TESTOSTERONE GEL,TOP
Clinical Criteria Summary
Document 174
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
Document 737
Indication & Patient Population
- Postmenopausal women (natural or surgically induced) with hypoactive sexual desire disorder (HSDD)
- Off-label use for other indications, including HSDD in premenopausal women, improvement in bone mineral density, or mood/cognition enhancement, is not recommended
Diagnosis & Clinical Criteria
- Persistent or recurrent deficiency or absence of desire for sexual activity with marked personal distress
- Symptoms not otherwise accounted for by a general medical or psychiatric condition (per DSM IV-TR)
- HSDD may be primary or secondary; lifelong or acquired; or generalized or situational
Dosing & Administration
- Starting dose: 1/10th of a 1% testosterone cream or gel approved for daily use in men (e.g., 5 mg [0.5 mL] from a 50 mg tube)
- Dose may be increased to 10 mg (1 mL) if needed
- Application sites: Back of the calf, upper outer thigh, or buttock
- Injections, pellets, and oral formulations are not recommended
Monitoring & Laboratory Requirements
- Baseline labs: Total testosterone level, sex hormone binding globulin (SHBG) level, liver function tests, lipid panel (and other labs as indicated)
- Maintain total testosterone concentrations within the physiologic premenopausal range per local laboratory reference ranges
- Check total testosterone levels 3 to 6 weeks after starting treatment and after any dose adjustments; once stable, monitor every 4 to 6 months
- Monitor for signs and symptoms of androgen excess
- Additional periodic testing: Breast exam, mammography, and pelvic exams as clinically indicated
Treatment Duration & Response Assessment
- Noticeable improvements are typically seen within 6 to 8 weeks of treatment
- Discontinue therapy after 6 months if there is no meaningful improvement
- Consider a drug holiday after 6 to 12 months to determine if treatment is still required
Contraindications & Exclusions
- Premenopausal women (insufficient evidence of benefit)
- Patients at high cardiometabolic risk (excluded from most studies)
- Baseline total testosterone levels in the mid-range to high range (indicates symptoms are likely unrelated to testosterone; therapy should not be initiated)
- Supraphysiologic dosing is not recommended
VA Dispensing & Supply Limitations
- Prefer unit dose tubes of 1% testosterone gel (50 mg testosterone per 5 grams of gel) over unit dose packets
- Federal law limits controlled substance dispensing to a maximum of 180 days’ supply
- VA pharmacies must fill prescriptions for partial boxes at the facility level to comply with the 180-day limit (e.g., 3 tubes for 30 days)
Document 738
Exclusion Criteria
- Patient is pregnant, lactating, or of childbearing potential
- Active breast cancer or other hormonally sensitive cancer
- Severe liver disease
- Baseline total testosterone level in the midrange or high range for premenopausal females (per local laboratory threshold)
- Uncontrolled severe cardiovascular or cerebrovascular disease
- Uncontrolled hyperlipidemia
- High risk of breast cancer
- Known thrombophilia or unprovoked venous thromboembolism
Inclusion Criteria
- Provider initiating treatment is a VA or VA Community Care women’s health provider, urologist, or other locally designated provider experienced in the treatment of HSDD
- Patient is naturally or surgically postmenopausal (perimenopausal patients meeting other criteria may be considered on an individual basis)
- Documented diagnosis of hypoactive sexual desire disorder (HSDD)
- Any modifiable factors and comorbidities contributing to HSDD have been acknowledged and addressed (e.g., physical factors, psychosocial factors, relationship issues, medications)
- Any concurrent medical conditions and modifiable risk factors that can be exacerbated by hormone treatment have been considered and addressed (e.g., sleep apnea, hypertension, diabetes, dyslipidemia, diseases worsened by fluid retention such as heart failure, renal impairment, hepatic impairment, obesity, depression/mood disorders)
Baseline Assessment & Laboratory Requirements
- Baseline total testosterone, sex hormone binding globulin (SHBG), and liver function tests obtained and evaluated
- Testosterone levels are not used to diagnose HSDD and do not predict treatment efficacy
- Elevated SHBG typically indicates nonresponders but may be elevated in patients on oral estrogens, thyroid replacement, or untreated hyperthyroidism; a trial of testosterone therapy may still be considered for patients with unmodifiable risk factors (e.g., thyroid replacement therapy)
Patient Education & Compliance Requirements
- Patient informed of and expressed clear understanding of potential risks, benefits, side effects, and limitations of hormone treatment and that use is off-label; discussion and patient understanding documented
- Patient agrees to avoidance of additional testosterone hormonal treatments (including compounded products, pellets, etc.)
- Patient expresses understanding on proper use of the product (e.g., transdermal use, correct dose, how to avoid transfer to others)
Clinical Considerations & Documentation
- Insufficient evidence exists to guide therapy; recommend careful risk/benefit evaluation and shared decision-making approach with documentation in the Federal Electronic Health Record (EHR)
- Individual cases that are exceptions to exclusion and inclusion criteria should be adjudicated at the local facility according to P&T Committee and Pharmacy Services policy and procedures
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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