Causes of transsexuality Docter and others, but opposed by Charles Allen Moser, Larry Nuttbrock, Julia Serano, and the World Professional Association for Transgender Health.<section end="factors" /> A 2008 study compared 112 male-to-female transsexuals (both androphilic and gynephilic), mostly already undergoing hormone treatment, with 258 cisgender male controls. Male-to-female transsexuals were more likely than cisgender males to have a longer version of a receptor gene (longer repetitions of the gene) for the sex hormone androgen or testosterone, which reduced its effectiveness at binding testosterone. The androgen receptor (NR3C4) is activated by the binding of testosterone or dihydrotestosterone, where it plays a critical role in
Transgender hormone therapy (male-to-female) suggesting a protective role of the male sex-determination chromosome. On the other hand, men with Klinefelter's syndrome (two X chromosomes and one Y chromosome), which causes hypoandrogenism, hyperestrogenism, and a very high incidence of gynecomastia (80%), have a dramatically (20- to 58-fold) increased risk of breast cancer compared to men with one X chromosome, closer to the rate of homogametic females. The incidences of breast cancer in karyotypical men (46,XY karyotype), men with Klinefelter's syndrome (47,XXY karyotype), and karyotypical women (46,XX karyotype) are approximately 0.1%, 3%, and 12.5%, respectively. Individuals with the 46,XY karyotype affected by complete androgen insensitivity syndrome