Coadministration of estradiol as hormone replacement therapy has not been studied, however, coadministration of estradiol as feminising hormone therapy (FHT) has been studied in transgender women. When estradiol was administered as part of feminizing hormone therapy to 20 HIV-infected Thai transgender women receiving efavirenz and emtricitabine/tenofovir-DF, estradiol AUC, Cmax and C24 decreased by 28%, 19% and 36%, respectively, likely due to enzyme induction by efavirenz. There was no significant change in tenofovir pharmacokinetics. Coadministration of estradiol (with spironolactone) and emtricitabine/tenofovir-DF (as PrEP) to 24 transgender women had no clinically significant impact on the AUC and Cmax of estradiol. In 15 transwomen receiving emtricitabine/tenofovir-DF (200/300 mg once daily) and estradiol as a feminizing hormone, plasma tenofovir Cmax, Cmin and AUC decreased by 20%, 11% and 24% when compared to a historical control group; emtricitabine Cmax, Cmin and AUC decreased by 7%, 11% and 14%. However, intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations in PBMCs were higher than previously reported in the literature. Administration of estradiol (2 mg, with cyproterone acetate 25 mg) as feminising hormone therapy (FHT) was studied in 20 transgender women alone and with emtricitabine/tenofovir-DF. Coadministration had no significant effect on estradiol AUC (1% increase), Cmax (8% increase) or C24 (5% decrease); tenofovir AUC and C24 decreased by 13% and 17%, but Cmax increased by 10%. When tenofovir diphosphate levels (the active metabolite) were determined in rectal tissue from transgender women receiving FHT and emtricitabine/tenofovir-DF  (n=4) and post menopausal cisgender women receiving emtricitabine/tenofovir-DF (n=3),  median concentrations of tenofovir disphosphate were lower in the transgender women (53674 fmol/g, range 23240-1170302) than in the cisgender women (185158 fmol/g, range 76265-223542). The clinical relevance of this is unknown.