Anabolic vs. Therapeutic Testosterone Dosing Threshold
Testosterone becomes anabolic rather than therapeutic at weekly doses exceeding 100–125 mg of testosterone enanthate or cypionate, corresponding to serum total testosterone levels above 600–1,000 ng/dL. 1, 2
Defining the Therapeutic-to-Anabolic Transition
Therapeutic Replacement Range
- Standard therapeutic dosing is 50–100 mg weekly (or 100–200 mg every 2 weeks) of testosterone enanthate/cypionate, targeting mid-normal serum levels of 450–600 ng/dL. 1
- This replacement dose maintains physiologic testosterone concentrations without producing supraphysiological peaks or anabolic tissue effects beyond normal virilization. 3, 1
- At 100 mg weekly, serum testosterone remains within the normal male range and serves purely to restore deficient endogenous production. 4, 2
Anabolic Dosing Threshold
- Doses of 300 mg weekly or higher consistently produce anabolic effects including dose-dependent increases in fat-free mass (+5.2 to +7.9 kg), muscle volume, and strength that exceed physiologic replacement. 2
- At 300 mg weekly, mean nadir testosterone concentrations reach 1,345 ng/dL—well above the upper limit of normal (approximately 1,000 ng/dL)—and produce measurable hypertrophy and strength gains. 2
- The dose-response relationship for muscle mass and strength is linear and highly correlated with log testosterone concentrations (r = 0.73, P = 0.0001), demonstrating clear anabolic effects above replacement doses. 2
The Gray Zone: 125–200 mg Weekly
- Doses of 125 mg weekly represent the lower boundary of anabolic dosing, producing modest but statistically significant increases in fat-free mass (+3.4 kg) and muscle volume compared to replacement doses. 2
- Serum testosterone at 125 mg weekly averages 542 ng/dL at nadir, which falls within the upper-normal range but begins to drive tissue anabolism beyond simple replacement. 2
- Peak levels 2–5 days after injection transiently exceed the upper limit of normal even with standard 100–200 mg biweekly dosing, though this does not constitute sustained anabolic use. 3, 5
Clinical Markers Distinguishing Therapeutic from Anabolic Use
Serum Testosterone Levels
- Target therapeutic levels are 450–600 ng/dL measured midway between injections; levels consistently above 1,000 ng/dL indicate supraphysiological dosing. 1, 2
- One patient receiving 125 mg exhibited abnormally high levels of 19.6 ng/mL (1,960 ng/dL), demonstrating individual variability in absorption and metabolism that can push therapeutic doses into the anabolic range. 5
Adverse Effect Profile
- Erythrocytosis risk escalates sharply with supraphysiological dosing, occurring in 43.8% of patients on injectable testosterone at higher doses versus 15.4% with transdermal preparations at replacement doses. 1, 6
- Hematocrit above 54% signals excessive androgen exposure and necessitates dose reduction or formulation change. 6
- Gonadotropin suppression (LH and FSH) occurs even at replacement doses but becomes more profound with anabolic dosing, beginning around day 5 post-injection. 5
Body Composition Changes
- Weight gain of 3 kg or more without changes in skinfold thickness suggests anabolic lean mass accrual rather than therapeutic replacement. 4
- Increases in shoulder and chest circumferences are specific markers of supraphysiological androgen effects, as these muscle groups are particularly androgen-sensitive. 4
Practical Algorithm for Dose Classification
Step 1: Assess Weekly Testosterone Dose
- ≤100 mg weekly = Therapeutic replacement 1
- 125–200 mg weekly = Borderline; assess serum levels and clinical response 2
- ≥300 mg weekly = Anabolic dosing 2
Step 2: Measure Serum Testosterone Midway Between Injections
- 450–600 ng/dL = Optimal therapeutic range 1
- 600–1,000 ng/dL = Upper-normal; acceptable if clinically indicated 3
1,000 ng/dL = Supraphysiological; anabolic 2
Step 3: Monitor for Anabolic Markers
- Hematocrit >54% = Dose reduction required 6
- Unexplained weight gain >3 kg = Possible anabolic effect 4
- Muscle hypertrophy beyond baseline restoration = Anabolic response 2
Important Caveats
- Individual pharmacokinetic variability means some patients achieve supraphysiological levels even at standard replacement doses, requiring dose adjustment based on measured serum levels rather than dose alone. 5
- Peak-to-trough fluctuations with biweekly dosing can produce transient supraphysiological peaks (mean 71 nmol/L or 2,050 ng/dL at 24–48 hours) even when trough levels are therapeutic; this does not constitute anabolic use unless sustained. 7
- Weekly dosing of 50–100 mg provides more stable levels and reduces the risk of inadvertent supraphysiological exposure compared to biweekly dosing of 100–200 mg. 1, 8
- Treatment to raise levels above the physiologic range is discouraged in clinical practice, though it is recognized that peak levels transiently exceed normal with standard injection dosages. 3