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      Does testosterone impair men's cognitive empathy? Evidence from two large-scale randomized controlled trials

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          Abstract

          The capacity to infer others' mental states (known as ‘mind reading’ and ‘cognitive empathy’) is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia. Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men ( n = 243 and n = 400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.

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          2nd to 4th digit ratios, fetal testosterone and estradiol.

          S Lutchmaya, S. Baron-Cohen, P Raggatt … (2004)
          The ratio of 2nd to 4th digit length (2D:4D) is sexually dimorphic (mean 2D:4D is lower in males than females) and is thought to be fixed early in development. 2D:4D has been reported to be related to fetal growth, hand preference, autism, Asperger's syndrome, sperm counts, family size, age at myocardial infarction in men and breast cancer in women. There is indirect evidence that 2D:4D is established in utero and is negatively related to prenatal testosterone and positively with prenatal estradiol. However, there are no studies which show direct relationships between fetal testosterone (FT), fetal estradiol (FE) and 2D:4D. To investigate the relationships between 2D:4D ratios and FT and FE from amniotic fluid. Cohort study. 33 children. Radioimmunoassays of FT and FE obtained from routine amniocentesis; 2D:4D ratios calculated from 2nd and 4th digit length of the right and left hands at age 2 years. A significant negative association between right 2D:4D ratio and FT/FE ratio, which was independent of sex. These preliminary findings lend support to an association between low 2D:4D and high levels of FT relative to FE, and high 2D:4D with low FT relative to FE.
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            Developmental basis of sexually dimorphic digit ratios.

            Z. Zheng, M J Cohn (2011)
            Males and females generally have different finger proportions. In males, digit 2 is shorter than digit 4, but in females digit 2 is the same length or longer than digit 4. The second- to fourth-digit (2D:4D) ratio correlates with numerous sexually dimorphic behavioral and physiological conditions. Although correlational studies suggest that digit ratios reflect prenatal exposure to androgen, the developmental mechanism underlying sexually dimorphic digit development remains unknown. Here we report that the 2D:4D ratio in mice is controlled by the balance of androgen to estrogen signaling during a narrow window of digit development. Androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas inactivation of ER-α increases growth of digit 4, which leads to a lower 2D:4D ratio. We also show that addition of androgen has the same effect as inactivation of ER and that addition of estrogen mimics the reduction of AR. Androgen and estrogen differentially regulate the network of genes that controls chondrocyte proliferation, leading to differential growth of digit 4 in males and females. These studies identify previously undescribed molecular dimorphisms between male and female limb buds and provide experimental evidence that the digit ratio is a lifelong signature of prenatal hormonal exposure. Our results also suggest that the 2D:4D ratio can serve as an indicator of disrupted endocrine signaling during early development, which may aid in the identification of fetal origins of adult diseases.
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              Fetal testosterone and autistic traits.

              Bonnie Auyeung, Simon Baron-Cohen, Emma Ashwin … (2009)
              Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the possibility of a link between autistic traits and fT levels measured in amniotic fluid during routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were completed by these women about their children (N=235), ages 6-10 years. Intelligence Quotient (IQ) was measured in a subset of these children (N=74). fT levels were positively associated with higher scores on the CAST and AQ-Child. This relationship was seen within sex as well as when the sexes were combined, suggesting this is an effect of fT rather than of sex per se. No relationships were found between overall IQ and the predictor variables, or between IQ and CAST or AQ-Child. These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits. These results need to be followed up in a much larger sample to test if clinical cases of ASC have elevated fT.
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                Author and article information

                Journal
                Title: Proceedings of the Royal Society B: Biological Sciences
                Abbreviated Title: Proc. R. Soc. B
                Publisher: The Royal Society
                ISSN (Print): 0962-8452
                ISSN (Electronic): 1471-2954
                Publication date Created: September 04 2019
                Publication date Created: September 11 2019
                Publication date (Electronic): September 04 2019
                Publication date (Print): September 11 2019
                Volume: 286
                Issue: 1910
                Page: 20191062
                Affiliations
                [1 ]BFI, Toronto, Ontario, Canada
                [2 ]Department of the Humanities and Social Sciences, California Institute of Technology, 1200 E California Boulevard, MC 228-77, Pasadena, CA 91125, USA
                [3 ]ZRT Laboratory, 8605 SW Creekside Place, Beaverton, OR 97008, USA
                [4 ]Department of Psychology, Nipissing University, 100 College Drive, North Bay, Ontario, Canada P1B 8L7
                [5 ]Department of Psychology, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6
                [6 ]Marketing Department, The Wharton School of the University of Pennsylvania, 3730 Walnut Street, Philadelphia, PA 19104, USA
                Article
                DOI: 10.1098/rspb.2019.1062
                PMC ID: 6742992
                PubMed ID: 31480979
                SO-VID: 5819184f-f9ed-4279-828d-bdf8cff2ebb2
                Copyright © © 2019
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