How the TRT Curve & E2 Calculator Works

Inputs → outputs: what each control changes

Ester

Esters mainly change how quickly testosterone is released from the injection site. The calculator uses a single absorption constant (ka) per ester and computes an implied half-life.

Active ratio means “how many mg of testosterone base are in 1 mg of ester.” This helps translate mg injected into mg testosterone released.

Dose & frequency

• Higher dose raises the whole curve.
• More frequent dosing usually smooths peaks/troughs (less “roller coaster”).
• All else equal, weekly load ≈ dose × (7 ÷ interval).

Weight

Weight is used as a rough volume proxy: heavier body mass → larger distribution volume → slightly lower concentration for the same released amount (a simplification).

Body fat, genetics, AI, responder

These primarily affect E2 prediction. The calculator is explicit about this: the testosterone curve is PK‑driven, while E2 is a scaled transform of testosterone.

hCG toggle

When enabled, the model adds a small constant testosterone “boost” based on weekly IU using a Hill‑curve (a simplified dose–response).

The math (complete, with formulas)

1) Single injection: Bateman function

The model uses a one‑compartment system with first‑order absorption (ka) and first‑order elimination (ke). For a single injection at time 0, the shape is:

C(t) ∝ (Dose · ka / (ke − ka)) · (e^(−ka·t) − e^(−ke·t))    for t ≥ 0

This is the classic “Bateman function,” commonly used for oral drugs but also a good first approximation for depot/absorption‑limited injections.

2) Multiple injections: superposition

For injections at times ti:

Total(t) = Σ C(t − ti) over all injections ti ≤ t

3) Converting to ng/dL (the pragmatic step)

The model output is scaled into typical lab units with an empirical factor (VOLUME_FACTOR) and an optional calibration multiplier:

Testosterone_ng/dL(t) = Total(t) · VOLUME_FACTOR · WeightFactor · Calibration_T

4) Estradiol simulation (ratio model)

E2_pg/mL(t) = Testosterone_ng/dL(t) · (BaseRatio · FatMod · GeneMod · AI · Responder)

BaseRatio defaults to 0.05 (5%), but calibration sets it to labE2 / labT so your future simulations start from your measured conversion ratio.

5) Calibration details (exactly what the tool does)

• It runs a “standard model” for your calibration dosing until a steady pattern appears (multiple half-lives).
• It reads the model at your selected timing (trough / peak / average) and computes: Calibration_T = labT / modelT.
• It sets BaseRatio = labE2 / labT and stores your baseline fat/gene settings so future changes reflect relative movement.

Testosterone ester pharmacokinetics (what science says)

Half-life varies by ester and oil

• Testosterone cypionate labeling states an intramuscular half-life of ~8 days. citeturn9search11turn9search4
• Testosterone enanthate is typically shorter than cypionate; the calculator uses ~4–5 days (absorption-limited), consistent with standard PK summaries. citeturn1search8
• Injectable testosterone undecanoate is much longer acting, and published phase‑I PK suggests ~21 days (tea seed oil) vs ~34 days (castor oil). citeturn1search0turn1search1

Why “ka” matters more than “ke” in depot injections

With oil depots, elimination from blood can be faster than release from the depot. In that case, the observed half‑life is governed by the slower process (“flip‑flop kinetics”). The calculator captures this by setting ke high and letting ka control the tail.

Route differences (IM vs SC)

The calculator assumes a depot-like release profile; real-life curves can differ with injection route, site, oil, needle depth, and individual blood flow. Reviews discuss feasibility and PK differences for subcutaneous administration. citeturn8search3

Lab timing & steady state (what guidelines say)

Endocrine Society monitoring recommendations

• Enanthate / cypionate: measure serum testosterone midway between injections, and adjust if mid-interval T is too high or too low. citeturn12view0
• Injectable undecanoate: measure at the end of the dosing interval (just before the next injection) and aim for low‑mid nadir levels. citeturn4view3

Steady state

Any repeated dosing schedule needs time to stabilize. The calculator’s “steady state” note is based on the ester’s effective half-life (roughly 4–5 half-lives to settle for first-order systems).

Estradiol science: aromatase, body fat, genetics, AI

Where estradiol comes from in men

Most estradiol in men is produced by aromatization of testosterone (and androstenedione) in peripheral tissues—especially adipose tissue. Aromatase is encoded by CYP19A1. citeturn1search5turn1search9

Body fat and obesity effects

Higher adiposity tends to increase aromatase expression/activity, which can shift the testosterone → estradiol balance. Reviews of obesity-related hypogonadism discuss altered sex steroid levels (including estradiol). citeturn1search2turn1search9

Reference ranges and assay differences

• Example lab reference interval (adult male, LC/MS/MS): 8–35 pg/mL. citeturn7view1
• Assay choice matters; many modern estradiol tests use LC‑MS/MS for improved specificity at low concentrations. citeturn10search3turn10search11

Why “too low” estradiol can be a problem

Rare aromatase deficiency cases show undetectable estradiol with skeletal consequences, and estradiol replacement improves bone parameters—evidence that estradiol matters in male physiology. citeturn10search12turn10search8

Aromatase inhibitors (AI): benefits and risks

AIs reduce aromatization (lowering estradiol and often raising gonadotropins/testosterone in some contexts), but they can affect bone metabolism. Reviews in men discuss these tradeoffs. citeturn10search1turn10search9

hCG science (what evidence supports)

Human chorionic gonadotropin (hCG) acts at the LH receptor and can stimulate Leydig-cell testosterone production. In controlled studies, relatively low-dose hCG helped maintain intratesticular testosterone in healthy men whose gonadotropins were suppressed by exogenous testosterone. citeturn11search0turn11search10

Limitations & how to use this safely

What the model does NOT capture

• Individual differences in absorption (IM vs SC), oil viscosity, injection site perfusion, and needle depth.
• Changes in SHBG over time or with dose, thyroid status, liver function, and medications.
• Free testosterone dynamics (total vs free can diverge substantially with SHBG changes).
• Feedback loops (LH/FSH suppression, aromatase up/down regulation, receptor sensitivity changes).
• Clinical safety markers (hematocrit, BP, lipids, sleep apnea, prostate monitoring).

Best practice workflow

1. Pick a dosing plan with a clinician.
2. Wait long enough for a stable pattern (weeks; longer for very long esters).
3. Draw labs at the guideline-recommended time (mid-interval for cyp/enan; trough for TU). citeturn12view0turn4view3
4. Use calibration to anchor the model to your measured response.
5. Only then use the simulator to explore “what-if” changes (mainly frequency changes and expected smoothing).