Photo by David Dvořáček on Unsplash

Sex in the brain

The title of this blog may look like a click-bait, nevertheless it is indeed about the sex in our brains. Gender versus sex discussions have been in philosophy, psychology, sociology and recently in cognitive neuroscience an interesting topic. The topic has many fundamental traits that are way beyond my understanding maturity, thus this article gets more into biological and cognitive research on sex differences.

Gender, a socially constructed role, is a combination of roles, behaviors, expressions, identities we assign to girls, boys, men, women and other diverse groups. Gender differences between the mentioned groups have more cultural rather than biological bases, which is a mirror of differential treatment against different genders. The main victims of this differential treatment have been women. Such gendered behavior reinforces subordination of women as a role. However, with the rise of Feminism and other gender rebel wave we have started to question the way we have treated this socially constructed role.

Just to be clear, women are not, and cannot be, subordinate to any other gender groups. Even more importantly, they dont have to be like men to be treated as equal. Right of being woman has to be characterized as being different from men. That’s where my curiosity arose to understand the differences between men and women, or to be more precise between male and female. Since gender is socially constructed and is simply learned, we can change it by “unlearning” those role definitions we have been taught. However, it’s important to understand where differences are innate to us as living creatures with different hormones that change not just how we look like and how we anatomically function, but also our brain and cognitive functioning.

The differences in sex and gender are not restrained to only genital organs and reproductive functioning, but it relates to our whole anatomical systems and pertains in whole our life cycle of being a human, from antenatal period, birth, childhood, adulthood, old age to death. Moreover, the sex-related differences, how X and Y chromosomes, hormones and muscle mass is set up, affect the behavior and identity of ours, whereas the gender differences, such as exposure to our environment, social constructions, poor nutrition, may lead to a genetic and epigenetic modifications.

Main sex differences happen to be on hormones. Testosterone, primarily found in male testes, but produced in small amount in female ovaries, can be also synthesized in the adrenal gland cortex. This means that, besides the classic steroidogenic organs, such as gonads, adrenals or even placenta, the biosynthesis of steroids also occurs in the brain. The same applies to the estrogens, sex hormones mainly produced in female ovaries.

Brain has a significant role in defining the sex differences. A mass which consists billions of neurons creating trillions of tiny junctions called synapses create a circuit that takes the role of communicating when neurotransmitters are released and received between neurons. Depending on the type, either excitatory or inhibitory, communication is either stimulated or silenced. The density, volume or the length of the transmissions are the basis of learning, memory and all our cognitive functioning. The molecular system that controls the strength of synapses is tuned by a host of molecules, such as enzymes, lipids and many other small molecules. These molecules are the subject of new drug discoveries based on which change it makes to how synapses work.

Studies have found that, although we think of estrogens as reproductive hormones in females, those hormones can exacerbate seizures or improve memory, by synthesizing in the brain. Similarly, testosterone can impact certain cognitive functioning. This sex-based difference is called as sexual dimorphism within brain and it brings new look into gender specific medicine in terms of risk-factors, epidemiology and treatment outcomes. The treatment and drug developments should include the sexual dimorphism when evaluating the outcome.

Another interesting research area is on identifying sex differences on psychosomatic illnesses that arise from mental states such as stress, depression and anxiety. When facing stress, we show acute responses which includes pounding heart, sweating and dilated pupils. These changes, also called “fight or flight responses”, mean we are preparing the body for action. Besides this fight or flight response, we also have a more “reasonable” top-down cognitive control on decisions when facing stress or other threats. Adrenal medulla is a significant player that extracts “stress hormones’, which takes input from different motor areas that involves planning and performance of movement. For example, primary motor cortex that controls axial body movement and posture supports the adrenal medulla on keeping us alive by overcoming the stress.

It is assumed that the risk of depression is higher in women than men. The main reason is on flood or depletion of gonadal hormones, especially in fetal development, puberty, pregnancy, post-partum and permimenopausal-menopause transition stages. Main emphasis for the bilogical reasons of depression is on hypothalamic-pituitary-adrenal (HPA) axis, a significant neuroendocrine stress system, which shows elevated basal cortisol levels, disrupted diurnal cortisol secretion patterns, and HPA negative feedback dysregulation when depression is present. In lab studies on non-human rodents, it was observed that a more profound HPA axis dysregulation due to chronic stress is seen in female rats when compared to male rates, characterized by higher corticosterone levels. Moreover, it is not just the pregnant female who is impacted by the stress and depression. The stress during pregnancy can cause an increased emotional response, such as depressive symptoms and attention deficits in infancy (mostly in infant boys) and increased risk for depression in adolescence. These effects though are resulting in different behavioral outcomes in boys and girls. Depressive symptoms can be seen in more girls, whereas attention deficits can be observed in boys.

Sex dimorphism can be seen as well in cell deaths as well in cardiovascular diseases (CVD). There are many types of cell deaths, including “classical” necrosis, apoptosis and autophagy. Male and female cells behave differently that determine the fates of those cells. The higher incidence of CVD in men and its increase in women after the onset of menopausal transition suggest that the sex-differences in steroid hormones play an important role in the development of the disease.

Estrogen interaction with neural networks can be seen in many dimensions and affect brain development. Thus the hormonal modulation of cognition and mood can be accounted to estrogen, which can be a factor in increased risk of developing dementia and depression compared to men. The sex differences can be seen in many areas of the brain, such as the hippocampus amygdala and neocortex. For example, the cortical mantle areas are thicker in women, as well as the ratios of grey to white matter can differ between sexes in human cortex. Moreover, it is assumed that the sex dimorphism in corpus callosum, nerve bundles that connect left and right cerebral hemispheres, can explain various psychological and behavioral differences.

Just to make it clear, none of the studies trying to explain the sex dimorphism could explicitly prove the significance of the differences. Since the neuroscience is still in its growth phase, there are many more unaccounted factors in those studies. Therefore, the arguments and proposals are still to be questioned.

At chromosomes dimension, the “two-sex model” where XX-chromosomes defining maleness, whereas XY-chromosomes defining femaleness is not straightforward. There are people who do not belong to any of these black-or-white categories. Besides these two, we may have XX and XY chromosomes together, or have a XXY or even XXXY chromosomes. Besides that, a person may have an androgen insensitivity and not respond to testosterone. Indeed, one may have a sex development disorder where the amount of sex chromosomes (46, XY kartotype) can be normal but no response to testosterone due to X-chromosomal genetic mutation can be present. As a result, a person can be phenotypically female despite having quite a high levels of testosterone.

Defining the role, functions, identity of person is ever more difficult due to sex differences being still unknown, thus there is no black or white group here. One can have balls but still be woman, or one can have no ovaries and still be woman, or one can still have testosterone but be resistant to it. How should you categorize those people? I’d say we do not have to. We should treat everyone as individuals and assign no predefined socially constructed roles or identities to them.

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