Transgender hormone therapy (male-to-female) males is associated with higher serum estrogen. Both estrogen and testosterone help to stimulate bone formation, especially during puberty. Estrogen is the predominant sex hormone that slows bone loss, even in men. In spite of the induction of breast development, transgender women who undergo HRT do not have an increased risk of breast cancer. Only a handful of cases of breast cancer have ever been described in transgender women who have undergone male-to-female HRT. This is in accordance with research in cisgender men in which gynecomastia has been found not to be associated with an increased risk of breast cancer,
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