Testosterone is an androgenic hormone. It is responsible for the development of the male external genitalia and secondary sexual characteristics. Male hypogonadism is a condition in which the body doesn't produce enough testosterone. Primary hypogonadism originates from testicular failure. Secondary hypogonadism originates in the hypothalamus or the pituitary gland; either type may be congenital or acquired, or both.
Testosterone circulates in the plasma as free (2-3%), bound to specific plasma proteins (sex hormone-binding globulin, SHBG) (98%) and bioactive or weakly bound to nonspecific proteins such as albumin. Measurement of the serum total testosterone concentration is usually an accurate reflection of testosterone secretion and is the initial test of choice. Measurement of the serum free testosterone concentration is necessary to determine if a low total testosterone is due to low sex hormone-binding globulin (SHBG) or to reduced testosterone production. Typically the testing is done as a fasting early morning lab, repeated the next day or within a week to confirm and then if testosterone therapy should be initiated checked once every 3-12 months.
In females, testosterones main role is as an estrogen precursor. In both genders, it also exerts anabolic effects and influences behavior. Women with polycystic ovary syndrome or androgen secreting tumors may have symptoms of hyperandrogenism based upon either clinical or biochemical signs. Measuring free testosterone instead of or in addition to total testosterone, is the most sensitive test to establish the presence of hyperandrogenemia.
Note: This medical policy does NOT address Gender Reassignment Services.
Measurement of serum total and/or free testosterone is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Measurement of serum total and/or free testosterone is considered not medically necessary for the following indications/diagnosis:
Screening in asymptomatic individuals
Sexual dysfunction such as erectile dysfunction or impotence
Services related to infertility
More than once every 3 to 12 months for individuals on testosterone therapy
Measurement of serum total and/or free testosterone is considered investigational if the following medical conditions are present:
Breast or prostate cancer
A palpable prostate nodule or induration (risk factor for prostate cancer)
A prostate-specific antigen level greater than 4 ng/mL (risk factor for prostate cancer)
A prostate-specific antigen level greater than 3 ng/mL and at high risk for prostate cancer
Men aged 66 years of age and older (due to greater risk for prostate cancer)
Untreated severe obstructive sleep apnea
Severe lower urinary tract symptoms
Uncontrolled heart failure
Myocardial infarction or stroke within the last 6 months
Co-morbidity of Thrombophilia
Currently taking opioids and/or glucocorticoids medications
Currently recovering from an acute illness
Measurement of serum testosterone (total and/or free) is considered medically appropriate for ANY ONE of the following:
Measurement of serum total testosterone for ANY ONE of the following:
Female with symptoms of overproduction of androgens (hyperandrogenemia); including but not limited to: amenorrhea (absence of menstrual periods), oligomenorrhea (infrequent or very light menstruation), decrease in breast size, increase in body hair in a male pattern (hirsutism) such as on the face, chin, and abdomen, clitoromegaly (enlargement of the clitoris), deepening of the voice, increase in muscle mass, temporal balding (thinning hair and hair loss)
Male with ALL of the following:
Age less than or equal to 65 years
Symptoms of hypogonadism; including but not limited to: incomplete or delayed sexual development, loss of body hair, very small testes (6 mL or less), low sperm count, breast discomfort, gynecomastia, eunuchoidal body proportions, low-trauma fracture, low bone mineral density, hot flushes, sweats, persistent low-grade depressive disorder, sleep disturbances, mild unexplained anemia, reduced muscle bulk and strength
Measurement of serum free testosterone for ANY ONE of the following:
Female with symptoms of overproduction of androgens (see examples above)
Male with ANY ONE of the following:
Decreased total serum testosterone
A medical diagnosis that could affect the sex hormone-binding globulin (SHBG), such as ONE or MORE of the following:
Obesity (BMI greater than or equal to 35)
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
2018 Guidelines from the Endocrine Society indicate testosterone (T) testing should be measured with a fasting morning total testosterone concentration initially. Because of day-to-day variations, repeat to confirmation a low total T level (30% of men with an initial low-T concentration have a normal T on repeat measurement). A free testosterone test should be obtained in individuals if the total T is near the lower limit of normal or who have a condition that alters sex hormone–binding globulin.
The lower limit of the normal total T harmonized to the CDC standard in healthy nonobese young men is 264 ng/dL (9.2 nmol/L); this limit could be used for total T assays that are CDC certified. However, the reference range may vary depending on the assay and reference population used. A harmonized reference range for free T has not been established.
The Mayo Clinic (www.mayomedicallaboratories.com) offers the following reference values:
Total testosterone ng/dL
Free testosterone ng/dL
men (>19 years)
women (> 20 years)
American Association of Clinical Endocrinologists (2002) Medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients. Endocrine Practice, 8, (9), 440-456.
American Urological Association. (2010) A consensus statement: toward excellence in testosterone testing. Journal of Clinical Endocrinology & Metabolism, 95 (10), 4542-4548.
Anawalt, B., Hotaling, J., Walsh, T., and Matsumoto, A. (2012, April) Performance of total testosterone measurement to predict free testosterone for the biochemical evaluation of male hypogonadism. Journal of Urology, 187 (4), 1369-73. Abstract retrieved July 16, 2018 from PubMed database.
Antonio, L., Wu, F., O’Neill, T., Pye, S., Ahern, T., Laurent, M., et al. (2016, July) Low free testosterone is associated with hypogonadal signs and symptoms in men with normal total testosterone. Journal of Endocrinology & Metabolism, 101 (7), 2647-2657. (Level 2 evidence)
Blue Cross Blue Shield Association. Medical Policy Reference Manual. (7:2017) Testosterone Replacement Therapies (5.02.23) Retrieved July 16, 2018 from BlueWeb. (49 articles and/or guidelines reviewed)
Canadian Medical Association. (2015, December) Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. Canadian Medical Association Journal, 187 (18), 1369-1377.
Center for Disease Control. Laboratory Procedure Manual. (2012) Total testosterone in serum. Retrieved July 16, 2018 from www.cdc.com.
Endocrine Society / European Society of Endocrinology. (2018, May) Testosterone therapy in men with hypogonadism: an endocrine society* clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 103(5), 1715-1744.
Endocrine Society. (2013, December) Diagnosis and treatment of polycystic ovary syndrome: an endocrine society* clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 98 (12), 4565-4592.
Mayo Clinic. May Medical Laboratories. (2018, July) Test ID: TTFB testosterone, total, bioavailable, and free, serum. Retrieved July 16, 2018 from www.mayomedicallaboratories.com.
Office on Women’s Health. (2016, January) A fact sheet on: polycystic ovary syndrome (PCOS). Retrieved July 16, 2018 from www.womenshealth.gov.
Shea, J., Wong, P., and Chen, Y. (2014) Free testosterone: clinical utility and important analytical aspects of measurement. Advanced Clinical Chemistry, (63), 59-84. Abstract retrieved July 16, 2018 from PubMed database.
Surampudi, P., Wang, C., and Swerdloff, R. (2012) Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy. International Journal of Endocrinology, Article ID 625434, 20 pages. (Level 2 evidence)
Travison, T., Vesper, H., Orwoll, E., Wu, F., Kaufman, J., Wang, Y., et al. (2017, April) Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the united states and Europe. Journal of Endocrinology & Metabolism, 102 (4), 1161-1173. (Level 2 evidence)
ORIGINAL EFFECTIVE DATE: 12/30/2018
MOST RECENT REVIEW DATE: 12/30/2018
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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