Testosterone Testing AHS – G2013

Description of Procedure or Service

Testosterone is a naturally occurring androgen hormone that is a hydroxy steroid ketone C19H28O2. Testosterone production is important for both males and females. Dysregulations in testosterone levels could lead to serious conditions in males and females leading to hypogonadism in men, polycystic ovary syndrome (PCOS) in women and other testosterone excess or deficiency conditions (Burtis and Ashwood, 1999).

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

BCBSNC will provide coverage for Testosterone Testing when it is determined to be medically necessary because the medical criteria and guidelines shown below are met.

Benefits Application

This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy.  

When Testosterone Testing is covered

1. Testing for serum total testosterone is considered medically necessary in symptomatic males being evaluated for androgen deficiency. For pre-pubescent males, the technology used for testing should be sensitive and specific enough to quantify accurately the low concentrations normally found in that population. 
2. Repeat testing for serum total testosterone is considered medically necessary in males with low initial serum testosterone results. Sample collection should occur in early morning, and at least one week after the initial test. 
3. Measurement of serum free testosterone and/or bioavailable testosterone is considered medically necessary if total testosterone is confirmed as borderline or low. 
4. Testing for serum total testosterone is considered medically necessary in symptomatic males being evaluated for conditions associated with androgen excess. For infants and pre-pubescent males, the technology used for testing should be sensitive and specific enough to quantify accurately the low concentrations normally found in that population. 
5. Testing for serum total testosterone is considered medically necessary in symptomatic females being evaluated for conditions associated with androgen excess (e.g., polycystic ovary syndrome and functional hypothalamic amenorrhea). The technology used for testing should be sensitive enough to detect the low concentrations normally found in females. 
6. Measurement of serum free testosterone and/or bioavailable testosterone is considered medically necessary in individuals suspected of having a disorder that is accompanied by increased or decreased SHBG levels. 
7. Testosterone measurements is considered medically necessary in monitoring treatment response in men taking enzyme inhibitors for prostate cancer. 
8. Testing for serum total testosterone is considered medically necessary in men receiving testosterone replacement therapy every 3-6 months for the first year after initiation of therapy, and annually thereafter. 
9. Testing for serum testosterone is considered medically necessary in genderdysphoric/gender-incongruent persons at baseline, during the treatment and for the therapy monitoring. 

When Testosterone Testing is not covered

1. Testing for serum total testosterone, free testosterone, and/or bioavailable testosterone is considered not medically necessary in asymptomatic individuals or in individuals with non-specific symptoms.
2. Testing for serum testosterone is considered not medically necessary for the identification of androgen deficiency in women. 
3. Salivary testing for testosterone is investigational.

Policy Guidelines

The steroid hormone testosterone plays a role in both male and female development and health. It is produced by the adrenal glands in both sexes, by the Leydig cells in males, and in small amounts by the ovaries in females. In males, testosterone is responsible for development of secondary sex characteristics, and regulates sex drive and muscle mass. In females, testosterone is primarily converted to estradiol, which serves to develop and maintain secondary sex characteristics in women.

Production of testosterone is controlled by the pituitary gland, specifically by luteinizing hormone (LH), via negative feedback. Most of the testosterone circulating in blood is bound to sex-hormone binding globulin (SHBG), and a lesser amount is bound loosely to albumin, while a very small fraction occurs in the biologically active or “free” form. “Bioavailable” testosterone is considered to be the combination of that which is free and that which is bound to albumin in circulation.

Low testosterone in boys can result in delayed puberty, and can indicate testicular failure. In adult males, decreases in testosterone production occur normally with age, typically starting gradually in the mid-40s, and more pronounced after 60 years of age. Significant decreases may result in symptoms such as fatigue, decreased libido, erectile dysfunction, depression, muscle weakness, and others. Unfortunately, these symptoms are not specific to testosterone deficiency.

Low testosterone levels are associated with diabetes, metabolic syndrome, cardiovascular disease, obesity, sleep apnea, and other disorders. Therefore, the evaluation of men with symptoms of testosterone deficiency should not be limited to measurement of testosterone levels. Co-morbid conditions that may be the underlying cause of the low testosterone should be investigated as well. Association of low testosterone with increased risk of death from all causes has been noted, providing additional impetus for accurate assessment and treatment.

For symptomatic individuals who are testosterone deficient, and in whom the symptoms are directly caused by low testosterone, testosterone replacement therapy may relieve symptoms and improve quality of life. However, concurrent improvements in healthy living are also recommended.

Additionally, testosterone elevations are associated with serious conditions, including tumors, hyperthyroidism, genetic disorders, including congenital adrenal hyperplasia, and polycystic ovarian syndrome (PCOS).

Applicable Federal Regulations

N/A

Guidelines and Recommendations

The Endocrine Society-Androgen Deficiency

Measurement of serum testosterone in males with specific symptoms such as incomplete or delayed sexual development, eunuchoidism, reduced libido, breast discomfort, shrinking testes, and others is recommended by The Endocrine Society. They also recommend consideration of serum testosterone evaluation for individuals with non-specific symptoms such as fatigue, depression, poor concentration, sleep disturbance, and others. Additionally, The Endocrine Society suggests that androgen deficiency not be evaluated during acute or sub-acute illness.

The Endocrine Society recommends use of total testosterone measurement from a morning sample, with confirmation by repeat testing for results that are low or borderline, or in those suspected of abnormal SHBG levels. Repeat testing should also include measurement of free or bioavailable testosterone. They note that all testing should be performed with reliable, validated assays.

The Endocrine Society recommends against androgen deficiency screening in the general population.

For men receiving testosterone replacement therapy, the Endocrine Society recommends monitoring serum testosterone levels 3 to 6 months after initiation of therapy (Bhasin et al, 2010).  

The Endocrine Society-Functional Hypothalamic Amenorrhea

Testosterone testing in addition to other endocrine laboratory tests is recommended as part of an initial endocrine assessment for women with clinical hyperandrogenism in the evaluation of suspected Functional Hypothalamic Amenorrhea (FHA) (Gordon et al, 2017).

The Endocrine Society-Polycystic Ovary Syndrome (PCOS)

Relative to the diagnosis of PCOS, the Endocrine Society identifies three criteria that may be evaluated: androgen excess, ovulatory dysfunction, and polycystic ovaries. Two of the three criteria are sufficient for diagnosis, and if both clinical criteria are met, they do not recommend testing for androgen excess. Androgen excess is characterized by elevated serum androgen levels such as elevated total, bioavailable, or free serum testosterone levels. Considering that serum testosterone levels are variable and poor standardization of the assays, Task Force recommends familiarity with local assays and does not define an absolute level that is diagnostic of PCOS or other causes of hyperandrogenism (Legro et al, 2013). 

The Endocrine Society-Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons

Testosterone levels monitoring is suggested at baseline and every 6-12 months during suppression of puberty treatment protocol in gender-dysphoric/gender-incongruent persons. The laboratory monitoring of testosterone levels is also suggested at baseline and every 6-12 months during induction of puberty protocol. Measurement of serum testosterone levels is suggested every 3 months until levels are in the normal physiologic male range during the monitoring of transgender males on gender-affirming hormone therapy. Testosterone testing is also needed midway between injections for monitoring of testosterone enanthate/cypionate injections, alternatively peak and trough levels could be measured to ensure levels remain in the normal male range. For parenteral testosterone undecanoate, testosterone should be measured just before the following injection. For transdermal testosterone, the testosterone level can be measured no sooner than after 1 week of daily application (at least 2h after application). For monitoring transgender females on gender-affirming hormone therapy, measurement of serum testosterone is indicated every 3 months (Hembree et al, 2017).

The American Association of Clinical Endocrinology (AACE)

The AACE recommends use of a morning sample for determination of serum total testosterone in individuals being evaluated for androgen deficiency. Additionally, AACE recommends repeat testosterone measurement and use of SHBG or free testosterone testing “if testosterone levels are low-normal and the symptoms and signs indicate hypogonadism.” For individuals receiving testosterone replacement therapy, AACE recommends measurement of serum testosterone levels every 3 - 4 months for the first year after initiation of therapy, as part of the overall monitoring of therapy effectiveness.

The British Columbia Medical Association

The British Columbia Medical Association recommends against screening for testosterone deficiency in asymptomatic individuals, and indicates that presence of erectile dysfunction alone is not sufficient to warrant serum testosterone testing. They also recommend against serum testosterone testing in females for the purpose of identifying hypoandrogenism (BCMA, 2011).

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 84402, 84403, 84410

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Scientific Background and Reference Sources

Bhasin, S., Cunningham, G.R., Hayes, F.J., Matsumoto, A.M., Snyder, P.J., Swerdloff, R.S., Montori, V.M. (2010). Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Vol. 95(6): 2536–2559

British Columbia Medical Association (2011). Testosterone Testing Protocol. Accessed February, 2014 

Burtis, C.A., and Ashwood, E.R. (1999). (eds): Tietz textbook of clinical chemistry. Saunders; 3rd edition. Philadelphia, USA.. ISBN: 0721656102

Buvat J, Maggi M, Guay A, et al. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med 2013;10:245–84.

Gordon, C.M, Ackerman, K.E., Berga, S.L., Kaplan, J.R., Mastorakos, G., Misra, M., Murad, M.H., Santoro, N.F., and Warren, M.P. (2017). Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 102(5), 1413–1439

Hembree, W.C., Cohen-Kettenis, P.T., Gooren, L., Hannema, S.E., Meyer, W.J., Murad, M.H., Rosenthal, S.M., Safer, J.D., Tangpricha, V., T’Sjoen, G.G. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, jc.2017-01658

Jack, G. and Zeitlin, S.I. (2004). The Role of Routine Serum Testosterone Testing: Routine Hormone Analysis Is Not Indicated as an Initial Screening Test in the Evaluation of Erectile Dysfunction. Reviews in Urology. Vol.6., No. 4. Retrieved on January 14, 2014 

Legro, R.S., Arslanian, S.A., Ehrmann, D.A., Hoeger, K.M., Murad, M.H., Pasquali, R., and Welt, C.K. (2013). Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 98(12), 4565–4592

McGill, J.J., Shoskes, D.A., and Sabanegh, E.S. (2012). Androgen deficiency in older men: Indications, advantages, and pitfalls of testosterone replacement therapy. Cleve Clin J Med. 79(11), 797-806. doi: 10.3949/ccjm.79a.12010. Retrieved on January 14, 2014

Morales, A., Bebb, R.A., Manjoo, P., Assimakopoulos, P., Axler, J., Collier, C., Elliott, S., Goldenberg, L., Gottesman, I., Grober, E.D., Guyatt, G.H., Holmes, D.T., Lee, J.C., and Canadian Men’s Health Foundation Multidisciplinary Guidelines Task Force on Testosterone Deficiency Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. (2015). CMAJ. Dec 8; 187(18): 1369–1377. PMCID: PMC4674408doi: 10.1503/cmaj.150033

Petak, S.M., Nankin, H.R., Spark, R.F., Swerdloff, R.S., Rodriguez-Rigau, L.J. and American Association of Clinical Endocrinologists. (2002). American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients—2002 Update. Endocrine Practice, 8(6),439-456.

Policy Implementation/Update Information

1/1/2019 New policy developed. BCBSNC will provide coverage for Testosterone Testing when it is determined to be medically necessary because the medical criteria and guidelines are met. Medical Director review. Policy noticed on 1/1/2019 for effective date 4/1/2019. (mco)