The study of the causes of transsexualism investigates gender identity formation of transgender people, especially those who are transsexual. Transsexual people have a gender identity that does not match their assigned sex, often resulting in gender dysphoria. The causes of transsexuality have been studied for decades.

The most-studied factors are biological. Studies beginning with Zhou in 1995 have found that trans women's brain structure (volume and density of neurons) is similar to cisgender (cis) women's and unlike cis men's, and trans men's is similar to cis men's, even when controlling for hormone use. A 2002 study by Chung suggested significant sexual dimorphism in the BSTc did not become established until adulthood, theorizing that either changes in fetal hormone levels produce changes in BSTc synaptic density and other factors which later lead to the observed differences in BSTc, or the differences are affected by the generation of a gender identity inconsistent with assigned sex. Studies in 2004 (Swaab), 2006 (Gooran) and 2008 (Garcia-Falgueras) confirmed earlier research finding that gender identity is influenced by brain structure. (Brain structure differences have also been noted between gay and heterosexual men, and lesbian and heterosexual women.) Studies have also found that both androphilic and gynephilic trans women's brain function and responses are like cis women's and unlike cis men's, or are intermediate between the two. Likewise, studies have found that gynephilic trans men have male-like white matter patterns (even before using hormones).

With regard to genetic factors, a study by Hare reported that trans women have a longer androgen receptor gene than cis men, which is less effective at binding testosterone, potentially preventing complete masculinization of the brain. (Prenatal androgen exposure or sensitivity, or lack thereof, is often cited mechanisms to explain observed brain-structure differences.) A study by Bentz found that trans men have a CYP17 allele distribution like cis men and unlike cis women. A twin study found that 33% of pairs of identical twins were both trans, compared to only 2.6% of non-identical twins who were raised in the same family at the same time, but were not genetically identical.

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