| c | u | dose | every | model |
|---|
| c | u | dose | model |
|---|
The cloud does not represent data points, it is a visual representation of the uncertainty in the model itself and it underestimates the total uncertainty. It only captures the uncertainty of something akin to a population mean, or more precisely the uncertainty over the parameters of the deterministic estradiol curve. It does not capture the full distribution of outcomes in the population at large. This is bound to change in the future once a better representation of this uncertainty gets implemented (which would include the additional population variability around the deterministic curve).
The emerging consensus is that the pharmacokinetics of estradiol ester depots is highly variable and depends on many factors that are not well understood and rarely taken into account. Those factors can lead to vastly different outcomes and are not well represented, if at all, in the current models. Those include, among others, the ester concentration, the type of oil used, the proportion and type of excipients such as benzyl benzoate that are present in the formulation, the injection site, whether the depot is injected intramuscularly or subcutaneously, the injection depth, individual differences in metabolism, and the presence of other drugs. Some of those confounding factors are sometimes captured to an extent in the uncertainty of the models, but only when the data is abundant and spans multiple studies done under different conditions. This is, of course, generally not the case. Several of those factors also apply to transdermal, oral, and sublingual estradiol. I am actively working to improve and generalize the current models in ways that will better capture this variability, but ultimately their accuracy and scope will always be limited by the data available.
All pharmacokinetic data used to infer intramuscular models has been redigitized from scratch from the original studies mentioned in the tfs meta-analysis. We further split per-patient data into individual datasets when possible. See the full list of references for more information. Note that pharmacokinetic data for estradiol enanthate (een im) and estradiol undecylate (eun im) is substantially sparser than for the other esters. The data for estradiol enanthate comes entirely from studies on Perlutal from the 80s and 90s. The data for estradiol undecylate comes from two studies (Vermeulen 1975 and the 1975 thesis of Geppert) which both stopped measuring estradiol levels at the 2 week mark, thus preventing the model from capturing the full pharmacokinetic profile of the elimination phase and with it an accurate estimate of the terminal half-life.
The data behind the estradiol undecylate model for subcutaneous depots using castor oil (eun casubq) was inferred on top of the eun im model by augmenting it with very sparse self-reported community data. Its predictions are highly uncertain.
The once-weekly patch model (patch ow) and twice-weekly patch model (patch tw) were from two studies by Houssain et al. and drug labels of Climara, Mylan, and Menostar drug labels. References can be found here.. In light of knowledge gathered from self-reported community data, please be advised that both models excessively underestimate the uncertainty which should be close to 10 times larger. The models will be improved to better reflect this in the future. Currently there is no way to change the wearing period of the patch in the interface (i.e. they are fixed at 3½ and 7 days) but it is planned for the future.
The data for the menstrual cycle comes from Stricker et al. 2006. Download the E2/P/LH/FSH data.
Data for target ranges is based on guidance from WPATH Standards of Care, Version 8 in addition to the Endocrine Society's Clinical Practice Guideline.
Note regarding "inapproprite WPATH regimens" presets
In the WPATH Standards of Care (Appendix C, page S254), several hormone replacement therapy (HRT) regimens for transfeminine people are listed. However, some of these recommendations might not align with WPATH's own guidelines and could even be harmful. Here's a breakdown of the issues.
- Problem with recommended 5-30 mg intramuscular injections every 2 weeks:
- The half-life of estradiol valerate and cypionate are approximately 4 and 8 days, respectively. Injecting every 2 weeks requires higher doses and can cause large fluctuations in hormone levels, leading to very high levels shortly after the injection and very low levels before the next injection. This can cause mood swings and potentially restart testosterone production in the last few days before the next injection.
- Using the lower dose limit (5 mg every 2 weeks), hormone levels may drop too low for monotherapy after about 7 days, potentially allowing testosterone production to restart, and further down below 100 pg/mL at odds with WPATH's own recommended levels.
- Using the upper dose limit (30 mg every 2 weeks), hormone levels could spike dangerously high (upwards of 2,000 pg/mL with EV and 1,000 pg/mL with EC), increasing the risk of blood clots for those predisposed to thrombotic events.
- Problem with recommended 2 to 10 mg intramuscular injections every week:
- Using the lower dose limit (2 mg every week), hormone levels may consistently stay below 150 pg/mL throughout the week with EC and during the second half of the week with EV, and below 100 pg/mL in the last 2 days of the week for both, which might necessitate using an anti-androgen to suppress testosterone.
- Using the upper dose limit (10 mg every week), hormone levels may consistently stay above 300-400 pg/mL, which is much higher than WPATH’s own recommended levels.
Acknowledgements
Initial idea and development by alix. Code improvement and refactoring by Meringue. Help with data digitization from Annie. Additional help from Diamond, GearKite, Jess, Xea, and idk2848.Encouragements, entertainment, feedback, and memetic pumping from
Torble Lea photino emily Izzy Ashley Sapphira
DISCLAIMER
This page, designed as a playground to explore estradiol pharmacokinetics, provides a simulation for informational and entertainment purposes only. The developer(s) cannot guarantee the accuracy of the predictions generated by the simulator. Users acknowledge that the software is offered "as is," without any warranties. The developer(s) assume no liability for direct or indirect damages, either physical, psychological, or otherwise, resulting from the use of the simulator. Users are strongly advised to exercise caution and seek professional medical advice for health-related queries.estrannaise.js is entirely client-side. Your data, whether entered, imported, stashed, or loaded from a shared url, remains exclusively within your browser and will never be transmitted to the developer(s) or any third-party by our application.
mit license (c) 2024 alix
JavaScript license information
estrannaise.js (v0.4.0)
If this kind of thing interests you, you can contact me on signal a1ix2.91 or by email _a1ix2_at_proton_dot_me_ (no underscores). For feedback, bugs, and feature requests submit an issue on github.
tipjars
xmr85Tz3LXEU65h6Lf6tjXLk744FMYW5f4yeTx1pVjsqURQ3YQxtawQJoMAcXDAtEbyFhBLZeEdsXGmpTy5RzzDCWQo6QvcvzE
btc1EK9wp876WhA8W3m7a1mR1Aka6LDsoWpCR
ltcltc1qz4auzjh0dtfqlu5yjk85tvz83aed60ajmy8src
eth0xccC52F9E0CFA1D365A69b5D624dA357192bb3c83