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.     

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) 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.     

Otoacoustic emissions,auditory evoked potentials and self-reported gender in people affected by disorders of sex development (DSD)

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) — (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46,XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) – the male-typical pattern – than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD.     

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.     

Effects of early androgens on sex-typed activities and interests in adolescents with congenital adrenal hyperplasia

The goal of this study was to examine the relation of early androgen exposure to sex-typed activities and interests in adolescence. Participants aged 9-19 years included 24 girls and 18 boys with congenital adrenal hyperplasia (CAH) and 16 unaffected sisters and 24 unaffected brothers who served as controls. Using standardized questionnaires, adolescents reported on their participation in sex-typed activities and interest in sex-typed occupations, and parents reported on the adolescents' activities. As hypothesized, girls with CAH showed sex-atypical preferences: increased interest in male-typical activities and careers and reduced interest in female-typical activities and careers compared to the unexposed control girls. These results extend findings of sex-atypical play in young girls with CAH and suggest that the sex-atypical activities and interests of females with CAH reflect direct effects of androgens on the developing brain rather than social responses to virilized genitalia. These results also suggest that population sex differences in activities and interests arise in part from sex differences in early androgens.     

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.     

Prenatal hormones and childhood sex segregation: playmate and play style preferences in girls with congenital adrenal hyperplasia

We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically developing children and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play.     

Low digit ratio 2D:4D in alcohol dependent patients

The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency.     

Gendered occupational interests: prenatal androgen effects on psychological orientation to Things versus People

There is considerable interest in understanding women's underrepresentation in science, technology, engineering, and mathematics careers. Career choices have been shown to be driven in part by interests, and gender differences in those interests have generally been considered to result from socialization. We explored the contribution of sex hormones to career-related interests, in particular studying whether prenatal androgens affect interests through psychological orientation to Things versus People. We examined this question in individuals with congenital adrenal hyperplasia (CAH), who have atypical exposure to androgens early in development, and their unaffected siblings (total N = 125 aged 9 to 26 years). Females with CAH had more interest in Things versus People than did unaffected females, and variations among females with CAH reflected variations in their degree of androgen exposure. Results provide strong support for hormonal influences on interest in occupations characterized by working with Things versus People.     

Digit ratio predicts sense of direction in women

The relative length of the second-to-fourth digits (2D:4D) has been linked with prenatal androgen in humans. The 2D:4D is sexually dimorphic, with lower values in males than females, and appears to correlate with diverse measures of behavior. However, the relationship between digit ratio and cognition, and spatial cognition in particular, has produced mixed results. In the present study, we hypothesized that spatial tasks separating cue conditions that either favored female or male strategies would examine this structure-function correlation with greater precision. Previous work suggests that males are better in the use of directional cues than females. In the present study, participants learned a target location in a virtual landscape environment, in conditions that contained either all directional (i.e., distant or compass bearing) cues, or all positional (i.e., local, small objects) cues. After a short delay, participants navigated back to the target location from a novel starting location. Males had higher accuracy in initial search direction than females in environments with all directional cues. Lower digit ratio was correlated with higher accuracy of initial search direction in females in environments with all directional cues. Mental rotation scores did not correlate with digit ratio in either males or females. These results demonstrate for the first time that a sex difference in the use of directional cues, i.e., the sense of direction, is associated with more male-like digit ratio.     

Digit Ratio (2D:4D) and Handgrip Strength in Hani Ethnicity

Introduction

The ratio of the length of the second finger to the fourth finger (2D:4D) in humans is considered as a putative marker of prenatal exposure to testosterone, and has been progressively adopted as one useful tool to evaluate the effect of prenatal hormones in some traits such as physical ability. Handgrip strength is one authentic measure of physical ability and is generally used on the anthropological research within an evolutionary viewpoint.

Methods

Here we present the first evidence on 2D:4D and handgrip strength on adult participants of Hani ethnicity and explore the relationship between digit ratio (2D:4D) and handgrip strength. We examined 2D:4D and handgrip strength of 80 males and 60 females at Bubeng village, in the Yunnan province of China.

Results

The mean 2D:4D in females was higher than that in males for each hand. Females showed significantly higher 2D:4D than males in the right hand rather than in the left hand. Males displayed significantly higher handgrip strength than females for both hands. Handgrip strength decreased with age for both sexes. A significant negative correlation between 2D:4D and handgrip strength was found in the right hand of males.

Conclusion

The relationship between 2D:4D and handgrip strength may be attributed to evolutionary drive of sexual selection operating on fetal programming.     

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.     

Digit ratio (2D:4D) and handgrip strength in subjects of Han ethnicity: Impact of sex and age

The ratio of the length of the second finger to the fourth finger (2D:4D) is considered to be a putative proxy of prenatal exposure to testosterone, and has been increasingly used as a promising tool to evaluate the impact of prenatal androgenization in humans in such traits as physical performance. In this study, for the first time, we present 2D:4D data on adult participants of Han ethnicity. We consider the sexual dimorphism of 2D:4D and handgrip strength, and also report the relationship between 2D:4D and handgrip strength of males and females. The sample consisted of 54 males and 55 females recruited from a remote village in the Qinling Mountains, China. We found sexual dimorphism of both 2D:4D and handgrip strength, i.e., males had lower 2D:4D and right‐left 2D:4D than females and greater handgrip strength than females. There was a sex‐specific correlation between 2D:4D and handgrip strength, i.e., 2D:4D in the right hand was negatively correlated with handgrip strength in males but not in females. This relationship may be driven by sexual selection operating on fetal programming. Am J Phys Anthropol 149:266–271, 2012. © 2012 Wiley Periodicals, Inc.     

Risk Preferences and Prenatal Exposure to Sex Hormones for Ladinos

Risk preferences drive much of human decision making including investment, career and health choices and many more. Thus, understanding the determinants of risk preferences refines our understanding of choice in a broad array of environments. We assess the relationship between risk preferences, prenatal exposure to sex hormones and gender for a sample of Ladinos, which is an ethnic group comprising 62.86% of the population of Guatemala. Prenatal exposure to sex hormones has organizational effects on brain development, and has been shown to partially explain risk preferences for Caucasians. We measure prenatal exposure to sex hormones using the ratio of the length of the index finger to the length of the ring finger (2D:4D), which is negatively (positively) correlated with prenatal exposure to testosterone (estrogen). We find that Ladino males are less risk averse than Ladino females, and that Ladino males have lower 2D:4D ratios than Ladino females on both hands. We find that the 2D:4D ratio does not explain risk preferences for Ladinos. This is true for both genders, and both hands. Our results highlight the importance of exploring the behavioral significance of 2D:4D in non-Caucasian racial groups.     

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 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.     

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.     

Personality and congenital adrenal hyperplasia: Possible effects of prenatal androgen exposure

Influences of early androgen exposure on personality were investigated. Participants were either exposed to abnormal levels of androgens prenatally due to congenital adrenal hyperplasia (CAH, 40 females, 29 males), or were unaffected relative controls (29 females, 30 males). Compared to female controls, females with CAH were less tender-minded (p < .001; 16 Personality Factor Inventory (16PF)), and reported greater physical aggression (p = .03; Reinisch Aggression Inventory) and less interest in infants (p < .001; Melson's Questionnaire), but did not differ in dominance (16PF). Males with CAH did not differ from male controls in interest in infants but were less dominant (p = .008), and more tender-minded (p = .033) and reported reduced physical aggression (p = .025). Thus, both males and females with CAH showed alteration in three of the four constructs assessed. Prenatal androgen exposure may shift some, but not all, personality characteristics in the male-typical direction in females. It may also be associated with a decrease in some aspects of male-typical personality development in males, although personality differences in males with CAH could relate to illness.     

Relative digit lengths and testosterone levels in Guinea baboons

A growing body of literature suggests that the ratio of the lengths of the second to fourth digits (2D:4D) on human hands is sexually dimorphic and associated with prenatal exposure to gonadal hormones, circulating serum testosterone, and a number of psychological and behavioral measures. Little research has investigated digit ratios in nonhuman species. In the present study, we investigated sex differences in digit ratios and their possible association with serum testosterone in a captive group of Guinea baboons (Papio papio). Contrary to the sex difference typically reported in humans, male baboons exhibited a substantially larger 2D:4D than did female baboons. Consistent with the human data, however, lower 2D:4D was associated with higher serum testosterone among the males. The present findings suggest that the relationship between digit ratios and male gonadal hormones may be phylogenetically well-conserved, although they also suggest possible species differences in the causal relationships between developmental mechanisms and sex-differentiated digit length patterns.