Digit Ratio (2D:4D; Right-Left 2D:4D) and Multiple Phenotypes for Same-Sex Attraction: The BBC Internet Study Revisited.

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.

An Association Between Left-Hand Digit Ratio (2D:4D) and Anthropometric Indexes in Chinese Children and Adolescents Aged 8-15 Years in Bengbu City.

OBJECTIVES: The digit ratio (2D:4D) is a possible marker of prenatal hormone exposure. The purpose of this study was to explore the relationships between digit ratio (2D:4D) and anthropometric indexes in Chinese children and adolescents. METHODS: This study is a cross-sectional study. A school-based survey among 685 children and adolescents aged 8-15 years were conducted by stratified cluster sampling. The length of index finger (2D) and ring finger (4D) of the left hand, height, sitting height (ST), weight, chest circumference (CC), waist circumference (WC), hip circumference (HC), and abdominal skinfold thickness (AST) were measured. Pearson correlation and multivariate linear regression were used to analyze associations between 2D:4D and above indexes. RESULTS: In girls, 2D:4D was positively related to WC, AST, waist-to-height (WHtR), waist-to-hip ratio (WHR) after adjusting for ages (p < 0.05). The WC, AST, WHtR, and WHR among girls with 2D:4D ≥ 1 were significantly higher than those among girls with 2D:4D < 1, respectively (p < 0.05). However, there was no correlations between digit ratio (2D:4D) and above anthropometric indexes in boys (p > 0.05). CONCLUSIONS: The 2D:4D was related to anthropometric indexes in girls, which suggests that the maternal prenatal hormone exposure might be related to the anthropometric indexes of their female offspring.

Potential Predictor of Epigenetic Age Acceleration in Men: 2D:4D Finger Pattern.

OBJECTIVES: Second to fourth digit ratio is widely known indicator of prenatal sex hormones proportion. Higher prenatal androgenization results in longer fourth finger and lower 2D:4D index. The aim of this study was to determine whether the 2D:4D digit ratio is associated with DNA methylation (DNAm) age dependently on sex. MATERIAL AND METHODS: The study included 182 adults (106 females and 76 males) with a mean age of 51.5 ± 13 years. The investigation consisted of three main parts: a survey, anthropometric dimensions measurements (fingers length) and methylome analysis using collected blood samples. Genome-wide methylation was analyzed using EPIC microarray technology. Epigenetic age and epigenetic age acceleration were calculated using several widely applied algorithms. RESULTS: Males with the female left hand pattern had more accelerated epigenetic age than those with the male pattern as calculated with PhenoAge and DNAmTL clocks. CONCLUSIONS: Finger female pattern 2D:4D above or equal to 1 in males is associated with epigenetic age acceleration, indicating that prenatal exposure to estrogens in males may be related to aging process in the later ontogenesis.

Sex-specific association between prenatal androgenization (second-to-fourth digit length ratio) and frontal brain volumes in adolescents.

Prenatal androgenization associates sex-dependently with behavior and mental health in adolescence and adulthood, including risk-taking, emotionality, substance use, and depression. However, still little is known on how it affects underlying neural correlates, like frontal brain control regions. Thus, we tested whether prenatal androgen load is sex-dependently related to frontal cortex volumes in a sex-balanced adolescent sample. In a cross-sectional magnetic resonance imaging study, we examined 61 adolescents (28 males, 33 females; aged 14 or 16 years) and analyzed associations of frontal brain region volumes with the second-to-fourth digit length ratio (2D:4D), an established marker for prenatal androgenization, using voxel-based morphometry in a region-of-interest approach. Lower 2D:4D (indicative of higher prenatal androgen load) correlated significantly with smaller volumes of the right anterior cingulate cortex (r-ACC; ß = 0.45) in male adolescents and with larger volumes of the left inferior frontal gyrus orbital part (l-IFGorb; ß = - 0.38) in female adolescents. The regression slopes of 2D:4D on the r-ACC also differed significantly between males and females. The study provides novel evidence that prenatal androgenization may influence the development of the frontal brain in a sex- and frontal brain region-specific manner. These effects might contribute to the well-known sex differences in risk-taking, emotionality, substance use, and depression. Future research is needed to elucidate the role of prenatal androgenization within the biopsychosocial model.

Influence of gonadal steroids on cortical surface area in infancy.

Sex differences in the human brain emerge as early as mid-gestation and have been linked to sex hormones, particularly testosterone. Here, we analyzed the influence of markers of early sex hormone exposure (polygenic risk score (PRS) for testosterone, salivary testosterone, number of CAG repeats, digit ratios, and PRS for estradiol) on the growth pattern of cortical surface area in a longitudinal cohort of 722 infants. We found PRS for testosterone and right-hand digit ratio to be significantly associated with surface area, but only in females. PRS for testosterone at the most stringent P value threshold was positively associated with surface area development over time. Higher right-hand digit ratio, which is indicative of low prenatal testosterone levels, was negatively related to surface area in females. The current work suggests that variation in testosterone levels during both the prenatal and postnatal period may contribute to cortical surface area development in female infants.

Associations of the digit ratio with adolescent behavior problems are inconsistent with an intrauterine androgenic origin.

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.

Association between the second- and fourth-digit ratio and oral squamous cell carcinoma.

OBJECTIVES: Using an established proxy measure of intra-utero testosterone and estrogen levels-the ratio of second- and fourth-digit lengths-we estimated its association with the oral cancer risk among a population from Southern India. MATERIAL AND METHODS: In a hospital-based case-control study, incident oral cancer cases (N = 350) and non-cancer controls (N = 371), frequency-matched by age and sex, were recruited from two major referral hospitals in Kerala, India. Structured interviews collected information on several domains of exposure via detailed life course questionnaires. Digit lengths were measured using a ruler in a standardized manner. Unconditional logistic regression was performed to estimate the odds ratios and 95% confidence intervals. RESULTS: Second- and fourth-digit ratio lower than 1, which indicates relatively higher intra-utero level of testosterone and lower intra-utero level of estrogen, was associated with higher oral cancer risk (OR = 1.60, 95% CI: 1.02-2.52), after accounting for several confounders. CONCLUSION: Our findings suggest that intra-utero hormonal levels measured by second- and fourth-digit ratio are associated with oral cancer risk. Further studies in different population should confirm these results.

Relationship of digit ratio with sexual steroid hormone receptor related genes - single nucleotide polymorphisms in a sample from Northern China.

BACKGROUND: Digit ratio, especially 2D:4D, is hypothesised as a potential biological marker of exposure to intrauterine sex hormones. The aim of this study was to investigate the association between 10 SNPs of sex steroid hormone receptor (SSHR) related genes and 2D:4D. SUBJECTS AND METHODS: 814 college students were randomly selected as research participants. After taking pictures of both hands of the participants, Image Pro Plus (IPP) software was used to measure 2D:4D. ESR1 (rs2228480 and rs3798758), ESR2 (rs944459, rs8006145, rs928554, and rs8018687), GPER1 (rs10269151 and rs12702047), and PGR (rs1042839 and rs500760) were genotyped using multiplex PCR. RESULTS: Females had significantly higher 2D:4D in both hands than male students (p < 0.05), and the R2D:4D of the Han population was significantly higher than that of the Hui population (p < 0.05). The number of females carrying the GPER1 G allele of rs12702047 was significantly higher than that of males (p < 0.05). The L2D:4D in males was significantly different in rs1042839, and the R2D:4D in the Han ethnicity was significantly different in rs3798758. Logistic regression analysis showed that rs12702047 was significantly associated with 2D:4D in both hands (p < 0.05). CONCLUSIONS: GPER1 rs12702047 may be involved in the formation of digit ratio by affecting phalanx development in the Chinese population.

The ratio of 2nd to 4th digit length and reproductive function of infertile male patients.

Purpose: To investigate the relationship between the ratio of index to ring finger lengths (2D:4D ratio), reflecting androgen exposure in utero, and reproductive function among men. Methods: Male patients (N = 180) who consulted for fertility issues participated in the study. The palms of both hands were scanned, and the 2D:4D ratio was calculated. Data on semen volume, sperm concentration and total motility, total and motile sperm counts, and serum hormone concentrations were obtained. Spearman correlation coefficients between the 2D:4D ratio and hormone and semen quality parameters were calculated. Results: The total sperm count was significantly negatively correlated with the 2D:4D ratio of the left hand (r = -0.154, p  = 0.039) but not with that of the right hand (r = -0.045, p  = 0.548). Testosterone showed weak negative correlations with the 2D:4D ratio in the left (r = -0.142, p  = 0.058) and right (r = - 0.149, p  = 0.046) hands. Follicle-stimulating hormone levels were negatively correlated with the 2D:4D ratios of the left (r = -0.173, p  = 0.020) and right (r = -0.164, p  = 0.027) hands. Other semen quality parameters or luteinizing hormone levels showed no significant correlation with the 2D:4D ratios. Conclusions: No clear associations were observed between the 2D:4D ratios and reproductive function.

Second and fourth (2D:4D) digit ratio in heroin and cannabis addicted patients.

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.

Associations of maternal anthropometrics with newborn anogenital distance and the 2:4 digit ratio.

STUDY QUESTION: Are maternal anthropometrics associated with anogenital distance (AGD) and 2:4 digit ratio (2:4D) in newborns? SUMMARY ANSWER: Select maternal anthropometrics indicative of obesity or increased adiposity are associated with elongated AGD in daughters. WHAT IS KNOWN ALREADY: Excessive maternal weight or adiposity before or in early pregnancy may impact child reproductive, and other hormonally mediated, development. AGD and 2:4D are proposed markers of in utero reproductive development. STUDY DESIGN, SIZE, DURATION: This study includes 450 mother/newborn dyads participating in the Illinois Kids Development Study (I-KIDS), a prospective pregnancy cohort from Champaign-Urbana, IL, USA. Participants included in the current study enrolled between 2013 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Most mothers in this study were college-educated (82%) and non-Hispanic White (80%), and 55% were under- or normal weight before pregnancy. Pregnant women aged 18-40 years reported pre-pregnancy weight and height to calculate pre-pregnancy BMI. At 8-15 weeks gestation, we measured waist and hip circumference, and evaluated weight, % body fat, visceral fat level, % muscle and BMI using bioelectrical impedance analysis. Within 24 h of birth, we measured newborn 2nd and 4th left/right digits to calculate the 2:4D. In daughters, we measured AGDAF (anus to fourchette) and AGDAC (anus to clitoris). In sons, we measured AGDAS (anus to scrotum) and AGDAP (anus to base of the penis). MAIN RESULTS AND THE ROLE OF CHANCE: Select maternal anthropometrics were positively associated with AGD in newborn daughters, but not sons. For example, AGDAC was 0.73 mm (95% CI: 0.15, 1.32) longer for every interquartile range (IQR) increase in pre-pregnancy BMI and 0.88 mm (95% CI: 0.18, 1.58) longer for every IQR increase in hip circumference, whereas AGDAF was 0.51 mm (95% CI: 0.03, 1.00) and 0.56 mm (95% CI: 0.03, 1.09) longer for every IQR increase in hip and waist circumference, respectively. Quartile analyses generally supported linear associations, but additional strong associations emerged in Q4 (versus Q1) of maternal % body fat and visceral fat levels with AGDAC. In quartile analyses, we observed only a few modest associations of maternal anthropometrics with 2:4D, which differed by hand (left versus right) and newborn sex. Although there is always the possibility of spurious findings, the associations for both measures of female AGD were consistent across multiple maternal anthropometric measures, which strengthens our conclusions. LIMITATIONS, REASONS FOR CAUTION: Our study sample was racially and ethnically homogenous, educated and relatively healthy, so our study may not be generalizable to other populations. Additionally, we may not have been powered to identify some sex-specific associations, especially for 2:4D. WIDER IMPLICATIONS OF THE FINDINGS: Increased maternal weight and adiposity before and in early pregnancy may lengthen the female AGD, which warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This publication was made possible by the National Institute for Environmental Health Sciences (NIH/NIEHS) grants ES024795 and ES022848, the National Institute of Child Health and Human Development grant R03HD100775, the U.S. Environmental Protection Agency grant RD83543401 and National Institute of Health Office of the Director grant OD023272. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA or NIH. Furthermore, the US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. This project was also supported by the USDA National Institute of Food and Agriculture and Michigan AgBioResearch. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Second-to-fourth digit ratio and age predicting the severity of androgenetic alopecia: a cross-sectional study.

Purpose: Androgenetic alopecia (AGA) is a common type of hair loss. Previous studies indicated that the relative length of the index and ring finger (2D:4D ratio) of AGA patients was lower than control. However, the correlation between 2D:4D ratio and disease severity is unclear. In this study, we sought to evaluate the relationship between digit ratio of the right hand and AGA severity in male patients.Materials and methods: The cross-sectional study was performed. Hamilton-Norwood scale was used to assess severity. The finger lengths of the right hand were measured using a digital caliper.Results: Our study found that the lower the right-handed 2D:4D ratio, the greater the risk of developing AGA and that the severity of AGA increases with age. Patients with moderate and severe AGA (grade 3 and above) had lower 2D:4D ratios and higher average age compared with patients with mild AGA (Norwood grade 2). Patients aged ≥37.5 with a 2D:4D ratio <0.947 were six times more likely to have moderate-to-severe androgenetic alopecia compared with the reference group (OR: 6.11; 95% CI: 1.96-19.04).Conclusions: Combining 2D:4D ratio and older age may help predict the severity risk of AGA, and offer a clinically accessible, non-invasive approach for patients to easily predict their future severity.

Digit ratio (2D:4D) and body mass index in the BBC Internet Study: prenatal sex steroids and a Trivers-Willard effect on body composition.

Digit ratio - a putative measure of prenatal sex steroids - may be related to body mass index (BMI). However, reports of correlations between 2D:4D and BMI have yielded mixed results with some studies showing no relationship while others have reported positive associations in men or women only. This study considers associations between self-reported 2D:4D and BMI in a large online survey (i.e. the BBC Internet Study). At the individual level, there was a weak positive association between 2D:4D and BMI in both sexes with greater effect sizes in women. Body mass index was positively related to age and negatively related to parental income; however, the relationship between 2D:4D and BMI was independent of both variables. At the national level, mean 2D:4D per country showed positive associations with mean national BMI but those correlations were restricted to females. It is concluded that BMI is positively related to low prenatal testosterone and high prenatal oestrogen. Parental income inequality may influence both prenatal sex steroids (through a 'Trivers-Willard' effect) and BMI such that increases in inequality result in reductions in prenatal testosterone and increases in BMI at the individual and national level.

Handgrip strength and 2D : 4D in women: homogeneous samples challenge the (apparent) gender paradox.

The length ratio between the second and the fourth digit (2D : 4D) is a retrospective, non-invasive biomarker for prenatal androgen exposure. It was found to be negatively correlated with handgrip strength (HGS) in men, but the evidence for women is mixed. Such studies in women call for increased detection sensitivity. The present study was designed to reduce potential confounding factors, especially age and ethnicity variation. We measured the digit ratios and HGS of 125 healthy women between 19 and 31 years of age from a remote region in Austria. 2D : 4D of both hands was significantly and negatively correlated with HGS (n = 125, right hand: r = -0.255, p = 0.002, left hand: r = -0.206, p = 0.011). Size, direction and significance of correlation coefficients remained stable when statistically controlling for age, body weight, body height, body mass index or hours of exercise per week. This yields theory-consistent evidence that HGS and 2D : 4D are clearly associated in women-when sufficiently reducing genetic variation (confounding 2D : 4D), the ontogenetic environment and age ranges (confounding HGS) in the study population. This finding implies similar organizing effects of prenatal androgens as in men, pointing to a more parsimonious developmental mechanism and a new look into its proximate and ultimate causes.

No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: ß = -0.001 (-0.008, 0.006); females: ß = -0.004 [-0.015, 0.007]; males: ß = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

2D:4D Digit Ratios in Adults with Gender Dysphoria: A Comparison to Their Unaffected Same-Sex Heterosexual Siblings, Cisgender Heterosexual Men, and Cisgender Heterosexual Women.

We compared gender dysphoria (GD) patients and their same-sex siblings in terms of their 2D:4D ratios, which may reflect prenatal exposure to androgen, one of the possible etiological mechanisms underlying GD. Sixty-eight GD patients (46 Female-to-Male [FtM]; 22 Male-to-Female [MtF]), 68 siblings (46 sisters of FtMs; 22 brothers of MtFs), and 118 heterosexual controls (62 female; 56 male) were included in the study. FtMs were gynephilic and MtFs were androphilic. We found that 2D:4D ratios in the both right hand (p < .001) and the left hand (p = .003) were lower in male controls than in female controls. Regarding right hands, FtM GD patients had lower 2D:4D ratios than female controls (p < .001) but their ratios did not differ from those of their sisters or male controls. FtM GD patients had no significant difference in their left-hand 2D:4D ratios compared to their sisters or female and male controls. While there was no significant difference in right hands between FtM's sisters and male controls, left-hand 2D:4D ratios were significantly higher in FtM's sisters (p = .017). MtF GD patients had lower right-hand 2D:4D ratios than female controls (p <.001), but their right-hand ratios did not differ from those of their brothers and male controls. There was no significant difference in left-hand 2D:4D ratios between MtF GD patients, and their brothers, or female and male controls. FtM GD patients showed significantly masculinized right-hand 2D:4D ratios, while there was no evidence of feminization in MtF GD patients.

Biomarkers of fetal conditions: Finger ridge-counts, facial fluctuating asymmetry, and digit ratio (2D:4D)-are they correlated in women?

OBJECTIVES: Fetal environmental conditions are crucial for life-long health. Direct measurements of developmental conditions are limited in humans; thus, several biomarkers of those conditions have been proposed: that is, finger ridge-counts, level of facial fluctuating asymmetry (FA), and digit ratio (2D:4D). Since all of these biomarkers share a similar gestational time of formation, we hypothesize that their values are significantly correlated. MATERIALS AND METHODS: Data were collected at the Mogielica Human Ecology Study Site in southern Poland among 234 women. Finger ridge-counts, level of facial FA, and 2D:4D have been measured. The two-step analyses included Pearson's correlations of simple values of the biomarkers and correlations of composite variables calculated based on principal component analysis. RESULTS: We did not find any statistically significant correlations between finger ridge-counts, FA, and 2D:4D in women. Similarly, we did not observe any correlations between three composites created from the biomarkers. DISCUSSION: Our results indicate that there are no relationships between the biomarkers, suggested as proxies of the quality of prenatal conditions, in a single population. This is the first study analyzing three different markers simultaneously. The lack of correlations may indicate that the tested biomarkers reflect, in fact, different environmental conditions, occurring in separate "critical windows" of development, or that the biomarkers are not valid as proxies of developmental conditions.

Digit ratio (2D:4D) and handedness: A meta-analysis of the available literature.

The Geschwind-Behan-Galaburda and sexual differentiation models predict an association between elevated foetal androgen exposure and left-handedness whereas the callosal hypothesis predicts the opposite. We present a meta-analysis of correlations between handedness and digit ratio (2D:4D), a putative marker of prenatal testosterone. Left-handedness predicted low (male-typical) right-hand digit ratio (R2D:4D), high (female-typical) left-hand digit ratio (L2D:4D), and low R2D:4D-L2D:4D directional asymmetry (D[R-L]). Effect sizes were extremely small and not moderated by sex or method of measuring handedness or 2D:4D. The same general pattern was observed after excluding the very large study (110,329 males, 90,412 females) of Manning and Peters ([2009]. Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study. Laterality: Asymmetries of Body, Brain and Cognition, 14(5), 528-540. doi:10.1080/13576500802637872); however, no significant effects for R2D:4D were observed once these samples were removed. The results do not confirm any theory linking prenatal androgens with handedness, so we speculate they instead reflect the mechanical action of writing causing subtle changes in the musculature and/or fat pads of the fingers. Gripping a pen/pencil might cause an increase in 2D relative to 4D (and/or decrease in 4D relative to 2D) resulting in higher ratios on the writing-hand; furthermore, this could differ between left- and right-handers due to writing in the left-to-right direction (as in English) having asymmetrical effects depending on which hand is used.

Usefulness of measurement of proximal phalanx length by using ultrasonography in newborn infants.

The purpose of this study was to compare digit lengths and proximal phalanx lengths in newborn infants by using ultrasonography (USG) and to examine sex differences between the ratio of the second digit (2D) and fourth digit (4D) of digit length and that of proximal phalanx length and the associations of digit length and proximal phalanx length with birth weight and birth height. Sixty newborn infants (28 males and 32 females) were recruited. Digit lengths were measured by using a transparent ruler and proximal phalanx lengths were measured by using USG. There were significant correlations between digit length and proximal phalanx length in the left and right hands. There was no significant correlation between 2D:4D ratios of digit lengths and 2D:4D ratios of proximal phalanx lengths measured by using USG. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males. Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.Impact statementWhat is already known on this subject? The ratio of the second digit (2D) and fourth digit (4D) has been used postnatally to provide a retrospective indication of the foetal hormonal environment. Digit lengths have been measured by using a direct method, photocopies, digital scans and radiographs, but the results of a study on measurement of digit lengths by using ultrasonography (USG) have not been reported.What do the results of this study add? Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males.What are the implications of these findings for clinical practice and/or further research? Measurement of proximal phalanx length by using USG may be useful for a study on gender differences in foetal development and the foetal hormonal environment. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.

Prenatal oestrogen-testosterone balance as a risk factor of migraine in adults.

BACKGROUND: Migraine is a common neurological disease with extremely debilitating, but fully reversible symptoms. Women suffer from migraine more often than men. It was assumed that fluctuation of oestrogen level during menstrual cycle is one of many factors responsible for more frequent migraine attacks. The second-to-fourth digit ratio (2D:4D) is considered as an indicator of prenatal sex steroids. Balance of prenatal androgens (testosterone) and oestrogen has been studied in numerous diseases that are affected by hormones. However, the relationship between migraine and the sex steroids balance in prenatal development is still unexplained. The aim of this paper is to provide an evidence of relationship between prenatal oestrogen and testosterone exposure following 2D:4D digit ratio, and migraine prevalence in adults. METHODS: We examined a group of 151 adults (33 males, 118 females) with migraine and a control group of 111 adults (45 males, 66 females). 2D:4D digit ratio of both hands was measured using sliding Vernier calliper. RESULTS: Significant differences were found in the right hand. Female migraineurs had lower value of 2D:4D ratio than the control group and the right 2D:4D was lower than left 2D:4D (Δ2D:4D), suggesting prenatal testosterone dominance. The opposite relationship was observed in males. Male migraineurs had higher value of 2D:4D ratio and Δ2D:4D was greater than the control group, suggesting prenatal oestrogen dominance. CONCLUSIONS: Our results suggest that depending on sex, different proportion of prenatal sex steroids might be a risk factor of migraine in adults. Women with migraine were presumably exposed in prenatal life to higher testosterone levels relative to oestrogen, while men with migraine were probably exposed in prenatal life to higher levels of oestrogen relative to testosterone.