Medical Policy: 02.01.49 

Original Effective Date: June 2012 

Reviewed: February 2017 

Revised: February 2017 

 

Benefit Application:

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.

 

Description:

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.

 

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:

  • 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

 

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:

  • Evidence is lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy.
  • Customized compounded hormones pose additional risks. These preparations have variable purity and potency and lack efficacy and safety data.

European Menopause and Andropause Society

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.”

 

US Food and Drug Administration

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).

 

Prior Approval:

 

 

Not applicable

 

Policy:

Subcutaneous hormone pellets containing estrogen alone or estrogen combinations (including bioidentical hormone formulations) are considered INVESTIGATIVE for all indications including but not limited to symptoms associated with genotypical 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 geno typical 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 the following conditions:

  • Delayed puberty in genotypical males greater than 14 years old with laboratory evidence of hypogonadism (only for a period of 1 year for this condition). It is unusual for a boy with constitutional delay of puberty to require more than two courses of androgen therapy before spontaneous puberty occurs.
  • Treatment of primary or secondary hypogonadism due to disorders of the testicles, pituitary gland, or brain.

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 conditions not listed above.

 

The use of Testopel dosage is limited to a maximum number of pellets per injection, based on labeling indications.

  

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.

 

Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 11980  Subcutaneous hormone pellet implantation (implantation of estradiol and/or testosterone pellets beneath the skin)
  • J3490  Unclassified drugs
  • S0189 Testosterone pellet, 75 mg

 

Selected References:

  • North American Menopause Society. Bioidentical Hormone Therapy
  • American College of Obstetricians and Gynecologists. ACOG Committee Opinion #532, November 2005 (Reaffirmed 2012): Compounded Bioidentical Menopausal Hormone Therapy
  • The Endocrine Society. Position Statement: Bioidentical Hormones. October 2006.
  • Institute for Clinical Systems Improvement (ICSI). Health Care Guideline: Menopause and Hormone Therapy (HT): Collaborative Decision-Making and Management Ninth Edition, October 2008.
  • Gallenberg, Mary. Mayo Foundation for Medical Education and Research (MFMER). Bioidentical hormones: Are they safer?. December 15, 2011.
  • Goodman NF, Cobin RH, Ginzburg SB, Katz IA, Woode DE. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause. Endocr Pract. November/December 2011; 17(Suppl 6).
  • Position Statement: The 2012 Hormone Therapy Position Statement of the North American Menopause Society. Menopause. January 17, 2012; 19(3): pp. 257-271.
  • FDA Consumer Health Information. Bio-Identicals: Sorting Myths from Facts. April 8, 2008. Accessed 3/25/2014.
  • National Institutes of Health (NIH). Menopausal Hormone Therapy Information. Last reviewed September 15, 2011. Accessed 3/25/2014.
  • Ruiz AD, Daniels KR, Barner JC, Carson JJ, Frei CR. Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study. BMC Womens Health. 2011 Jun 8; 11: 27.
  • Conaway E. Bioidentical hormones: an evidence-based review for primary care providers. J Am Osteopath Assoc. 2011 Mar;111(3):153-64.
  • Sood R, Shuster L, Smith R, Vincent A, Jatoi A. Counseling postmenopausal women about bioidentical hormones: ten discussion points for practicing physicians. J Am Board Fam Med. 2011 Mar-Apr; 42(2):202-10.
  • U.S. Food and Drug Administration. Compounded menopausal hormone therapy questions and answers.
  • Wierman ME, Wiebke A, Basson R, et al. Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2014:99;3489-3510.
  • Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause 2004; 11:356.
  • Takahashi K, Manabe A, Okada M, et al. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas 2000; 34:169.
  • Xu L, Freeman G, Cowling BJ, Schooling CM (2013).Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials BMC Med, 11, 108.
  • Fda.gov. "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". N.p., 2015. Web. 8 May 2015.
  • Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late‐onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2008;159:507‐514.
  • Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. Feb 18 2016;374(7):611-624. PMID 26886521
  • Dimopoulou C, Ceausu I, Depypere H, et al. EMAS position statement: Testosterone replacement therapy in the aging male. Maturitas. Feb 2016;84:94-99. PMID 26614257
  • Morales A, Bebb RA, Manjoo P, et al. Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. CMAJ. Dec 8 2015;187(18):1369-1377. PMID 26504097
  • Crowley, W., Pitteloud, N., et al. (2016) Diagnosis nad treatment of delayed puberty. UptoDate, updated 2/2016

 

Policy History:

  • February 2017 - Annual Review, Policy Revised
  • February 2016 - Annual Review, Policy Revised
  • March 2015 - Annual Review, Policy Revised
  • April 2014 - Annual Review, Policy Revised
  • May 2013 - Annual Review, Policy Revised
  • June 2012 - New Policy

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.

 

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.