An Interactive Web Simulator for Estradiol Levels with Injectable Estradiol Esters

By Aly | First published July 16, 2021 | Last modified April 12, 2023

Links to go straight to the simulator: Original Simulator and Advanced Simulator

Estradiol is frequently used in injectable form in transfeminine hormone therapy. Injectable estradiol is employed in the form of estradiol esters such as estradiol valerate and estradiol cypionate, which are prodrugs of estradiol that are slowly released from a depot formed at the injection site. These esters are most commonly formulated as oil solutions and are administered via intramuscular or subcutaneous injection. Injectable estradiol is a popular choice among transfeminine people as well as some clinical providers as it has a number of advantages over other estradiol routes and forms. For instance, it allows for easy and inexpensive attainment of higher estradiol levels that can be useful in transfeminine people for achieving better testosterone suppression. This is particularly true in the case of estradiol monotherapy, a therapeutic approach in which an antiandrogen isn’t employed.

Clinically used injectable estradiol preparations were developed many decades ago and are not as commonly used in medicine as estradiol preparations like oral and transdermal estradiol. In fact, injectable estradiol has been discontinued in many countries in favor of non-injectable preparations. In relation to the preceding, research and review material on the pharmacokinetics of these preparations are limited and are scattered throughout the scientific literature. For most of the published concentration–time curves of circulating estradiol with injectable estradiol esters, only a single injection has been administered and the different doses that have been employed have been few. The scarce and obscure information on the pharmacokinetics of these formulations presents challenges for transfeminine people and their clinicians when it comes to understanding the estradiol levels that may result with injectable estradiol preparations. This is particularly true in relation to repeated injections of injectable estradiol formulations at varying doses and injection intervals, which is how these preparations are used in transfeminine hormone therapy. A proper understanding of the estradiol levels with injectable estradiol is important for transfeminine people for avoiding estradiol levels that are too low—which can result in inadequate testosterone suppression and therapeutic efficacy—while also avoiding estradiol levels that are too high—which may produce unnecessary side effects and risks (e.g., Aly, 2020).

To help with overcoming these obstacles, I’ve developed an interactive web app for simulating estradiol levels with injectable estradiol preparations. This simulator can be found at the following page:

Here is a screenshot of the simulator that shows what it looks like and what it can do:

The app simulates estradiol levels with a selection of major injectable estradiol preparations. These preparations include injectable estradiol benzoate (EB) in oil, estradiol valerate (EV) in oil, estradiol cypionate (EC) in oil and as a microcrystalline aqueous suspension, estradiol enanthate (EEn) in oil, estradiol undecylate (EU) in oil, and polyestradiol phosphate (PEP). Options are available in the simulator for specifying injectable estradiol dose (mg), single versus repeated injections, injection interval (days, weeks, or months), units for estradiol concentrations (pg/mL or pmol/L), x-axis maximum value (or time interval to graph) (days), and y-axis max value (or estradiol concentration interval to graph) (pg/mL or pmol/L). One preparation can be simulated at a time or all of the supported injectable estradiol preparations can be graphed together at the same time. When all injectable preparations are simulated at once, the legend can be interacted with to hide or show individual preparations.

The estradiol curves produced by the app are simulations based on available data from published studies with the supported injectable estradiol preparations. The accuracy of the curves is limited by the quality and quantity of these data. In other words, the curves are only estimates, and true estradiol levels with a given preparation may be different than what is shown. It is notable in this regard that estradiol curves with a given injectable estradiol preparation vary considerably between studies, with different levels and curve shapes apparent. There are many potential factors which may contribute to this variability, such as formulation, injection specifics (like injection site, volume, and technique), the type and calibration of blood test used, differing subject characteristics (like age, weight, etc.), and research matters like sampling error. The simulator is not able to take into account these potential variables as data on their influences are scarce and not well-defined. An assumption of the simulator is that estradiol levels and curve shapes scale linearly with dose, which may or may not actually be the case. Lastly, it must be made clear that the estradiol curves correspond to the averages of many people, and individual estradiol levels and curve shapes vary substantially even with the same injectable estradiol preparation. For these varied reasons, the simulator cannot tell a given person what their exact estradiol levels with a given injectable estradiol regimen will be. It can only be used as a guide to roughly estimate where one’s estradiol levels most plausibly could be. In relation to this, estradiol levels, as well as testosterone suppression, should be monitored and verified with blood work to ensure that they are in desired ranges.

A literature review and informal meta-analysis of available estradiol concentration–time data with injectable estradiol preparations was conducted to determine the appropriate estradiol curves for the different estradiol esters included in the simulator. Data were collected from the literature, processed, and modeled using pharmacokinetic models. This work can be found at the following page:

The meta-analysis was not able to derive a reasonable curve for injectable estradiol undecylate due to lack of adequate published data for this ester for modeling. Because of the historical and theoretical importance of estradiol undecylate as an injectable estradiol ester however, it was desirable to nonetheless construct a curve of some form for estradiol undecylate so that it could be included in the simulator. In order to do this, a curve was instead fit to a well-known study for injectable testosterone undecanoate (testosterone undecylate; TU) (Behre et al., 1999) and area-under-the-curve estradiol levels were scaled to be appropriate for those with a given dose of estradiol undecylate based on data with other injectable estradiol preparations. This approach is reasonable as estradiol undecylate and testosterone undecanoate have fairly similar fat solubilities (Table) due to being very similar in chemical structure and as fat solubility is the key property dictating the release rates and curve shapes of these preparations. Accordingly, the resulting curve for estradiol undecylate roughly accords with the reported clinical durations of this ester (Table). In any case, it should be cautioned that the estradiol undecylate curve is not based on real data for this estradiol ester and is only hypothetical or “just for fun”.

The simulator and the curves for the different injectable preparations included may be updated in the future with improvements and new features. Extension of the simulator to other hormonal preparations like injectable testosterone, sublingual estradiol, and estradiol pellets would be fairly straightforward and could be done in the future. However, it would require additional meta-analysis and much further work.

A special thank you to Violet and Lila for their indispensable input and guidance on modeling topics during the work on this project. An additional thanks to Violet for deriving a special three-compartment pharmacokinetic model that was used in the simulator. Please also check out Violet’s own work-in-progress TransKit and Tilia projects—pharmacokinetic tools tailored for transgender hormone therapy.


Update 1: New Advanced Simulator

Since the release of the injectable estradiol simulator, a more advanced version of the simulator with additional options and functionality has been developed. This advanced simulator was created by Luna via modification of Aly’s original simulator code. It uses the same data (i.e. injectable estradiol curves) as the original simulator, but has the following new features: (1) simulate multiple traces at once; (2) stop after X doses (dose limit); (3) start trace at steady state; and (4) show cis woman menstrual cycle (median, 5th percentile, and 95th percentile estradiol levels; data from Abbott (2009)). The advanced injectable estradiol simulator was released on October 5, 2022 and can be found at the following page:

Here is a screenshot of the advanced simulator and its capabilities:

Update 2: Literature Mentions

Since Transfeminine Science’s injectable estradiol simulator was released in mid-2021, it has been mentioned and cited in the scientific literature in a number of publications (see Aly, 2021).


  • Abbott Laboratories. (2009). Estradiol. Architect System. Abbott Park, Illinois/Wiesbaden, Germany: Abbott Laboratories. [PDF]
  • Behre, H. M., Abshagen, K., Oettel, M., Hubler, D., & Nieschlag, E. (1999). Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. European Journal of Endocrinology, 140(5), 414–419. [DOI:10.1530/eje.0.1400414]