Medical Policy: 02.01.49
Original Effective Date: June 2012
Reviewed: February 2021
Revised: February 2021
This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Menopause is a normal, natural sign of aging. There is a long list of physical changes that geno typical women may experience around menopause, which may be related to menopause or aging- or both. Some of these symptoms include hot flashes, sleep disturbances, night sweats and vaginal dryness and decreased sex drive.
Several prescription drugs are available to help relieve menopause-related symptoms. Hormone therapy has been shown to be the most effective intervention for management of these symptoms.
This policy is specifically related to subcutaneously implanted hormone pellets. The individual pellets are smaller than a grain of rice and are implanted into the subcutaneous tissue, where they provide a slow continuous release of hormone into the bloodstream. The pellets are implanted in the lower abdomen or buttocks. The procedure is done in a physician's office with the use of a local anesthetic and a small incision for insertion. The release of the drug continues over a 3-6 month period. FDA approval for the use of testosterone subcutaneous implantation is currently only for males. Additionally, the role of testosterone therapy in men with sexual dysfunction with low, borderline normal, and normal testosterone levels is not well defined.
Subcutaneous implantable pellets made up of estradiol, estrogen, or testosterone in combination with estrogen or estradiol has been custom compounded by pharmacists according to physician specifications. However, none of these are FDA approved for U.S. distribution and their safety and efficacy has not been adequately demonstrated in well-designed clinical trials.
There is a long list of potential adverse effects that could occur with testosterone replacement, as follows:
Persistently low testosterone levels refer to serum levels below the lower limit of normal on at least 2 occasions when measured in the early morning (»8:00 A.M.). The threshold lower limit for serum testosterone levels is not standardized. The Endocrine Society has recommended a lower limit for normal levels of 300 ng/dL for total testosterone and 9.0 ng/dL for free testosterone. Joint guidelines from several European and American specialty societies have recommended that replacement therapy be considered at serum total testosterone levels less than 350 ng/dL.
More specific symptoms of hypogonadism, as classified by the Endocrine Society, include the following1,):
European and American specialty societies recommend that replacement testosterone therapy be considered at serum total testosterone levels less than 300-350 ng/dL. The testing methods for testosterone vary, and the level of deficiency is not standard with providers.
The following principles should guide testosterone therapy:
The American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice and the Practice Committee of the American Society for Reproductive Medicine make the following conclusions and recommendations:
The AUA recommends that testosterone therapy is not indicated for the treatment of erectile dysfunction in patients with a normal serum testosterone level. Also, the role of testosterone therapy in men with sexual dysfunction with low, borderline normal, and normal testosterone levels is not well defined.
A position statement was published by the European Menopause and Andropause Society (EMAS) in 2016 on testosterone replacement therapy in the aging male made the following relevant recommendations: “Risks and benefits of TRT should be very carefully weighed up in testosterone deficient aging men with or without pre-existing heart disease, until evidence from large randomized prospective trials regarding cardiovascular safety of TRT becomes available.”
In 2018, the Endocrine Society updated its guidelines for testosterone therapy with the following conclusions:
Testosterone is FDA-approved as replacement therapy only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain that cause hypogonadism (FDA, 2015). However, the FDA has become aware that testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging. The benefits and safety of this use have not been established (FDA, 2015).
The FDA advises that health care professionals should prescribe testosterone therapy only for men with low testosterone levels caused by certain medical conditions and confirmed by laboratory tests (FDA, 2015). Health care professionals should make patients aware of the possible increased cardiovascular risk when deciding whether to start or continue a patient on testosterone therapy. Patients using testosterone should seek medical attention immediately if symptoms of a heart attack or stroke are present, such as chest pain, shortness of breath or trouble breathing, weakness in one part or one side of the body, or slurred speech. The FDA is requiring that the manufacturers of all approved prescription testosterone products change their labeling to clarify the approved uses of these medications (FDA, 2015).
The FDA is also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone. The FDA cautions that prescription testosterone products are approved only for men who have low testosterone levels caused by certain medical conditions. The benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man’s symptoms seem related to low testosterone (FDA, 2015).
Based on the available evidence from studies and expert input from an FDA Advisory Committee meeting, the FDA has concluded that there is a possible increased cardiovascular risk associated with testosterone use (FDA, 2015).
Some hormones for menopause are called “bio-identical” by their sellers because they claim they are identical to hormones made in a woman’s body. These hormones are made from plant estrogens and are said to be a natural form of Menopause Hormone Therapy with fewer risks. These products have not been approved by FDA.
Many “bio-identical” hormones are compounded in pharmacies. Compounding is generally a practice in which ingredients are combined, mixed, or altered to create a medication tailored to the needs of an individual patient.
Although the clinical observations described above suggest that the decline in testosterone with age may have several adverse consequences, the impact of testosterone replacement in older men with low serum testosterone and hypogonadal symptoms has been unclear. Trials have been limited by small sample size, inclusion of asymptomatic men with low-normal testosterone levels, and variable testosterone regimens. A committee of the Institute of Medicine of the National Academy of Sciences Committee reviewed available studies and concluded in 2002 that no beneficial effects of administering testosterone have been well established. The US Food and Drug Administration (FDA) reviewed the evidence and reached the same conclusion in 2015, and they directed manufacturers of testosterone products to state in their labels that these products are approved only for men with low testosterone due to known causes.
Subcutaneous hormone pellets containing estrogen alone or estrogen combinations (including Estradiol and bioidentical hormone formulations) are considered investigational for all indications including, but not limited to, symptoms associated with female menopause, because there are no FDA-approved formulations of these products.
The use of testosterone pellets, specifically Testopel, in genotypical women is considered investigational as the FDA indications are only for the use in genotypical males. The literature does not support off-label use for menopausal symptoms or decreased libido.
Testopel use in genotypical males is considered medically necessary for men without a history of prostate cancer, in the office setting, in the following conditions:
The use of subcutaneous hormone pellets in genotypical men, outside of the use of Testopel, is considered investigational. Testopel is the only FDA approved subcutaneous pellet approved at this time.
Safety and efficacy of Testopel in genotypical men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. The use of Testopel is considered investigational for genotypical male menopause, hypogonadism due to aging, erectile dysfunction, and for all other age-related conditions not listed above.
Other uses of implantable testosterone pellets 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.
The use of Testopel dosage is limited to a maximum number of pellets per injection, based on labeling indications. Safety is of concern for pellet implantation beyond the labeling indications. The dosage guideline for the testosterone pellets for replacement therapy in androgen-deficient males, per product label, is 150mg to 450mg subcutaneously every 3 to 6 months. The dosing interval is individualized because some patients will require redosing as early as every 3 months while others may not require redosing for up to 6 months.
At the current time, there is lack of medical and scientific evidence to support the efficacy and safety of customized subcutaneous hormone replacement regimes utilizing bioidentical hormones. Well-designed and controlled clinical trials are needed to provide evidence of improved net health outcomes with compounded bioidentical hormone replacement, subcutaneously inserted over conventional hormone therapies. The FDA issued a safety communication in 2015, warning against the use of testosterone products for low testosterone due to aging.
Androgen: A general term for any male sex hormone.
Endogenous: Developing or originating within the body.
Hypogonadism: An inadequate gonadal function, marked by deficiencies in the secretion of gonadal hormones and spermatogenesis.
Orchiectomy: Excision of one or both testes, done when a testis is seriously injured or diseased (as in testicular cancer).
Subcutaneous: Under the skin.
To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
*CPT® is a registered trademark of the American Medical Association.