The term was introduced to English in 1949 by , and popularized by in 1966, around the same time was coined and began to be popularized. Since the 1990s, has generally been used to describe the subset of people who desire to transition permanently to the gender with which they identify and who seek medical assistance (for example, ) with this. However, the concerns of the two groups are sometimes different; for example, transsexual men and women who can pay for medical treatments (or who have institutional coverage for their treatment) are likely to be concerned with and establishing a durable legal status as their gender later in life.
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 (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 in the 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), 2008 (Garcia-Falgueras), and 2010 (Rametti) confirmed earlier research finding that gender identity is influenced by brain structure. However, some of these studies are limited as they include a small number of tested individuals. Brain structure differences have also been noted between and men, as well as and heterosexual women as part of extensive research on . Studies have also found that both 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 such as Rametti's have found that trans men have male-like white matter patterns (even before using hormones), regardless of sexual orientation.
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Sex is commonly understood to be based on a person’s genitals and reproductive organs; these anatomical details are thought to define a person as male or female. Gender is often understood to refer to gender identity, meaning your internal sense of yourself as female, male, or other, regardless of biology.