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The term was probably created by Carl Buijs , a transsexual man from the Netherlands, in 1995. Along with the less commonly used cissexual, it originated as a way to shift the focus off of a marginalized group, by defining not only the minority group but also the majority. This is based upon the hypothesis that categorizing everyone will illustrate a difference between equal alternatives, whereas singling out the minority group implies some deviance, immorality, or defect on the part of the labeled group. Some transgender people hope that the use of the word cisgender will increase mainstream acceptance and eventually remove the taboos. Others point out that the term heterosexual is very widely used but seems to have done little for the gay rights movement. However, prior to 1995, there was no standard word used to describe non-transgender people without the use of negative prefixes while still avoiding terms like "normal", "born" or "genetic" (women or men).

Many (particularly transsexual) communities use the term "non-transsexual" or "non-trans", perhaps because the more scientific-sounding term "cisgendered" has not yet gained popularity or widespread usage in everyday English. Others, however, consider it inappropriate to define any group by what they are not.

Cisgender can be used in place of less accurate terms such as biological or genetic male or female since transgender people are also "biologically" (and not made from some non-biological material), while the "genetically"-argument fails when one considers the genetic variations present in intersex people. Born male or female is equally inaccurate, since transgender and transsexual people feel that they are born with a male or female gender identity irrespective of their physiological sex. The use of the term real male or female is both inaccurate, because each and every point that is usually attributed to "real" (=cisgender) women either does not apply to all cisgender women either, or to transwomen and/or many intersex women as well, or to transmen as well, who are usually not counted as "real women". (The same of course applies to "real men".) When used comparatively these expressions are often seen as disrespectful to and by transgender and transsexual people.

The origination and use of cisgender can be compared to the reclamation of profaneProfanity is a word choice or usage which many consider to be offensive. The original meaning of the term was restricted to blasphemy, sacrilege or taking God's name in vain profane speech or swear word , especially expressions such as "God damn it", "go words and hate speechHate speech is a controversial term for speech intended to hurt and intimidate someone because of their race, ethnicity, national origin, religion, sexual orientation, disability, or other personal characteristics, or to incite violence or prejudicial act, such as niggerThe word nigger is a highly controversial term used in many countries, specifically those in the British and American political axis, to refer to individuals with dark skin, especially those of African origin who were racially classified by the outdated t and queer.

Some have perhaps jokingly commented that if trans people can be called tranniesTranny is a term with multiple meanings: Transistor radio Transmission on an automobile Transparency ( photographic slide) Transgender or transsexual person ( slang), either as an adjective or noun. Many feel that it is offensive, on par with words like f for short, then cisgender people can be called "cissies".