What is XYOSTED (testosterone enanthate) used for?

What is XYOSTED?

XYOSTED is a subcutaneous testosterone enanthate auto-injector approved by the FDA for testosterone replacement therapy in adult men with hypogonadism due to primary or secondary causes, including testicular failure, gonadotropin deficiency, or pituitary-hypothalamic injury. 1

FDA-Approved Indications

XYOSTED (testosterone enanthate subcutaneous injection) is specifically indicated for: 1

• Primary hypogonadism (congenital or acquired) due to:

  • Testicular failure from cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy 1

• Hypogonadotropic hypogonadism (congenital or acquired) due to:

  • Gonadotropin or LHRH deficiency 1
  • Pituitary-hypothalamic injury from tumors, trauma, or radiation 1

• Delayed puberty in carefully selected males with familial patterns of delayed puberty 1

• Metastatic mammary cancer in postmenopausal women (1-5 years post-menopause) with advancing inoperable disease 1

Critical FDA Contraindication

XYOSTED is NOT approved for age-related hypogonadism ("low T" from aging alone), as safety and efficacy have not been established in this population. 1 This is a crucial distinction, as the FDA specifically requires this labeling based on concerns about cardiovascular risk and lack of proven benefit in men without structural or genetic causes of hypogonadism. 2

Dosing and Administration

XYOSTED is administered as a weekly subcutaneous injection that patients self-administer: 3, 4

• Starting dose: 75 mg once weekly 3, 4
• Dose adjustments: Can be modified to 50 mg or 100 mg weekly based on testosterone trough levels measured at week 6 3, 4
• Target trough levels: 350-650 ng/dL (12.1-22.5 nmol/L) 3

The subcutaneous auto-injector achieved therapeutic testosterone levels in 92.7% of patients, with mean trough concentrations of 487.2 ng/dL at 52 weeks. 4

Key Advantages Over Traditional Formulations

XYOSTED offers several clinical advantages compared to intramuscular testosterone injections: 3, 4

• Virtually painless: Over 95% of patients reported no injection-related pain 4
• More stable testosterone levels: Smaller peak-to-trough fluctuations compared to intramuscular injections 3, 4
• Lower erythrocytosis risk: Subcutaneous administration may reduce the 43.8% erythrocytosis rate seen with intramuscular testosterone enanthate 2, 5
• Self-administration: Patients can inject themselves weekly, avoiding clinic visits 3, 4
• No transference risk: Unlike gels, there is no risk of transferring testosterone to partners or children through skin contact 2, 5

Safety Profile and Monitoring

The most common adverse effects in the 26-week registration trial were: 3

• Increased hematocrit (≥52%): 7.5% of patients 3
• Injection-site hemorrhage: 4.5% 3
• Injection-site bruising: 3.0% 3
• Increased PSA: 3.0% 3

Blood pressure monitoring is essential, as mean systolic BP increased by 3.7 mmHg over 12 weeks with 24-hour ambulatory monitoring. 3 This numerically small but consistent increase requires clinical attention, particularly in men with pre-existing hypertension.

Required monitoring includes: 5

• Testosterone levels at 2-3 months after initiation or dose changes, then every 6-12 months 5
• Hematocrit monitoring for erythrocytosis 2, 5
• PSA and digital rectal exam in men over 50 years 6
• Blood pressure assessment 3

Clinical Context and Evidence Quality

The American College of Physicians guidelines emphasize that testosterone therapy in men with low testosterone (without classical hypogonadism) provides only small improvements in sexual function and quality of life, with little to no benefit for physical functioning, energy, vitality, or cognition. 2 Effect sizes were small even when statistically significant, and long-term safety data beyond 1 year remain limited. 2

The evidence for cardiovascular safety remains uncertain, with the FDA requiring labeling changes in 2015 regarding possible increased risk of heart attack and stroke, though this may reflect high-risk patient populations rather than the medication itself. 2 Injectable formulations may carry higher cardiovascular risk than transdermal preparations due to fluctuating testosterone levels. 2, 5

Common Pitfalls to Avoid

• Do not prescribe for "age-related low T" alone without documented structural/genetic causes of hypogonadism, as this is off-label and lacks FDA approval 1
• Do not skip baseline testosterone confirmation with two fasting morning measurements before initiating therapy 2
• Do not forget to prescribe sharps containers for safe needle disposal 5
• Do not overlook cardiovascular risk assessment before initiating therapy, particularly in men with recent cardiovascular disease 2