Oestrogen for feminising hormone treatment comes in different preparations. The most commonly used routes of administration are transdermal (gel or patches) and oral (tablets). Another potential route of administration is sublingual, which involves dissolving a specially manufactured tablet under the tongue, where it is quickly absorbed by the blood vessels under the tongue. This article covers some important considerations regarding sublingual oestrogen.
Pharmacology
Sublingual administration of oestrogen involves dissolving a specially manufactured tablet under the tongue. The oestrogen is absorbed by the blood vessels under the tongue and rapidly enters the bloodstream. Sublingual absorption is very quick compared to absorption of oral oestrogen. Hence, the administration of sublingual oestrogen results in a very high peak concentration of oestrogen within 1 hour of administration, followed by a rapid fall in concentration as the oestrogen is metabolised and excreted (Doll et al., 2022). By contrast, oral oestrogen results in a peak concentration 8 hours after administration, followed by a slower fall in concentration. This has implications for dosing, effectiveness, and monitoring.
Dosing
Doses of sublingual oestrogen are generally equivalent to doses of oral oestrogen, but the dose frequency may differ. Due to the rapid absorption, it has sometimes been recommended to split the dose of sublingual oestrogen so that it is administered twice daily. For example, a daily oestrogen dose of 2mg may be administered as 1mg in the morning and 1mg in the evening. However, recent research has found no difference in effectiveness between once-daily and twice-daily administration of sublingual oestrogen (Cortez et al. 2024).
Effectiveness
A recent study has found that transdermal oestrogen was more effective at suppressing testosterone levels than sublingual oestrogen (Cortez et al., 2024). This is likely to be because the transdermal route results in more continuous absorption of oestrogen, which appears to be more effective at testosterone suppression, whereas the sublingual route results in discontinuous absorption.
Monitoring
Due to the rapid absorption and high peak concentrations produced by sublingual oestrogen, the concentrations of oestrogen in the body throughout the day may be more variable with sublingual oestrogen than with oral or transdermal oestrogen. Hence, blood monitoring of oestrogen levels may need to be timed more meticulously. In general, it is advisable to wait at least 4 hours after the administration of sublingual oestrogen dose before performing a blood test for oestrogen levels. This is in order to avoid misleadingly high results from the initial peak.
References
- Cortez, S., Moog, D., Lewis, C., Williams, K., Herrick, C. J., Fields, M. E., Gray, T., Guo, Z., Nicol, G., and Baranski, T. (2024). “Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial”. Journal of the Endocrine Society, 8(8): bvae108.
- Doll, E., Gunsolus, I., Thorgerson, A., Tangpricha, V., Lamberton, N., and Sarvaideo, J. L. (2022). “Pharmacokinetics of Sublingual Versus Oral Estradiol in Transgender Women”. Endocrine Practice, 28(3): 237-242.