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.     

Digit ratio (2D:4D) and behavioral differences between inbred mouse strains

Digit ratio (2D:4D) is a trait, which is sexually differentiated in a variety of species. In humans, males typically have shorter second digits (2Ds) (index fingers) compared to fourth digits (4Ds) (ring fingers) whereas females' fingers are more equal in length. Smaller, more masculine, digit ratios are thought to be associated with higher prenatal testosterone levels, greater sensitivity to prenatal androgens or both. Men with more masculine digit ratios have shown increased ability, achievement and speed in sports and tend to report that they are more physically aggressive. Previous research has shown the same sexually differentiated pattern in the hind paws of laboratory mice as in human hands, males have lower 2D:4D than females. We measured hind paw digit ratio in mice of eight inbred strains. These measurements were made while blind to strain, sex and whether the paw was from the left or right side. We found large differences in digit ratio between the strains and suggest that inbred mice are a promising system for investigating the correlation between digit ratio and behavioral traits.     

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.     

The ratio of 2nd to 4th digit length and male homosexuality

Sexual orientation may be influenced by prenatal levels of testosterone and oestrogen. There is evidence that the ratio of the length of 2nd and 4th digits (2D:4D) is negatively related to prenatal testosterone and positively to oestrogen. We report that (a) 2D:4D was lower in a sample of 88 homosexual men than in 88 sex- and age-matched controls recruited without regard to sexual orientation, (b) within the homosexual sample, there was a significant positive relationship between mean 2D:4D ratio and exclusive homosexuality, (c) overall, there was a decrease in 2D:4D from controls to homosexual men to bisexual men and (d) fraternal birth order, a positive predictor of male homosexuality, was not associated with 2D:4D in a sample of 240 Caucasian men recruited without regard to sexual orientation and 45 homosexual men.Further work is needed to confirm the relationships between 2D:4D and sexual orientation. However, these and other recent data tend to support an association between male homosexuality and high fetal testosterone. Very high testosterone levels may be associated with a sexual preference for both men and women.     

Masculinized finger length patterns in human males and females with congenital adrenal hyperplasia

The ratio of the length of the second digit (2D) to the length of the fourth digit (4D) is greater in women than in men. Since androgens are involved in most somatic sex differences and since the sexual dimorphism in 2D:4D is stable from 2 years of age in humans, it was hypothesized that finger length pattern development might be affected by early androgen exposure. Human females with congenital adrenal hyperplasia (CAH) are exposed prenatally to higher than normal levels of adrenal androgens, providing an opportunity to test the effects of early androgen exposure on digit ratios. The 2D:4D was calculated for females with CAH, females without CAH, males with CAH, and males without CAH. Females with CAH had a significantly smaller 2D:4D on the right hand than did females without CAH. Males with CAH had a significantly smaller 2D:4D on the left hand than did males without CAH. A subset of six males with CAH had a significantly smaller 2D:4D on both hands compared with their male relatives without CAH. These results are consistent with the idea that prenatal androgen exposure reduces the 2D:4D and plays a role in the establishment of the sex difference in human finger length patterns. Finger lengths may therefore offer a retrospective marker of perinatal androgen exposure in humans.     

The use of digit ratios as markers for perinatal androgen action

Since the ratio of the second-to-fourth finger length was first proposed as a marker for prenatal androgen action in 1998, over 100 studies have been published that have either further tested the association between the digit ratio and prenatal androgens, or employed digit ratios as a marker to investigate the association between prenatal androgens and a variety of outcomes, including behavior, fertility, and disease risks. Despite the clear demand for an adult marker of prenatal androgen action and increased use of digit ratios as such a marker, its validity remains controversial. This review (1) evaluates current evidence for the relationship between digit ratios and prenatal androgens (using experimentation with animal models, amniotic testosterone, and congenital adrenal hyperplasia case-control studies), (2) describes opportunities for future validation tests, and (3) compares the potential advantages and disadvantages of digit ratio measures with more established methods for studying the effects of prenatal androgens.     

Digit ratio (2D:4D) and rowing ergometer performance in males and females

Fetal and adult testosterone may be vital in the establishment and maintenance of sex-dependent abilities associated with male physical competitiveness. It has been shown that digit ratio (2D:4D) is negatively associated with prenatal testosterone, and it is also negatively associated with ability in sports such as football, skiing, middle distance running, and endurance running, which are dependent upon an efficient cardiovascular system. The relationship between digit ratio and sports requiring high power (physical strength) output in addition to well-developed cardiovascular systems has not been defined. This study investigated this association in male and female young adult rowers. Participants (77 male and 70 female) were student rowers encompassing a range of abilities from the University of Cambridge. Bilateral digit measurements were taken blind from each subject using Mitutoyo vernier calipers. Rowing performance over 2,000 m was assessed using the Concept 2 rowing ergometer. Significant negative correlations were observed between 2,000 m ergometer performance and male digit ratios, which persisted following adjustment for rowing experience and height. However, no such significant association was found in females despite a comparable sample size. Our data indicate that digit ratio is a predictor of ability in rowing, a sport which requires both cardiovascular efficiency and high power output, in males but not females. This in turn suggests that fetal testosterone exposure has long-term effects on traits associated with physical power in males but not females, suggesting a sex-difference in the capacity to respond to such exposures.     

Digit ratio, color polymorphism and egg testosterone in the Australian painted dragon

Variation in exposure to sex hormones during early development contributes to phenotypic plasticity in vertebrate offspring. As a proposed marker for prenatal sex hormone exposure and because of their association with various physiological and behavioral characteristics, digit ratio and/or digit length have received notable interest within the field of evolutionary ecology. However, the validity of digit measures as a proxy of prenatal sex hormone exposure is controversial and only few studies have provided direct evidence for the link between digit development and prenatal sex hormones. Here, we report morph- and sex-specific variation in digit ratio in wild painted dragon lizards (Ctenophorus pictus). Lizards expressing a yellow bib have significantly larger third-to-fourth toe ratios (3D:4D) than lizards without a bib. Males have significantly smaller 3D:4D than females. Furthermore, we show that experimental elevation of yolk testosterone significantly increases 3D:4D in hatchling painted dragon lizards, but has no influence on hatchling size. Our results provide direct and indirect evidence for the involvement of prenatal sex steroids in digit development and it is suggested that digit ratio may be used as a biomarker for prenatal steroid exposure in this reptilian species. As such, digit ratio may provide a useful tool to study temporal or spatial differences in the proximate hormonal mechanisms modulating physiological and behavioural phenotypes.     

Relationship between the 2D:4D and prenatal testosterone,adult level testosterone,and testosterone change: Meta-analysis of 54 studies

The ratio between the hands' second to the fourth finger (2D:4D) is commonly hypothesized to result from prenatal testosterone. The 2D:4D has also been hypothesized to relate to adult-level testosterone and, more recently, to the testosterone response to a challenging situation. In the present work, we tested these core assumptions. Drawing from, in total, 54 studies and 8077 participants, we investigated whether the 2D:4D is related to adult level testosterone (44 studies), testosterone change (6 studies), and prenatal testosterone (10 studies). We found no evidence of the relationship between the above testosterone types and digit ratios. Furthermore, there was no relationship between testosterone and the right and left 2D:4D, male and female 2D:4D, and the 2D:4D and testosterone measurement (i.e., measured in blood or saliva). However, we found some evidence that prenatal testosterone measured in amniotic fluid (but not cord blood) might be related to the digit ratios—further studies are necessary to validate this observation. In summary, considering the current state of knowledge, any conclusions drawn from the assumption of the digit ratios as the proxy for testosterone (prenatal, adult level, or testosterone change under a challenging situation) warrant great caution.     

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.     

The relationships between otoacoustic emissions and relative lengths of fingers and toes in humans

Both otoacoustic emissions (OAEs) and the relative length of the index and ring fingers (the 2D:4D ratio) exhibit large sex differences, and both exhibit masculinization effects in female homosexuals and bisexuals. Because these sex differences exist in young children, the implication is that both types of measure are affected by prenatal androgen exposure, but it has been unknown to what degree these two types of measure are related. Accordingly, OAEs and the relative lengths of the fingers and the toes were measured in 59 heterosexual females, 55 heterosexual males, 29 homosexual females, and 33 homosexual males. The correlations between the two types of measure were unexpectedly quite low in both the heterosexual and nonheterosexual groups. For example, the correlation between number of spontaneous OAEs per ear and 2D:4D was less than 0.25, for both sexes and both sexual orientations. One interpretation of these results is that the prenatal hormonal mechanisms producing the sex differences in OAEs differ in quality, degree, or timing from those producing the sex differences in relative finger length. That is, OAEs and 2D:4D may be windows onto slightly different prenatal processes or times during prenatal development. Measures of mental-rotation ability also were obtained on these participants, and those correlations with relative finger length also were small.     

Evolution of sexual dimorphism in the digit ratio 2D:4D--relationships with body size and microhabitat use in iguanian lizards

The ratio between lengths of digit II and IV (digit ratio 2D:4D) is a morphological feature that likely affects tetrapod locomotor performances in different microhabitats. Modifications of this trait may be triggered by changes in steroids concentrations during embryo development, which might reflect direct selection acting on digit ratio or be solely a consequence of hormonal differences related for example to body size. Here we apply both conventional and phylogenetic analyses on morphological data from 25 lizard species of 3 families of Iguania (Iguanidae, Polychrotidae, and Tropiduridae), in order to verify whether selective pressures related to locomotion in different microhabitats could override the prenatal developmental cues imposed on the digit ratio 2D:4D by differences in body size between males and females. Data suggest that this trait evolved in association with ecological divergence in the species studied, despite the clear effect of body size on the digit ratio 2D:4D. The ecological associations of size-corrected digit ratios were restricted to one sex, and females of species that often use perches exhibited small digit ratios in the front limbs, which translated into larger sexual dimorphism indexes of arboreal species. The results, together with the subsequent discussion, provide outlines for further investigation about possible developmental mechanisms related to the evolution of adaptive changes in digit lengths that may have occurred during the evolution of ecological divergence in squamates.     

Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D–5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.     

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.     

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.     

Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies

A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence.     

2D:4D ratios predict hand grip strength (but not hand grip endurance) in men (but not in women)

In humans, the ratio of the second digit to the fourth digit — the 2D:4D ratio — is a sexually dimorphic trait (men, on average, exhibit lower 2D:4D ratios than do women) that is influenced by prenatal testosterone exposure, but not by circulating testosterone levels in adulthood. Consequently, 2D:4D ratios are commonly used as indirect measures of prenatal testosterone exposure. Many studies have examined the associations of 2D:4D ratios with sexually dimorphic adaptations that are thought to be influenced by such exposure, including physical prowess. The existing literature, however, remains unclear as to (1) whether 2D:4D ratios are more closely linked to strength or to endurance; and (2) whether 2D:4D ratios are linked with physical prowess for both men and women. In 100 men and 122 women, the relationship of 2D:4D ratios with maximum voluntary contraction (MVC) scores (hand grip strength) and maximum endurance time (MET) scores (local muscular endurance) using a hand dynamometer was examined. Controlling for age, height, weight, and average digit length, we found that 2D:4D ratios significantly predicted MVC scores in men, but not in women. 2D:4D ratios did not significantly predict MET scores for either sex. These results suggest that prenatal testosterone exposure in this sample is significantly related to hand grip strength in men, but not in women (and to local muscular endurance in neither sex), and, therefore, that strength, rather than local muscular endurance, potentially drives the relationship between 2D:4D ratios and physical prowess.     

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.     

Selective breeding for a behavioral trait changes digit ratio

The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D:4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D:4D ratio is lower (i.e. more "masculinized") in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D:4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D:4D. This apparent "feminization" in mice is opposite to the relationship seen between 2D:4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D:4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes.     

Digit Ratio (2D∶4D) Differences between 20 Strains of Inbred Mice

The second to fourth digit ratio (2D∶4D) is sexually differentiated in a variety of species, including humans, rats, birds, and lizards. In humans, this ratio tends to be lower in males than in females. Lower digit ratios are believed to indicate increased prenatal testosterone exposure, and are associated with more masculinized behavior across a range of traits. The story seems more complicated in laboratory mice. We have previously shown that there is no sex difference in the digit ratios of inbred mice, but found behavioral evidence to suggest that higher 2D∶4D is associated with more masculinized behaviors. Work examining intrauterine position effects show that neighbouring males raise pup digit ratio, suggesting again that higher digit ratios are associated with increased developmental androgens. Other work has suggested that masculinization is associated with lower digit ratios in lab mice. Here, we examine the fore- and hindlimb digit ratios of 20 inbred mouse strains. We find large inter-strain differences, but no sexual dimorphism. Digit ratios also did not correlate with mice behavioral traits. This result calls into question the use of this trait as a broadly applicable indicator for prenatal androgen exposure. We suggest that the inbred mice model presents an opportunity for researchers to investigate the genetic, and gene-environmental influence on the development of digit ratios.