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

https://academicworks.medicine.hofstra.edu/cgi/viewcontent.cgi?article=1952&context=articles

Sex differences in anxiety and depression clinical perspectives

Female and male brains differ. Differences begin early during development due to a combination of genetic and hormonal events and continue throughout the lifespan of an individual. Although researchers from a myriad of disciplines are beginning to appreciate the importance of considering sex differences in the design and interpretation of their studies, this is an area that is full of potential pitfalls. A female's reproductive status and ovarian cycle have to be taken into account when studying sex differences in health and disease susceptibility, in the pharmacological effects of drugs, and in the study of brain and behavior. To investigate sex differences in brain and behavior there is a logical series of questions that should be answered in a comprehensive investigation of any trait. First, it is important to determine that there is a sex difference in the trait in intact males and females, taking into consideration the reproductive cycle of the female. Then, one must consider whether the sex difference is attributable to the actions of gonadal steroids at the time of testing and/or is sexually differentiated permanently by the action of gonadal steroids during development. To answer these questions requires knowledge of how to assess and/or manipulate the hormonal condition of the subjects in the experiment appropriately. This article describes methods and procedures to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.

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Strategies and Methods for Research on Sex Differences in Brain and Behavior

Autism Spectrum Conditions (ASC) are much more common in males, a bias that may offer clues to the etiology of this condition. Although the cause of this bias remains a mystery, we argue that it occurs because ASC is an extreme manifestation of the male brain. The extreme male brain (EMB) theory, first proposed in 1997, is an extension of the Empathizing-Systemizing (E-S) theory of typical sex differences that proposes that females on average have a stronger drive to empathize while males on average have a stronger drive to systemize. In this first major update since 2005, we describe some of the evidence relating to the EMB theory of ASC and consider how typical sex differences in brain structure may be relevant to ASC. One possible biological mechanism to account for the male bias is the effect of fetal testosterone (fT). We also consider alternative biological theories, the X and Y chromosome theories, and the reduced autosomal penetrance theory. None of these theories has yet been fully confirmed or refuted, though the weight of evidence in favor of the fT theory is growing from converging sources (longitudinal amniocentesis studies from pregnancy to age 10 years old, current hormone studies, and genetic association studies of SNPs in the sex steroid pathways). Ultimately, as these theories are not mutually exclusive and ASC is multi-factorial, they may help explain the male prevalence of ASC.

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Why Are Autism Spectrum Conditions More Prevalent in Males

OBJECTIVE: The goal of this overview is to examine male/female differences in psychopathology in light of the known effects of gonadal steroids, especially estradiol, on neural function. METHOD: The epidemiology of specific psychopathological syndromes is highlighted with respect to male/female differences and discussed against the backdrop of recent neuroendocrine findings. RESULTS: A number of differences between the sexes in rates of illness and course of illness are documented, with Alzheimer's disease, schizophrenia, alcoholism, and mood and anxiety disorders each illustrating slightly different hormone-mediated risks and buffers. CONCLUSIONS: Estrogens are neuroprotective with respect to neuronal degeneration, growth, and susceptibility to toxins. The cyclic fluctuations of estrogens and progesterone enhance the response to stress, which confers susceptibility to depression and anxiety. (Am J Psychiatry 1997; 154:1641–1647)

Psychopathology in Women and Men: Focus on Female Hormones

In humans, the influence of prenatal sex hormones on the fetal brain and subsequent postnatal development has had limited study because of the apparent inaccessibility of hormone levels in normal fetuses. We propose that amniotic fluid obtained via midtrimester amniocentesis can be assayed for fetal hormone levels during the period thought to be important for sexual differentiation of the brain. Amniotic fluid samples from midgestation (N = 70) were assayed for levels of testosterone and follicle-stimulating hormone, and significant sex differences were observed (ps less than .001), with some degree of overlap between the sexes. The possibility of applying hormone levels obtained from amniotic fluid to the study of postnatal development is discussed.

Betty Bartleman

Papers

A window for the study of prenatal sex hormone influences on postnatal development.