Individuals who identify themselves as transgender have gender identities that do not match their anatomical sex. Females who identify as male, also known as female-to-male transgender (FTM), may opt to undergo hormonal and surgical treatment in order to transition to the male phenotype, including high-dose testosterone treatment to develop male secondary sexual characteristics and surgical procedures. Currently, the recommendation is for the patient to have a hysterectomy within five years of initiating testosterone therapy to decrease the risk of developing endometrial cancer. However, long-term testosterone treatment has not been proven to cause an increased risk of endometrial cancer. With the use of gene expression and immunohistochemical studies, this study aimed to show no upregulation of genes associated with proliferation (Ki-67) and endometrial cancer (ZIC2) in endometrial tissue from FTM individuals treated with long-term testosterone compared to endometrial tissue from postmenopausal women, premenopausal women with benign endometrium, and women with endometrial cancer. Our findings showed that Ki-67 and ZIC2 expression in the FTM samples was significantly lower than in the endometrial cancer samples. Our findings call into question the concept that long-term testosterone treatment causes neoplastic changes in endometrial tissue and the need for routine hysterectomy in these patients. / 2018-07-11T00:00:00Z