About this Research Topic

Background

Sexual differentiation of the brain is derived from the sex steroids’ effects on the developing brain during a restricted critical window. Brain masculinization is induced by estradiol produced from testosterone by the aromatase enzyme in the brain, matching chromosomic sex, gonads and genitals, to a male gender identity. In contrast, the lack of early exposure to testosterone in females allows the development of a feminized brain, in concordance with their feminized phenotype and female gender identity.

However, gender and sex do not always match. Transgender women are born with male genitalia and are assigned as male at birth, but they have a feminine gender. Similarly, transgender men are born with female genitalia, are assigned as females at birth, but they have a masculine gender. Transgender individuals generally experience gender dysphoria due to the persistent incongruence between the birth-assigned sex and their experienced gender identity. Therefore, they often seek gender affirmative cross-sex hormone therapy, with or without surgery, to align their physical features with their gender.

The origin of gender dysphoria seems to be multifactorial. It might be associated with altered sexual differentiation of the brain, potentially as a consequence of a genetic vulnerability that implicates variations of the sensitivity of the nuclear receptors (AR, ERα and ERβ) to their ligand. Another process involved is DNA methylation, since it is implicated in mammalian brain development and plasticity.

People with gender dysphoria experience severe body dysphoria, have a more negative body image and an altered body representation, that is reflected in altered functioning of associated brain regions. Gender affirmative hormone treatment, which aligns the body with the experienced gender, may similarly affect brain structure and function. In addition, hormone treatment has been suggested to have extensive effects on various physiological processes.

Many individuals with gender dysphoria suffer from serious mental health problems that may or may not be alleviated by hormone interventions, such as puberty suppression by Gonadotropin Releasing Hormone analogues (GnRHa) and cross-sex hormone treatment. Longitudinal studies, covering various levels from molecular processes to behavior, are needed to chart the impact of sex hormones on the development of gender dysphoria during childhood, adolescence, and adulthood.

This Research Topic welcomes basic science and clinical manuscripts. Original research papers as well as reviews that add value to our current knowledge about the developmental origins and the influence of hormonal interventions on the mental and physical health trajectories of people with gender dysphoria may be submitted.
Potential topics include, but are not limited to the following:
• Gender dysphoria, gender variance and mental health in childhood/adolescence/adulthood
• Trends in Prevalence, Treatment, and Regrets
• Hormonal interventions for gender dysphoria – longitudinal evidence
- (Developmental) psychology perspective
- Cognitive psychology perspective
- Neurobiological perspective
- Endocrine & physical health perspective
- (Epi)genetic perspective
• Role of androgens, estrogens, and aromatase in sexual differentiation of the brain
• Role of genetics and epigenetics in gender dysphoria

Keywords: gender dysphoria, metylation, brain sexual differentiation, body perception, sex hormone treatment

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