ANDROGENS (PREAUTHORIZATION REQUIRED)

X.66





X.66 ANDROGENS (PREAUTHORIZATION REQUIRED)


Description

 

Testosterone, the primary androgen produced in the testes, is responsible for a variety of physiologic functions that include: the normal growth and development of male sex organs, maintenance of secondary sex characteristics, stimulating and maintaining sexual function in men, the growth spurt of that seen in adolescence, increasing lean body mass and weight, increasing the formation of clotting factors in the liver, and stimulating the production of red blood cells. In certain medical conditions such as hypogonadism, the endogenous level of testosterone falls below normal levels. Primary hypogonadism (congenital or acquired) includes conditions such as testicular failure due to cryptorchidism, bilateral torsion, orchitis, or vanishing testis syndrome; bilateral orchidectomy; and inborn errors in the biosynthesis of testosterone. Secondary hypogonadism (congenital or acquired), also called hypogonadotropic hypogonadism, includes conditions such as idiopathic or gonadotropin LHRH deficiency or pituitary-hypothalamic injury resulting from tumors, trauma, or radiation. 

Symptoms are dependent on age, severity of androgen deficiency, duration of androgen deficiency, individual sensitivity to androgen, and comorbid illness.  Signs and symptoms other than sexual dysfunction include hot flushes or sweats, decreased energy, depression, sleep disturbance, reduced muscle mass and strength, and/or increased body fat. “More specific” symptoms of hypogonadism, as classified by the Endocrine Society include: Incomplete or delayed sexual development, decreased libido, decreased spontaneous erections, breast discomfort, gynecomastia, loss of axillar and/or pubic body hair, very small (<5 mL) or shrinking testes, infertility due to low sperm count, height loss due to vertebral fractures, low trauma fractures, low bone density.

 

 

 

According to UpToDate, “If the serum testosterone is below normal on two occasions, a serum LH concentration should be measured to distinguish primary from secondary hypogonadism.” Furthermore, it states that, “If the serum testosterone concentration is subnormal, supranormal serum LH and FSH concentrations indicate primary hypogonadism and values that are not supranormal indicate secondary hypogonadism. Clearly elevated gonadotropin values are indicative of primary hypogonadism even if the serum testosterone concentration is in the low-normal range. Some men with primary hypogonadism present with a subnormal sperm count, high serum FSH, but normal serum testosterone and LH concentrations. This pattern indicates seminiferous tubule damage but normal testosterone production by the Leydig cells is still normal.” According to the Endocrine Society's Clinical Practice Guideline for Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes, men greater than 40 years old who have baseline prostate specific antigen (PSA) greater than 0.6 ng/ml and a diagnosis of primary hypogonadism or hypogonadotropic hypogonadism, should receive a digital rectal examination and have PSA level checked before initiating treatment.

 

 

 

TESTOSTERONE AND TESTOSTERONE LEVELS

 

Testosterone is produced in males, primarily by the testes, in response to stimuli from the hypothalamic and pituitary glands. Low testosterone is caused by deficient production of the hormone and is also known as androgen deficiency. Primary androgen deficiency results from failure of testosterone production at the testicular level in the presence of normal hypothalamic and pituitary function. Secondary androgen deficiency results from failure of the pituitary gland to produce androgen-stimulating hormones (luteinizing hormone, follicle-stimulating hormone). It can be caused by dysfunction at the hypothalamic or pituitary level.

 

 

 

Treatment

 

There are numerous Food and Drug Administration (FDA)?approved formulations of testosterone available for replacement therapy. For most delivery preparations, approval was based on the ability to increase levels to the normal range, not on demonstration of beneficial clinical outcomes.

 

 

 

Oral Testosterone

 

The most common forms of oral testosterone in clinical use are testosterone enanthate and testosterone cypionate, which are generally dosed twice daily. Oral testosterone is readily absorbed from the intestine and is rapidly metabolized by the liver. The rapid metabolism in the liver limits its clinical utility because it is difficult to maintain steady serum levels. In addition, the first pass through the liver may increase the probability of liver toxicity.

 

 

 

Intramuscular Testosterone

 

Testosterone undecanoate is an intramuscular depot preparation that is slowly absorbed into the circulation. It is administered by deep intramuscular injection every 10 to 14 weeks and thus has the advantage of infrequent dosing. Disadvantages of this preparation include the intramuscular injection route, which can be painful, and also inconsistent rates of absorption. Inconsistent absorption can lead to fluctuating testosterone levels, with associated fluctuations in clinical symptoms.

 

 

 

Topical Patch

 

Topical testosterone patches are available and can be applied to nongenital skin areas. Patches are generally dosed once per day and result in stable testosterone levels over time. A limiting factor in the use of patches is the development of skin irritation at the patch site in a high percentage of users.

 

 

 

Topical Gel

 

A number of topical testosterone gel preparations are commercially available. They range in strength from 1% to 2% and result in stable serum levels. The gel is applied daily to nongenital skin areas. Precautions need to be taken to avoid transmission of the drug to others by direct contact. Therefore it is recommended that the gel is placed on covered skin, and that handwashing is performed after application.

 

 

 

 

 

Buccal Tablets

 

Buccal tablets are commercially available and applied twice per day to the gums over the upper incisors.

 

Testosterone is absorbed through the buccal mucosa into the systemic circulation.

 

 

 

Subcutaneous Pellets

 

Another depot formulation is a subcutaneous testosterone pellet. The pellets are placed subcutaneously in the buttocks, abdominal wall, or thigh under local anesthesia. They are replaced every 3 to 6 months.

 

Limitations include the need for minor surgical procedures, and local reactions at the implantation site

 

(eg, infections, fibrosis).

 

 

 

ADVERSE EVENTS OF TESTOSTERONE THERAPY

 

There are many potential adverse effects that could occur with testosterone replacement, including, but not limited to:

 

-Prostate-related events, including development or worsening of prostate cancer, prostatic hypertrophy, increases in PSA levels, and symptoms of prostatism

 

-Cardiovascular events

 

-Adverse changes in lipid profile

 

-Erythrocytosis and increases in hematocrit

 

-Precipitation or worsening of sleep apnea

 

-Liver toxicity

 

-Suppression of spermatogenesis

 

-Acne

 

-Worsening of male pattern baldness

 

-Gynecomastia.

 

-Sleep Apnea

 

 

 

MONITORING STRATEGIES FOR PATIENTS ON TESTOSTERONE THERAPY

 

Monitoring of testosterone replacement should be performed beginning 3 to 6 months after replacement is initiated to ascertain whether serum levels are restored to the normal range, to determine whether clinical symptoms have improved, and to monitor for adverse effects.

 

 

 

Recommendations for monitoring for testosterone-related adverse events have been provided by Endocrine Society guidelines on testosterone therapy in men with androgen deficiency.  These recommendations include:

 

 

 

  1. Determine hematocrit levels at baseline, at 3 to 6 months, and then annually. If the hematocrit level is above 54%, stop therapy until the hematocrit level decreases to a safe level, evaluate the patient for hypoxia and sleep apnea, and reinitiate therapy at a reduced dose.

 

 

 

  1. Repeating bone mineral density of the lumbar spine, femoral neck, and hip after 1 to 2 years of testosterone therapy in hypogonadal men with osteoporosis or low trauma fracture.

 

 

 

  1. In men 40 years of age or older who have a baseline prostate-specific antigen (PSA) concentration greater than 0.6 ng/mL, conduct a digital examination of the prostate and PSA measurement before initiating treatment, at 3 to 6 months, and then in accordance with evidence based guidelines for prostate cancer screening, depending on the age and race of the patient.

 

 

 

  1. Obtain urologic consultation if there is:

     

    1. An increase in serum or plasma PSA concentration greater than 1.4 ng/mL within any 12-month period of testosterone treatment.

    2. A PSA velocity of more than 0.4 ng/mL per year using the PSA level after 6 months of testosterone administration as the reference. PSA velocity should be used only if there are longitudinal PSA data for more than 2 years.

    3. Detection of a prostatic abnormality on digital rectal examination.

    4. American Urological Association/International Prostate Symptom Score above 19.

 



Dates

  • Original Effective
    01-01-2016
  • Last Review
    11-06-2024
  • Next Review
    11-13-2025

Policy

 

Injectable Testosterone Products

 

Depo-Testosterone (Testosterone Cypionate)

 

I. Testosterone cypionate injection may be considered medically necessary as testosterone replacement therapy in males for the following indications when ALL of the numbered criteria in the applicable diagnosis category are met:

 


A. Primary hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchiectomy (serum testosterone not indicated), and 

2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

B. Hypogonadotropic hypogonadism

 

1. Documentation in the patient’s medical records that the drug is used for hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma or radiation, and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 
3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

  1. Treatment of delayed puberty

    1. Documentation in the patient’s medical records of limited or no signs of puberty and
    2. Testosterone is being used short term (4 to 6 months) to stimulate puberty

 

II. Initial use of testosterone cypionate can be approved for 12 months at the following FDA approved dosing:

 

  1. Primary hypogonadism and hypogonadotropic hypogonadism: 50 to 150 mg IM every week based on patient response and presence of adverse effects.

  2. Treatment of delayed puberty: 50-200 mg IM once every 2-4 weeks for a limited period. Or, 40-50 mg/m2/dose IM monthly for 6 months.

 

III. Prior to initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone as noted above

  • PSA lab  

    • In patients 40 years of age and older OR

    • In patients <40 years of age if strong family history of prostate cancer

  • CBC/Hematocrit

  • Prostate exam 

 

IV. After initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone at one week intervals when adjusting testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • PSA lab every 3 to 6 months in the first year of treatment

  • CBC/Hematocrit at one week intervals when adjusting testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity  

 

V. For renewal of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone annually

  • PSA lab annually

  • CBC/Hematocrit annually

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity

  • Prostate exam annually

 

VI. Renewal of testosterone cypionate can be approved for 12 months if the current total testosterone level is NOT greater than the testing laboratory’s upper limit of normal range, including copies of these lab results that show the reference laboratory normal range. 

 

 

VII. Use of testosterone cypionate may be considered medically necessary as an off-label use for the treatment of the following conditions: 

 

A. For the treatment of delayed puberty in males
B. Female-to-male transgender reassignment: In the management of gender identity disorder in those age 19 and older

 

VIII. All other uses of testosterone cypionate are considered investigational including, but not limited to, their use in the treatment of pediatric patients (unless for delayed puberty), sexual dysfunction in both men (e.g., erectile dysfunction) and women (e.g., decreased libido), post-menopausal symptoms, depression, and for the enhancement of athletic performance. 

 

 

Testosterone Enanthate (Delatestryl, Xyosted)

 

I. Testosterone enanthate injection may be considered medically necessary as testosterone replacement therapy in males for the following indications when ALL of the numbered criteria in the applicable diagnosis category are met:

 

A. Primary hypogonadism

1. Documentation in the patient’s medical records that the drug is used for primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchiectomy (serum testosterone not indicated), and 

2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and
3. Diagnosis of primary hypogonadism is confirmed by:

 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

B. Hypogonadotropic hypogonadism

 

1. Documentation in the patient’s medical records that the drug is used for hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma or radiation, and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw.

 

C. Treatment of delayed puberty 

1. Documentation in the patient’s medical records of limited or no signs of puberty and
2. Testosterone is being used short term (4 to 6 months) to stimulate puberty 

 

D. Metastatic breast cancer: Palliative treatment of breast cancer that is inoperable in women  

 

II. Initial use of testosterone enanthate can be approved for 12 months at the following FDA approved dosing:

 

1. Primary hypogonadism and hypogonadotropic hypogonadism:

           a. Delatestryl: 50 to 150 mg IM every week based on patient response and presence of adverse effects.

           b. Xyosted: 75 mg, administered subcutaneously once a week


2. Treatment of delayed puberty: 

a. Delatestryl: 50—200 mg IM once every 2—4 weeks 

  OR

b. Delatestryl: 40—50 mg/m2/dose IM monthly

 

3. Treatment of breast cancer: 200-400 mg IM once every 2-4 week.

 

III. Prior to initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

  • Serum testosterone as noted above

  • PSA lab  

    • In patients 40 years of age and older OR

    • In patients <40 years of age if strong family history of prostate cancer 

  • CBC/Hematocrit

  • Prostate exam  

 

IV. After initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone at one week intervals when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • PSA lab every 3 to 6 months in the first year of treatment

  • CBC/Hematocrit at one week intervals when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity  

 

V. For renewal of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone annually

  • PSA lab annually

  • CBC/Hematocrit annually

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity

  • Prostate exam annually 

 

VI. Renewal of testosterone enanthate can be approved for 12 months if the current total testosterone level is NOT greater than the testing laboratory’s upper limit of normal range, including copies of these lab results that show the reference laboratory normal range. 

 

VII. All other uses of testosterone enanthate are considered investigational including, but not limited to, their use in the treatment of pediatric patients (unless for delayed puberty), sexual dysfunction in both men (e.g., erectile dysfunction) and women (e.g., decreased libido), post-menopausal symptoms, depression, and for the enhancement of athletic performance. 

 

Testopel pellets (Implantable testosterone pellets) 

I. Testopel may be considered medically necessary as testosterone replacement therapy in males for the following indications when ALL of the numbered criteria in the applicable diagnosis category are met: 

A. Primary hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchiectomy (serum testosterone not indicated), and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

B. Hypogonadotropic hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma or radiation, and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and
3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw.

 

C. Treatment of delayed puberty 

1. Documentation in the patient’s medical records of limited or no signs of puberty and
2. Testosterone is being used short term (4 to 6 months) to stimulate puberty  

 

II. Initial use of Testopel can be approved for 12 months at the FDA approved dosing of 2-6 pellets (150 mg - 450 mg) subcutaneously every 3 to 6 months 

 

III. Prior to initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo: 

  • Serum testosterone as noted above

  • PSA lab  

    • In patients 40 years of age and older OR

    • In patients <40 years of age if strong family history of prostate cancer 

  • CBC/Hematocrit

  • Prostate exam 

 

IV. After initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo: 

  • Serum testosterone between the 4-6 week interval when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment  

  • PSA lab every 3 to 6 months in the first year of treatment

  • CBC/Hematocrit between the 4-6 week interval when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity  

 

V. For renewal of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo: 

  • Serum testosterone annually

  • PSA lab annually

  • CBC/Hematocrit annually

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity

  • Prostate exam annually 

VI. Renewal of Testopel can be approved for 12 months if the current total testosterone level is NOT greater than the testing laboratory’s upper limit of normal range, including copies of these lab results that show the reference laboratory normal range. 

 

VII. All other uses of Testopel are considered investigational including, but not limited to, their use in the treatment of sexual dysfunction in both men (e.g., erectile dysfunction) and women (e.g., decreased libido), post-menopausal symptoms, depression, and for the enhancement of athletic performance. 


Aveed (Testosterone Undecanoate) 

  1. Testosterone undecanoate injection may be considered medically necessary as testosterone replacement therapy in adult males when ALL of the numbered criteria in the applicable diagnosis category are met: 

A. Primary hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchiectomy (serum testosterone not indicated), and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

B. Hypogonadotropic hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma or radiation, and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

  1. Initial use of Testosterone undecanoate can be approved for 12 months at the FDA approved dosing of 3 ml (750 mg) injected IM, followed by 3 ml (750 mg) injected after 4 weeks, then 3 ml (750 mg) injected every 10 weeks thereafter 

 

III. Prior to initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone as noted above

  • PSA lab  

    • In patients 40 years of age and older OR

    • In patients <40 years of age if strong family history of prostate cancer 

  • CBC/Hematocrit

  • Prostate exam  

IV. After initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone between the 4-6 week interval when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment  

  • PSA lab every 3 to 6 months in the first year of treatment

  • CBC/Hematocrit between the 4-6 week interval when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity  

 

V. For renewal of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone annually

  • PSA lab annually

  • CBC/Hematocrit annually

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity

  • Prostate exam annually 

 

VI. Renewal of Testosterone undecanoate can be approved for 12 months if the current total testosterone level is NOT greater than the testing laboratory’s upper limit of normal range, including copies of these lab results that show the reference laboratory normal range.

 

VII. All other uses of Testosterone undecanoate are considered investigational including, but not limited to, their use in the treatment of pediatric patients as the safety and efficacy of Aveed in males less than 18 years old have not been established, sexual dysfunction in both men (e.g., erectile dysfunction) and women (e.g., decreased libido), post-menopausal symptoms, depression, and for the enhancement of athletic performance. 

 

Topical Testosterone Products  

 

  1. Androderm, AndroGel, Axiron, Bio-T-Gel, Fortesta, Natesto, Striant, Testim, Testosterone, or Vogelxo may be considered medically necessary when trial of preferred agents has failed (see criteria D. below) and ALL of the numbered criteria in the applicable diagnosis category are met: 

 

   A. Primary hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchiectomy (serum testosterone not indicated), and 

2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by:

 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

B. Hypogonadotropic hypogonadism 

1. Documentation in the patient’s medical records that the drug is used for hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma or radiation, and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and
3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

          C. AIDS/HIV-associated wasting syndrome: in males or females with  

1. Documentation in the patient’s medical record of unexplained involuntary weight loss (>10% baseline body weight) with obvious wasting OR body mass index <18.5 kg/m2 AND all other causes of weight loss have been ruled out, and 

2. In male patients, diagnosis of hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw. 

 

D.   Documentation in the patient’s medical record of trial and failure/intolerance/contraindication to both preferred topical androgen agents Androgel and Axiron  

 

  1. Initial use of Topical testosterone products can be approved for 12 months at the FDA approved dosing listed in the tables below. 

 

III. Prior to initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo: 

  • Serum testosterone as noted above

  • PSA lab  

    • In patients 40 years of age and older OR

    • In patients <40 years of age if strong family history of prostate cancer 

  • CBC/Hematocrit

  • Prostate exam 

 

IV. After initiation of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo:

 

  • Serum testosterone between the 4-6 week interval when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • PSA lab every 3 to 6 months in the first year of treatment

  • CBC/Hematocrit at 4 to 6 week intervals when adjusting Testosterone dose, then when lab value is within acceptable range repeat testing can be performed up to 3 times within the first year of treatment

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity  

V. For renewal of testosterone for Primary hypogonadism or Hypogonadotropic hypogonadism, it is medically appropriate for patients to undergo: 

  • Serum testosterone annually

  • PSA lab annually

  • CBC/Hematocrit annually

  • Se Estradiol as clinically indicated due to risk for VTE e.g. patients with diabetes or obesity

  • Prostate exam annually 

  1. Renewal of Topical testosterone products can be approved for 12 months if the current total testosterone level is NOT greater than the testing laboratory’s upper limit of normal range, including copies of these lab results that show the reference laboratory normal range. 
     

  2. All other uses of Topical testosterone products are considered investigational including, but not limited to, their use in the treatment of pediatric patients, their use in the treatment of sexual dysfunction in both men (e.g., erectile dysfunction) and women (e.g., decreased libido), post-menopausal symptoms, depression, and for the enhancement of athletic performance.

 

Oral/Nasal Testosterone Products

 

I. Android, Androxy, Methitest, Natesto, Testred may be considered medically necessary when ALL of the numbered criteria in the applicable diagnosis category are met:  

A. Primary hypogonadism 

1. Documentation in the patient’s medical record that the drug is used for primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchiectomy (serum testosterone not indicated), and 

2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and
3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw.

 

B. Hypogonadotropic hypogonadism 

1. Documentation in the patient’s medical record that the drug is used for hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, pituitary-hypothalamic injury from tumors, trauma or radiation, and
2. Patient has multiple symptoms of hypogonadism (see Notes below for examples), and 

3. Diagnosis of primary hypogonadism is confirmed by: 

  • at least two morning (7AM-11AM) total testosterone levels that are <300 ng/dL to include copies of results from laboratory that include the reference laboratory normal range, date, and time of blood draw.

 

C. Treatment of delayed puberty 

1. Documentation in the patient’s medical record of limited or no signs of puberty and
2. Testosterone is being used short term (4 to 6 months) to stimulate puberty

 

D. Metastatic breast cancer: Palliative treatment of breast cancer that is inoperable in women

 

  1. Initial approval of Oral testosterone products can be approved at the FDA approved dosing listed in the tables below: up to 6 months for delayed puberty and 12 months for other indications 

  2. Renewal of Oral testosterone products can be approved for 12 months if the current total testosterone level is NOT greater than the testing laboratory’s upper limit of normal range, including copies of these lab results that show the reference laboratory normal range. 

  3. All other uses of Oral testosterone products are considered investigational including, but not limited to, their use in the treatment of sexual dysfunction in both men (e.g., erectile dysfunction) and women (e.g., decreased libido), post-menopausal symptoms, depression, and for the enhancement of athletic performance. 

NOTES: 

Symptoms of hypogonadism, as classified by the Endocrine Society include:  

  1. Incomplete or delayed sexual development

  2. Decreased libido

  3. Decreased spontaneous erections

  4. Breast discomfort

  5. Gynecomastia

  6. Loss of axillar and/or pubic body hair

  7. Decreased shaving frequency

  8. Hot flashes

  9. Very small (<5 mL) or shrinking testes

  10. Infertility due to low sperm count

  11. Height loss due to vertebral fractures

  12. Low trauma fractures

  13. Low bone density.



Program Quantity LImits

 

Brand (generic)

Quantity Per Day Limit (or as noted)

Topical Androgen Products

 

Androderm® (testosterone transdermal system)

 

2 mg/day transdermal system

1 patch

4 mg/day transdermal system

1 patch

AndroGel® / Testosterone (testosterone gel)

 

1% gel, 25 mg/2.5 gm packetb

2 packets

1% gel, 50 mg/5 gm packetb

2 packets

1% gel, 75 gm pump (1.25 gm/actuation; 60 actuations/pump)

10 gm/day

(4 pumps/30 days)

1% gel, 2 x 75 gm pump (1.25 gm/actuation; 60 actuations/pump)

10 gm/day

(4 pumps/30 days)

1.62% gel, 20.25 mg/1.25 gm packet

1 packet

1.62% gel, 40.5 mg/2.5 gm packet

2 packets

1.62% gel, 75 gm pump (1.25 gm/actuation; 60 actuations/pump)

5 gm/day

(2 pumps/30 days)

Axiron® (testosterone solution)

 

30 mg/1.5 mL, 90 mL pump

120 mg/day

(2 pumps/30 days)

Bio-T-Gel™ (testosterone gel)

 

1% gel, 25 mg/2.5 gm packet

2 packets

1% gel, 50 mg/5 gm packet

2 packets

Fortesta™ / Testosterone (testosterone gel)

 

2% gel, 60 gm pump

80 mg/dayb,c

(2 pumps/30 days)

Natesto™ (testosterone nasal gel)

 

5.5 mg/actuation, 7.32 gm pump (60 actuations/pump)

0.732 gram/day (3 pumps/30 days)

Striant® (testosterone buccal system)

 

30 mg buccal system

2 systems

Testim® / Testosterone (testosterone gel)

 

1% gel, 5 gm tube

2 tubes

Vogelxo™ / Testosterone (testosterone gel)

 

1% gel, 50 mg/5 gm tube

2 tubes

(300 gm/30 days)

1% gel, 50 mg/5 gm packet

2 packets

(300 gm/30 days)

1% gel, 12.5 mg/actuation, 75 gm pump (carton of 2 pumps)

4 pumps/30 days

(300 gm/30 days)

Injectable Androgen Products

 

Aveed™ (testosterone undeconoate)

 

250 mg/mL, 3 mL vial

1 vial/28 days

Delatestryl® (testosterone enanthate)a,b

 

200 mg/mL, 5 mL multiple dose vial

1 vial/28 days

Depo-Testosterone® (testosterone cypionate)b

 

100 mg/mL, 10 mL multiple dose vial

1 vial/28 days

200 mg/mL, 1 mL vial

10 vials/28 days

200 mg/mL, 10 mL multiple dose vial

1 vial/28 days

Testone CIK (testosterone cypionate)

 

200 mg/mL, 1 ml vial

4 vials/28 days

Testopel® (testosterone pellets)

 

75 mg

6 pellets/90 days

 

                    

 

 FDA APPROVED INDICATIONS AND DOSAGE1-11,17-22,27,29,30,34,35,39-41,43,44

 

 

 

Topical Androgen Products

 

Agent

Indication

Androderm®

(testosterone transdermal system)

 

2 mg/day, 4 mg/day transdermal system

 

 

For testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

-Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.

-Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation.

AndroGel® / Testosterone

(testosterone gel)

1% gel:

25 mg/2.5 gm packetb

50 mg/5 gm packetb

75 gm pump (12.5 mg testosterone/actuation; 60 actuations/pump)

1.62% gel:

75 gm pump (20.25 mg testosterone/actuation; 60 actuations/pump)

20.25 mg/1.25gm packet

40.5 mg/2.5 gm packet

 

Axiron®  

(testosterone soln)

30 mg/1.5 mL, 90 mL pump

 

Fortesta™ / Testosterone

(testosterone gel)

2% gel

 

Natesto™

(testosterone nasal gel)

 

Striant®

(testosterone buccal system)

30 mg buccal system

 

Testim® /Testosterone

 (testosterone gel)

1% gel

For testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: 

-Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.

-Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation.

Vogelxo™/Testosterone

 (testosterone gel)

1% gel

For testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

-Primary hypogonadism

-Hypogonadotropic hypogonadism (congenital or acquired)

Bio-T-Gel™

(testosterone gel)

1% gel

 

 

 

Oral Androgen and Anabolic Products

 

 

Agent

Indication

Android®

(methyltestosterone)

10 mg capsuleb

 

Methitest®

(methyltestosterone)

10 mg tablet

 

Testred®

(methyltestosterone)

10 mg capsuleb

Males:

Androgen replacement therapy related to the following:

-Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsions, orchitis, vanishing testis syndrome; or orchidectomy

-Hypogonadotropic hypogonadism (congenital or acquired) - idiopathic gonadotropin or LHRH deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation

-Delayed puberty in males 

Females:

Palliative treatment of breast cancer in women

Androxy®

(fluoxymesterone)

10 mg tablet

Males:

-Androgen replacement therapy in male hypogonadism

-Treatment of delayed puberty in males

Females:

Inoperable breast cancer

Anadrol-50®

(oxymetholone)

50 mg tablet

Treatment of anemias caused by deficient red cell production. Acquired aplastic anemia, congenital aplastic anemia, myelofibrosis and the hypoplastic anemias due to the administration of myelotoxic drugs often respond

danazol

[Danocrine®]a

 

50 mg, 100 mg, 200 mg capsule

 

-Fibrocystic breast disease

-Angioedema prophylaxis in patients with hereditary angioedema

-Endometriosis amenable to hormone management

Oxandrin®

(oxandrolone)b

 

2.5 mg, 10 mg tablet

-Adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, severe trauma, and in some patients without definite pathophysiologic reasons  who fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis

 

 

Injectable Androgen Products

 

Agent

Indication

Delatestryl®

(testosterone enanthate)b,c

 

200 mg/mL

Males:

For replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone:

-Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy

-Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. Prior to puberty, androgen replacement therapy needed during adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty

-Delayed puberty

Females:

Palliative treatment of breast cancer that is inoperable in women

Testone CIK

(testosterone cypionate)

 

200 mg/mL

Replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone:

-Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.

-Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

Testopel®

(testosterone pellets)

 

75 mg

 

-Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchiectomy

-Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation.

-Delayed puberty in males

Aveed™

(testosterone undecanoate)

 

250 mg/mL

-Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchiectomy

-Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation

 

a – Brand drug no longer available; available as generic only.

 

b – Generic available.             

 

c – Brand drug has been discontinued by the manufacturer but may still be available.

 

 

 

FDA Labeled Contraindications

 

Topical Androgen Products

 

Agent

Contraindications

Androderm

Androgel / Testosterone

Axiron

Bio-T-Gel

Fortesta / Testosterone

Natesto

Striant

Testim / Testosterone  

Vogelxo / Testosterone

1.       Men with carcinoma of the breast or known or suspected carcinoma of the prostate

2.       Women who are or may become pregnant, or who are breastfeeding

Injectable Androgen Products

 

Agent

Contraindications

Aveed (testosterone undecanoate)

1.       Men with carcinoma of the breast or known or suspected carcinoma of the prostate

2.       Women who are or may become pregnant or are breastfeeding

3.       Hypersensitivity to Aveed or any of its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate)

Delatestryl (testosterone enanthate)

Testapel

1.       Men with carcinoma of the breast or known or suspected carcinoma of the prostate

2.       Women who are or may become pregnant

Depo-Testosterone (testosterone cypionate)

1.       Men with carcinoma of the breast or known or suspected carcinoma of the prostate

2.       Women who are or may become pregnant

3.       Patients with serious cardiac, hepatic or renal disease

Severe liver disease: Child Pugh Grade III-IV (or refractory)

Severe renal disease: Stage 4 Severe CKD (GFR=15-29 mL/min) or Stage 5 End Stage CKD (GFR <15 mL/min)

Testone CIK

1.       Known hypersensitivity to the drug

2.       Males with carcinoma of the breast

3.       Males with known or suspected carcinoma of the prostate gland

4.       Women who are or who may become pregnant

5.       Patients with serious cardiac, hepatic or renal disease

Oral Androgen Products

 

Agent

Contraindications

Android

Methitest

Testred

1.       Male patients with prostate cancer or breast cancer

2.       Pregnant women

Androxy

1.       Known or suspected prostate cancer

2.       Men with breast cancer

3.       Women who are or may become pregnant

Oral Androgen Products

 

Agent

Contraindications

Anadrol-50

1.       Carcinoma of the prostate or breast in male patients

2.       Carcinoma of the breast in females with hypercalcemia (normal calcium blood values range from 8.5 to 10.2 mg/dL and may vary slightly among different laboratories); androgenic anabolic steroids may stimulate osteolytic resorption of bones

3.       Women who are or may become pregnant

4.       Nephrosis or the nephrotic phase of nephritis

5.       Severe hepatic dysfunction: Child Pugh Grade III-IV (or refractory)

Danazol

1.       Breast-feeding

2.       Pregnancy

3.       Porphyria

4.       Vaginal bleeding

5.       Cardiac disease

6.       Severe hepatic disease: Child Pugh Grade III-IV (or refractory)

7.       Severe renal disease, including renal failure: Stage 4 Severe CKD (GFR=15-29 mL/min) or Stage 5 End Stage CKD (GFR <15 mL/min)

Oxandrin (oxandrolone)

1.       Known/suspected carcinoma of prostate or male breast

2.       Carcinoma of the breast in females with hypercalcemia (normal calcium blood values range from 8.5 to 10.2 mg/dL and may vary slightly among different laboratories); androgenic anabolic steroids may stimulate osteolytic bone resorption

3.       Pregnancy

4.       Nephrosis, the nephrotic phase of nephritis

8.       Hypercalcemia (normal calcium blood values range from 8.5 to 10.2 mg/dL and may vary slightly among different laboratories)

 

 

 



Quick Code Search

Use this feature to find out if a procedure and diagnosis code pair will be approved, denied or held for review. Simply put in the procedure code, then the diagnosis code, then click "Add Code Pair". If the codes are listed in this policy, we will help you by showing a dropdown to help you.

Procedure

Enter at least the first 3 characters of the code


Diagnosis

Enter at least the first 3 characters of the code


Codes

      
          Full Description
            SUBCUTANEOUS HORMONE PELLET IMPLANTATION (IMPLANTATION OF ESTRADIOL AND/OR TESTOSTERONE PELLETS BENEATH THE SKIN)
      
          Full Description
            Injection, testosterone cypionate, 1 mg
      
          Full Description
            Injection, testosterone enanthate, 1 mg
      
          Full Description
            Injection, testosterone undecanoate, 1 mg
      
          Full Description
            Unclassified drugs
      
          Full Description
            Testosterone pellet, 75 mg




References

2015

AndroGel 1% prescribing information. AbbVie Inc. May 2015.
2015

AndroGel 1.62% prescribing information. AbbVie Inc. May 2015.
2015

 

Axiron prescribing information. Lilly USA. May 2015.

 
2015

 

Fortesta prescribing information. Endo Pharma, Inc. May 2015.

 
2015

Striant prescribing information. Actient Pharmaceuticals LLC. May 2015
2015

Testim prescribing information. Auxilium Pharma, Inc. May 2015.
2005

Oxandrin prescribing information. Savient Pharma, Inc. June 2005. 
2004

Anadrol-50 prescribing information. Unimed Pharma, Inc. August 2004
2015

 

Delatestryl prescribing information. Endo Pharma, Inc. May 2015.

 
2011

Clinical Pharmacology. http://www.clinicalpharmacology-ip.com/default.aspx Accessed on September 28, 2011
2010

Shalender B, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2010;95:2536-2559.
2008

Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Eur j Endocrinology 2008;(159): 507-514.
2010

Basaria S, Coviello AD, Travison T, et al. Adverse events associated with testosterone administration. N Engl J Med 2010;363(2):109-122.
1998

Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998;129:18-26.
1997

Coodley GO, Coodley MK. A trial of testosterone therapy for HIV-associated weight loss. AIDS. 1997 Sep;11(11):1347-52.
2010

Bushby K, Finkel R, Birnkrant D, et al. for the DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan;9(1):77-93.
2011

American Congress of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin No. 93: diagnosis and management of vulvar skin disorders. Obstet Gynecol. 2008 May;111(5):1243-53. Accessed October 2011
2011

Endocrine Society. Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006 Oct;91(10):3697-710. Available at: http://www.endo-society.org/guidelines/final/upload/Androgens_in_Women_CG.pdf. Accessed October 2011
2014

Depo-Testosterone prescribing information. Pfizer. June 2014
2014

Testosterone Gel [Bio-T-Gel] prescribing information. Teva Pharmaceuticals USA. July 2014.
1998

Miller K, Corcoran C, Armstrong C, et al. Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab. 1998;83:2712-2725
2004

Dolan S, Wilkie S, Aliabadi N, et al. Effects of testosterone administration in human immunodeficiency virus-infected women with low weight. Arch Intern Med. 2004;164:897-904
2015

Aveed Prescribing Information. Endo Pharmaceutical Solutions Inc. May 2015.
2014

Vogelxo prescribing information. Upsher-Smith Laboratories, Inc. June 2014.
2014

Methitest Prescribing Information. Global Pharmaceuticals, Division of Impax Laboratories Inc. June 2014
2014

Testred Prescribing Information. Valeant Pharmaceuticals North America LLC. July 2014
2014

Management of Erectile Dysfunction (2005). American Urology Association. http://www.auanet.org/education/guidelines/erectile-dysfunction.cfm.  Accessed October 2014.
2015

 

Natesto Gel prescribing information. Endo Pharmaceuticals Inc. May 2015.

 
2014

Testone CIK prescribing information. Asclemed USA, Inc. December 2014
2016

Testopel Prescribing Information. Endo Pharmaceuticals, Inc, Oct 2016.
2015

Androderm prescribing information. Actavis Pharma, Inc. May 2015.

 
2015

FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use  March 2015. Accessed 6.10.2015 at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM436270.pdf

Revisions

12-01-2023

Policy reviewed at Medical Policy Committee meeting on 11/8/2023 – no changes to policy.
09-29-2023

Added age limit of 19 and older for female to male transformation
01-23-2023

Removed termed testosterone codes - C9023, J0900, J1060, J1070, J1080, J1090, J3120, J3130, J3140, J3150.
10-27-2017

The patient meets ONE of the following pretreatment (baseline) level requirements:

Two total serum testosterone level that is below the testing laboratory’s lower limit of the normal range or is less than 300 ng/dL (Levels must be drawn between 7:00 a.m. - 11:00 a.m.)  OR

Two free serum testosterone level that is below the testing laboratory’s lower limit of the normal range  (Levels must be drawn between 7:00 a.m. - 11:00 a.m.)

10-12-2017

Adding 11980 to policy, this code only applies to women.
01-31-2017

Policy revised