Currentblue cross blue shield - tennesseePolicy N/A

Testosterone Testing Policy

Defines clinical coverage criteria and reimbursement policy for serum total, free, and bioavailable testosterone testing (and related hormone testing) including indications, repeat testing, monitoring schedules, and excluded tests (e.g., salivary testing) for symptomatic males, females with androgen excess, transgender care, and specific diagnostic scenarios.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyTestosterone Testing Policy

Policy CodePolicy N/A

Change TypeAdoption of Avalon recommendation

Effective DateN/A

Next Review DateN/A

Key ActionUse serum total testosterone assays certified by the CDC HoSt/Testosterone program and document early-morning fasting specimen collection with repeat testing when diagnosing hypogonadism.

SourceLink

POLICY UPDATE CHANGES

Effective date recorded as 7/1/2023 reflecting adoption of Avalon policy recommendation.

9Covered indications

6Not-covered items

3Assay/SHBG notes

4Professional societies cited

136FDA device records (testosterone)

Coverage Summary

This policy defines clinical coverage for serum total testosterone, free testosterone, and bioavailable testosterone testing (and related hormone testing such as SHBG, albumin, LH, FSH, prolactin, and estradiol) for diagnostic evaluation, monitoring, and specific populations. Covered indications include symptomatic males evaluated for androgen deficiency or androgen excess, repeat/confirmatory total testosterone testing with recommended morning/fasting collection, targeted measurement of free or bioavailable testosterone when total testosterone is borderline/low or when SHBG-altering conditions exist, monitoring during prostate cancer therapy and testosterone replacement (per recommended intervals), evaluation in transgender/gender-dysphoric care, and testing for selected cancer survivorship scenarios. Excluded tests and non-covered situations include salivary testosterone testing and free or bioavailable testosterone ordered as primary testing without prior serum total testosterone, testing in asymptomatic individuals or for identifying androgen deficiency in women, and routine measurement of dihydrotestosterone except in specified congenital/ambiguous genitalia diagnoses.

Thresholds and Monitoring Frequency

Total testosterone diagnostic cutoff (AUA)< 300 ng/dL

EAU diagnostic threshold (repeat guidance)< 12 nmol/L; repeat total testosterone on at least two separate occasions when below

NCCN castrate testosterone target< 50 ng/dL

Monitoring frequency on TRTEvery 3-6 months for the first year, then annually thereafter

Timing for repeat testingAt least one week after initial test; two separate early morning fasting samples

Medical-Necessity Criteria

Covered / Meets Coverage Criteria

Testing MEETS COVERAGE CRITERIA when the following conditions are met:

Testing for serum total testosterone in symptomatic males being evaluated for androgen deficiency.
Repeat testing for serum total testosterone in males with low initial serum testosterone results; sample collection should occur in early morning, after fasting, and at least one week after the initial test.
Measurement of serum free testosterone, SHBG, and/or albumin in males with hypogonadism, gynecomastia, and/or other forms of testicular hypofunction when total testosterone is confirmed as borderline or low.
Testing for serum total testosterone in symptomatic males being evaluated for conditions associated with androgen excess.

Operational Guidance & Guideline Recommendations

EAU recommendations for diagnosis and testing of hypogonadism

Recommendations as stated by the European Association of Urology (EAU):

Check for concomitant diseases, drugs and substances that can interfere with testosterone production/action.
Measure total testosterone in the morning (7:00 to 11:00) and in the fasting state with a reliable method.7:00-11:00
Repeat total testosterone on at least two separate occasions when below 12 nmol/L and before starting testosterone therapy.12 nmol/L

Provider Actions & Billing Impact

Prior Authorization

Assay certification recommendation

Use serum total testosterone assays certified by the CDC HoSt/Testosterone program; testing is strongly recommended to be performed on certified assays.

Documentation Required

Repeat testing and specimen timing

Document early morning, fasting specimen collection (typically between 7:00 and 11:00) and perform repeat total testosterone on at least two separate occasions when diagnosing hypogonadism; if initial low, repeat at least one week after the initial test.

Coding & Regulatory References

No procedure/cpt/HCPCS/ICD codes provided in part 1mixed

No codes listed

Regulatory / device approvals referencedmixed

FDA device records (testosterone)	Search of FDA Device database on 10/25/2021 yielded 136 records for 'testosterone'
FDA device records (estradiol)	Estradiol testing has been approved by the FDA in a wide array of methodologies (FDA search noted)
FDA device records (prolactin)	Search of FDA-approved device database on 10/25/2021 yielded 98 different records for 'prolactin'
FDA device records (FSH)	Search of FDA-approved device database on 10/25/2021 yielded 22 devices for FSH
FDA device records (LH)	Search of FDA-approved device database on 10/25/2021 yielded 24 devices for LH

mixedCovered

No codes listed

No specific CPT, HCPCS, or ICD procedure codes are listed in this section of the brief. For assay and device context, FDA device record searches are referenced (e.g., a 10/25/2021 search yielding 136 'testosterone' device records), and CDC HoSt certification information and published assay validation studies are cited to inform analytic considerations.

Definitions

Definitions: Bioavailable testosterone — the amount of free testosterone plus albumin-bound testosterone. CDC HoSt/Testosterone program — the Centers for Disease Control and Prevention Hormone Standardization program that certifies and calibrates testosterone assays to a reference standard (certified assays must be within ±6.4% of the CDC target). LDT (Laboratory-Developed Test) — a clinical test developed and validated in-house by a laboratory, regulated under CLIA as high-complexity but not FDA-approved/cleared. LOH (Late Onset Hypogonadism) — age-related testosterone deficiency syndrome (guideline thresholds and diagnostic approaches described elsewhere in the policy).

Revision History

2023-07-01adoptionLatest

Adopted Avalon policy recommendation 7/1/2023; Effective date recorded as 7/1/2023 reflecting adoption of Avalon policy recommendation.

policy_summary

Testing meets coverage criteria for serum total testosterone in symptomatic males, repeat early-morning fasting testing when low, measurement of free/SBHG/albumin when total testosterone borderline or low, and monitoring on therapy every 3–6 months first year then annually.

exclusion

Policy Summary

Payerblue cross blue shield - tennessee

PolicyTestosterone Testing Policy

Policy CodePolicy N/A

Change TypeAdoption of Avalon recommendation

Effective DateN/A

Next Review DateN/A

Key ActionUse serum total testosterone assays certified by the CDC HoSt/Testosterone program and document early-morning fasting specimen collection with repeat testing when diagnosing hypogonadism.

SourceLink

On This Page

Measurement of serum free testosterone using a medically accepted algorithm based on total serum testosterone, SHBG, and/or albumin or bioavailable testosterone in individuals suspected of having a disorder accompanied by increased or decreased SHBG levels.

Testing for serum total testosterone measurements in monitoring treatment response in men taking enzyme inhibitors for prostate cancer.

Testing for serum total testosterone in men receiving testosterone replacement therapy every 3-6 months for the first year after initiation of therapy, and annually thereafter.

Testing for serum total testosterone in gender-dysphoric/gender-incongruent persons at baseline, during treatment and for therapy monitoring.

For males with gynecomastia, serum estradiol testing MEETS COVERAGE CRITERIA ONCE in a lifetime prior to initiating testosterone therapy.

Testing for serum total testosterone in symptomatic females being evaluated for conditions associated with androgen excess, provided the technology used is sensitive enough to detect low concentrations normally found in females.

Not Covered / Does Not Meet Coverage Criteria

Testing DOES NOT MEET COVERAGE CRITERIA in the following situations:

Testing for serum free testosterone and/or bioavailable testosterone as primary testing (i.e., in the absence of prior serum TOTAL testosterone testing) DOES NOT MEET COVERAGE CRITERIA.
Testing for serum total testosterone, free testosterone, and/or bioavailable testosterone DOES NOT MEET COVERAGE CRITERIA in asymptomatic individuals or in individuals with non-specific symptoms.
Testing for serum testosterone DOES NOT MEET COVERAGE CRITERIA for the identification of androgen deficiency in women.
Salivary testing for testosterone DOES NOT MEET COVERAGE CRITERIA.
Measurement of serum dihydrotestosterone DOES NOT MEET COVERAGE CRITERIA except when diagnosing 5-alpha reductase deficiency in individuals with ambiguous genitalia, hypospadias, or microphallus.

Notes / Assay Standards and SHBG Considerations

Operational notes and conditions that modify testing interpretation or selection:

NOTE 1: It is STRONGLY RECOMMENDED that serum total testosterone testing be performed on an assay certified by the CDC HoSt/Testosterone program (assay standardized to within ±6.4% of the CDC reference standard).±6.4%
NOTE 2: Conditions associated with decreased SHBG include: obesity; diabetes mellitus; use of glucocorticoids, progestins, and androgenic steroids; nephrotic syndrome; hypothyroidism; acromegaly; polymorphisms in the SHBG gene.
per 2018 Endocrine Society
NOTE 3: Conditions associated with increased SHBG include: aging; HIV disease; cirrhosis and hepatitis; hyperthyroidism; use of some anticonvulsants; use of estrogens; polymorphisms in the SHBG gene.
per 2018 Endocrine Society
Free testosterone measurement methods: For men who initially test low total testosterone, who test near the lower limit, or who have conditions that alter SHBG, free testosterone can be measured either by an accepted algorithm (total testosterone, SHBG, albumin) or by equilibrium dialysis rather than direct analog immunoassays.
equilibrium dialysis gold standard; avoid direct analog immunoassays
Sample collection recommendations: morning collection (typically between 7 and 11 am), fasting; repeat total testosterone on at least two separate occasions when low.
repeat at least one week after initial test

Consider measurement of sex hormone-binding globulin (SHBG) and calculation of free testosterone when indicated.

Calculated free-testosterone < 225 pmol/L has been suggested as a possible cut off for diagnosis of late onset hypogonadism.< 225 pmol/L

Analyse luteinising hormone (LH) and follicle-stimulating hormone (FSH) serum levels to differentiate primary vs secondary hypogonadism.

Consider prolactin (PRL) measurement if low desire (or other suggestive signs/symptoms) and low or low-normal testosterone is present.

Perform pituitary MRI in secondary hypogonadism with elevated PRL or specific symptoms of a pituitary mass and/or other anterior pituitary hormone deficiencies.

Perform pituitary MRI in secondary severe hypogonadism (total testosterone < 6 nmol/L).< 6 nmol/L

Screen for late onset hypogonadism (including in T2DM) only in symptomatic men.

Do not use structured interviews and self-reported questionnaires for systematic screening for LOH due to low specificity.

Endocrine Society / Other guideline monitoring recommendations

Monitoring and investigation recommendations from guideline summaries:

Investigate for secondary or reversible causes of hypogonadism in all men with testosterone deficiency syndrome.
Recommend assessment of response and adverse effects at three and six months after onset of therapy.3 and 6 months
Testosterone levels should be assessed at three and six months after onset of therapy and then annually thereafter if stable.3 and 6 months, then annually
Measurement of SHBG with calculated free or bioavailable testosterone should be restricted to men with symptoms of testosterone deficiency and equivocally low testosterone levels.

IGHG / PanCareSurFup recommendations for survivors

Guidance for childhood cancer survivors:

Clinical measurement of testicular volume and of FSH and inhibin B might be reasonable for identification of impaired spermatogenesis when semen analysis is declined or not possible.
Measurement of testosterone concentration in an early morning blood sample at clinically appropriate intervals is reasonable in postpubertal survivors treated with radiotherapy exposing testes to ≥ 12 Gy or with TBI.≥ 12 Gy
If early morning sample not possible, or with prior low-normal testosterone or clinical signs of hypogonadism, measure LH in addition to testosterone.

NCCN recommendations (selected)

NCCN guidance excerpts relating to testosterone testing in cancer care:

Document castrate level of testosterone if clinically indicated when assessing progression for prostate cancer; monitor physical exam and PSA every 3-6 months.3-6 months
Continue ADT to maintain castrate serum testosterone levels (<50 ng/dL).<50 ng/dL
Close monitoring of PSA and testosterone levels and possibly imaging is required when using intermittent ADT, especially during off-treatment periods.
For pituitary tumors, measure serum prolactin and LH/FSH; for suspected/confirmed adrenocortical carcinoma, measure DHEA-S and testosterone; for hypercortisolemic Cushing's, measure ACTH.

Testosterone is produced in males (Leydig cells) and females (ovaries and adrenals) and circulates as total, free, and protein-bound forms with SHBG and albumin as principal binding proteins; bioavailable testosterone denotes free plus albumin-bound fractions. Assay variability is substantial across laboratories and platforms, with traditional methods including radioimmunoassay and automated immunoassays and higher-accuracy methods using LC-MS/MS / ID-LC-MS/MS. Immunoassay-based measurements, particularly direct analog free testosterone immunoassays and some salivary immunoassays, have documented inaccuracies and proportional errors at low concentrations. Equilibrium dialysis is the gold standard for free testosterone but is technically demanding; accepted clinical approaches include calculated free testosterone using algorithms based on total testosterone, SHBG, and albumin or measurement by equilibrium dialysis. The CDC Hormone Standardization (HoSt/Testosterone) program certifies and calibrates total testosterone assays to a reference (acceptance limit ±6.4%), and the policy strongly recommends use of CDC-certified assays to reduce inter-assay variability and improve analytic validity.

Evidence / Key Items

CDC HoSt acceptance limit±6.4% from target value

Reported ID/LC-MS/MS reportable range2.5 - 1000 ng/dL (0.09 - 34.7 nM); LOD 0.36 ng/dL

AUA diagnostic threshold reportedTotal testosterone < 300 ng/dL

EAU guideline year2021 (recommendations on measurement timing, thresholds, and repeat testing)

NCCN castrate guidanceMaintain castrate serum testosterone < 50 ng/dL; document and monitor every 3-6 months

Billing Rule

Estradiol testing for gynecomastia

For males with gynecomastia, serum estradiol testing meets coverage criteria once in a lifetime prior to initiating testosterone therapy; document the indication when ordering.

Documentation Required

Use of free testosterone measurement

Measure free or bioavailable testosterone only when total testosterone is borderline/low or when conditions that alter SHBG exist; use accepted calculation algorithms (based on total T, SHBG, albumin) or equilibrium dialysis rather than direct analog immunoassays.

Denial Risk

Not covered scenarios — denial risk

Claims for the following scenarios do NOT meet coverage criteria and risk denial: salivary testosterone testing; primary free or bioavailable testosterone testing without prior total testosterone; testing in asymptomatic individuals or for non‑specific symptoms; and testosterone testing to identify androgen deficiency in women.

Documentation Required

Timing and repeat testing

Collect total testosterone in the morning (7:00–11:00) on a fasting sample and repeat on at least two separate occasions when below threshold (e.g., below 12 nmol/L per EAU); repeat at least one week after the initial low test before initiating therapy.

Documentation Required

Monitoring after therapy initiation

When initiating testosterone therapy, assess response and adverse effects at about 3 and 6 months; measure testosterone levels at those times and then annually thereafter if stable.

Documentation Required

Use of SHBG/free testosterone testing

Restrict measurement of SHBG with calculated free or bioavailable testosterone to men who have symptoms of testosterone deficiency and equivocally low total testosterone results.

Documentation Required

Investigate secondary causes

Investigate for secondary or reversible causes in all men with testosterone deficiency syndrome; measure LH and FSH to differentiate primary versus secondary hypogonadism and consider measuring prolactin when clinical signs or low/low‑normal testosterone suggest pituitary involvement.

Documentation Required

Imaging indications (pituitary MRI)

Order pituitary MRI for secondary hypogonadism when prolactin is elevated or there are symptoms/signs of a pituitary mass or other anterior pituitary hormone deficiencies; consider MRI in secondary severe hypogonadism when total testosterone is < 6 nmol/L.

Documentation Required

Cancer survivor testing (postpubertal, ≥12 Gy or TBI)

In postpubertal childhood cancer survivors treated with radiotherapy exposing the testes to ≥12 Gy or with total body irradiation (TBI), measure early morning testosterone at clinically appropriate intervals; if a morning sample is not possible or prior low‑normal results or signs are present, measure LH in addition to testosterone.

Not covered: primary free/bioavailable testosterone testing without prior total testosterone, testing in asymptomatic or non-specific symptoms, salivary testosterone testing, and testosterone testing to identify androgen deficiency in women.

assay_standard

Strong recommendation that serum total testosterone testing be performed on assays certified by the CDC HoSt/Testosterone program (acceptance limit ±6.4% from target); CDC standardized ID-LC-MS/MS reportable range 2.5–1000 ng/dL with LOD 0.36 ng/dL.

method_note

Equilibrium dialysis is gold standard for free testosterone; immunoassays for free testosterone are inaccurate and not recommended; use accepted calculation algorithms (TT, SHBG, albumin) or equilibrium dialysis.