How can Xyosted (testosterone enanthate) be administered subcutaneously (SubQ) when other testosterone replacement therapies are typically administered intramuscularly (IM)?

Xyosted Subcutaneous Administration: Formulation Design Enables Alternative Route

Xyosted (testosterone enanthate) can be administered subcutaneously because it uses a novel autoinjector system with a specialized formulation designed for subcutaneous delivery, delivering smaller weekly doses (50-100 mg) through a short 27-gauge needle that achieves therapeutic testosterone levels equivalent to traditional intramuscular injections. 1

Key Formulation Differences

The critical distinction is not the testosterone ester itself, but rather the delivery system and dosing strategy:

• Xyosted utilizes a prefilled single-use autoinjector with a five-eighths-inch 27-gauge needle specifically engineered to eject high-viscosity testosterone solutions subcutaneously 1
• Traditional testosterone enanthate/cypionate formulations use larger volumes (1-3 mL) with longer needles (1-1.5 inches, 21-23 gauge) designed for deep intramuscular penetration 2
• The autoinjector system overcomes the viscosity challenge that historically limited subcutaneous testosterone delivery 1

Pharmacokinetic Equivalence

Subcutaneous testosterone enanthate achieves comparable therapeutic outcomes to intramuscular administration:

• Weekly subcutaneous doses of 50-150 mg produce serum testosterone levels within the normal male range (mean steady-state: 422.4 ng/dL at 50 mg, 895.5 ng/dL at 100 mg) 1
• Subcutaneous administration demonstrates dose-proportional pharmacokinetics with low variation compared to 200 mg intramuscular injections 1
• Both routes achieve target mid-normal testosterone levels of 450-600 ng/dL when properly dosed 2
• No significant differences in clinical outcomes exist between intramuscular and subcutaneous formulations when testosterone levels are appropriately maintained 3

Clinical Evidence Supporting Subcutaneous Route

Multiple studies confirm subcutaneous testosterone efficacy:

• In 63 female-to-male transgender patients, subcutaneous testosterone cypionate/enanthate (50-150 mg weekly) achieved normal male-range testosterone levels across a wide BMI range (19.0-49.9 kg/m²) 4
• A pilot study of 22 hypogonadal men using weekly subcutaneous testosterone enanthate achieved 100% success in maintaining both peak and trough levels within normal range 5
• Among 22 patients who switched from intramuscular to subcutaneous, all had mild (n=2) or marked (n=20) preference for subcutaneous injections; none preferred intramuscular 4

Advantages of Subcutaneous Administration

The subcutaneous route offers several clinical benefits:

• Significantly less discomfort compared to intramuscular injections, with only minor and transient local reactions in 9 of 63 patients (14%) 4
• Easier self-administration using shorter needles in accessible sites (thighs, abdomen) 2, 4
• More stable testosterone levels with weekly dosing compared to biweekly intramuscular injections 2
• Lower risk of erythrocytosis compared to intramuscular formulations due to more consistent serum levels without supraphysiological peaks 3, 2

Dosing Strategy Differences

The subcutaneous approach requires modified dosing:

• Subcutaneous testosterone typically uses 50-100 mg weekly, whereas traditional intramuscular uses 100-200 mg every 2 weeks 2, 1
• Weekly subcutaneous dosing provides more stable day-to-day testosterone levels compared to the peak-trough fluctuations of biweekly intramuscular injections 2
• The smaller, more frequent dosing pattern is better suited to subcutaneous absorption kinetics 1

Common Pitfalls to Avoid

• Do not assume all testosterone enanthate products are interchangeable—Xyosted's autoinjector system and concentration are specifically designed for subcutaneous use 1
• Avoid using standard intramuscular testosterone vials with insulin syringes for subcutaneous injection without proper dose adjustment and monitoring, though this off-label approach has been studied 5
• Traditional intramuscular formulations in large volumes (>1 mL) are not appropriate for subcutaneous administration due to absorption limitations and local tissue tolerance 2

Monitoring Remains Identical

Regardless of administration route:

• Measure testosterone levels 2-3 months after initiation or dose change, targeting mid-normal values of 450-600 ng/dL 2
• For subcutaneous weekly dosing, levels can be checked at any time during the dosing interval due to more stable concentrations 1
• Monitor hematocrit, PSA, and clinical response every 6-12 months once stable 2