Causes of Gender Incongruence
The etiology of gender incongruence remains incompletely understood, but current evidence points to a complex interplay of prenatal and early postnatal hormonal influences on brain development, with possible genetic contributions, rather than a single identifiable cause.
Current Understanding of Etiology
The most recent guideline evidence indicates that neither biological nor psychological studies provide a fully satisfactory explanation for gender incongruence 1. The 2025 MASCC guideline defines gender incongruence as "a marked and persistent incongruence between an individual's experienced gender and the assigned sex" 2, but deliberately avoids specifying causation, reflecting the current state of scientific uncertainty.
Biological Factors
Prenatal Hormonal Influences
Animal studies consistently demonstrate that prenatal and early postnatal androgens can permanently organize brain structures and behavior patterns 3. However, the translation to humans is far from straightforward:
- Studies of individuals with congenital adrenal hyperplasia (CAH) show that prenatal androgen exposure leads to masculinized behavior and toy preferences, but the majority still maintain a female gender identity when raised as girls 3
- Individuals with 5α-reductase deficiency often develop male gender identity at puberty despite female rearing, suggesting prenatal/postnatal androgens may masculinize the brain independent of social factors 3
- Complete androgen insensitivity syndrome patients develop feminine gender identity despite XY chromosomes, supporting the role of androgen receptors in brain masculinization 3
Recent research using 2D:4D digit ratios (a biomarker of prenatal testosterone) found feminized ratios in transwomen and masculinized ratios in transmen, supporting prenatal testosterone's role 4.
Genetic and Neurobiological Factors
- Behavioral genetic studies suggest heritable components to atypical gender identity development in children 1
- Brain imaging studies show transgender individuals have altered connectivity in body perception networks, potentially underlying gender dysphoria 5, 6
- Transgender individuals demonstrate functional brain activation patterns more similar to their experienced gender than assigned sex when processing gender-relevant stimuli 6
Critical Limitations
The evidence from intersex conditions cannot be directly extrapolated to typical gender incongruence 3. Most individuals with prenatal androgen exposure do not develop gender incongruence, and most transgender individuals have no identifiable hormonal abnormalities 1.
Psychosocial Factors
The 2009 Endocrine Society guideline explicitly states that retrospective psychological studies investigating etiology are intrinsically unreliable due to self-report bias 1. No comprehensive understanding exists of how social, familial, or environmental factors interact with biological predispositions.
Minority stress is not a cause but rather a consequence that exacerbates psychological distress in those with gender incongruence 7.
Clinical Implications
What This Means for Practice
- Gender incongruence is not caused by parenting, trauma, or social influence - these factors may affect expression or distress but not the underlying identity
- No single test or assessment can identify causation in individual patients
- The timing of brain masculinization/feminization likely occurs prenatally and in early postnatal life (ages 1-6 months), making it irreversible by the time patients present clinically 3
Common Pitfalls to Avoid
- Do not search for a "cause" to "fix" - gender incongruence is not a disorder requiring etiological treatment
- Do not assume hormonal abnormalities - most transgender individuals have normal hormone levels for their assigned sex 1
- Do not conflate gender incongruence with intersex conditions - these are distinct phenomena with different underlying mechanisms 2, 8
Evidence Quality Assessment
The evidence base is weak and heterogeneous. Animal studies provide mechanistic insights but have limited applicability to humans. Human studies are predominantly retrospective, cross-sectional, or involve small samples of intersex individuals whose experiences may not generalize. The 2009 Endocrine Society guideline 1 acknowledges this explicitly, and no subsequent guideline has substantially revised this assessment.
The most scientifically honest position is that gender incongruence arises from complex developmental processes involving prenatal hormonal influences on brain sexual differentiation, with possible genetic contributions, but the specific mechanisms remain unclear and likely vary between individuals.