What is the current understanding of the biological basis of transgender identity?
Executive summary
Current research finds multiple lines of biological evidence — genetic variants, prenatal hormone pathways, and brain structural and functional differences — that together suggest gender identity has a substantial biological component, but no single “transgender gene” or simple biological cause has been identified and findings remain incomplete and sometimes contradictory [1] [2] [3]. Leading researchers and reviews caution that biology interacts with social and developmental factors, and critics warn that a search for a single biological cause risks ideological misuse or biological essentialism [4] [5] [6].
1. Genetic signals: hints, not a single cause
Multiple genetic studies report associations between variants in sex-steroid signaling genes and transgender identities — for example a large study of 380 transgender women found certain variants in a dozen genes involved in estrogen and androgen pathways were overrepresented versus cisgender male controls [2] [1] — but reviewers emphasize gender identity is likely polygenic and multifactorial rather than traceable to one mutation, and replication across diverse samples remains limited [4] [7].
2. Hormones and prenatal development: the organisational hypothesis
A consistent thread in the literature is the “organisational” role of prenatal sex steroid exposure shaping brain development in ways that can influence later gender identity; studies link genes that affect androgen and estrogen signalling and enzymes that control hormone levels to gender incongruence, and clinical observations such as differing 2D:4D ratios and hormone-sensitive pathways have been interpreted through that lens [1] [8] [9]. Authorities caution, however, that hormone-related findings do not deterministically predict identity and must be read as contributors within a complex developmental milieu [1] [10].
3. Brains: shifted, unique, and not simply “male” or “female”
Neuroimaging and post-mortem work report that many transgender people show brain structural or functional characteristics that more closely resemble people who share their gender identity than people who share their natal sex, and large-scale meta/mega-analytic work (ENIGMA) describes a distinct “brain phenotype” in transgender persons rather than a simple shift toward the opposite sex [11] [3] [12]. Machine‑learning classifiers trained to predict biological sex from brain structure also perform worse on transgender samples, supporting the idea of a non-binary, mixed or unique neuroanatomical profile [13] [12].
4. Limits, contradictions and methodological caveats
The literature is marked by small samples, heterogeneous methods, population biases (many studies on untreated or narrowly defined clinical samples), and inconsistent replication, and critical reviews argue some reported differences may be overstated or misinterpreted if social and developmental influences aren’t adequately controlled [5] [14]. Prominent commentators also warn that the pursuit of a singular “cause” risks reinforcing biological essentialism and could be politically weaponized, so scientific humility about limits and context is imperative [6] [5].
5. What this means for medicine, policy and public understanding
Clinically and ethically, many professional reviews conclude that accumulating biological evidence supports treating gender identity as a real, deeply held human trait with biological underpinnings, which can inform medical care and reduce stigma, but they simultaneously call for more rigorous, diverse research and for caution in translating findings into social policy or coercive practices [15] [10] [1]. In short, biology appears to contribute materially to why some people are transgender, but it is neither simple nor sufficient to explain every individual case, and responsible interpretation must balance scientific curiosity with respect for rights and lived experience [10] [4].