Blogs, word-of-mouth, and small studies from the 1990s in the premature ovarian insufficiency
and menopause populations have suggested sublingual or transdermal estradiol may be safer
and/or more effective than an oral formulation. Sublingual administration entails holding the
estrogen tablet under the tongue and allowing it to dissolve, where its absorption is
enhanced by the rich vascularization under the tongue. According to Price et al., sublingual
administration results in rapid absorption with significantly higher estradiol levels than
does comparable oral dosing. This is likely because sublingual administration will bypass
metabolism by the intestines and liver. The transdermal route, which also bypasses first-pass
metabolism, is not associated with an increased venous thromboembolic risk nor a significant
increase in plasma triglycerides or HDL-cholesterol levels. As such, transdermal estrogen is
often preferred over oral formulations, although it is relatively expensive and not
accessible to many transgender women. Conversely, sublingual administration of estrogen
tablets is widely available and could be a cost-effective alternative to transdermal
estrogen. However, there are no well-conducted studies that have evaluated the safety and
efficacy of sublingual estrogen therapy in the transgender population. This pilot study will
elucidate how estrogen levels in the blood change following sublingual versus oral
administration of estradiol in transgender women. This data may be used later to design
larger studies on safety and efficacy.
Additionally, analyzing a dosage method that patients themselves have tried independently and
found effective is also important. This approach incorporates intelligence from the
transgender community into our research, creating new knowledge that is supported by data but
is founded in existing community insights. Thus, the outcomes of this research have the
potential to integrate patient input while also aiding in the development of safety
recommendations, with the goal of better caring for our transgender patients.
Primary aim. To establish the pharmacokinetics of sublingual estradiol versus oral estradiol
in transgender women.