LCD L39086: Treatment of Males with Low Testosterone

Compliance with the provisions in this policy may be monitored and addressed through post payment data analysis and subsequent medical review audits.

Covered Indications

Treatment with testosterone is medically reasonable and necessary when prescribed for:

• Symptomatic hypogonadism (congenital or acquired) due to a disorder of the testicles, pituitary gland, or brain

• Delayed male puberty

• Gender dysphoria in a member who is able to make an informed decision to engage in hormone therapy

This A/B MAC expects that the establishment of a diagnosis of primary hypogonadism will be undertaken with at least 2 separate fasting serum testosterone levels, taken on 2 different days, drawn prior to 10 AM, and obtained from identical laboratories. A single luteinizing hormone (LH) or follicle stimulating hormone (FSH) level will also be drawn. Elevated LH/FSH confirms primary hypogonadism and the potential need for replacement hormone. If the 2 testosterone determinations are low AND the LH/FSH level(s) are also low, pituitary disease (including a serum prolactin) or chronic diseases should be assessed. ONLY secondary hypogonadism that is due to a medical disorder of the testicles, pituitary gland, or brain will be considered reasonable and necessary for treatment with testosterone. Prescribing and monitoring parameters will include:

• Prostate-specific antigen (PSA) testing must be done within the last 12 months prior to prescribing testosterone AND there will be ongoing monitoring throughout therapy.

• Hematocrit must be evaluated prior to prescribing testosterone AND there will be ongoing monitoring throughout therapy.

• Digital prostate exam must be done within the last 12 months prior to prescribing testosterone AND there will be ongoing monitoring throughout therapy.

• Where replacement is indicated, the dose of replacement therapy should be the least amount necessary to obtain a serum testosterone in the low normal range. There will be ongoing monitoring of testosterone levels throughout therapy.

• Testosterone replacement can be administered by many routes. The current preferred routes are by transdermal preparations.

• Due to United States (U.S.) Food and Drug Administration (FDA) listed warnings about possible thromboembolic disease, increase in erythrocythemia, cardiovascular risk, and stroke, the clinical records shall reflect that these issues were discussed with the patient before initiating therapy.

• Documentation of the symptoms, signs, physical examination, and required laboratory tests must be available in the chart if requested.

Limitations

The following uses of testosterone are considered NOT medically reasonable and necessary:

• Patients with hypogonadism due to aging also known as late-onset hypogonadism (LOH)

• Idiopathic hypogonadism not due to disorder of the testicles, pituitary gland, or brain

• Male menopause

• Patients with a breast cancer diagnosis

• Patients with a prostate cancer diagnosis unless previously undergone a radical prostatectomy and disease free for at least 2 years

• Patients with thrombophilia or patients who have had a myocardial infarction (MI), cardiac revascularization, or a stroke within the past 6 months

• Patients with a prostate nodule or induration, a PSA > 4 ng/mL or > 3 ng/mL in men at increased risk of prostate cancer (e.g., African American men or those who have a first-degree relative with diagnosed prostate cancer)

• Patients with a hematocrit > 48%

• Patients interested in reproduction

Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS National Coverage Determinations (NCDs), and all Medicare payment rules.

The redetermination process may be utilized for consideration of services performed outside of the reasonable and necessary requirements in this Local Coverage Determination (LCD).

Background

Testosterone is the main androgen secreted by the testes, and the testes are the major source of circulating androgens in males. Testosterone is present in the body in 3 forms: free testosterone (FT), albumin bound testosterone, and testosterone bound to serum hormone binding globulin (SHBG). Albumin bound testosterone readily dissociates to FT. SHBG tightly binds the testosterone it carries and this form is not bioavailable. Testosterone levels are controlled by interaction of the testicular-pituitary-hypothalamic axis. Primary hypogonadism is failure of the testes to produce testosterone and is accompanied by elevated LH and/or FSH . Causes of primary hypogonadism include, but are not limited to, Klinefelter syndrome (KS), cryptorchidism, some types of chemotherapy, radiation to the testes, trauma, torsion, infectious orchitis, human immunodeficiency virus (HIV) infection, anorchia syndrome, and myotonic dystrophy. Secondary hypogonadism is disruption of the testicular-pituitary-hypothalamic pathway. These patients will typically have low or normal LH and FSH levels. Causes of secondary hypogonadism include hyperprolactinemia; severe obesity; iron overload syndromes; the use of opioids, glucocorticoids, or androgen-deprivation therapy with gonadotropin-releasing hormone agonists; androgenic–anabolic steroid (AAS) withdrawal syndrome; idiopathic hypogonadotropic hypogonadism; hypothalamic or pituitary tumors or infiltrative disease; head trauma; and pituitary surgery or radiation. In other cases, the decline in gonadal function, as may occur gradually with aging, may not be a clearly pathological process. This process is known as LOH. 1 As men age, their serum concentrations of total testosterone (TT) gradually decrease. Furthermore, SHBG increases with age, thus the normal course of aging is to further decrease the total bioavailable testosterone.

Testosterone products have been approved by the FDA for replacement therapy in men with primary or secondary hypogonadism caused by specific, well-recognized medical conditions. On the basis of this replacement use, the FDA has required only that testosterone products reliably bring low serum testosterone concentrations into the normal range, defined as the concentrations seen in healthy young men. The FDA has not mandated that clinical trials show improvements in signs or symptoms of hypogonadism in order for a testosterone product to be approved. 2

Testosterone prescriptions for men have increased substantially in recent years. One study found that in 2011, 3.7% of the men 60 years or older were taking some form of testosterone. 3 Yet, as many as 25% of the 11 million men over the age of 40 who were prescribed such treatment had not undergone testosterone testing in the 12 months prior to beginning an androgen. 4 This increase in prescribing may be due to direct to consumer marketing for “low testosterone syndrome” as well as conflicting prescribing guidelines. 5