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 Males
Testosterone 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 Females
Women 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 GUIDELINES 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:
- 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
- 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:
- Estrogen excess/use
- HIV infection
- Levothyroxine use
- Nephrotic syndrome
- Androgenic steroid, progestin, or glucocorticoid use
- Insulin resistance
Benefits will not be provided for the following contract exclusions:
- Services and supplies related to infertility, artificial insemination, intrauterine insemination and in-vitro fertilization regardless of any claim of Medical Necessity.
- For treatment related to sex transformations, sexual function, sexual dysfunctions or inadequacies regardless of Medical Necessity.
Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
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.
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Human immunodeficiency virus [HIV]
Human immunodeficiency virus [HIV] disease
Benign neoplasm of ovary
D27.0 - D27.01
Benign neoplasm of ovary code range
242.00 - 242.91
Thyrotoxicosis with or without goiter
E05.00 - E05.91
Thyrotoxicosis [hyperthyroidism] code range
Acromegaly and gigantism
Acromegaly and pituitary gigantism
Other anterior pituitary disorders
Other disorders of pituitary gland
Iatrogenic pituitary disorders
Other ovarian failure
Other primary ovarian failure
Polycystic ovarian syndrome
Postablative testicular hypofunction
Postprocedural testicular hypofunction
Other testicular hypofunction
Dysmetabolic syndrome X
Depressive disorder, not elsewhere classified
Major depressive disorder, single episode, unspecified
Alcoholic cirrhosis of liver
Alcoholic fibrosis and sclerosis of liver
K70.30 - K70.31
Alcoholic cirrhosis of liver code range
Cirrhosis of liver without mention of alcohol
Unspecified cirrhosis of liver
Other cirrhosis of liver
581.0 – 581.9
N04.0 - N04.9
Nephrotic syndrome code range
Hypertrophy of breast
Hypertrophy of breast
Atrophy of breast
Atrophy of breast
Other and unspecified ovarian cyst
Unspecified ovarian cysts
Other ovarian cysts
Hypertrophy of clitoris
Other specified noninflammatory disorders of vulva and perineum
Absence of menstruation
Scanty or infrequent menstruation
Irregular menstrual cycle
Other specified irregular menstruation
Irregular menstruation, unspecified
Alopecia, unspecified [Male pattern baldness in female]
Androgenic alopecia, unspecified
Nonscarring hair loss, unspecified
Acne excoriee des jeunes filles
Muscular wasting and disuse atrophy, not elsewhere classified
M62.50 - M62.59
Muscle wasting and atrophy, not elsewhere classified
Other malaise and fatigue
Flushing [Hot flashes in males]
Other voice and resonance disorders [Deepening of the voice in female]
Other voice and resonance disorders
Long-term (current) use of steroids
Long term (current) use of inhaled steroids
Long term (current) use of systemic steroids
Long-term (current) use of other medications
Other long term (current) drug therapy
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