How the TRT Curve & E2 Calculator Works

Change log

• 2026-02-16: Tuned cypionate, Sustanon, and undecanoate release profiles with component lag support to better match expected peak timing and long-tail behavior.
• 2026-02-16: Added uncertainty-band visualization (+/-15%), active-ratio corrections, calibration/fat clamps, and Bateman/performance safeguards.
• 2026-02-16: Added scenario smoke validation (golden checks) and aligned documentation to current engine behavior.
• 2026-02-12: Added Sustanon 250 as a 4-ester blend model (propionate + phenylpropionate + isocaproate + decanoate) with route-aware component absorption.
• 2026-02-12: Updated Female mode starting values to a more realistic HRT-oriented baseline while keeping Male defaults unchanged.
• 2026-02-12: Added per-sex profile memory so switching Male/Female restores each mode’s most recent values in-session.
• 2026-02-12: Expanded this explainer with explicit route, sex, compounds, and calibration equations.

Inputs → outputs: what each control changes

Ester

Esters mainly change how quickly testosterone is released from the injection site. Single-esters use one absorption constant (ka), while Sustanon is modeled as a weighted 4-component blend (each component with its own ka and active ratio).

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

* Sustanon active ratio is the weighted blend average in this model.
** Blend ka values in this model:
  • Cypionate: early 0.50 + depot 0.087 (with a 0.6 day release lag).
  • Sustanon: propionate 0.85, phenylpropionate 0.35, isocaproate 0.08, decanoate 0.03 (1/day), with delayed decanoate release (up to 6 days).
*** Terminal half-life shown from the slowest blend component in the model.

Sex mode & starting profiles

• Male mode keeps the original simulator defaults unchanged.
• Female mode now starts from an HRT-oriented baseline (lower testosterone dose, weekly cadence, lower body weight, and SubQ default route).
• The app keeps per-sex profile memory in-session, so switching between Male/Female restores the last values used in each mode.

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).

Injection route (IM vs SubQ)

Route changes the effective absorption constant: SubQ uses a modestly reduced ka, which usually lowers peaks and raises troughs at the same weekly load.

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.

Enhanced compounds (TRT++)

Primo, EQ, and Mast are implemented as dose-aware E2 pressure modifiers. They are directional and heuristic, and intentionally conservative.

Scenarios and compare mode

You can save full protocol snapshots to local storage and overlay a selected scenario as a dashed comparison curve for both T and E2 charts.

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 − Lag_i) over all injections ti ≤ t

For performance, contributions older than ~7 effective half-lives are skipped (remaining amount is less than 1%).

2b) Sustanon blend superposition

For each injection j at time tj and component i in {prop, phenylprop, isocaproate, decanoate}:

Dose_i = Dose_total × Fraction_i × ActiveRatio_i

Sustanon_Total(t) = Σj Σi Bateman(t − tj − Lag_i, Dose_i, ka_i_effective, ke)

Sustanon fractions used:
propionate 12%, phenylpropionate 24%, isocaproate 24%, decanoate 40%

3) Route-aware absorption and release lag

ka_effective = ka_ester × RouteFactor

RouteFactor = 1.00 (IM), 0.83 (SubQ)

For Sustanon, RouteFactor is applied per component (ka_i_effective = ka_i × RouteFactor).

For formulations with delayed release, each component can use a lag:

Bateman_input_time = t − ti − Lag_i

In the current model this is used for cypionate (short depot lag), Sustanon decanoate (later tail contribution), and undecanoate oils.

4) 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

5) Estradiol simulation (full multiplier model)

E2_pg/mL(t) = Testosterone_ng/dL(t)
             × [BaseRatio × FatRel × GeneRel × AI × Responder × SexAromatase × CompoundMod]

FatMod(f) = min(2.5, 0.8 + 0.03 × max(0, f − 10)^1.2)

If calibrated and enabled:
  FatRel  = FatMod(current) / FatMod(calibration_fat)
  GeneRel = GeneMult(current) / GeneMult(calibration_genetics)

If standard mode:
  FatRel  = FatMod(current)
  GeneRel = GeneMult(current)

SexAromatase = 1.00 (male), 1.16 (female)

6) Enhanced compounds modifier

CompoundMod = max(0.55, 1 − PrimoDrop − EQDrop − MastDrop)

PrimoDrop = min(0.22, PrimoDose_mg_per_week / 2600) if enabled else 0
EQDrop    = min(0.18, EQDose_mg_per_week / 3300) if enabled else 0
MastDrop  = min(0.05, MastDose_mg_per_week / 6000) if enabled else 0

BaseRatio defaults by sex mode (male/female presets), but calibration sets it to labE2 / labT so future simulations start from your measured conversion ratio.

7) 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 = clamp(labT / modelT, 0.4, 2.5).
• It sets BaseRatio = labE2 / labT and stores your baseline fat/gene settings so future changes reflect relative movement.
• The calibration toggle can be switched on/off without deleting stored factors, so you can instantly compare personalized vs standard modeling.

8) Female HRT-oriented starting profile

Female mode now opens with an HRT-oriented starter profile to avoid male-dose defaults being applied accidentally.

Female starter profile (UI defaults when switching to Female):
- Injection method: SubQ
- Dose: 8 mg
- Frequency: every 7 days
- Weight: 65 kg
- Body fat: 28%
- Ester: cypionate

Male starting values are intentionally unchanged.

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).

IM vs SubQ: absorption differences

The simulator now includes an injection route selector. Intramuscular (IM) and subcutaneous (SubQ) injections both work clinically, but SubQ is often experienced as a slightly slower-release depot in day-to-day practice.

• IM mode: baseline ester absorption constants are used as-is.
• SubQ mode: absorption is modeled as modestly slower (about 15-20% lower ka).
• Practical implication: SubQ can show slightly flatter peaks and a smoother curve at the same weekly dose.

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

Why the calculator emphasizes the green zone

Aromatase converts androgens into estradiol continuously. In TRT planning, the goal is usually not to "crush" E2 or let it run unchecked, but to keep most of the curve inside a clinically reasonable symptom-compatible band (the chart's green zone).

• Too low: joint pain, low mood, low libido, sleep issues may become more likely.
• Too high: fluid retention, mood volatility, breast tissue sensitivity, BP/headache issues can increase for some users.
• Most useful pattern: trend + symptoms + timed labs together, not one isolated number.

Enhanced compounds (Primo, Mast, EQ)

The TRT++ panel adds optional adjunct compounds to support scenario testing. These are simplified modifiers, not prescribing tools.

• Primobolan (Primo): modeled with mild-to-moderate E2-lowering pressure as dose increases.
• Equipoise (EQ): modeled with mild E2-reducing pressure, especially at higher weekly doses.
• Masteron (Mast): modeled with minimal direct AI effect; practical use is often symptom-contextual rather than pure aromatase suppression.

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).

About the shaded bands

The charts include a +/-15% model range band around the central trajectory to discourage false precision. It is a visual uncertainty aid, not a formal confidence interval derived from patient-level variance data.

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).