References
This page summarizes the core findings used in the simulator, including consolidated pharmacokinetic ranges, implementation assumptions, and source citations.
Key Findings
Injectable estradiol and testosterone esters act as depot formulations: the esterified hormone forms a local depot after injection and is released over time, then hydrolyzed to the parent hormone in circulation.
The model uses first-order absorption and elimination, with ester-specific half-life ranges and apparent V/F coefficients to represent depot kinetics and distribution at clinically observed scales.
Consolidated Pharmacokinetic Parameter Ranges
| HRT Ester | Absorption Half-life (h) | Elimination Half-life (h) | Bioavailability (F) | Apparent V/F (L/kg) |
|---|---|---|---|---|
| Estradiol Valerate | 14.00 - 20.00 | 84.00 - 120.00 | 1.00 | 250.00 - 350.00 |
| Estradiol Cypionate | 16.80 - 36.00 | 90.00 - 240.00 | 1.00 | 350.00 - 450.00 |
| Estradiol Enanthate | 11.00 - 14.00 | 134.00 - 180.00 | 1.00 | 400.00 - 550.00 |
| Testosterone Cypionate | 13.60 | 97.20 - 192.00 | 0.95 | 160.00 - 180.00 |
| Testosterone Enanthate | 3.04 | 108.00 | 0.95 | 150.00 - 190.00 |
| Testosterone Propionate | 1.20 | 19.20 | 0.95 | 160.00 - 190.00 |
| Testosterone Undecanoate | 4.90 - 5.50 | 501.60 - 813.60 | 0.95 | 140.00 - 160.00 |
Mathematical Modeling Guide
The simulator implements a one-compartment first-order depot model:
C(t) = [Dose x F x ka / (Vd x (ka - ke))] x (e-ket - e-kat)
Rate constants are computed from half-lives as k = ln(2) / t1/2. Apparent volume is weight-scaled as V = (V/F coefficient in L/kg) x body weight (kg).
Clinical display units are produced after conversion from model mass/volume units:
- Estradiol output: pg/mL
- Testosterone output: ng/dL
Clinical Default Archetypes Used in the Documentation
- TRT: common starting point 100 mg weekly, with broader clinical customization ranges around 50-200 mg weekly or 200-400 mg every 2 weeks.
- Feminizing GAHT: common injectable starting points around 4 mg estradiol valerate or 2 mg estradiol cypionate weekly, with broader customization in the low-to-moderate weekly dose range.
Core Pharmacokinetic Literature
- Dusterberg B, Nishino Y (1982). Pharmacokinetic and pharmacological features of oestradiol valerate. Maturitas. DOI: 10.1016/0378-5122(82)90064-0
- Oriowo MA, et al. (1980). A comparison of the pharmacokinetic properties of three estradiol esters. Contraception. DOI: 10.1016/S0010-7824(80)80018-7
- Silva-Bernal D, et al. (2019). Quantification of estradiol cypionate in plasma and application in a pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis. DOI: 10.1016/j.jpba.2019.03.045
- Dusterberg B, et al. (2008). Pharmacokinetics and biotransformation of estradiol valerate. Hormone Research. DOI: 10.1159/000180039
- Sierra-Ramirez JA, et al. (2011). Comparative pharmacokinetics/pharmacodynamics after subcutaneous and intramuscular estradiol cypionate. Contraception. DOI: 10.1016/j.contraception.2011.03.014
- Bi C, et al. (2018). Population PK/PD modeling of depot testosterone cypionate. CPT: Pharmacometrics & Systems Pharmacology. DOI: 10.1002/psp4.12287
- Zitzmann M, Nieschlag E (2007). Androgen substitution with long-acting testosterone undecanoate. The Aging Male. DOI: 10.1080/13685530601063689
- Vervalcke M, et al. (2024). Estradiol valerate pharmacokinetics in assigned-male-at-birth individuals. Endocrine Abstracts. DOI: 10.1210/clinem/dgaf015
- Herndon J, et al. (2023). Population pharmacokinetics of subcutaneous and intramuscular testosterone enanthate. Journal of the Endocrine Society. DOI: 10.1210/jendso/bvad059
- Fujioka M, et al. (1986). Pharmacokinetic properties of testosterone propionate in normal men. Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/jcem-63-6-1361
- Yin X, et al. (2021). Population pharmacokinetics of intramuscular testosterone undecanoate. CPT: Pharmacometrics & Systems Pharmacology. DOI: 10.1002/psp4.12704
- White WB, et al. (1998). The pharmacokinetics of intravenous estradiol. Pharmacotherapy. DOI: 10.1002/j.1875-9114.1998.tb03160.x
- Macheras P (1984). Quick method for the calculation of the absorption rate constant. International Journal of Pharmaceutics. DOI: 10.1016/0378-5173(84)90063-2
Supplemental Sources
- FDA clinical pharmacology review documents (testosterone products): accessdata.fda.gov
- Population PK/PD summary article mirror: PMC5915615
- Pharmacokinetics of testosterone (background): wikipedia.org/wiki/Pharmacokinetics_of_testosterone
- Pharmacokinetics of estradiol (background): wikipedia.org/wiki/Pharmacokinetics_of_estradiol
- Estradiol cypionate entry: wikipedia.org/wiki/Estradiol_cypionate
- Estradiol enanthate entry: wikipedia.org/wiki/Estradiol_enanthate
- Testosterone undecanoate entry: wikipedia.org/wiki/Testosterone_undecanoate
- Drug absorption from oil depot background: ResearchGate publication
Note: This simulator is for educational visualization. Citations are provided for transparency about assumptions, not as direct clinical dosing guidance.