Prenatal Testosterone Levels Research Articles

Stretched penile length and anogenital distance in Egyptian boys aged one month to five years

In children with isolated unilateral undescended testis mechanical anomalies are commonly implicated and a diagnosis of simple hypospadius implies that the rest of the external genitalia are normal. Patients with disorders of sexual development, by contrast, have other associated genital anomalies including micropenis and should be referred to the endocrinologist for hormonal assessment before surgical correction of undescended testis or hypospadius. Early diagnosis of abnormal penile size is important but proper assessment begins with defining the normal population-specific age-appropriate reference range. Anogenital distance (AGD) reflects prenatal and early postnatal testosterone levels. The aim of our study was to establish mean reference values and percentile curves for strtetched penile length (SPL) and AGD in healthy Egyptian males from the age of one month to five years and to determine the mean monthly increase in SPL and AGDs from 1 to 13 months of age (a reflection of mini-puberty). This was a descriptive cross-sectional study conducted in Cairo University and Mataria Hosptals, Egypt to determine SPL and AGD in 2972 Egyptian males aged from one month to five years from October 2016-December 2018. In addition, we measured length/height, weight and body mass index. SPL increased gradually from a mean±SD of 3.55±0.51cm in the first year of life to 5.52±0.67cm by five years of age with a growth from 1 to 12 months of life of 0.6cm. SPL showed smaller values in infants 6-9 months old compared to younger infants. AGD increased from 7.48±1.47cm in the first year of life to 12.83±0.58cm by 5 years of age with a growth from 1 to 12 months of 4.34cm. SPL and AGD Z-scores correlated positively with each other and with age (months), and Z-scores of height/length, weight and BMI (p<0.001). The rapid increases in SPL and AGD observed in our study group in the first few months of life reflect the effects of mini-puberty. The fact that SPL and AGD correlated positively with other anthropometric measurements suggests that SPL and AGD may be controlled by nutritional and/or hormonal factors. We suggest that waning testosterone levels marking the end of minipuberty might explain smaller values for SPL in our group of 6-9 month old infants compared with younger infants. We have not included children under one month old. It is important for each country to develop its own national percentile curves for all growth parameters. This will allow the physician to identify normal differences in the population and to pick up disorders at an age when intervention may yield better results We have developed percentile curves for SPL and AGD that can be used as references for Egyptian male infants and young children.

The Relationship between Prenatal Testosterone (2D:4D), Big 5 Personality Traits and GRIT in Different Cultural Contexts

Digit ratio (2D:4D; a putative correlate of prenatal testosterone) has been shown to be predictive of important personality factors such as mental toughness, optimism and academic achievement. However, to date no study has attempted to investigate prenatal testosterone levels as a predictor of GRIT (persistency and constancy) and the Big 5 personality traits Openness to experience, Conscientiousness, Extraversion, Agreeableness and Neuroticism. Research has also alluded to the potential gender and cultural differences in biological underpinnings of psychological functioning. This study included a sample of Dubai and UK undergraduate students and examined associations between prenatal testosterone (2D:4D), GRIT and Big 5 personality traits (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism). UK and Dubai participants followed the same testing procedure and completed a self-report measure for GRIT and Big 5 personality traits, followed by providing a right-hand scan, which was later used to measure 2D:4D using Vernier Callipers. Results showed that in Dubai participants, the measured psychological variables explained a greater amount of variance in 2D:4D than in UK participants. Openness to experience was a strong significant predictor of 2D:4D in Dubai participants whereas, GRIT, conscientiousness and openness to experience were all significant predictors of 2D:4D for UK participants.

Gut Microbiota and Gender in Autism Spectrum Disorders.

Gender dimorphism in autism spectrum disorders (ASD) is well known; however, the reasons for gender differences in autism are poorly understood. There are several hypotheses that might explain male prevalence in ASD, including increased levels of androgens, "extreme male brain," and a combination of elevated levels of prenatal testosterone in conjunction with prenatal stress. In this comprehensive review, differences in the gut microbiome and metabolome in humans and animals are described to explain gender differences in individuals with ASD, effects on behavior and social interactions and the impact of antibiotics, probiotics and fecal transplants. The bidirectional relationship between sex hormones and intestinal microbiota could also be relevant. Such interactions have been described in autoimmune diseases, but thus far, are not implicated in ASD. Since intestinal microbiota may affect behavior, it is possible that the prevalence of ASD in boys may be associated with more significant changes in the intestinal microbiome than in affected girls.

Overconfidence and the 2D:4D ratio

This paper tests whether prenatal testosterone levels are related to overconfidence. We use a non-intrusive method called 2D:4D ratio to measure prenatal exposure to testosterone of subjects. Using data collected from students from a large university in Brazil, we find that testosterone is positively correlated with higher levels of overconfidence. We also find support that males and self-declared white persons are associated to higher overconfidence levels comparatively to females and self-declared non-white persons, respectively. We also find that the marginal effect of prenatal testosterone on overconfidence is higher for left-handed than for right-handed persons. This means that the role of the prenatal testosterone, as measured by the 2D:4D ratio, on overconfidence is more relevant to left-handed persons. Our work presents empirical evidence that prenatal testosterone is an important predictor of individuals’ overconfidence behavior and that biological traits either attenuate or exacerbate such relationship.

2D:4D Suggests a Role of Prenatal Testosterone in Gender Dysphoria

Gender dysphoria (GD) reflects distress caused by incongruence between one’s experienced gender identity and one’s natal (assigned) gender. Previous studies suggest that high levels of prenatal testosterone (T) in natal females and low levels in natal males might contribute to GD. Here, we investigated if the 2D:4D digit ratio, a biomarker of prenatal T effects, is related to GD. We first report results from a large Iranian sample, comparing 2D:4D in 104 transwomen and 89 transmen against controls of the same natal sex. We found significantly lower (less masculine) 2D:4D in transwomen compared to control men. We then conducted random-effects meta-analyses of relevant studies including our own (k = 6, N = 925 for transwomen and k = 6, N = 757 for transmen). In line with the hypothesized prenatal T effects, transwomen showed significantly feminized 2D:4D (d ≈ 0.24). Conversely, transmen showed masculinized 2D:4D (d ≈ − 0.28); however, large unaccounted heterogeneity across studies emerged, which makes this effect less meaningful. These findings support the idea that high levels of prenatal T in natal females and low levels in natal males play a part in the etiology of GD. As we discuss, this adds to the evidence demonstrating the convergent validity of 2D:4D as a marker of prenatal T effects.

Predicting infant–father attachment: the role of pre- and postnatal triadic family alliance and paternal testosterone levels

ABSTRACT This longitudinal study examined whether prenatal family alliance and prenatal paternal testosterone levels predicted infant–mother and infant–father attachment security and whether this association was mediated by postnatal family alliance and postnatal paternal testosterone levels. In 105 couples expecting their first child, family alliance was assessed in the third trimester of pregnancy with the prenatal version of the Lausanne Trilogue Play (LTP). Family alliance was measured again 6 months postnatally, using the LTP. Fathers provided testosterone samples prenatally and at 6 months postnatally. Infant–parent attachment was assessed with the Attachment Q-Sort (AQS) at 24 months. Results indicated an increase in paternal testosterone levels from the pre- to the postnatal period. A more positive prenatal family alliance predicted higher infant–father attachment security at 24 months, but not infant–mother attachment security. The association between prenatal family alliance and attachment security was not mediated by postnatal family alliance or postnatal paternal testosterone levels. This study highlights the significance of prenatal family relations, and the need to consider in research and practice the divergent effects of prenatal family alliance patterns on the emerging infant–mother and infant–father attachment relationships. The underlying hormonal mechanisms during the transition to fatherhood are important targets for future research.

Depression Is Associated With the Absence of Sex Differences in the 2D:4D Ratio of the Right Hand.

The 2D:4D digit ratio reflects prenatal testosterone relative to estradiol exposure of a developing embryo. Higher levels of prenatal testosterone have been related to lower 2D:4D ratios. In addition, higher 2D:4D ratios have been associated with female gender, neuroticism, and depression severity. Therefore, the present study investigated whether 2D:4D ratios differ between inpatients with major depression and matched healthy controls and whether 2D:4D ratios correlate with depression severity. We examined 139 inpatients diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria and 137 healthy controls regarding 2D:4D ratios of both hands and BDI-II scores. While we observed significant sex differences in the 2D:4D ratio of the right hand in the healthy control group (women on average showed a significantly higher 2D:4D ratio), no such differences were found in the group of depressed patients. The 2D:4D digit ratios did not correlate with depression severity even when examined for group and sex separately. We conclude that major depression is associated with an absence of sex differences in the 2D:4D ratio.

The second to fourth digit (2D:4D) ratios, smoking, and problem drinking in a young adult university student sample

BackgroundRelative length of second finger to fourth finger (2D:4D ratio) has been shown to be a putative indirect marker of the amount ofin utero testosterone levels. 2D:4D ratios are claimed to be inversely associated with prenatal testosterone levels. ObjectiveWe aimed to investigate whether 2D:4D ratios are independently associated with smoking and problem drinking in young adults. MethodsWe recruited a convenience sample of 661 university students and used the CAGE questionnaire to identify problem drinking. Smokers were assessed with the Fagerström Test for Nicotine Dependence (FTND). Impulsivity was measured with the Barratt Impulsiveness Scale. Results: 2D:4D ratios were lower in students who were problem drinkers than in those who were non-drinkers or non-problematic drinkers (t=−2.07, p = .039 for right hand; t=−2.02, p = .044 for left hand). 2D:4D ratios were comparable between regular smoker students and non-smoker or irregular smoker students. Problem drinking or regular smoking were not independently associated with 2D:4D ratios in regression analyses. However, 2D:4D ratios on both hands associated negatively with CAGE scores (95% CI: −6.24 to −.64, p = .016 for right hand; 95% CI: −6.68 to −.41, p = .027 for left hand) and positively with FTND scores (95% CI: 1.58–27.06, p = .028 for right hand; 95% CI: 5.06–29.03, p = .006 for left hand) independently of the effects of age, sex, and impulsivity. ConclusionPrenatal testosterone levels, as indirectly assessed by 2D:4D ratios, are independently associated with the severity of alcohol abuse and nicotine dependence when other factors such as sex, age, and impulsivity are considered.

Prenatal testosterone exposure is associated with delay of gratification and attention problems/overactive behavior in 3-year-old boys

Sex differences in self-control become apparent during preschool years. Girls are better able to delay their gratification and show less attention problems and overactive behavior than boys. In this context, organizational effects of gonadal steroids affecting the neural circuitry underlying self-control could be responsible for these early sex differences. In the present study testosterone levels measured in amniotic fluid (via ultra performance liquid chromatography and tandem mass spectrometry) were used to examine the role of organizational sex hormones on self-control. One hundred and twenty-two 40-month-old children participated in a delay of gratification task (DoG task) and their parents reported on their attention problems and overactive behavior. Girls waited significantly longer for their preferred reward than boys, and significantly more girls than boys waited the maximum period of time, providing evidence for sex differences in delay of gratification. Boys that were rated as suffering from more attention problems and overactive behavior waited significantly shorter in the DoG task. Amniotic testosterone measures were reliable in boys only. Most importantly, boys who waited shorter in the DoG task and boys who were reported to suffer from more attention problems and overactive behavior had higher prenatal testosterone levels. These findings extend our knowledge concerning organizational effects of testosterone on the brain circuitry underlying self-control in boys, and are of relevance for understanding how sex differences in behavioral disorders are connected with a lack of self-control.

The role of sex hormones and social determinants in assessment of facial attractiveness.

The current study is focused on assessing the factors of attractiveness of opposite-sex individuals based on evaluating photographs of their faces. When assessing the attractiveness, factors of both, the assessed individual and the assessor play a role. The relationship of the preference for partners based on their physical appearance with the markers of prenatal testosterone is not fully understood. Sex hormone levels were measured in saliva, while age, social status, income and occupation were recorded. A total of 30 women and 35 men were enrolled. The identified factors determining the attractiveness of menare their age and prenatal testosterone level (second-to-fourth digit ratio - 2D:4D). The attractiveness of men is more influenced by the factors of evaluating women, namely the rating assigned to the men positively correlates with age, 2D:4D, and salivary estradiol of the evaluating women. The attractiveness of women correlated negatively with age and positively with prenatal exposure to androgens (2D:4D).The women with lower estradiol were rated higher by men who themselves had low estradiol levels. The attractiveness did not correlate with current testosterone. This study contributes to the knowledge on the role of sex hormones in human sexuality and partner choice. Further studies should include genetic factors of testosterone metabolism. (Tab. 4, Ref. 23).

Role of 2nd Digit: 4th Digit Ratio(2D: 4D Ratio) in Establishing the Biological Profile of an Individual

Introduction: The process of identification focuses mainly on establishing the biological profile byestimating the sex, age and stature which significantly narrows down pool of suspects. The 2D:4D ratiois a sexually dimorphic trait which is influenced by prenatal estrogen and testosterone levels. Studies alsosuggest that there might be strong relationship of this ratio and stature and age well. This study is taken incombination of all the 3 primary parameters of biological profile and co-related with that of 2D:4D ratio.And there is no such study conducted in this part of Karnataka.Aims and Objectives: To study the role of 2D;4D ratio in establishing the biological profile(Sex, Age andstature) of an individual by manual digital measurements and digital print measurements.Material and Method: Hundred first year medical students (n=100) (males= 50 and females =50) of S.N. Medical college, Bagalkot were included in the study. Authentic proof of age was collected and heightmeasured by stadiometer and 2d:4d by digital callipers for both hands. SPSS 17.0 used to analyse the data.Results: In Males, the ratio varied from 0.89 to 1.04 with mean and standard deviation of 0.97 ± 0.03 onright side and on left side it varied from 0.85 to 1.03 with mean ± SD of 0.98 ±0.04. While in females ratiovaried from 0.91 to 1.11 with Mean ± SD of 0.97±0.04 on right side and on left side it varied from 0.83 to1.12 and Mean ± SD of 0.98 ±0.04 on left sideBased on the mean 2D:4D ratio for both the sexes, 0.97 on right and 0.97 on left side, sectioning point wasderived. When all the cases below and equal to 0.97 were considered as males and those above 0.97 wereconsidered as females, one could accurately determine the sex up to 90% accuracy.Conclusions: 2D:4D ratio can be effectively and accurately used to establish the biological profile of anindividual which can help forensic experts and medicolegal experts to narrow down the pool of suspectsin crime or identify the victims of crime, mass disasters, road traffic accidents etc. Moreover 2D:4D, ratiorelatively less time consuming, and cost effective.

Associations of Bisexuality and Homosexuality with Handedness and Footedness: A Latent Variable Analysis Approach

Non-right-handedness appears to be more common among bisexuals and homosexuals than among heterosexuals, which might be indirect evidence of effects of prenatal androgen exposure. Current data suggest higher prenatal testosterone levels among bisexual and homosexual women, but are inconclusive for men. This study examined the association between sexual orientation and non-right-handedness for sex differences and whether higher rates of mixed-handedness, rather than left-handedness, might be the driving factor. This allowed for more specific tests regarding the predictions of two competing theories of prenatal androgen exposure, the Geschwind–Galaburda theory and the callosal hypothesis, than in previous research. Being a potentially better indicator of cerebral lateralization than handedness, associations with footedness were also explored. To counter inconsistencies and shortcomings of previous research, we utilized two large discovery and replication datasets (ns = 2368 and 1565) and applied latent variable analysis to reliably classify lateral preferences (i.e., handedness, footedness). This maximized the statistical conclusion validity and allowed for direct tests of replicability. Sexual orientation was differentially associated with lateral preferences among men and women. Associations among women were consistent with predictions of the Geschwind–Galaburda theory, whereas among men they were consistent with predictions of the callosal hypothesis. The results were further consistent with models of homosexuality that suggest a role of parental epigenetic marks on sexually dimorphic fetal development. Research efforts should be increased with regard to footedness and epigenetic theories of homosexuality.

Journal Digest

Journal Digest

Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory

Elevated levels of prenatal testosterone may increase the risk for autism spectrum conditions (autism). Given that polycystic ovary syndrome (PCOS) is also associated with elevated prenatal testosterone and its precursor sex steroids, a hypothesis from the prenatal sex steroid theory is that women with PCOS should have elevated autistic traits and a higher rate of autism among their children. Using electronic health records obtained from the Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2014, we conducted three matched case-control studies. Studies 1 and 2 examined the risk of PCOS in women with autism (n = 971) and the risk of autism in women with PCOS (n = 26,263), respectively, compared with matched controls. Study 3 examined the odds ratio (OR) of autism in first-born children of women with PCOS (n = 8588), matched to 41,127 controls. In Studies 1 and 2 we found increased prevalence of PCOS in women with autism (2.3% vs. 1.1%; unadjusted OR: 2.01, 95% CI: 1.22–3.30) and elevated rates of autism in women with PCOS (0.17% vs. 0.09%, unadjusted OR: 1.94 CI: 1.37–2.76). In Study 3 we found the odds of having a child with autism were significantly increased, even after adjustment for maternal psychiatric diagnoses, obstetric complications, and maternal metabolic conditions (unadjusted OR: 1.60, 95% CI: 1.28–2.00; adjusted OR: 1.35, 95% CI: 1.06–1.73). These studies provide further evidence that women with PCOS and their children have a greater risk of autism.

Self-confidence, Overconfidence and Prenatal Testosterone Exposure: Evidence from the Lab.

This paper examines whether foetal testosterone exposure predicts the extent of confidence and over-confidence in own absolute ability in adulthood. To study this question, we elicited incentive-compatible measures of confidence and over-confidence in the lab and correlate them with measures of right hand 2D:4D, used as as a marker for the strength of prenatal testosterone exposure. We provide evidence that men with higher prenatal testosterone exposure (i.e., low 2D:4D ratio) are less likely to set unrealistically high expectations about their own performance. This in turn helps them to gain higher monetary rewards. Men exposed to low prenatal testosterone levels, instead, set unrealistically high expectations which results in self-defeating behavior.

Testosterone and intrasexual competition in men: is there any relation with digit ratio (2D:4D)?

Digit ratio 2D:4D is a sexually dimorphic characteristic and it is believed that this difference is related to high levels of prenatal testosterone and circulating testosterone in men. High levels of testosterone are also associated with traits related to competitiveness. Therefore, this study aimed to examine the relation between intrasexual competition and 2D:4D in men. One hundred thirteen college men answered a questionnaire to measure their scores of intrasexual competition and donated a saliva sample to measure their testosterone levels; finally, the finger length from both hands was measured. It was found a positive correlation between testosterone levels and intrasexual competition scores, and a negative correlation between testosterone levels and left 2D:4D. Finally, we did not find a significant association between digit ratios 2D:4D and intrasexual competition scores. Our study shows that men with higher testosterone levels also have higher intrasexual competition scores and lower values of left digit ratio 2D:4D. Further studies will have to take into account fluctuations in testosterone over the time to observe if the relation between competitiveness scores and digit ratios 2D:4D becomes significant.

Prenatal testosterone and theory of mind development: Findings from disorders of sex development

Women on average perform better than men on the “Reading the Mind in the Eyes” test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives. A total number of 158 individuals participated in the study; 19 with 5α-RD-2, 17 with CAH, 18 women with CAIS, 52 matched unaffected men and 52 matched unaffected women. All subgroups were around 20 years of age. Women with CAH scored significantly lower on RMET than control women and CAIS individuals. CAIS individuals scored significantly higher than control men and participants with 5α-RD. Statistically, CAIS individuals' performance on RMET was similar to control women's, women with CAH did not differ significantly from control men and 5α-RD-2 individuals scored significantly lower than control men. These results, which are in line with previous theories, illustrate that performance on the RMET, as an index of ToM, may be influenced by variations in prenatal androgens levels.

Second to fourth digit ratio (2D:4D), tomboyism, and temperament

This study examines the relationship between 2D:4D, a proxy for levels of prenatal testosterone, and rating oneself as a “tomboy” as well as the relationship between Fisher's hormone-based temperament factors and tomboyism. Salmon (2015) reported a relationship between female erotic fiction preferences and lower 2D:4D ratios in addition to a link between tomboyism and such preferences. The results of the current study indicate that lower 2D:4D ratios are associated with increasing tomboy scores and that tomboyism is associated with higher scores on the testosterone component of Fisher's temperament model as well as a marginal negative association with the estrogen/oxytocin factor. This lends support to Fisher's model as well as documenting the relationship between 2D:4D and tomboyism in a non-clinical population.

Prenatal and pubertal testosterone affect brain lateralization

After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in puberty. We performed a longitudinal study, investigating the relationship between prenatal testosterone concentrations in amniotic fluid, pubertal testosterone concentrations in saliva, and brain lateralization (measured with functional Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric Faces and Word Generation tasks. Thirty boys and 30 girls participated in this study at the age of 15 years. For boys, we found a significant interaction effect between prenatal and pubertal testosterone on lateralization of Mental Rotation and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal testosterone was positively related to the strength of lateralization in the right hemisphere, while in the boys with high prenatal testosterone levels, pubertal testosterone was negatively related to the strength of lateralization. For Word Generation, pubertal testosterone was negatively related to the strength of lateralization in the left hemisphere in boys. For girls, we did not find any significant effects, possibly because their pubertal testosterone levels were in many cases below quantification limit. To conclude, prenatal and pubertal testosterone affect lateralization in a task-specific way. Our findings cannot be explained by simple models of prenatal testosterone affecting brain lateralization in a similar way for all tasks. We discuss alternative models involving age dependent effects of testosterone, with a role for androgen receptor distribution and efficiency.

Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (−34 T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering

Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 −34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder.