Comparison of Estrone/Estradiol Ratio and Levels in Transfeminine Individuals on Different Routes of Estradiol

Estradiol for gender-affirming hormone therapy can be taken in different routes: oral, sublingual, transdermal patch or gel, and injectable estradiol. We aimed at comparing the estrone and estradiol ratios and levels achieved in each of these different routes of estradiol.

We conducted a retrospective chart review of transfeminine individuals attending an endocrinology clinic in Toronto, Canada. Study participants were grouped according to the route of estradiol administration: oral, injectable, transdermal, and sublingual. Our primary outcome was the estrone/estradiol ratio (E1/E2). Our secondary outcomes were the estradiol and estrone levels in each of these four groups.

We included 286 patients. The oral estradiol group had the highest E1/E2 ratio (9.28), followed by the sublingual group (6.88). Both the transdermal and injectable groups had substantially lower E1/E2 ratios (2.22 and 0.84, respectively). We observed a large variability of the E1/E2 ratio in the oral and sublingual groups, whereas the transdermal and the injectable groups' ratios had much smaller standard deviation. The mean estradiol in the injectable group (1557 pmol/L, 424.1 pg/mL) was markedly higher than the estradiol levels observed in all other routes of estradiol.

Our data demonstrate significantly different E1/E2 ratios in the four different routes of estradiol administration, with oral and sublingual routes having the highest E1/E2 ratios followed by transdermal and injectable routes.