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.

Premenstrual dysphoric disorder is associated with the longer length from clitoris to urethra

Background Premenstrual dysphoric disorder (PMDD) is a common, recently recognized, psychiatric condition among reproductive women, reflecting abnormal responsivity to ovarian steroids. Moreover, the potential organizational effect of prenatal sex hormones during PMDD has got attentions, but there have been considerably less of researches on this topic. The aim of this research was to investigate the possible role of prenatal androgen in the PMDD. Methods Anogenital distance (AGD), the distance between a woman’s clitoris and her urethral meatus (CUMD), left and right 2D:4D ratios were measured in 77 subjects (25 patients with PMDD), as these anthropometric indicators are considered to indirectly reflect prenatal androgen exposures in utero. Results Patients with PMDD had a longer CUMD than controls (25.03 ± 4.73 vs. 22.07 ± 4.30, P = 0.008), while there were no significant difference between PMDD group and control group in the AGD and right and left 2D:4D ratios. Conclusion Atypical high prenatal androgen exposure might predispose individuals to be susceptible to PMDD.

P–632 Examination of temporal changes in phenotype and gut microbiome during the process of growth in polycystic ovary syndrome (PCOS) model induced by prenatal androgen exposure

Study question From when do abnormality in gut microbiome and phenotypes of PCOS appear during the process of growth? Summary answer Reproductive phenotypes of PCOS appear from 6 weeks and metabolic phenotypes from 12 weeks onward. Alteration in gut microbiome appears as early as 4 weeks. What is known already The etiology of PCOS remains largely unknown, however PCOS is considered as a complex multigenic disorder with strong epigenetic and environmental influence. Previous studies have suggested that fetal over-exposure to androgens could be the main factor of the development of PCOS after birth. On the other hands, recent studies on both human and PCOS rodent models have demonstrated the association between PCOS and alteration of gut microbiome in adulthood. Furthermore, it was recently reported that gut microbiome in obese adolescent with PCOS is different from obese adolescent without PCOS. Study design, size, duration A rodent PCOS model induced by prenatal dehydroepiandrosterone (DHT) exposure was applied to this study. Phenotypes and gut microbiome were compared between PCOS model mice (n = 12/group) and control mice (n = 10/group) at each stage of growth; 4 weeks (prepuberty), 6 weeks (puberty), 8 weeks (adolescent), 12 weeks (young adult), and 16 weeks (adult). The determinants for PCOS phenotypes are onset of puberty, estrous cycle, morphology of ovaries, serum testosterone level, body weight, and insulin resistance. Participants/materials, setting, methods Pregnant dams were subcutaneously injected on days of 16, 17, and 18 of gestation with either sesame oil for control groups or sesame oil containing 250µg of DHT for prenatal DHT groups. The evaluation of PCOS phenotypes and gut microbiome in female offspring were performed at each stage of growth. For examination of gut microbiota, next generation sequencing and bioinformatics analysis of 16S rRNA genes were performed on DNA extracted from mouse fecal samples. Main results and the role of chance Prenatal DHT mice exhibited delayed puberty onset, disrupted estrous cycle, and significantly increased testosterone levels from 6 weeks onward. Significantly increased atretic antral follicles were observed in prenatal DHT mice at 6, 12, and 16 weeks. Prenatal DHT mice showed significantly decreased body weight at 4, 6, 8 weeks and increased body weight from 12 weeks onward. As for gut microbiome, alpha-diversity was significantly different between control and prenatal DHT mice from 8 weeks onward and beta-diversity was significantly different at 6 and 8 weeks. Altered composition of gut microbiota was observed as early as 4 weeks. At phylum level, Firmicutes are significantly increased in prenatal DHT mice at 4 and 8 weeks and decreased at 16 weeks. Actinobacteria phylum showed significant decrease at 6 and 8 weeks in prenatal DHT mice. At genus level, relative abundance of several bacterial taxa significantly differed between control and prenatal DHT mice; some taxa, such as Allobaculum, Adlercreutzia, Bilophila, Clostridium, Gemella, Gemmiger, Roseburia, Ruminococcus, Staphylococcus, and Sutterella, exhibited constant increase or decrease in prenatal DHT mice during the process of growth. Interestingly, Roseburia was never detected in prenatal DHT mice, while approximately half of control mice harbored Roseburia at 12 and 16 weeks. Limitations, reasons for caution It is not clearly determined whether alteration in gut microbiome is cause or result of PCOS development, although the changes in gut microbiome seemed to precede the appearance of typical PCOS phenotypes in the present study. Mouse model does not completely recapitulate human PCOS. Wider implications of the findings: Our findings suggest that prenatal androgen exposure causes alteration of gut microbiome from pre-puberty onward, even before PCOS phenotypes become apparent. Intervention for girls at risk of PCOS with pre/pro-biotics may prevent them from developing PCOS in future. Trial registration number Not applicable

Investigating the reliability and sex differences of digit lengths, ratios, and hand measures in infants

Hands and digits tend to be sexually dimorphic and may reflect prenatal androgen exposure. In the past years, the literature introduced several hand and digit measures, but there is a lack of studies in prepubertal cohorts. The available literature reports more heterogeneous findings in prepubertal compared to postpubertal cohorts. The comparability of the available studies is further limited by the study design and different measurement techniques. The present study compared the reliability and sex differences of available hand and digit measures, namely digit lengths of 2D, 3D, 4D, 5D, digit ratios 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D, relative digit lengths rel2, rel3, rel4, rel5, directional asymmetry of right and left 2D:4D (Dr-l), hand width, length, and index of 399 male and 364 female 6-month-old German infants within one study using only indirect and computer-assisted measurements. The inter-examiner reliability was excellent while the test-retest reliability of hand scans was only moderate to high. Boys exhibited longer digits as well as wider and longer hands than girls, but smaller digit ratios, with ratios comprising the fifth digit revealing the largest effect sizes. Other hand and digit ratios revealed sex differences to some extent. The findings promote the assumption of sexual dimorphic hand and digit measures. However, by comparing the results of the available literature, there remains an uncertainty regarding the underlying hypothesis. Specifically in prepubertal cohorts, i.e. before the influence of fluctuating hormones, significant effects should be expected. It seems like other factors than the influence of prenatal androgens contribute to the sexual dimorphism in hand and digit lengths.

Markers of Prenatal Androgen Exposure Correlate With Online Sexual Compulsivity and Erectile Function in Young Men

Pornography addiction and sexual dysfunction are increasingly prevalent in young men. Previous studies suggest that prenatal androgen exposure plays a role in addiction and sexual functionality. Here, we tested whether lower second-to-fourth finger length ratio (2D:4D) and later age at spermarche, both putative indicators of higher androgen levels in utero, correlate with online sexual compulsivity (OSC scale of ISST), erectile function (IIEF-5), and ejaculatory control (PEPA) in 4,370 young men (age IQR: 25–26 years) of the Cohort Study on Substance Use Risk Factors. Statistical analyses revealed that lower 2D:4D correlated with higher scores on the OSC scale. Moreover, higher age at spermarche correlated with higher OSC scores and decreased erectile function. Interestingly, OSC severity, but not the frequency of pornography use, correlated negatively with erectile function and ejaculatory control. This is the first study to associate two independent proxies of prenatal testosterone level with OSC. These findings provide novel insight into intrauterine predisposition of sexual behavior and related sexual function in adulthood.

Understanding the associations of prenatal androgen exposure on sleep physiology, circadian proteins, anthropometric parameters, hormonal factors, quality of life and sex among healthy young adults – BOAT international, multicentre study protocol (Preprint)

UNSTRUCTURED Background The ratio of second finger length to fourth finger length (2D:4D) is considered to be a negative correlate of prenatal androgen exposure and a positive correlate of prenatal oestrogen. Therefore males, on average, have a lower value of 2D:4D ratio as compared to females. Coincidentally, various brain regions are sensitive to prenatal androgen exposure, and their function in adulthood may be influenced by these prenatal actions of sex hormones. An example of such a brain region is the preoptic area which is involved in sleep and sexual functions. The objective of this study is to assess the relationship between prenatal androgen exposure (indicated by the 2D:4D ratio) and various physiological (sex hormone levels, sleep-wake parameters), psychological (mental health), as well as sexual parameters in young healthy adults. Methods The study consists of two phases: 1. In Phase I, we will conduct a survey-based study and anthropometric assessments (including 2D:4D ratio, body mass index) in healthy young adults. Using validated questionnaires, we will collect self-report data on sleep quality, sexual function, sleep chronotype, anxiety and depressive symptoms. 2. In Phase II, a sub-sample of Phase I will have polysomnography, physiological and genetic assessments. The sample recruited to this phase will comprise 100 healthy adults in each institution involved. Sleep architecture data will be obtained using a portable polysomnography. Venous blood will be drawn before and after polysomnograpy night and urine sample will be obtained in the morning. The level of testosterone, estradiol, progesterone, luteinizing hormone, follicle stimulating hormone, prolactin, melatonin and circadian regulatory proteins (CLOCK, TIM, PER) and a few miRNAs expression level, will be measured. The rest and activity cycle will be monitored using an actigraphy for a 7 days period. Discussion The impact of the study may help to better understand the role of plausible prenatal androgen exposure on sleep physiology, mental health and sexual quality of life in young adults.

An association between body image dissatisfaction and digit ratio among Chinese children and adolescents

Body image dissatisfaction (BID) is a negative evaluation of personal physical characteristics, including dissatisfaction with body shape, gender, sexual organs, appearance and so forth, and it plays an important role in growth and development. The second-to-fourth digit ratio (2D:4D) is recognized as a putative indicator of intra-uterine testosterone to estrogen ratio exposure, and it has been observed that higher levels of fetal testosterone exposure are associated with a lower 2D:4D. The present paper contributes to a better understanding of the biological underpinnings of BID by analyzing BID and the digit ratio (2D:4D). We found that the 2D:4D was positively related to appearance dissatisfaction in boys with first spermatorrhea, which means that low prenatal androgen exposure may increase boys’ dissatisfaction with their appearance. In girls with breast development being lower than Tanner stage II, their 2D:4D was negatively related to their body shape dissatisfaction, which means that high prenatal androgen exposure may increase girls’ dissatisfaction with their body shape. These results suggest that the prenatal androgen exposure level might play an important role in the body image dissatisfaction of the offspring.

Clitoris to Urethral Meatus Distance is Not Affected by the Obesity Compared to the Anogenital Distance

Background The distance between clitoris and urethral meatus (CUMD) for women has been considered to likely reflect the extent of prenatal androgen exposure, being similar to the anogenital distance (AGD) and the digit length ratio. But no published work has examined the association between the CUMD and the AGD or digit ratio and the effect of body weight on CUMD and AGD.Methods The CUMD and AGD (including AGD-AC, from the anus to the anterior clitoris; AGD-AF, from the anus to the posterior fourchette) measurements for 117 women (18-45 years) were taken using a digital caliper, and the digit ratios were measured from photos by a digital camera. Meanwhile, data of their height, weight, and body mass index (BMI) were collected at same time. Results In bivariate correlation analyses of all 117 subjects, two AGD measurements (AGD-AC and AGD-AF) were moderately correlated with one another (r=0.474, p<0.001), but the correlation between AGD-AC and CUMD was weak (r=0.172, p=0.063). Both AGD-AC and AGD-AF were notably correlated with weight (r=0.290, p=0.002 and r=0.189, p=0.041; respectively) and BMI (r=0.341, p<0.001 and r=0.204, p=0.027; respectively), whereas the CUMD was not affected by weight or BMI. Exclusion of obese individuals, the CUMD of 86 non-overweight subjects was obviously correlated with the AGD-AC (r=0.236, p=0.028). Conclusion These results indicated that the CUMD could be a marker of prenatal androgen exposure without influence of body weight, superior to AGD-AC or AGD-AF.