2D:4D ratios in the first 2 years of life: Stability and relation to testosterone exposure and sensitivity

The relative lengths of the 2nd and 4th digits (2D:4D) may provide an easily measurable and stable anthropometric index of prenatal androgen exposure, but no study has examined the development of 2D:4D in infancy and the potential impact of neonatal testosterone levels. We collected 2D:4D ratios from 364 children between 0 and 2 years of age. Saliva samples were collected from 236 of these children 3 months after birth and analyzed for testosterone. In addition, 259 children provided DNA samples which were genotyped for the CAG repeat polymorphism in the androgen receptor. There was substantial variability across age in 2D:4D. Sex differences were small compared to adults and did not consistently reach statistical significance. This suggests that 2D:4D may not function well as a proxy measure of prenatal testosterone exposure in infancy. In addition, the interaction of salivary T and CAG repeats predicted right hand digit ratio at 12 months and left hand digit ratio at 12 months and 24 months in males. The interaction of salivary testosterone and CAG repeat length also predicted change in left hand 2D:4D from 2 weeks to 12 months in males. This suggests that 2D:4D in adults may reflect, in part, neonatal testosterone exposure. No significant relationships were observed within females. No significant relationships were observed when salivary testosterone and CAG repeats were examined independent of each other. Results have important implications for the design and interpretation of studies which use 2D:4D as a proxy measure of prenatal testosterone exposure.     

Digit ratio (2D:4D) and physical fitness in males and females: Evidence for effects of prenatal androgens on sexually selected traits

It has been suggested that male achievement in sports and athletics is correlated with a putative measure of prenatal testosterone the 2nd to 4th digit ratio (2D:4D). It is not known whether this association also extends to females, or whether the association results from an effect of testosterone on behavior (such as exercise frequency) or on physical fitness. Here, we report for the first time data from two studies which consider associations between 2D:4D and physical fitness in females in addition to males: Study I--in a sample of teenage boys (n = 114) and girls (n = 175), their 'physical education grade' was negatively associated with 2D:4D of the right hand (boys), and right and left hand (girls), and Study II-among a sample of young men (n = 102) and women (n = 77), a composite measure of physical fitness was negatively related to right hand 2D:4D in men and left hand 2D:4D in women. We conclude that 2D:4D is negatively related to physical fitness in both men and women. In Study II, there was evidence that the relationship between physical fitness and 2D:4D in men was mediated through an association with exercise frequency. Thus, 2D:4D in males may be a negative correlate of frequent exercise which then relates to achievement in sports and athletics.     

2D:4D finger-length ratios in children and adults with gender identity disorder

Previous research suggests that prenatal testosterone affects the 2D:4D finger ratio in humans, and it has been speculated that prenatal testosterone also affects gender identity differentiation. If both things are true, then one would expect to find an association between the 2D:4D ratio and gender identity. We measured 2D:4D in two samples of patients with gender identity disorder (GID). In Study 1, we compared the 2D:4D ratios of 96 adult male and 51 female patients with GID to that of 90 heterosexual male and 112 heterosexual female controls. In Study 2, we compared the 2D:4D ratios of 67 boys and 34 girls with GID to that of 74 control boys and 72 control girls. In the sample of adults with GID, we classified their sexual orientation as either homosexual or non-homosexual (in relation to their birth sex) to examine whether or not there were any within-group differences as a function of sexual orientation. In the sample of adult men with GID (both homosexual and non-homosexual) and children with GID, we found no evidence of an altered 2D:4D ratio relative to same-sex controls. However, women with GID had a significantly more masculinized ratio compared to the control women. This last finding was consistent with the prediction that a variance in prenatal hormone exposure contributes to a departure from a sex-typical gender identity in women.     

Bonobos have a more human-like second-to-fourth finger length ratio (2D:4D) than chimpanzees: a hypothesized indication of lower prenatal androgens

The ratio of the second-to-fourth finger lengths (2D:4D) has been proposed as an indicator of prenatal sex differentiation. However, 2D:4D has not been studied in the closest living human relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). We report the results from 79 chimpanzees and 39 bonobos of both sexes, including infants, juveniles, and adults. We observed the expected sex difference in 2D:4D, and substantially higher, more human-like, 2D:4D in bonobos than chimpanzees. Previous research indicates that sex differences in 2D:4D result from differences in prenatal sex hormone levels. We hypothesize that the species difference in 2D:4D between bonobos and chimpanzees suggests a possible role for early exposure to sex hormones in the development of behavioral differences between the two species.     

Digit ratio (2D:4D) and the spatial representation of magnitude

Digit ratio (as a putative indicator of prenatal androgen exposure) is related to a range of sexually dimorphic abilities, including spatial skills and mathematical ability. This study examined a phenomenon known as the SNARC effect (Spatial Numerical Association of Response Codes), which is taken as evidence of a mental representation of magnitude along a left-right-oriented number line, with low magnitudes associated with the left side of space, and high numbers with the right side of space. Participants made a parity judgement of numbers with responses made with a left key to odd numbers and a right key to even numbers. This was reversed for a second block of trials. Response times to numbers one to nine with both the right and left hand were calculated, and regression analyses conducted to analyse whether lower magnitudes were responded to faster with the left hand and higher magnitudes with the right hand. Participants with lower (more masculine) digit ratios on the right hand showed a stronger SNARC effect compared to participants with high digit ratios. This pattern of results was also found when the analyses were conducted separately for men and women. Results from left hand digit ratios indicated that only low digit ratio females showed a significant SNARC effect. These findings add to a growing literature on the relationship between digit ratio and cognitive abilities; in this case, simple cognitive representations that are accessed automatically rather than complex skills such as mental rotation or "mathematics" where a variety of solution strategies may be utilised.     

Testing the prenatal androgen hypothesis: measuring digit ratios, sexual orientation, and spatial abilities in adults

The present study examined whether the following variables putatively associated with prenatal androgens are inter-related in women: spatial abilities, sexual orientation, and 2nd to 4th finger (digit) length ratio (2D:4D). Participants were 99 healthy premenopausal women tested in the menstrual phase of the ovarian cycle between 0800 and 0930 hr. Women completed the Kinsey scales of sexual orientation, and were either strictly heterosexual (HS; N=79) or not-strictly heterosexual (NHS; N=20). Photocopies of the two hands were collected, and participants completed the revised Vandenberg Mental Rotations test, the Paper Folding test, and a short version of the Guilford-Zimmerman Spatial Orientation Test. Results showed that NHS women exhibited superior spatial ability relative to HS women. No significant difference was found between the HS and NHS women in the 2D:4D digit ratio. There was no association between the digit ratio and spatial performance. These results support an association between increased spatial abilities and heteroflexible sexual orientation, which may possibly be mediated by high prenatal androgens.     

Testosterone enhancement during pregnancy influences the 2D:4D ratio and open field motor activity of rat siblings in adulthood

In humans, the relationship between the prenatal testosterone exposure and the ratio of the second and the fourth digits (2D:4D) has been extensively studied. Surprisingly, data on this relationship have thus far been lacking in experimental animals such as rats. We studied the effect of maternal testosterone enhancement during pregnancy on the digit ratio and open field activity of adult progeny in Wistar rats. Elevated levels of maternal testosterone resulted in lower 2D:4D ratios and an elongated 4D on the left and right forepaws in both males and females. We found no sex difference in 2D:4D in control animals. In the open field test, control females were more active than control males and testosterone females, while the activity of testosterone females did not differ from that of control males. We found a positive correlation between motor activity and the right forepaw 2D:4D ratio of control males and females. Prenatal exposure to testosterone resulted in the disappearance of this correlation in both males and females. Our results show that elevated levels of testosterone during the prenatal period can influence forepaw 4D length, 2D:4D ratio, and open field motor activity of rats, and that these variables are positively correlated. Thus, this approach represents a noninvasive and robust method for evaluating the effects of prenatal testosterone enhancement on anatomical and physiological parameters.     

The second to fourth digit ratio and variation in the androgen receptor gene

The second to fourth digit ratio (2D:4D) is sexually dimorphic, with lower mean values in males compared to females. It has been suggested that the sex difference in 2D:4D is determined prenatally, 2D:4D is negatively related to prenatal testosterone and positively to prenatal oestrogen, and that 2D:4D is a marker for levels of sex steroids during brain organisation. There is growing evidence that many sex-dependent behaviours are correlated with 2D:4D. However, there is no direct evidence for an effect of prenatal sex steroids on the digit ratio. The response to prenatal testosterone is dependent on the amount produced and the foetal sensitivity to the hormone. Variation in the X-linked androgen receptor gene (AR) determines sensitivity to testosterone. Alleles of AR with low numbers of CAG triplets respond to testosterone with high transactivational activity, while high numbers of CAG's are associated with increased insensitivity to testosterone. We show in a sample of 50 men (49 Caucasian subjects, 1 Caucasian/Chinese subject) that 2D:4D is a phenotypic correlate of AR structure. Right-hand 2D:4D was positively correlated with CAG number and individuals with low 2D:4D in their right hand compared to left hand had AR alleles with low CAG numbers. We discuss the implications of our findings for our understanding of the aetiology of 2D:4D, its relationships with sex-dependent behaviours, and the evolutionary implications of variation in 2D:4D and AR.     

Differences in the 2nd to 4th digit length ratio in humans reflect shifts along the common allometric line

Ratios often lead to biased conclusions concerning the actual relationships between examined traits and comparisons of the relative size of traits among groups. Therefore, the use of ratios has been abandoned in most comparative studies. However, ratios such as body mass index and waist-to-hip ratio are widely used in evolutionary biology and medicine. One such, the ratio of the 2nd to the 4th finger (2D : 4D), has been the subject of much recent interest in both humans and animals. Most studies agree that 2D : 4D is sexually dimorphic. In men, the 2nd digit tends to be shorter than the 4th, while in women the 2nd digit tends to be of the same size or slightly longer than the 4th. Nevertheless, here we demonstrate that the sexes do not greatly differ in the scaling between the 2nd and 4th digit. Sexual differences in 2D : 4D are mainly caused by the shift along the common allometric line with non-zero intercept, which means 2D : 4D necessarily decreases with increasing finger length, and the fact that men have longer fingers than women. We conclude that previously published results on the 2D : 4D ratio are biased by its covariation with finger length. We strongly recommend regression-based approaches for comparisons of hand shape among different groups.     

Digit length ratios predict reactive aggression in women, but not in men

Considerable evidence suggests that digit length and dermatoglyphic asymmetry patterns in the hand are affected by early exposure to androgens. Because androgens play an important role in sexual differentiation of morphological and behavioral traits, digit length patterns often display sex differences. When present, sex differences in digit lengths are more pronounced on the right side as compared to the left side. Moreover, the ratio of the second to fourth digit length (2D:4D) in the right hand is inversely correlated with testosterone (T) in men. Because T is implicated in agonistic behavior, 2D:4D may be used as a marker of androgen exposure and subsequent behavioral variation in adulthood. Consequently, we investigated the relationships among 2D:4D, directional asymmetry of 2D:4D (left hand 2D:4D minus right hand 2D:4D) as a variant of T, and human reactive aggression. One hundred young men (n = 51) and women (n = 49) participated in our experiments (mean age = 20.1 years). Participants called two noncompliant confederates to solicit donations for a fictitious charity organization and selected follow-up letters after the calls. The force exerted when hanging up the phone and the "tone" of the follow-up letters were used to assess reactive aggression. High aggression scores were associated with high directional asymmetry of 2D:4D and masculinized (low) right hand 2D:4D, only in females and under high provocation. Directional asymmetry of 2D:4D was positively correlated with T in males (pooled data, n = 97). Taken together, these data confirm the predominantly right-sided influence of androgens on digit length and suggest that digit length ratios may be associated with female reactive aggression when sufficient provocation is present.     

Second to fourth digit ratio (2D:4D) and concentrations of circulating sex hormones in adulthood

Background  

The second to fourth digit ratio (2D:4D) is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating concentrations of sex hormones and SHBG measured in adulthood was associated with 2D:4D.     

Finger-length ratios show evidence of prenatal hormone-transfer between opposite-sex twins

Finger-length ratio (second to fourth finger; 2D:4D) has been associated with various measures thought to be related to prenatal androgens. In addition, hormone-transfer theory posits that hormones can transfer between twins. We examined 2D:4D in same-sex (SS) and opposite-sex (OS) dizygotic twins to test both propositions. Results show that 2D:4D is masculinized in OS females compared to SS females. This provides strong evidence that 2D:4D is laid down prenatally, and that hormones (likely androgens) can transfer from male to female fetuses. Implications for developmental timeframes for both hormone-transfer and 2D:4D are discussed.     

Individual differences in women''s facial preferences as a function of digit ratio and mental rotation ability

The second-to-fourth digit ratio (2D:4D) and mental rotation (MR) ability are sexually dimorphic traits that appear early in development and have been correlated with exposure to prenatal androgens (Grimshaw, Sitarenios, & Finegan, 1995; Lutchmaya, Baron-Cohen, Raggatt, Knickmeyer, & Manning, 2004). The current study examined how 2D:4D and MR differences among women of European descent (N=41) were related to their (a) preferences for male faces: attractive (ATM), short-term (STM), and long-term mate (LTM), and (b) psychological femininity and masculinity, as measured by the Bem Sex-Role Inventory (BSRI) (Bem, 1981). To examine potential changes in facial preferences over their menstrual cycle, participants' preferences were measured during two experimental sessions separated by 2 weeks. The results indicated that (a) femininity scores decreased with decreasing 2D:4D, (b) masculinity scores increased with faster MR, (c) women preferred a more masculine male face for an STM than for an LTM, and (d) preference changes over the menstrual cycle varied systematically with 2D:4D. When compared with women with high 2D:4D ratios, low 2D:4D women (e) preferred a more masculine LTM, (f) recalled less parental bonding, (g) had shorter intimate relationships, and (h) reported more menstrual irregularity. The results are interpreted as support for an interactive hormonal theory of physical attraction.     

The relative lengths and weights of metacarpals and metatarsals in baboons (papio hamadryas)

The lengths and weights of metacarpals and metatarsals were measured in two collections of baboon skeletons-33 animals, all born and raised in the wild, and 60 animals, nearly all born and raised in captivity. For both length and weight, ratios were constructed for all possible pairings of the five bones in each individual hand and foot. The pattern of results was not identical for the two collections, but substantial sex differences existed in both collections for many of the ratios calculated. Nearly all of the large sex differences were in the direction of the length or weight ratio being smaller for males than for females. For the length ratios showing the largest sex differences, those differences were larger for the right hand than for the left, and larger for the left foot than for the right, but this pattern was less evident for the weight ratios. Some length ratios for human fingers show sex differences of the sort seen in the metacarpals and metatarsals of these baboons, and the human differences in relative length exist early in life. The implication is that the marked sex difference in androgen exposure during prenatal development may effect the relative size of the individual bones of the extremities in male and female humans and baboons. The relative sizes of the bones of the hand and foot may provide helpful supplemental information on the relations between species, thus making the study of hand and foot bones in other primates and mammals worthwhile.     

Experimental manipulation of yolk testosterone affects digit length ratios in the ring-necked pheasant (Phasianus colchicus)

In humans, most of the mammals and one bird species studied so far, the relative length of individual digits is sexually dimorphic. Most studies of humans have been concerned with the ratio between second (2D) and fourth digits (4D), whereas some studies of humans and other mammals have also investigated other digit ratios. Inter- and intra-sexual variation in 2D:4D may depend on differential exposure to androgens during embryonic life, and the genetic mechanisms linking 2D:4D to androgens may be mediated by Hox genes. Because Hox genes are conserved in vertebrates, similar patterns of variation in digit ratios might be expected across vertebrate classes. The observation of correlations between digit ratios and physiological, psychological and performance traits in humans has generated interest in exploring the possibility that digit ratios are a marker of embryonic exposure to androgens, which have diverse consequences on several phenotypic traits. However, the hypothesis that digit ratios depend on androgen effects during development has never been tested experimentally. In this study, we increased testosterone concentration in ring-necked pheasant eggs and measured length ratios between the second, third and fourth digits of both feet in fully grown offspring. Females from testosterone-injected eggs had larger 2D:3D in the left foot, whereas this was not the case in males. The other digit ratios were unaffected by hormone treatment in both sexes. However, digit ratios showed no sexual dimorphism among controls. Thus, present results are consistent with the hypothesis that variation in testosterone levels during development affects digit ratios.     

Digit ratio (2D:4D) and performance in male surfers

The relative length of the second and fourth digits (2D:4D) is thought to be negatively related to prenatal testosterone and positively related to prenatal estrogen. Low 2D:4D has been linked to various measures of performance in a range of sports (e.g., soccer, rugby). In this study, we consider the relationship between 2D:4D and performance among male surfers. Our sample comprised 46 competitors in the Men's 5-star Professional World Qualifying Series surfing competition in Newquay, United Kingdom, in 2009. Three experienced surfing coaches rated the participants for overall surfing ability. The coach's ratings were significantly correlated with one another and an overall measure of surfing performance was obtained by calculating the mean of the 3 ratings. In addition, the final placing of the Newquay competition was used as an additional performance measure. Mean 2D:4D (SD) was as follows: right 0.994 (0.023) and left 0.976 (0.028). We found that right 2D:4D (but not left 2D:4D or right-left 2D:4D) was significantly negatively correlated with coaches' ratings (r(s) = 0.58) and the competition result (r(s) = 0.30). It appears that in line with other sports that low right 2D:4D (high prenatal testosterone and low prenatal estrogen) correlates to high surfing ability in men.     

Heritability of digit ratio (2D:4D) in rhesus macaques (<Emphasis Type=Italic>Macaca mulatta</Emphasis>)

The second-to-fourth digit ratio (2D:4D) is a putative biomarker for prenatal androgen effects, which has been widely employed to study androgenic-programming effects on shaping sex-linked traits and behaviours in humans. This approach is now increasingly applied to non-human species. Heritability studies of 2D:4D in both humans and zebra finches indicate substantial genetic contributions to the expression of this trait. This study examines the heritability of 2D:4D in rhesus macaques, based on the resemblance of mother–infant dyads, to see how these compare with human values. Results suggest that familial resemblance in 2D:4D is also strong in rhesus monkeys. Heritability estimates were within the range of estimates from human studies. These preliminary results suggest that the strength of heritability of 2D:4D may generalize across taxa.