TESTOSTERONE PREFILLED SYRINGE

Clinical Criteria Summary

Active prostate cancer
Active breast cancer
Uncontrolled or untreated erythrocytosis (e.g., Hematocrit >48%)
Severe, untreated Obstructive Sleep Apnea (OSA)
Unevaluated Prostate Specific Antigen (PSA) level greater than 4 ng/mL or PSA greater than 3 ng/mL in individuals with risk factors for prostate cancer
Severe lower urinary tract symptoms (International Prostate Symptom Score [IPSS] >19)
Inadequately controlled congestive heart failure
Acute Coronary syndrome (ACS), stroke (CVA), or revascularization procedure in the last 4 months
Thrombophilia or history of unprovoked venous thromboembolism
Severe liver disease or renal failure
Desire for future fertility
Active, unaddressed anabolic steroid misuse

Hypogonadism diagnosed by at least one clinical sign or symptom consistent with androgen deficiency
HIV infected men with low testosterone levels and weight loss
Receiving high doses of glucocorticoids who have low testosterone levels (daily dose greater than 5mg of prednisone or equivalent for at least 6 months)
Status post bilateral orchiectomy or unilateral orchiectomy (with documented atrophy of second testicle)
Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism and signs/symptoms of hypogonadism

Document that other potential treatable causes of symptoms of low testosterone levels and their suspected etiologies have been addressed
Two, unequivocally low baseline, fasting, total testosterone levels (determined based on local laboratory assay and patient specific factors), at least one week apart, between 8am - 10am
Prior to initiation, potential risks and benefits discussed and documented in the medical record
Baseline Hemoglobin and Hematocrit, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and prolactin levels assessed
Discussion regarding prostate cancer screening and monitoring occurred; if shared decision-making results in screening, PSA is measured

For patients with Klinefelter Syndrome, Kallmann Syndrome, or Pan-hypopituitarism, a single baseline testosterone level is sufficient
Free testosterone assessment recommended if concern for Sex Hormone Binding Globulin (SHBG) alterations exists (e.g., elderly, obesity, diabetes, liver or HIV disease, medications such as anticonvulsants/anabolic steroids/progestins, thyroid disease); acceptable measurement methods include equilibrium dialysis or calculation using total testosterone, SHBG, and albumin levels
For patients on long-standing TRT (>1 year) without documentation, the requirement for two low baseline serum total testosterone levels may be waived case-by-case
Risk factors for prostate cancer include African-American background, first-degree relative with prostate cancer, and exposure to Agent Orange

• Men presenting with specific symptoms: erectile dysfunction, low libido, decreased frequency of morning erections, new unexplained gynecomastia, decreased body hair, eunuchoid features on exam, small testes, loss of male hair and gynecomastia
• Men with findings associated with hypogonadism: infertility, unexplained anemia, fractures
• Men with a history of conditions likely to cause hypogonadism: traumatic brain injury, orchiectomy, pituitary dysfunction, testicular trauma, chronic opioid use

• Serum total and/or free testosterone must be unequivocally and consistently low
• Measurements must be obtained in the early morning (6–10 am), fasting state, and confirmed on at least two separate occasions
• Total testosterone levels <150 ng/dL require evaluation for secondary/central hypogonadism
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must be measured to distinguish primary from secondary hypogonadism
• Abnormal immunoassay results must be confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS)
• Free testosterone should be measured when conditions affecting sex hormone-binding globulin (SHBG) are present: obesity, diabetes mellitus, glucocorticoid use, nephrotic syndrome, thyroid disease, acromegaly, androgen/estrogen use, liver disease
• Harmonized lower limit of normal for total testosterone is 264 ng/dL for CDC-certified assays with normal SHBG

• Active prostate or breast cancer
• Uncontrolled/untreated erythrocytosis (initial hematocrit >48% or 54% on TRT)
• Severe, untreated obstructive sleep apnea
• Elevated prostate-specific antigen (PSA) (>4 ng/mL)
• Severe lower urinary tract symptoms
• Inadequately controlled congestive heart failure
• Acute coronary syndrome, stroke, or revascularization procedure within 4 months
• Thrombophilia or history of unprovoked venous thromboembolism
• Severe liver disease or renal failure
• Active, unaddressed anabolic steroid misuse
• Desire for future fertility

• Discontinue TRT if symptoms do not significantly and consistently improve after 6–12 months despite testosterone levels within the reference range
• Monitor testosterone (including free/bioavailable), hemoglobin, hematocrit, and PSA at 3–6 months after initiation, again at 12 months
• Dose adjustments indicated if testosterone falls outside laboratory limits or total testosterone exceeds 900 ng/dL
• Discontinue testosterone if hematocrit exceeds 54%
• Blood draw timing: midway between injections for injectable formulations; 2–8 hours after application for gel once steady-state is achieved (typically after ≥1 week)
• PSA monitoring: baseline, repeated at 12 months, then annually (or sooner if clinically indicated)

• Endocrinology: Total testosterone <150 ng/dL with inappropriately normal or decreased LH/FSH; new/established contraindications to TRT; gynecomastia due to hypogonadism
• Urology (for males receiving TRT): PSA rising >1.4 ng/mL from baseline or >4 ng/mL at any time; lack of improvement or intolerance of PDE-5 inhibitors

• Human chorionic gonadotropin (HCG) reserved for hypogonadotropic hypogonadism in men seeking to maintain fertility (restricted to endocrinology and infertility specialists)
• Clomiphene may be considered on a case-by-case basis in males with hypogonadotropic hypogonadism desiring fertility prior to HCG use