pk-reference

name	pk-reference
description	Pharmacokinetics reference for estradiol simulator implementation

PK Simulator Reference

Key References

• estrannaise.js: https://github.com/WHSAH/estrannaise.js (3-compartment model + MCMC)
• TFS Injectable E2 Simulator: https://transfemscience.org/misc/injectable-e2-simulator/
• TFS Meta-Analysis: https://transfemscience.org/articles/injectable-e2-meta-analysis/

Model Architecture (from estrannaise.js)

• Three-compartment pharmacokinetic model with decaying baseline
• MAP estimation + MCMC for parameter inference
• Baseline model: constant before administration → decaying exponential after
• Combined with 3-compartment PK model for full estradiol curve

Supported Ester Types & Approximate Half-Lives

• Estradiol Valerate (EV) IM: absorption t½ ~1.5-2 days, elimination t½ ~3-5 days
• Estradiol Cypionate (EC) IM: elimination t½ ~8-10 days
• Estradiol Enanthate (EEn) IM: sparse data, from Perlutal studies
• Estradiol Undecylate (EUn) IM: very sparse data (Vermeulen 1975, Geppert 1975)
• Oral estradiol: ~5% bioavailability due to first-pass, rapid absorption
• Sublingual: higher peak, shorter duration than oral
• Transdermal patch: zero-order absorption approximation
• Transdermal gel: similar to patch but higher absorption variability

Implementation Notes for Dart Port

• Pure Dart computation, no external dependencies
• Run in Isolate for UI responsiveness
• Support steady-state (repeated doses) and arbitrary regimens
• Must include uncertainty visualization (confidence band)
• Prominent disclaimer: "Simulation only. Individual variation ±50%+. Use actual blood tests."

WPATH/Endocrine Society Target Ranges

• E2: 100-200 pg/mL (some guidelines up to 300)
• Total T: <50 ng/dL
• Display as colored bands on simulation chart