BACKGROUND: The second-to-fourth digit ratio (2D:4D) is thought to reflect prenatal exposure to sex steroids. We investigated the relationship between 2D:4D and odds of prostate cancer.
METHODS: Data were collected in PROtEuS, a population-based case-control study conducted in Montréal, Canada (2005-2012), including 1931 incident prostate cancer cases aged < 76 years and 1994 population controls. In-person interviews elicited information on potential risk factors. Digit lengths were measured by interviewers applying a standard protocol. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders.
RESULTS: The OR of prostate cancer for a standard deviation increase in 2D:4D was 0.91 (95 % CI: 0.85-0.98). For less and more aggressive cancers, ORs were 0.93 (95 % CI: 0.87-1.00) and 0.85 (95 % CI: 0.77-0.93), respectively. There was an interaction with ancestry (p=0.04), whereas the OR among men of African descent was 1.23 (95 % CI: 0.96-1.57, based on 128 cases).
CONCLUSIONS: Findings suggest an inverse association between 2D:4D and odds of overall prostate cancer, more pronounced for aggressive cancers. This supports the notion that high levels of testosterone in utero, estimated by a low 2D:4D ratio, are associated with a higher risk of prostate cancer. Contrastingly, a high digit ratio was associated with greater cancer odds among participants of African descent. Upon replication, 2D:4D could prove to be an easily measured marker of prostate cancer risk.

The \'organizational-activational hypothesis\' posits that the fetal environment has a lasting impact on offspring physical, cognitive, and behavioral phenotype. An established biomarker for human prenatal testosterone exposure is the second-to-fourth digit ratio (2D:4D). While related facial characteristics and their social perceptions have been investigated in young adults, studies focusing on younger or older age groups are scarce. Standardized facial photographs of 17 Austrian boys aged 4 to 11 years were each rated by 162 adults in Austria (78 female, 84 male) for masculinity, dominance, physical strength, maturity, independence, cuteness, and prettiness. Following high interrater agreement (Cronbach\'s alphas >0.96), average ratings per face were subjected to a principal component analysis. The first principal component (52 % var. expl.) correlated positively with the boys\' age (r = 0.685), whereas the second principal component (37 % var. expl.) reflected organizational effects of prenatal androgen exposure (i.e. androgenization), as shown by a negative correlation with the boys\' 2D:4D (r = -0.487). Geometric morphometrics was employed to extract the facial shapes corresponding to these two principal components. Overall, adults consistently attributed masculinity in line with prenatal testosterone exposure, whereby masculinity was assessed as neither pretty nor cute. In contrast to findings within adults, boys\' face ratings of dominance and physical strength did not correspond with their masculinity assessments, but rather with the social attributions reflecting age-related developmental progress (maturity and independence). This adds an ontogenetic layer of complexity. Prenatal testosterone exposure influences the development of boys\' facial features, which in turn even shape social stereotypes in adults.

OBJECTIVE: Prosocial behavior such as helping and sharing develops early in childhood. Yet very few studies have investigated physiological and relational factors shaping prosociality among children. Here, we systematically examined the role of prenatal androgen exposure alongside prestige, dominance, and friendship in 3-6-year-old preschoolers\' prosocial sharing with familiar peers.
METHODS: We tested a sample of 65 children, predominately of European descent. We used a cost-free direct-interaction prosocial choice task to assess children\'s prosocial tendencies. Second-to-fourth digit ratio (2D:4D) was used as a retrospective biomarker for prenatal androgen exposure. Prestige was measured through behavioral observations of interaction partners and visual regard, dominance through teacher questionnaires, and friendship via peer preference assessments.
RESULTS: We found that children acted prosocially when tested with a familiar peer. Children with lower 2D:4D (higher prenatal androgen exposure) behaved more prosocially. Further, there were marginal associations between the donors\' prosocial tendencies and their visual regard as a proxy of their prestige (positive effect) and their teacher-rated dominance relative to the recipient (negative effect). Neither age, sex, nor friendship influenced prosocial choices.
CONCLUSIONS: Prenatal androgen exposure, approximated via 2D:4D, was associated with prosocial behavior. In contrast to previous research in older children, higher exposure was related to stronger prosocial tendencies, which corresponds to earlier findings on fairness in adults. Our findings point towards a potential role of sex steroids in the early development of children\'s social behavior, but they have to be interpreted with caution due to the small sample size of the current study. Nevertheless, they underscore the importance of integrating biological and psychological perspectives, while also highlighting the significance of studying the development of prosocial behavior within peer groups.

BACKGROUND: To evaluate the relationship of the second to fourth digit ratio (2D:4D), a biomarker of prenatal sex hormone exposure, with wrist ratio (WR), wrist-palm ratio (WPR), body mass index (BMI), waist-hip ratio (WHR), and handgrip strength (HGS) in different carpal tunnel syndrome (CTS) severity.
METHODS: This study involved 90 female participants (aged 18 to 83) with CTS. According to CTS severity, the participants were divided into four groups: normal, mild, moderate, and severe. All parameters of hand anthropometry and body fat distribution were measured, and the mean 2D:4D, WR, WPR, HGS, BMI, and WHR values were compared based on CTS severity. Data were collected with a visual analog scale (VAS) for pain and a Likert (LS) scale for numbness severity.
RESULTS: The mean age, 2D:4D, WD, WW, WR, WPR, BMI, and HGS values showed a significant differences between CTS severity groups. We found that lower 2D:4D and higher WPR and BMI were associated with increased risk of CTS (AUC = 0.728) after removing the effect of age. Bilateral hands were affected in 38.9 % (70/180) of participants. Regression analysis showed that lower HGS can be used as independent variable for predicting the females having bilateral affected hands. The LS score was considerably higher in the severe and moderate groups. Also, the VAS score was significantly higher in the severe group.
CONCLUSIONS: The findings of the study demonstrated an association between 2D:4D, WPR, and BMI among women, emphasizing the effect of intrauterine sex hormone exposure on late life CTS severity.

The etiology of addiction has not yet been fully elucidated. The ratio between the length of the second and fourth fingers (2D:4D ratio) has been linked with prenatal androgen concentrations, but also with addictive behvaiors. Aim: The present study aimed to evaluate the differences of 2D:4D ratio of individuals with cannabis and heroin addiction by examining them together with the control group. A total of sixty two male patients (33 opiate use disorder and 29 cannabis use disorder) with substance use disorder and the twenty-nine healthy controls were included in the present investigation. We obtained the lengths of 2D and 4D of the subjects by using sensitive calipers and calculated the 2D:4D. Heroin-addicted patients had lower 2D:4D ratio in in the right hand (significant difference between control group) (p < 0.001), there was no significant difference found between heroin-cannabis (p = 0.242) and control-cannabis 2D:4D ratios (p < 0.06). In the left hand, it was significant between the heroin-control groups (p < 0.037) and the cannabis-control groups (p < 0.023), while it was not significant between the heroin-cannabis groups (p = 1). In conclusion, we suggest that heroin-and cannabis addicted patients seem to have a lower ratio of 2D:4D compared to healthy control subjects. Our findings can be considered promising as to whether prenatal hormonal factors are important in the etiopathogenesis of addiction.

Same-sex attraction may be linked to low prenatal androgen (in men) and high prenatal androgen (in women). Digit ratio (2D:4D) is thought to be a negative correlate of prenatal androgen and right-left 2D:4D (Dr-l) to reflect lateralized differences in sensitivity to prenatal androgen. Lower 2D:4D has been reported for lesbians compared to heterosexuals, but links to high 2D:4D in gay men are less clear. The largest study thus far (the BBC Internet study) found no significant difference between the 2D:4D of lesbians and heterosexual women but a higher 2D:4D in gay men compared to heterosexual men. Here we consider the possibility that low and high prenatal androgen is associated with same-sex attraction in men (n = 108,779) and women (n = 87,742), resulting in more than two phenotypes. We examined the associations between 2D:4D, Dr-l, and same-sex attraction scores in the BBC Internet study. In contrast to the earlier report, which considered sexual orientation in categories, there were positive linear associations in men (right and left 2D:4D, but not Dr-l) and negative linear associations in women (right 2D:4D and Dr-l, but not left 2D:4D). There were no curvilinear relationships for right and left 2D:4D. However, Dr-l showed a U-shaped association with same-sex attraction in men. Thus, (1) high prenatal androgen may be implicated in female homosexuality, while both low and high prenatal androgen may be implicated in male homosexuality, and (2) large side differences in sensitivity to androgen may be associated with elevated same-sex attraction in men.

Digit ratio (2D:4D) is considered a biomarker of prenatal androgen activity, the prenatal hormone exposure may affect children\'s psychology and behavior.
The aim of this study was to analyze the associations between 2D:4D ratio and behavior problems in Chinese preschool children, and to provide ideas for early intervention of children\'s behavior problems.
A total of 548 Chinese preschool children aged 3-6 years were recruited using a stratified cluster sampling method. The Child Behavior Checklist (CBCL) was used to assess the children\'s behavior. Basic information of the children and their parents was also collected, finger length was directly measured by electronic vernier caliper.
We found that sex and age of the child, mother\'s educational level, and whether the child was an only child were the influencing factors of behavior problems (P < 0.05). Right-handed 2D:4D was negatively correlated with parent-reported anxiety/depression (P < 0.05), father-reported aggression (P < 0.05) and attention problems (P < 0.01), that is, high levels of testosterone may increase the risk of anxiety and depression, our results were in contrast to previous studies.
The 2D:4D ratio may be related to behavior problems among Chinese preschool children, and prenatal testosterone exposure may be an important factor affecting behavior problems.

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.

A low second-to-fourth digit ratio (2D:4D) is a purported biomarker of increased intrauterine androgenic exposure, presumably linked to postnatal behavior. We aimed to examine the associations between 2D:4D and adolescence behavior problems expected from high (externalizing and attention problems) or low (internalizing problems) prenatal androgen exposure. We conducted a cross-sectional study of 1042 Colombian schoolchildren aged 11-18 y. We examined whether caliper-assessed 2D:4D was associated with behavior problems per the Youth Self-Report questionnaire. Mean problem standardized score point differences were estimated between hand- and sex-specific quintiles of 2D:4D with use of multivariable linear regression. Lower right-hand 2D:4D was associated with decreased externalizing and internalizing behavior problem scores. Corresponding lowest-to-median quintile adjusted mean differences (95% CI) were -4.6 (-7.5, -1.7) and -3.5 (-6.4, -0.6) points in boys; and -3.4 (-5.9, -0.9) and -3.5 (-6.2, -0.8) points in girls. Lower right-hand 2D:4D was also related to less attention and thought problems in boys, and to less social problems among girls. Associations were nonlinear, apparent only below 2D:4D medians, and stronger with the right than the left hand. In conclusion, right-hand 2D:4D is related to behavior problems in adolescence in directions that are not fully consistent with an androgenic exposure origin.

The challenges of terrestrial existence may mean that the early development of tetrapod limb traits is linked to the development of the urogenital system and sex steroids. One such limb trait is the sex-dependent ratio of the lengths of the 2nd and 4th digits (2D:4D). Direct evidence for the association between early sex steroids and offspring 2D:4D can be obtained by manipulating foetal sex hormones. However, this is not ethically permissible in humans. It is widely accepted that 2D:4D is a biomarker for early foetal sex hormones in tetrapods but the link in humans remains controversial. Here we review the evidence that (i) manipulation of sex steroids in early development leads to sex-dependent changes in 2D:4D throughout the tetrapods, and (ii) maternal sex steroids cross the placenta and thus are associated with offspring 2D:4D in both non-human and human animals. We suggest a research focus on associations between human maternal sex steroids and offspring 2D:4D to clarify the link between 2D:4D and early sex steroids. A protocol is proposed to examine the correlation between 1st-trimester maternal sex steroids and offspring 2D:4D. Such an association may explain the existence and medium effect size of the human sex difference in 2D:4D.