Pharmacokinetic and pharmacodynamic study of various doses oral and transdermal estrogen found that transdermal estradiol 75mcg patches most closely approximated physiologic estrogen levels in agonadal girls with Turner syndrome. (1)
Mean serum estradiol concentrations were closest to those of the control group in the high-dose transdermal group (114 +/- 31pg/ml transdermal, 96 +/- 11pg/ml for controls) for. Levels in the low dose transdermal and high dose groups were similar. Levels were lowest in the low dose oral group. Estrone (e1) concentrations were higher the oral groups, likely because of hepatic and intestinal conversion. LH/FSH suppression was equal in both high dose groups, but more pronounced in the low dose transdermal vs. oral. In all cases gonadotropins did not fully normalize (particularly FSH, which responds in part to inhibin, which is absent in hypogonadal states).
It is unclear if pharmacologic studies in Turner syndrome females are applicable in those with male physiology or genetics. For example, transwomen’s skin and connective tissue may have different absorption characteristics with respect to transdermal delivery systems. It is also unclear if targeting physiologic estradiol levels is an appropriate clinical target for medical transition. While estrone is generally considered to have minimal estrogenic activity, it may serve as an estrogen reservoir and may explain why patients describe feeling “different” on oral vs. transdermal preparations with similar serum levels. Lastly, measurement of serum estrogens is wrought with difficulties and this study was not adequately powered to draw firm conclusions.