Prenatal Androgen Action Research Articles

Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort.

Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls? In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood. AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome. In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years. AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and SD scores (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (r) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve. In boys, AGD/body size-index SD score correlated significantly between infancy and 9 years, strongest for AGDas (r = 0.540 P > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (P > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low. The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys. In boys, AGDas, relative to body size, correlated from infancy to 9 years, suggesting that AGD in infancy can be considered a non-invasive marker of later reproductive health. Further follow-up studies are needed to evaluate long-term individual tracking of AGD as well as assessment of childhood AGD as early marker of adult reproductive health. This study was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, the Municipality of Odense, Denmark, the University of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, the Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), Sygeforsikring Danmark (journalnr. 2021-0173), the Collaborative Foundation between Odense University Hospital and Rigshospitalet, and Helsefonden. There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported. N/A.

Anogenital distance in a cohort of 169 infant boys with uni- or bilateral cryptorchidism including 18 boys with vanishing testes.

Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)? Length of AGD seemed to differ in different groups of patients with cryptorchidism. AGD, which is used as an indicator of prenatal androgen action, tends to be shorter in boys with cryptorchidism compared to unaffected boys. Shorter AGDs have also been reported in boys with hypospadias, in men with poor semen quality, and in men with testicular cancer. A prospective descriptive cohort study was performed using data from consecutively selected boys with cryptorchidism (n = 169) operated in a single center over a period of 3 years (September 2019 to October 2022). AGD was measured in 169 infant boys, at 3 to 26 months of age, during anesthesia with a vernier caliper measuring the distance from the anus to the base of the scrotum (AGDAS) and from the anus to the anterior base of the penis (AGDAP) in two body positions according to the methods by 'The Infant Development and the Environment Study' (TIDES) and 'Cambridge Baby Growth Study', resulting in four mean values per patient (TIDES AGDAS/AP and Cambridge AGDAS/AP). Normal values for AGD by age were set by our hospital Department of Growth and Reproduction based on a large cohort of healthy infant boys (n = 1940). Testicular biopsies were performed at orchidopexy as a clinical routine. The germ cell number (G/T) and type Ad spermatogonia number (AdS/T) per cross-sectional tubule of at least 100 and 250 tubules, respectively were measured and related to normal samples. Blood samples were obtained by venipuncture for measuring serum LH, FSH, and inhibin B. They were analyzed in our hospital Department of Growth and Reproduction where the normal reference was also established. Correlations between the four mean AGD measurements for each boy were evaluated by Spearman rank correlation analyses. The AGD measurement of every boy was transferred to the multiple of the median (MoM) of the normal AGD for age and named MoM AGD. There were 104 boysoperated for unilateral, and 47 boys operated for bilateral, undescended testes, whereas 18 boys had vanished testis including one boy with bilateral vanished testes. Only 6% of cases with vanished testes had a MoM AGD higher than the normal median compared to 32% with undescended testes (P < 0.05). MoM AGD increased with the age at surgery for boys with vanished testis (Spearman r = 0.44), but not for boys with undescended testes (Spearman r = 0.14). Boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism (P < 0.005) and (P < 0.000001). Although being the largest published material of AGD measurements of infant boys with cryptorchidism, one limitation of this study covers the quite small number of patients in the different groups, which may decrease the statistical power. Another limitation involves the sparse normal reference material on G/T and AdS/T. Finally, there are currently no longitudinal studies evaluating AGD from birth to adulthood and evaluating childhood AGD in relation to fertility outcome. Our study is hypothesis generating and therefore the interpretation of the results should be regarded as exploratory rather than reaching definite conclusions. The study findings are in agreement with literature as the total included group of boys with cryptorchidism exhibited shorter than normal AGDs. However, new insights were demonstrated. Boys with vanished testis had shorter AGDs compared to unaffected boys and to boys with undescended testes. This finding challenges the current concept of AGD being determined in 'the masculinization programming window' in Week 8 to 14 of gestation. Furthermore, boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism, suggesting that the lack of fetal androgen in hypogonadotropic hypogonadism is not that significant. No external funding was used and no competing interests are declared. The trial was not registered in an ICMJE-recognized trial registry.

The association of prenatal amniotic sex hormones and digit ratio (2D:4D) in children aged 5 to 70 months: A longitudinal study.

The sex difference of the 2D:4D digit ratio (female > male)-a proposed marker for prenatal testosterone exposure-is well established. Studies suggest it already exists in utero and is of moderate effect size in adulthood. However, evidence for the claim that 2D:4D reflects prenatal androgen action is limited, and the sex difference may exhibit lability during childhood. In the present study, 244 mothers were recruited in the course of an amniocentesis examination (performed between gestational weeks 14 and 18). Prenatal testosterone (T) and estradiol (E) levels were determined from amniotic fluid for boys and girls. The majority (97.4%, n = 114) of available female T levels (n = 117) were found below the level of quantification. Therefore, only male amniotic fluid data (n = 117) could be included for the analysis of associations between amniotic sex hormones (T levels and T to E ratio (T/E)) and 2D:4D. The families were then invited to each of the five consecutive follow-ups (ages: 5, 9, 20, 40, and 70 months) where children's 2D:4D was measured for both hands. The alternative marker D[r-l] reflects the directional asymmetry of 2D:4D (right subtracted by left 2D:4D) and was subsequently calculated as an additional measure for prenatal T exposure. No significant correlations between amniotic T or the T/E ratio (measured between week 14 and 18 of gestation) with 2D:4D respectively D[r-l] were observed for any time point. There was a significant sex difference (females > males) and a significant age effect with moderate correlations of 2D:4D between time points. 2D:4D increased between 20 and 40 months and between 40 and 70 months of age. The findings raise questions regarding the applicability of 2D:4D as a marker for prenatal androgen action and are discussed in terms of the reliability of obtained digit ratio data as well as in terms of the developmental timing of amniocentesis.

The Second to Fourth FINGER Length Ratio(2D:4D) and Its Relationship with Body Composition Parameters in Korean Young Adults

Purpose: Body composition status is influenced by changes in sex hormones, and this status is also closely related to normal daily life and the risk of various chronic diseases. On the other hand, the relative length of the second and fourth fingers(2D:4D ratio) has been proposed as a marker of prenatal androgen action of sensitivi-ty to testosterone, with a lower 2D:4D being associated with high androgen exposure.In this study, it was ex-amined the relationship between the 2D:4D ratio and various body composition parameters measured by bioe-lectric impedance analysis(BIA) in young adults to determine the usability of the 2D:4D ratio as a predictor of finger length- related diseases. Method: Ninety-three healthy individuals(60 men and 33 women, age 17-19 years) participated. Subjects’ body weight and height were measured, and body mass index(BMI) was calculated. Body fat mass, % body fat, % abdominal fat, skeletal mass, % muscle mass, and % bone mineral density was measured using BIA. SMI(skeletal muscle index) was calculated. The lengths of the second and fourth fingers of the right and left hands were measured using a electronic digital caliper, and the 2D:4D ratio and difference of the digit ratio between the right and left hands(Dr-l) were also calculated. The differences in anthropometric and body com-position variables between males and females was analyzed using independent t-test. Pearson’s correlation coefficient was used to determine the relationship between finger length measures(the 2D:4D ratio and Dr-l) and body composition parameters. The significance level was considered as p ≤ 0.05 at all stages. Results: In this study, significant sexually dimorphic differences were found in all results of the anthropomet-ric measures and body composition parameters, excluding Dr-l and % abdominal fat. The height and weight of men were significantly higher than that of women, and the variable related to fat-free mass of men among body composition was significantly higher than that of women. On the other hand, women were significantly higher than men in variables related to body fat mass. As the main findings about the correlation results be-tween the finger length measures and the body composition parameters, there was a significant difference in the 2D:4D ratio between males and females, but all variables except male muscle mass were not significantly correlated with finger length measures. Conclusion: Although the 2D:4D ratio has been proposed as a marker of prenatal androgen action and of sensitivity to testosterone, these results found in this study suggest that finger length measures may not be a preventive indicator for predicting body composition differences and diseases associated with sex hormones and finger length parameters.

Prenatal Androgen Excess Impairs Sexual Behavior in Adult Female Mice: Perspective on Sexual Dysfunction in PCOS

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders worldwide, affecting 5-20% of reproductive aged women [1]. PCOS is characterised by androgen excess, oligo- or anovulation, and polycystic ovarian morphology [1]. PCOS patients also experience sexual dysfunction, including decreased sexual desire, increased sexual dissatisfaction and gender dysphoria [2-4]. The origins of PCOS-related sexual difficulties remain unidentified, but may be related to impaired central mechanisms regulating sexual behaviours. Prenatally androgenized (PNA) mice recapitulate the PCOS phenotype and exhibit alterations in the neuronal network regulating reproductive function [5], providing a powerful, pathology-based model to unravel the biological origins of sexual dysfunction in PCOS. Here, we aimed to determine whether female sexual behaviours are impaired in the PNA mouse model of PCOS. To model PCOS, female dams received injections of dihydrotestosterone (PNA) or oil vehicle (VEH) daily from gestational day 16-18. Adult female offspring were ovariectomized and implanted with a silastic capsule of estradiol to examine the female-typical sexual behaviour: lordosis as well as partner preference. We also examined a potential masculinisation of the brain by replacing the estradiol implant by a testosterone implant then testing the female for male-like sexual behaviours. PNA females exhibited significantly reduced lordosis behaviour compared to VEH females (p<0.01). In contrast, partner preference and male-like sexual behaviour were not different between PNA and VEH females. In addition, using Open-field test and elevated-plus maze, we observed no effect of prenatal androgen exposure on locomotion and anxiety. These results highlight, for the first time, that prenatal exposure to the non-aromatisable androgen, DHT, impairs female receptivity only without masculinisation. These findings support the use of the PNA mouse model of PCOS to identify the neuronal targets of prenatal androgen action and to determine the mechanisms by which prenatal androgen excess impairs lordosis. Taken together, this study introduce a novel perspective on the origins of sexual dysfunction in women with PCOS and indicate the need for further investigation into the mechanisms of androgen excess on the female brain and sexual function. [1] Lizneva D et al, Fertil Steril. 2016;106:6-15. [2] Fliegner M et al, Geburtshilfe Frauenheilkd. 2019;79:498-509.[3] Kowalczyk R et al, Acta Obstet Gynecol Scand. 2012;91:710-4.[4] Mansson M et al, Eur J Obstet Gynecol Reprod Biol. 2011;155:161-5. [5] Ruddenklau A, Campbell RE. Endocrinology. 2019 Oct 1;160(10):2230-2242.

Anogenital Distance in Healthy Infants: Method-, Age- and Sex-related Reference Ranges.

The use of anogenital distance (AGD) in clinical and epidemiological settings is increasing; however, sex-specific reference data on AGD and data on longitudinal changes in AGD in children is scarce. To create age-, sex-, and method-related reference ranges of AGD in healthy boys and girls aged 0-24 months, to assess the age-related changes in AGD and to evaluate the 2 predominantly used methods of AGD measurement. The International AGD consortium comprising 4 centers compiled data from 1 cross-sectional and 3 longitudinal cohort studies (clinicaltrials.gov [NCT02497209]). All data were collected from population-based studies, recruiting from 4 maternity or obstetric centers (United States, Cambridge [United Kingdom], Odense, and Copenhagen [Denmark]). This study included a total of 3705 healthy, mainly Caucasian children aged 0-24 months on whom 7295 measurements were recorded. AGDAS (ano-scrotal), AGDAF (ano-fourchette), AGDAP (ano-penile), AGDAC (ano-clitoral), AGD body size indices (weight, body mass index [BMI], body surface area, and length), and intra- and interobserver biases. We created age-specific reference ranges by centers. We found that AGD increased from birth to 6 months of age and thereafter reached a plateau. Changes in AGD/BMI during the first year of life were minor (0-6% and 0-11% in boys and girls, respectively). Reference ranges for AGD can be used in future epidemiological research and may be utilized clinically to evaluate prenatal androgen action in differences-in-sex-development patients. The increase in AGD during the first year of life was age-related, while AGD/BMI was fairly stable. The TIDES and Cambridge methods were equally reproducible.

No effects of androgen receptor gene CAG and GGC repeat polymorphisms on digit ratio (2D:4D): a comprehensive meta-analysis and critical evaluation of research

A series of meta-analyses assessed whether differentially efficacious variants (CAG and GGC repeat-length polymorphisms) of the human androgen receptor gene are associated with digit ratio (2D:4D), a widely investigated putative pointer to prenatal androgen action. Extensive literature search strategies identified a maximum of 18 samples (total N=2909) vs. 5 samples (N=1497) for the CAG-related vs. GGC-related meta-analyses, respectively. In contrast to a small-sample (N=50) initial report, widely cited affirmatively in the literature, meta-analysis of the entire retrievable evidence base did not support any associations between CAG variants and right-hand, left-hand, or right-minus-left-hand 2D:4D. Effects of GGC variants on digit ratios likewise were almost exactly null. For the CAG literature, time trend analysis indicated shrinking effects among more recent studies. Both quantitative and qualitative citation analyses documented that citation bias exists in the research literature: CAG-related studies yielding larger effects were cited more frequently within the same time unit, and the initial, unreplicated report continued to be cited frequently and mostly solely as well as confirmatively, while non-replications were cited much less often. The meta-analytical null findings, along with several further strands of evidence consistent with these, undermine one validity claim for 2D:4D as a retrospective pointer to prenatal testosterone action. Discussed are alternative interpretations of the evidence and avenues for future research.

Association between Digital Finger Ratio (2D:4D) and Salivary Testosterone level in Combative Sports and Non-Sportsmen

The second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with fitness and sports performance. But there very few studies which has evaluated the association between 2D:4D and the circulating levels of testosterone hormone. The objectives of the study were to examine the difference between 2d:4d and salivary testosterone hormone in 107 male combative sportsmen (42 = boxers, 37 = wrestlers & 28 = judokas) and 150 non-sportsmen (NSM) Length of index finger and ring finger of both left and right hand was measured with the help of digital vernier caliper. We found a significant difference in the digital finger ratio 2d:4d between the combative sportsmen and non sportsmen (Boxers v/s NSM t value -7.73, P < 0.01, Wrestlers v/s NSM t value – 5.60, P < 0.01 & Judokas t value – 4.75, P < 0.01). Further significant difference (Boxers v/s NSM t value -17.59, P < 0.01, Wrestlers v/s NSM t value – 18.03, P < 0.01 & Judokas t value – 13.75, P < 0.01) in the level of salivary testosterone hormone (pg/ml) between the combative sportsmen and non sportsmen was found. We suggest that low right-left 2D:4D is a predictive marker of testosterone receptiveness in men trained for the combative sports and this association is programmed by the action of prenatal testosterone.

Digit ratios (2D:4D), postnatal testosterone and eye contact in toddlers

Previous research has shown an association between eye contact and prenatal testosterone measured in amniocenteses samples. The purpose of this study was to test the association between eye contact and prenatal androgen action measured via second to fourth digit ratios (2D:4D ratios), and to explore the relationship between eye contact and postnatal testosterone levels. Participants included 72 children, between the ages of 18 and 24 months, and their parents. Salivary testosterone levels were obtained when children were 3-months old. At 18-months, 2D:4D ratios were measured and parent–child dyads participated in an 8-min play session that was recorded and later coded for duration and frequency of eye contact. Results indicated that larger 2D:4D ratios (indicative of lower androgen levels) significantly predicted longer duration and more frequency of eye contact, while postnatal testosterone levels were unrelated to eye contact. These novel findings suggest prenatal androgens may influence the emergence of social development.

The Left Hand Second to Fourth Digit Ratio (2D:4D) Is Not Related to Any Physical Fitness Component in Adolescent Girls

IntroductionThe second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with fitness and sports performance, although results are not univocal. Most studies however focus on a single aspect of physical fitness or one sports discipline.MethodsIn this study the 2D:4D ratio of 178 adolescent girls (age 13,5–18 y) was measured on X-rays of the left hand. The relation between 2D:4D digit ratio and multiple aspects of physical fitness (balance, speed of limb movement, flexibility, explosive strength, static strength, trunk strength, functional strength, running speed/agility, and endurance) was studied by correlation analyses and stepwise multiple regression. For comparison the relation between these physical fitness components and a selected number of objectively measured anthropometric traits (stature, mass, BMI, somatotype components and the Bayer & Bailey androgyny index) are presented alongside the results of 2D:4D digit ratio.ResultsLeft hand 2D:4D digit ratio (0.925±0.019) was not significantly correlated with any of the physical fitness components nor any of the anthropometric variables included in the present study. 2D:4D did not enter the multiple stepwise regression for any of the physical fitness components in which other anthropometric traits explained between 9,2% (flexibility) and 33,9% (static strength) of variance.ConclusionUnlike other anthropometric traits the 2D:4D digit ratio does not seem to be related to any physical fitness component in adolescent girls and therefore most likely should not be considered in talent detection programs for sporting ability in girls.

The Left Hand Second to Fourth Digit Ratio (2D:4D) Does Not Discriminate World-Class Female Gymnasts from Age Matched Sedentary Girls

IntroductionThe second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with sports performance, although results are not univocal. If this relation exists, it is most likely to be detected by comparing extreme groups on the continuum of sports performance.MethodsIn this study the 2D:4D ratio of world-class elite female artistic gymnasts (n = 129), competing at the 1987 Rotterdam World-Championships was compared to the 2D:4D ratio of sedentary age-matched sedentary girls (n = 129), alongside with other anthropometric characteristics including other sexually dimorphic traits such as an androgyny index (Bayer & Bayley) and Heath-Carter somatotype components (endomorphy, mesomorphy, ectomorphy) using AN(C)OVA. 2D:4D was measured on X-rays of the left hand.ResultsLeft hand 2D:4D digit ratio in world class elite female gymnasts (0.921±0.020) did not differ significantly from 2D:4D in age-matched sedentary girls (0.924±0.018), either with or without inclusion of potentially confounding covariates such as skeletal age, height, weight, somatotype components or androgyny index. Height (161.9±6.4 cm vs 155.4±6.6 cm p<0.01), weight (53.9±7.6 kg vs 46.2 6.3 kg p<0.01), BMI (20.51±2.41 kg/m2 vs 19.05±1.56 kg/m2), skeletal age (15.2±1.1 y vs 14.5±1.2 y p>0.01), somatotype components (4.0/3.0/2.9 vs 1.7/3.7/3.2 for endomorphy (p<0.01), mesomorphy (p<0.01) and ectomorphy (p<0.05) respectively) all differed significantly between sedentary girls and elite gymnasts. As expressed by the androgyny index, gymnasts have, on average, broader shoulders relative to their hips, compared to the reference sample. Correlations between the 2D:4D ratio and chronological age, skeletal age, and the anthropometric characteristics are low and not significant.ConclusionAlthough other anthropometric characteristics of sexual dimorphism were significantly different between the two samples, the present study cannot discriminate sedentary girls from world-class female gymnasts by means of the left hand 2D:4D ratio.

1451 THE ASSOCIATION BETWEEN MALE PATTERN BALDNESS AND SECOND TO FORTH FINGER RATIO WITH PROSTATE CANCER- A PROSPECTIVE COHORT STUDY

You have accessJournal of UrologyProstate Cancer: Detection and Screening II1 Apr 20121451 THE ASSOCIATION BETWEEN MALE PATTERN BALDNESS AND SECOND TO FORTH FINGER RATIO WITH PROSTATE CANCER- A PROSPECTIVE COHORT STUDY David Margel, Seetha Venkateswaran, Abbas Darwish, Antonio Finelli, John Trachtenberg, Karen Chadwick, and Neil Fleshner David MargelDavid Margel Toronto, Canada More articles by this author , Seetha VenkateswaranSeetha Venkateswaran Toronto, Canada More articles by this author , Abbas DarwishAbbas Darwish Toronto, Canada More articles by this author , Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , Karen ChadwickKaren Chadwick Toronto, Canada More articles by this author , and Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1945AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgens play a role in the development of androgenic alopecia, commonly known as male pattern baldness. The ratio of the lengths of index and ring fingers (2D:4D) is also a marker of exposure to sex hormones, with low 2D:4D being indicative of high prenatal androgen action. Retrospective case control studies have demonstrated an association between male pattern baldness and 2D:4D ratio and prostate cancer. The aim of this study was to validate these findings in a prospective cohort. METHODS Upon approval from our local ethical review board we prospectively enrolled 196 consecutive patients referred to a prostate biopsy. Finger lengths were measured using a digital vernier calliper, and the 2D:4D ratio was calculated. Male pattern baldness was assessed on a scale of 0-4 using the standardized Norwood classification (0= no balding, 1= frontal balding, 2= Mild vortex, 3=moderate vortex and 4=severe vortex). We performed all measurements prior to the biopsy thus blinded to the pathology outcome. We performed a univariable and multivariable analysis to associate 2D:4D ratio and male pattern baldness with prostate cancer diagnosis at biopsy. The multivariable model included the two main predictors (male pattern baldness and 2D:4D ratio) as well age, digital rectal examination (normalvs abnormal) and PSA. RESULTS The median (IQR) age and PSA of our cohort was 64 (59-70) and 5.8 (4.1-8.4), respectively. Overall 109 patients (55%) were diagnosed with prostate cancer. On univariable analysis male pattern baldness was associated with prostate cancer (p for trend=0.03). However 2D:4D ratio was not. On multivariable analysis male pattern baldness remained a significant predictor of prostate cancer. Furthermore, we noted a dose response effect- the more severe balding patterns were more strongly associated with prostate cancer (Frontal balding OR 2.0 (95%CI 1.1-6.6); mild vortex OR 2.1 (95%CI 1.5-5.2); moderate vortex OR 2.5 (95%CI 1.2-7.1); severe vortex OR 2.9 (95%CI 1.1-4.3). CONCLUSIONS In a prospective cohort we found that male pattern baldness was an independent predictor of prostate cancer. Further studies are needed in order to assess whether the inclusion of male pattern baldness can contribute to existing models to predict prostate cancer prior to biopsy. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e588 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Margel Toronto, Canada More articles by this author Seetha Venkateswaran Toronto, Canada More articles by this author Abbas Darwish Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Karen Chadwick Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Second to fourth digit ratio (2D:4D) and prostate cancer risk in the Melbourne Collaborative Cohort Study

Background:The ratio of the lengths of index and ring fingers (2D:4D) is a marker of prenatal exposure to sex hormones, with low 2D:4D being indicative of high prenatal androgen action. Recent studies have reported a strong association between 2D:4D and risk of prostate cancer.Methods:A total of 6258 men participating in the Melbourne Collaborative Cohort Study had 2D:4D assessed. Of these men, we identified 686 incident prostate cancer cases. Hazard ratios (HRs) and confidence intervals (CIs) were estimated for a standard deviation increase in 2D:4D.Results:No association was observed between 2D:4D and prostate cancer risk overall (HRs 1.00; 95% CIs, 0.92–1.08 for right, 0.93–1.08 for left). We observed a weak inverse association between 2D:4D and risk of prostate cancer for age <60, however 95% CIs included unity for all observed ages.Conclusion:Our results are not consistent with an association between 2D:4D and overall prostate cancer risk, but we cannot exclude a weak inverse association between 2D:4D and early onset prostate cancer risk.

Relative importance of prenatal and postnatal androgen action in determining growth of the penis and anogenital distance in the rat before, during and after puberty

Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p < 0.0001). However, altered endogenous androgen exposure may confound interpretation of changes in adults exposed prenatally/postnatally to DBP/flutamide. We conclude that AGD provides a lifelong guide to prenatal androgen exposure (in the MPW) whereas penis size reflects both prenatal + postnatal androgen exposure. At the group treatment level, prepubertal measurement of either AGD or penis size accurately predicts their size in adulthood.

High 3D:5D ratio: A possible correlate of externalizing and internalizing problems: An exploratory study

Background and Objectives: The second to fourth (2D:4D) digit ratio is a sexually dimorphic trait which has been studied to examine the association between fetal hormones and a variety of behaviors. Lower 2D:4D ratios, suggestive of exposure to higher levels of prenatal testosterone, have been associated with male-linked disorders, while higher 2D:4D ratios, suggestive of exposure to weaker prenatal androgen action, have been associated with female-linked disorders. Past research has concentrated on the 2D:4D ratio, whereas the relationship between other ratios, such as the 3D:5D ratio, and psychopathology has not much been studied before. Therefore, the aim of this study was to assess the correlation between the 2D:4D and 3D:5D ratio, and internalizing as well as externalizing symptoms, in a large non-clinical sample (143 boys, 150 girls) of white Caucasian children aged 7 to 13 years. Methods: Externalizing and internalizing symptoms were assessed with the Child Behavior Checklist (CBCL). Results: The 3D:5D ratio in boys and in girls was positively associated with scores on Externalizing Problems. Further, in girls only, the 3D:5D ratio was positively correlated to scores on Internalizing Problems. Conclusions: The 3D:5D ratio can be considered a correlate of externalizing and internalizing problems in children from the general population.

The Association Between 2D:4D Ratios and Sociosexuality: A Failure to Replicate

Researchers investigating the role of biological factors in the development and maintenance of interest in uncommitted sexual activity (i.e., sociosexuality) have reported that greater prenatal androgen action in women, as inferred by the ratio of the 2nd to 4th digit, is associated with greater interest in uncommitted sexual relationships, as measured by scores on the Sociosexuality Orientation Inventory (SOI) (Clark, 2004). This evidence suggesting a rather extensive role for prenatal factors in human mating behavior has been cited over 20 times in the literature. However, despite this indication of the impact of the research results on theories of human sex differences, there are no published replications of the original finding. For that reason, the association between 2D:4D ratios and sociosexuality was evaluated in two studies. In the first study, using methodology similar to the original report, no significant association between 2D:4D ratios and SOI scores was found either in women (n = 25) or men (n = 25). Next, to test the possibility that moderating factors, such as menstrual cycle phase and circulating testosterone levels, influence the strength of the association between 2D:4D ratios and sociosexuality, salivary hormone levels and behaviors were measured during the early follicular and mid-luteal phase of the menstrual cycle in women not using hormonal contraceptives (n = 40) and at two time points in women using oral contraceptives (n = 44) and in men (n = 42). Women and men in this study showed the expected sex differences in hormone levels and behavior. However, circulating hormones and 2D:4D ratios were unrelated to measures of sociosexuality obtained at the two test sessions. In sum, these data suggest that factors other than prenatal and circulating hormones explain the sex differences in self-reports of sociosexuality.

Relationships of Toe-Length Ratios to Finger-Length Ratios, Foot Preference, and Wearing of TOE Rings

Sexually differentiated digit ratios of the hand (2D:4D and other) are currently widely studied, owing to their presumed role as a retrospective diagnostic window into prenatal androgen action. This study was only the second one (following McFadden & Shubel, 2002) to examine all 6 possible finger-length ratios (excluding the thumb) and all 10 possible toe-length ratios (including the big toe). Data from a sample of 59 male and 69 female Austrian adults (M age = 27 yr., SD = 7.9) were collected. Replicating the prior study, the majority of toe-length ratios exhibited significant sex differences, which was similar to finger-length ratios, but of weaker effect size. Ipsilateral correlations of toe-length and finger-length ratios were largely absent, except for those of corresponding or adjacent length ratios of the right body side among women. However, these associations were directionally opposite, such that among women, feminized finger-length ratios corresponded to masculinized toe-length ratios. Foot preference (among both sexes) and wearing of toe rings (among women) were not correlates of toe-length ratios. Discussed are implications of these findings for digit ratio research, along with ideas for further inquiry on this topic.

Lack of Association between Digit Ratio (2D:4D) and Assertiveness: Replication in a Large Sample

Findings regarding within-sex associations of digit ratio (2D:4D), a putative pointer to long-lasting effects of prenatal androgen action, and sexually differentiated personality traits have generally been inconsistent or unreplicable, suggesting that effects in this domain, if any, are likely small. In contrast to evidence from Wilson's important 1983 study, a forerunner of modern 2D:4D research, two recent studies in 2005 and 2008 by Freeman, et al. and Hampson, et al. showed assertiveness, a presumably male-typed personality trait, was not associated with 2D:4D; however, these studies were clearly statistically underpowered. Hence this study examined this question anew, based on a large sample of 491 men and 627 women. Assertiveness was only modestly sexually differentiated, favoring men, and a positive correlate of age and education and a negative correlate of weight and Body Mass Index among women, but not men. Replicating the two prior studies, 2D:4D was throughout unrelated to assertiveness scores. This null finding was preserved with controls for correlates of assertiveness, also in nonparametric analysis and with tests for curvilinear relations. Discussed are implications of this specific null finding, now replicated in a large sample, for studies of 2D:4D and personality in general and novel research approaches to proceed in this field.

Digit ratio (2D:4D) predicts sporting success among female fencers independent from physical, experience, and personality factors

Research particularly focusing on male athletes and popular sports (running and soccer) suggests associations of lower (masculinized) second-to-fourth digit ratio (2D:4D), a putative marker of prenatal androgen action, with better sports performance. Studies focusing on women, non-mainstream sports, or controlling for covariates relevant for sporting success are still sparse. This study examined associations between 2D:4D and performance of both male and female athletes active in fencing (a non-mainstream sport dominated by male participants), while controlling for covariates. National fencing rankings and 2D:4D of 58 male and 41 female Austrian tournament fencers (mean age 24 years) were correlated. Among female, but not male, fencers, lower 2D:4D was related to better national fencing rankings. 2D:4D still accounted for incremental variance (12%) in fencing success, when the effects of salient performance factors (age, body mass index, years of fencing, training intensity, and the personality variables achievement, control, harm avoidance, and social potency) were controlled for (totaling 35% attributable variance). Athletes active in the most aggressive form (the sabre) had lower 2D:4D than those active in the other forms (épée and foil fencing). Sporting success in adult life might be partly prenatally programmed via long-lasting extragenital effects of testosterone.

Brief communication: Familial resemblance in digit ratio (2D:4D)

Familial resemblance in the second-to-fourth digit ratio (2D:4D), a proxy for prenatal androgen action, was studied in 1,260 individuals from 235 Austrian families. In agreement with findings from twin studies of 2D:4D, heritability estimates based on parent-child and full-sib dyad similarity indicated substantial genetic contributions to trait expression (57% for right hand, 48% for left hand 2D:4D). Because twin studies have found nonadditive genetic as well as shared environmental effects on 2D:4D to be negligible or nil, these family-based estimates in all likelihood reflect the narrow-sense (additive genetic) heritability of the trait. Directional (right-minus-left) asymmetry in 2D:4D was only weakly heritable (6%). The pattern of same-sex and different-sex parent-child and full-sib correlations yielded no evidence for X-linked inheritance. This is surprising, considering evidence for associations of male 2D:4D with sensitivity to testosterone (functional variants of the X-linked androgen receptor gene). 2D:4D was particularly strongly heritable through male lines (father-son and brother-brother correlations), thus raising the possibility that Y-linked genes (such as the sex-determining region SRY) might influence 2D:4D expression.