TESTOSTERONE INJ,SOLN
Clinical Criteria Summary
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Exclusion Criteria
- 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
Inclusion Criteria
- 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
Additional Pre-Initiation Requirements
- 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
Clinical & Laboratory Considerations
- 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
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Indications for Evaluation
- • 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
Laboratory & Biochemical Assessment Criteria
- • 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
Contraindications to Testosterone Replacement Therapy (TRT)
- • 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
Initiation, Monitoring, & Dosing Parameters
- • 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)
Specialist Referral Criteria
- • 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
Alternative Therapies & Specific Clinical Scenarios
- • 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