Free Testosterone Testing

POLICY NUMBER

L.2.04.405

DESCRIPTION

Testosterone is an endogenous androgen. Androgens are responsible for normal growth and development of male sex organs. Testosterone is produced by the testes and is involved in the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; development of male hair distribution (e.g., beard, pubic, chest and axillary hair); laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution. In women, small amounts of testosterone are produced by the ovaries and adrenal glands. As in men, testosterone is thought to influence pubertal development, sexual function, bone density, muscle mass, erythropoiesis, energy, cognitive function, and mood in women.

Free Testosterone Measurement in MalesTestosterone is present in the blood as "free" testosterone (1-4%) or bound testosterone (~98%). Measurement of the serum total (free plus protein-bound) testosterone concentration is usually an accurate reflection of testosterone secretion and is the initial test of choice. Men who are overweight (BMI 25 to 29 kg/m2) and obese (BMI ≥30 kg/m2) tend to have lower serum concentrations of sex hormone binding globulin (SHBG) and, therefore, lower serum concentration of total testosterone. To the degree that the low total serum testosterone concentration is due to the low SHBG, the free testosterone concentration is normal. However, men who are obese may also have low free testosterone concentrations. These abnormalities were shown in a report from the European Male Aging Study, in which data from 3220 men ages 40 to 79 at eight sites were analyzed. At all ages, both total testosterone and SHBG concentrations were lower in overweight men than in men of normal weight and lower yet in obese men. Free testosterone, however, was similar in normal weight and overweight men, but lower in obese men.

In short, obese men may have a low total serum testosterone concentration because of a combination of low SHBG and secondary hypogonadism. Measurement of the serum free testosterone concentration is necessary to determine if an obese man’s low total testosterone is due only to low SHBG or to secondary hypogonadism as well. Measurement of the serum free testosterone concentration is worthwhile only when it is suspected that an abnormality in testosterone binding to sex hormone-binding globulin coexists with hypogonadism. Measurement of the serum free testosterone in a laboratory capable of performing this assay accurately will distinguish between a binding abnormality and hypogonadism in an obese male.

Free Testosterone Measurement in FemalesWomen with polycystic ovary syndrome are considered to have hyperandrogenism based upon either clinical or biochemical signs (presence of hirsutism, acne, or alopecia on exam, or elevated serum androgen). Thus, in someone with clinical signs of hyperandrogenism, one could argue that biochemical testing is not necessary. However, most expert groups suggest initial measurement of a total testosterone concentration in women who present with hirsutism. If there are concerns about a possible androgen-secreting tumor causing the hyperandrogenism (onset of hirsutism with rapid progression, signs of virilization such as deepening of the voice or clitoromegaly), measuring serum dehydroepiandrosterone sulfate (DHEA-S) as well as total testosterone to look for adrenal sources of hyperandrogenism is recommended. Some groups recommend measuring free testosterone instead of or in addition to total testosterone, because it is the most sensitive test to establish the presence of hyperandrogenemia. However, commercially available free testosterone assays are often unreliable. If measured, it should be done in a reliable endocrine lab.

If serum free testosterone is measured, the following points should be kept in mind:

• Serum free testosterone should be performed by equilibrium dialysis and only in those few laboratories that specialize in endocrine testing.

• The free testosterone concentration, as calculated from the total testosterone, SHBG, and albumin concentrations, may also be reliable, but there are many different equations for this calculation and they give vastly different results, some of which reflect the results obtained by equilibrium dialysis better than others. Consequently, it is essential that the result be compared with the normal range for the laboratory that performed the assay.

• Free testosterone measured by an analog method, which is the assay most commonly offered by hospital and commercial laboratories, does not correlate with the results of equilibrium dialysis. This test gives misleading information and should never be ordered. 

POLICY

Measurement of serum free testosterone is considered medically necessary to distinguish between a sex hormone-binding globulin (SHBG) abnormality and hypogonadism in obese males with symptoms of hypogonadism (See Policy Guidelines) if the total serum testosterone level is low.

Measurement of serum free testosterone is considered medically necessary to diagnose hyperandrogenism in symptomatic females (See Policy Guidelines).

Measurement of serum free testosterone is considered medically necessary in patients with a medical diagnosis that may increase or decrease SHBG levels (See Policy Guidelines).

Measurement of serum free testosterone is considered not medically necessary to diagnose testosterone deficiency in non-obese males with symptoms of hypogonadism.

Measurement of serum free testosterone is considered not medically necessary when performed for screening purposes in asymptomatic patients (absence of signs, symptoms, or disease).

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Symptoms hypogandism in males covered under this policy are malaise, fatigue, lethargy, hot flashes, muscle loss, depression, or decreased libido. If the only symptom is Erectile Dysfunction or Impotence, the laboratory testing is not covered.  

Symptoms of overproduction of androgens in females include the following:

• Hyperandrogenism:

  • Acne

  • Amenorrhea (absence of menstrual periods)

  • Oligomenorrhea (infrequent or very light menstruation)

  • Changes in female body contours

  • Decrease in breast size

  • Increase in body hair in a male pattern (hirsutism) such as on the face, chin, and abdomen

  • Oily skin

• Virilization:

  • Clitoromegaly (enlargement of the clitoris)

  • Deepening of the voice

  • Increase in muscle mass

  • Temporal balding (thinning hair and hair loss)

Medical diagnoses affected SHBG levels include the following:

• Increase

  • Hyperthyroidism

  • Cirrhosis

  • Estrogen excess/use

  • HIV infection

  • Anticonvulsants

  • Levothyroxine use

• Decrease

  • Hypothyroidism

  • Acromegaly

  • Nephrotic syndrome

  • Androgenic steroid, progestin, or glucocorticoid use

  • Insulin resistance

  • Cachexia/malnutrition

Benefits will not be provided for the following contract exclusions:

1. Services and supplies related to infertility, artificial insemination, intrauterine insemination and in-vitro fertilization regardless of any claim of Medical Necessity.

2. For treatment related to sex transformations, sexual function, sexual dysfunctions or inadequacies regardless of Medical Necessity.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

10/01/2013: New policy added.

08/18/2015: Medical policy revised to add ICD-10 codes.

01/15/2016: Code Reference section updated to make the following corrections: N64.9 should be L64.9 and N65.9 should be L65.9.

06/07/2016: Policy number L.2.04.405 added. Policy Guidelines updated to add medically necessary definition.

09/08/2016: Code Reference section updated to make correction: ICD-10 diagnosis code D27.01 should be D27.9.

09/30/2016: Code Reference section updated to add new ICD-10 diagnosis codes N83.201 - N83.299.

10/06/2017: Code Reference section updated to remove deleted ICD-10 diagnosis codes N83.20 and N83.29.

05/31/2018: Deleted outdated references and updated links in Sources section.

10/01/2021: Code Reference section updated to add new ICD-10 diagnosis codes F32.A.

10/14/2022: Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

09/28/2023: Code Reference section updated to add new ICD-10 diagnosis codes E88.810, N04.20, N04.21, N04.22, and N04.29, effective 10/01/2023.

10/18/2023: Policy reviewed; no changes.

08/16/2024: Code Reference section updated to add ICD-10 diagnosis codes Q98.0 - Q98.4.

12/04/2024: Policy reviewed. Policy statements unchanged. Sources updated. Code Reference section updated to remove deleted ICD-10 diagnosis code E88.81.

SOURCE(S)

1. DynaMed - Polycystic ovary syndrome

2. Endocrine Physician Advisory Committee

3. http://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_Testosterone_LCMSMS

4. Ovarian overproduction of androgens -

   http://www.nlm.nih.gov/medlineplus/ency/article/001165.htm

5. Performance of Total Testosterone Measurement to Predict Free Testosterone for the Biochemical Evaluation of Male Hypogonadism. Bradley D. Anawalt et al. The Journal of Urology, Volume 187, Issue 4, Pages 1369-1373, April 2012 -

   http://www.jurology.com/article/S0022-5347(11)05773-9/abstract

6. Polycystic Ovarian Syndrome fact sheet -

   https://owh-wh-d9-dev.s3.amazonaws.com/s3fs-public/documents/fact-sheet-pcos.pdf

7. Total Testosterone or Free Testosterone? Allan S. Brett, MD reviewing Anawalt BD et al. The Journal of Urology, 2012 April -

   http://www.jwatch.org/jw201204120000001/2012/04/12/total-testosterone-or-free-testosterone

8. UptoDate® - Androgen production and therapy in women

9. UptoDate® - Causes of secondary hypogonadism in males

10. UptoDate® - Clinical features and diagnosis of male hypogonadism

11. UptoDate® - Diagnosis of polycystic ovary syndrome in adults

12. UptoDate® - Evaluation of premenopausal women with hirsutism

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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