High quality empirical data assessing morbidity and mortality and cancer incidence among transgender people are almost non-existent. Sex hormone treatment of conditions in older non-transgender people might as yet be taken as the best available analogy to hormone administration to aging transgender persons. Testosterone administration to transgender men carries little risk with regard to cardiovascular disease and cancer. A dose adaptation may be needed in men with a high hematocrit or cardiac insufficiency. In transgender men, even after breast ablation, breast cancer may occur in residual mammary tissue. Treatment with estrogens (specifically oral ethinylestradiol) of transgender women, particularly in combination with progestins, carries a significant relative risk of developing cardiovascular disease (almost a twofold incidence compared to the general population). The dose of estrogens may have to be reduced with aging. A change from oral to probably safer transdermal estrogens must be considered. Though rare, tumors of the breasts, prostate, meninges and pituitary have been encountered. Based upon the available expertise, initiation of cross-sex hormone treatment in elderly subjects is without disproportionate risks.