T patches have been approved in Europe for replacement therapy in surgical menopausal women with hypoactive sexual desire. Long-term safety of T administration in women is still unknown. No data exists on the effects of T on the endometrium. The aim of this study is to evaluate the effects of high T doses administered for at least one year on the endometrium.

Endometrial biopsies from 30 FtM treated with T (i.m. injection of 100 mg Testoviron Depot /10 days), 30 postmenopausal women (M) undergoing vaginal hysterectomy and 5 premenopausal women (PrM) undergoing hysteroscopy for infertility problems were collected. Endometrial proliferation was evaluated on the basis of histopathology and expression of the Ki-67. Both M and PrM women had not received hormonal treatment for at least one year.

In FtM T and estradiol (E) levels were increased to above normal female levels (T= 4.2+3.4 ng/mL; E=57.5+39.4 pg/mL). At histological analysis, FTM and M had atrophic endometrium and PrM women had proliferative endometrium. The mean Ki-67 expression in the endometrium was similar in FtM and M (1.1+1.1% and 0.6+0.9%) while it was higher in PrM (42.6 + 17.1; vs. FtM and M p= <0.05).

Our data suggests that long term, high dose T treatment does not stimulate endometrial proliferation in FtM subjects. Exogenous T administration appears to contrast proliferative effects of estrogens on endometrium.