengths of the 2nd and 4th digits (2D:4D) is considered an index of prenatal exposure to androgen. Indeed, androgen receptors have been linked to digit length, but estrogen receptors are rarely investigated in this context. Thus, we investigated the association between estrogen receptor 1 (ESR1) genetic polymorphisms and 2D:4D in school-aged children. (...) Boys with the GG genotype at rs9340799 had a significantly lower 2D:4D in the right hand than boys with the AA/AG genotype (−0.96% lower, 95% confidence interval: −1.68 to −0.24). However, this association was detected only in boys born to non-smoking mothers. No significant differences were found between rs9340799 polymorphisms and 2D:4D among girls. There was also no link between 2D:4D and polymorphisms at rs2234693 and rs2077647. These data suggest that rs9340799 polymorphisms in ESR1 may contribute to digit length and 2D:4D."
(Nishimura, Yoko, Kimihiko Moriya, Sumitaka Kobayashi, Atsuko Araki, Fumihiro Sata, Takahiko Mitsui, Sachiko Itoh et al. "Association between ESR1 polymorphisms and second to fourth digit ratio in school-aged children in the Hokkaido Study." Steroids (2018).)


Digit ratios not only affected by prenatal testosterone (but probably by testosterone-to-estradiol ratios)

"The analysis of the variability in digit ratios provides additional information regarding the magnitude of the potential influence of androgens on digit ratios from both hands. Women with  CAIS  did  not  show  a  reduced  variability  in  digit  ratios,  which  would  be  expected  if androgens solely affect this measure. This is also a replication of the findings from the previ-ous digit ratio study in women with CAIS (Berenbaum et al. 2009) and again indicates that variations  in  digit  ratios  do  not  only  reflect  variations  in  prenatal  androgen  levels,  but  are also under the influence of other factors. In line with these findings, a meta-analysis of digit ratio studies has found that the magnitude of the digit ratio sex difference is smaller than the difference in amniotic testosterone levels (Hönekopp and Watson 2010), and classifica-tion of men and women according to their digit ratios was not very accurate (Berenbaum et al. 2009).Because estradiol receptors in women with CAIS are functional, estrogens might also play an  important  role.  It  has  been  suggested,  for  example,  that  sex  differences  in  digit  ratios result from differences in digit adiposity (Wallen 2009). Because both estradiol and andro-gen receptors have been found in fat tissue, these sex differences might be more strongly related to differences in testosterone-to-estradiol (T:E) ratios, instead of testosterone effects alone (Manning et al. 2014). This view is also in line with the negative association that was found between fetal T:E ratios and digit ratios at age two (Lutchmaya et al. 2004), although it is unknown whether this association is still found in adult digit ratios. (...)
Taken  together,  the  present  results,  along  with  results  from  previous  studies,  are  suggestive of an androgenic influence on both digit ratios and CEOAE amplitudes, while additional non-androgenic  factors  are  also  reflected  in  these  measures  obtained  in  adulthood.  Consequently,  both  measures  cannot  be  assumed  to  provide  a  reliable  indication  of  prenatal androgen  levels,  and  usage  of  these  measures  for  this  purpose  is  not  recommended,  as  it is likely to result in spurious associations. Further research is needed to clarify which other factors might be involved in the sexual differentiation of digit ratios and CEOAEs and what their exact timing and mechanisms of action would be."
(Van Hemmen, Judy, Peggy T. Cohen-Kettenis, Thomas D. Steensma, Dick J. Veltman, and Julie Bakker. "Do sex differences in CEOAEs and 2D: 4D ratios reflect androgen exposure? A study in women with complete androgen insensitivity syndrome." Biology of sex differences 8, no. 1 (2017): 11.)


Maternal urinary sexual hormone levels correlate with offspring 2D:4D in Titi monkeys

"The second‐to‐fourth digit (2D:4D) ratio is a sexually‐dimorphic biomarker for prenatal sex hormone exposure. We investigated whether titi monkeys (Plecturocebus cupreus) exhibit sexually‐dimorphic 2D:4D ratio, and whether variation in 2D:4D ratio correlates with maternal testosterone and estrogen levels during early pregnancy. Subjects were 61 adult titi monkeys (32 males, 29 females). For 26 subjects, maternal urine samples were collected approximately 15–20 weeks before birth and assayed for testosterone and estrone conjugate (E1C). Titi monkeys exhibited a human‐like pattern of sexual dimorphism in right‐hand 2D:4D ratio, with females exhibiting higher 2D:4D ratio than males (β = −0.29, p = 0.023). For left‐hand 2D:4D ratio, high levels of maternal E1C predicted low offspring 2D:4D ratio (β = −0.48, p = 0.009). For right‐hand 2D:4D ratio, high levels of testosterone (β = −0.53, p = 0.005) and testosterone‐to‐E1C ratio (β = −0.41, p = 0.028) predicted low offspring 2D:4D ratio. For 2D:4D ratio asymmetry (right‐hand – left‐hand), high levels of testosterone (β = −0.43, p = 0.03) and testosterone‐to‐E1C ratio (β = −0.53, p = 0.003) predicted low (right‐biased) asymmetry. This is the first report of sexually‐dimorphic 2D:4D ratio in New World monkeys, and the results support a growing literature suggesting prenatal sex hormones may modulate offspring 2D:4D ratio."
(Baxter, Alexander, et al. "Sexual Dimorphism in Titi Monkeys’ Digit (2D: 4D) Ratio is Associated with Maternal Urinary Sex Hormones During Pregnancy." Developmental Psychobiology.)


Study in rats shows no effect of prenatal testosterone treatment on 2D:4D in rats

"The effect of prenatal testosterone on the lengths of the dig-its  was  formerly  studied  in  both  mice  and  rats  (6,  8,  9).  These  studies have reported a positive correlation between testosterone concentration and the length of 4D (2, 6, 8, 9) resulting in a lower 2D:4D (9). In contrast, our results did not show any prolongation of 4D after prenatal testosterone treatment. There are only a few studies reporting no effect of prenatal T on the length of 2D (6, 8). In our study, both treatments resulted in the shortening of 2D, an effect also reported by Talarovičová et al (9). Huber et al (8) showed  no  effect  of  either  T  or  F  on  2D:4D.  Similarly,  in  our  study, there were no differences in the 2D:4D among treatments. These results are in contrast with previously published studies (6, 9) showing a relationship between the concentration of testoster-one and a lower 2D:4D.
(...)
The current study has limitations that should be pointed out. In the present study, the testosterone administration was restricted to the last week of gestation. The use of different doses of testoster-one during different periods of gestation may be more informative. Despite some limitations, to the best of our knowledge, this is the fi rst study analyzing the effect of prenatal hyperandrogenism on 2D:4D in relation to sex differences in laboratory rats using two different  methodologies.  The  results  of  the  anogenital  distance  measurements suggest that the dose of testosterone was adequate. Despite these fi ndings, in both sexes, prenatal testosterone, exog-enous or endogenous, had no effect on the 2D:4D. The results of our study can be explained by Manno et al (2008), who reported that the intrauterine formation of 2D and 4D is a complex process (31). This process can also be related to different testosterone me-tabolites  and  other  steroids  hormones,  not  only  to  testosterone.  In  conclusion,  the  results  of  our  study  demonstrate  that  the  2D:4D does not refl ect prenatal androgen exposure. The effect of prenatal testosterone was observed only in the decreased lengths of 2D and 4D compared to controls. Further studies focusing on the infl  uence of estrogen and other testosterone metabolites in dif-ferent periods of gestation on 2D:4D are necessary."
(Suchonova, M., V. Borbelyova, E. Renczes, B. Konecna, B. Vlkova, J. Hodosy, D. Ostatnikova, and P. Celec. "Does the 2nd and 4th digit ratio reflect prenatal androgen exposure?." Bratislavske lekarske listy 120, no. 9 (2019): 703-710.)


In water voles, 2D:4D digit ratio reliably associated with maternal androgen status

"The 2D : 4D digit ratio in males and females of a water vole (Arvicola amphibius L.) was measured. The analysis of the dependence of this index on gender and the morphophysiological characteristics of the mother (body weight after parturition, testosterone level during pregnancy) was carried out. A similarity was found between littermates in terms of finger index. It was found that the androgen status of the mother during pregnancy and the body weight of the mother after parturition reliably affect the 2D : 4D ratio. The conclusion about the possibility of using the 2D : 4D digit ratio in environmental population studies as a marker of prenatal hormone-related maternal effects was made."
(Nazarovaa, G. G., Proskurnyaka, L. P., & Yuzhika, E. I. (2020). Dependence of the Ratio of the Lengths for the Second and Fourth Fingers (2D: 4D) on the Prenatal Development Conditions in Water Vole (Arvicola amphibius L.). RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY, 51(1).)


Sex difference in 2D:4D not caused by differences in body size

"Introduction
Previous studies suggest that the second to fourth digit ratio (2D:4D) is higher in females than in males. Others claim that this is due to difference in overall body size. It is unclear which, if any, anthropometric measures may impact the ratio.
Aim
To investigate sexual dimorphism of the 2D:4D ratio in seven-year-old children, and associations between 2D:4D and other anthropometric measurements showing difference between girls and boys at this age.
Methods
A total of n=778 children were included in the present analyses. Measurements of finger lengths were performed by digital measurement in hand photocopies. The anthropometric measurements studied were birthweight, recumbent height at birth, present weight, height, BMI, body fat percentage and waist circumference. Sex differences in anthropometric measures (including 2D:4D) were analysed together with correlation between the studied measures.
Results
We found a small but significant difference in 2D:4D between the sexes: boys having a lower ratio than girls. There were no correlations between 2D:4D and any of the anthropometric measurements.ConclusionThere is a sexual dimorphism in 2D:4D that cannot be explained by boys being larger than girls. 2D:4D does not correlate to any of the anthropometric measurements assessed in the present study, and therefore they do not need to be considered confounders in furthers studies involving 2D:4D ratio."

 

2D:4D increases slightly with age in children, but rank order remains stable

"It has been hypothesised that the ratio between the length of the 2nd and 4th digits (2D:4D) is a correlate of prenatal sex steroids, and this relationship is strongest for the right hand. Furthermore, it has been suggested that 2D:4D is sexually dimorphic, the dimorphism is determined early, and 2D:4D among children is stable with growth. Here, we present the first longitudinal study of right and left hand 2D:4D. Our sample was 108 (54 males) Jamaican children. The first measurements were made in 1998 when mean age was 9.68 ± 1.39 years, and a second set of measurements were made in 2002. We found that: (i) there was a small increase in 2D:4D with age which was lowest in the right hand; (ii) 2D:4D was sexually dimorphic, the means for males and females differed in the same direction in the 1998 and 2002 samples, and the sex difference was significant in the 1998 but not in the 2002 sample; (iii) the correlation between the 1998 and 2002 measurements of 2D:4D was high, indicating that rank order of the ratio was stable across year groups; and (iv) the rate of change in 2D:4D did not differ significantly across year groups. We conclude that 2D:4D increases slightly with age in children with the effect less marked for the right hand (i.e. the hand which is likely to show the strongest association with prenatal steroids), 2D:4D is sexually dimorphic from an early age, and the rank order of 2D:4D is stable in children."
(Trivers, R., Manning, J., & Jacobson, A. (2006). A longitudinal study of digit ratio (2D: 4D) and other finger ratios in Jamaican children. Hormones and behavior, 49(2), 150-156.)


Study finds that digit ratio is not a good marker of individual differences in prenatal androgen exposure

"We report the strongest evaluation of the value of 2D:4D as a biomarker for early androgen exposure. Individuals with 46,XY karyotype but no effective prenatal androgen exposure due to complete androgen insensitivity syndrome had digit ratios that were feminized: they were higher than those of typical men and similar to those of typical women. Nevertheless, the effect was modest in size, and there was considerable within-group variability and between-group overlap, indicating that digit ratio is not a good marker of individual differences in prenatal androgen exposure."
(Berenbaum, S. A., Bryk, K. K., Nowak, N., Quigley, C. A., & Moffat, S. (2009). Fingers as a marker of prenatal androgen exposure. Endocrinology, 150(11), 5119-5124.)


Study findings casts doubt on the reliability of the 2D:4D measure as a biomarker for prenatal androgen exposure

  • "We retrospectively study the second-to-fourth digit ratio (2D:4D) in youth with classical Congenital Adrenal Hyperplasia (CAH) and controls.
  • We replicated previously reported associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase in 2D:4D throughout development).
  • The associations between 2D:4D and CAH diagnosis were small and statistically indistinguishable from zero, in the full sample and within sex.
  • Our findings cast doubt on the reliability of the 2D:4D measure as a biomarker for prenatal androgen exposure in behavioral research."

(Nave, G., Koppin, C. M., Manfredi, D., Richards, G., Watson, S. J., Geffner, M. E., ... & Kim, M. S. (2020). No Difference in 2D: 4D Ratio between Youth with Elevated Prenatal Androgen Exposure due to Congenital Adrenal Hyperplasia and Controls. BioRxiv.)

 

Sex differences in the fingers of children are highly correlated with adult finger length ratios

"This paper reports the results of a study using serial radiographs to test for both sex differences in the fingers of infants and children and for a relationship between sex differences in the children and infant finger and adult finger length ratios. This is the first study using long-term serial data to evaluate the validity of finger length ratios as markers. We found not only that sex differences in finger length ratios arise prior to puberty, but that sex differences in the fingers of children are highly correlated with adult finger length ratios. Our results strongly encourage the further use of finger length ratios as markers of perinatal testosterone action."

(McIntyre, M. H., Ellison, P. T., Lieberman, D. E., Demerath, E., & Towne, B. (2005). The development of sex differences in digital formula from infancy in the Fels Longitudinal Study. Proceedings of the Royal Society B: Biological Sciences, 272(1571), 1473-1479.)



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