BlueCross and BlueShield of Montana Medical Policy/Codes
Subcutaneous Hormone Implants
Chapter: Drugs - Medical Benefit
Current Effective Date: September 24, 2013
Original Effective Date: September 24, 2013
Publish Date: June 24, 2013
Description

Subcutaneous doses of testosterone can be delivered by implantation of the drug in pellet form 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 three to six month period, eliminating patient compliance with dosing schedules.  Since the drug bypasses gastrointestinal and most liver metabolism, bioavailability can be increased.

Subcutaneous testosterone pellets have recently been approved by the FDA.  These pellets are meant for replacement therapy in males when congenital or acquired endogenous androgen absence or deficiency is associated with primary or secondary hypogonadism including, but not limited, to conditions such as:

  • Testicular failure due to cryptorchidism; or
  • Bilateral torsion, orchitis; or
  • Vanishing testis syndrome; or
  • Inborn errors in testosterone biosynthesis; or
  • Bilateral orchidectomy.

Hypogonadotropic hypogonadism (secondary hypogonadism) conditions include gonadotropin-releasing hormone (GnRH) deficiency or pituitary-hypothalamic injury as a result of surgery, tumors, trauma, or radiation, and are the most common forms of hypogonadism seen in older adults.

Delayed puberty is clinically defined by the absence or incomplete development of secondary sexual characteristics bounded by an age at which 95 percent of children of that sex and culture have initiated sexual maturation.  According to the National Center for Health Statistics, the upper 95th percentile in the United States for age for boys is 14 years (i.e., an increase in testicular size being the first sign), and for girls is 12 years (breast development being the first sign).

The onset of sexual maturation (puberty) takes place when the hypothalamus gland begins to secrete a chemical signal called gonadotropin-releasing hormone.  The pituitary gland responds to this signal by releasing hormones called gonadotropins, which stimulate the growth of the sex organs (the testes in boys and the ovaries in girls).  The growing sex organs secrete the sex hormones testosterone in boys and estrogen in girls.  These hormones cause the development of secondary sex characteristics, including facial hair and muscle mass in boys, breasts in girls, and pubic and underarm hair and sexual desire (libido) in both sexes.

The treatment for delayed puberty depends on its cause.  An adolescent who is naturally late in developing needs no treatment, although if the adolescent is severely stressed by the lack of development or development is extremely delayed, some doctors may give supplemental sex hormones to begin the process sooner.  If boys show no sign of puberty or bone maturation by age 15, they may be given a 4- to 8-month course of testosterone injections.  Testosterone induces puberty, causes the development of some masculine characteristics (virilization), and does not jeopardize adult height potential.  When an underlying disorder is the cause of delayed puberty, puberty usually proceeds once the disorder has been treated.  Genetic disorders cannot be cured, although replacing hormones may help sex characteristics develop.  Surgery may be needed for adolescents with tumors.

Estrogen therapy is used primarily to treat the symptoms of menopausal and postmenopausal women (i.e., hot flashes, vaginal dryness) and to decrease the risk of osteoporosis and cardiovascular disease.  Estrogen replacement therapy has also been investigated for the prevention of menstrual migraine headaches and to prevent or reduce neural degeneration in Alzheimer’s disease and Parkinson’s disease.

Typical methods of estrogen administration include oral tablets, intramuscular injections, vaginal creams, and transdermal patches.  Estrogen pellets are sometimes combined with testosterone implants to enhance the effects of hormone replacement therapy (HRT).

NOTE: Currently there are no implantable estrogen pellets have received FDA approval.

Policy

Prior authorization is recommended for cognitive rehabilitation/therapy. To authorize, call Blue Cross and Blue Shield of Montana (BCBSMT) Customer Service at 1-800-447-7828 or fax your request to the Medical Review Department at 406-441-4624. A retrospective review will be performed if services are not prior authorized.

Medically Necessary

This policy does not address the use of a non-biodegradable drug delivery implant when utilized for purposes of contraception.

Blue Cross and Blue Shield of Montana (BCBSMT) may consider subcutaneous testosterone pellets (Testopel™) medically necessary for the following Food and Drug Administration (FDA) approved indications in males:

  • Primary Hypogonadism (congenital or acquired);
  • Hypogonadotrophic hypogonadism (congenital or acquired);

Not Medically Necessary

BCBSMT considers subcutaneous testosterone pellets (Testopel™) not medically necessary for treatment of delayed puberty not resulting from hypogonadism.

Advanced Member Notice of Financial Liability for Denied Services

When the criteria for coverage is not met, BCBSMT encourages all participating providers to have a member complete and sign an Advanced Member Notification (AMN) form, stating that BCBSMT will not cover this service, supply, device, or drug. If an AMN is signed prior to delivery of the service, participating providers can balance bill the member. If an AMN is not signed, participating providers are financially liable for the service and cannot balance bill the BCBSMT member for denied services. Services deemed Not Medically Necessary, or Investigational that are provided by an out-of-state (Montana) or Out-of-Network provider are the financial responsibility of the member regardless of a completed AMN.

Refer to the Advanced Member Notification medical policy for more information.  The AMN form is available at www.bcbsmt.com (Click on Providers and then Forms).

Investigational

BCBSMT considers subcutaneous testosterone pellets experimental, investigational and unproven for all non-FDA approved indications including, but not limited to, symptoms associated with menopause.

Subcutaneous estradiol hormone pellet implants are considered experimental, investigational and unproven including but not limited to use as hormone replacement therapy (HRT) for female menopause.

Rationale for Benefit Administration

This medical policy was developed through consideration of peer reviewed medical literature, FDA approval status, accepted standards of medical practice in Montana, Technology Evaluation Center evaluations, and the concept of medical necessity. BCBSMT reserves the right to make exceptions to policy that benefit the member when advances in technology or new medical information become available.

The purpose of medical policy is to guide coverage decisions and is not intended to influence treatment decisions. Providers are expected to make treatment decisions based on their medical judgment. Blue Cross and Blue Shield of Montana recognizes the rapidly changing nature of technological development and welcomes provider feedback on all medical policies.

When using this policy to determine whether a service, supply or device will be covered, please note that member contract language will take precedence over medical policy when there is a conflict.

Rationale

According to the American Association of Clinical Endocrinologists (AACE), men with decreased testosterone levels may experience a higher incidence of osteoporosis, sexual dysfunction, fatigue, cardiovascular disease and disturbances in mood.

Testosterone hormone replacement can be delivered by mouth, intramuscular injection, topically or subcutaneously by testosterone pellets.  Testosterone pellets have been approved by the FDA for the treatment of congenital or acquired androgen deficiency as a result of primary or secondary hypogonadism.

In a discussion on delayed puberty, the American Academy of Pediatrics (AAP) stated that most cases of delayed puberty are simply variants of normal development and not cause for alarm.  Generally speaking, the “late bloomers” usually catch up to their peers, and sometimes surpass them.

Although secondary or tertiary hormonal treatments with androgens are indicated for palliation therapy in post-menopausal women with metastatic breast cancer, subcutaneous testosterone implants are not indicated for these uses and should not be used by females due to lack of controlled evaluations.

The use of implantable estradiol pellets when used as hormone replacement therapy (HRT) for treatment for symptoms of menopause is not approved by the U.S. Food and Drug Administration (FDA).  The published peer reviewed literature does not demonstrate safety and utility in short- or long-term therapy.

There have been several randomized controlled studies and uncontrolled clinical trials evaluating implantable estradiol pellets.  These implants have been shown to produce unpredictable and fluctuating serum concentrations of estrogen.  The FDA’s Fertility and Maternal Health Drugs Advisory Committee (January 1988) unanimously agreed to terminate compassionate investigative new drug (IND) programs for estrogen pellets as a last-resort treatment of menopausal disorder.  The committee noted “the risk of bleeding and infection, the lack of information on release dates rates, difficulty in reversibility of the drug, increased feasibility of over-dosage of the drug, and increased risk of non-compliance with safety measures [such as] the addition of progestin.”

Estradiol therapy was compared with placebo and with oral and transdermal therapy.  The studies had relatively few subjects considering the large number of women candidates for HRT.  None of the studies were completely blinded.  Symptom relief was largely based on subjective and patient-reported results.  These studies could be subject to bias based on placebo effect.  Only three studies that measured the effect of estrogen implant on bone density directly compared estrogen replacement therapy implants with other methods of estrogen administration.

The North American Menopause Society (NAMS) has recently updated its 2010 recommendations regarding the use of postmenopausal hormone therapy (HT) based on evidence accumulated subsequent to the previous report.  In the decade since the first publication of the results from the Women’s Health Initiative, the society has accumulated evidence to indicate that multiple factors influence the effects of hormone therapy, including the type of estrogen used, the way the hormones are given, the age and recency of menopause of the woman taking the medication.  These factors also determine the risks associated with hormone therapy. 

The North American Menopause Society (NAMS) Position Statement published in 2012 highlighted the following findings:

  • For relief of hot flashes, combined estrogen-progestogen therapy (EPT) should be used in women with a uterus as progestogen protects the uterine lining from the cancer-promoting effects of estrogen alone.
  • The duration of treatment differs for estrogen therapy (ET) and combined EPT.  For EPT, duration is limited by the increased risk of breast cancer and breast cancer mortality associated with three to five years of use.  A more favorable risk-benefit profile was observed for ET used for a mean duration of seven years of use; thus, estrogen therapy may provide more flexibility in terms of duration of use.
  • Women with premature menopause who are otherwise appropriate candidates for hormone therapy (HT) can use HT at least until the median age of natural menopause (age 51 years). Longer duration of treatment can be considered if needed for symptom management.
  • Although ET did not increase breast cancer risk in the Women’s Health Initiative (WHI), there is a lack of safety data supporting the use of ET in breast cancer survivors, and one randomized controlled trial reported an increased likelihood of recurrence of breast cancer among ET users.
  • Both transdermal and low-dose oral estrogen have been associated with lower risks of venous thrombosis and stroke than standard doses of oral estrogen, but evidence from randomized controlled trials is not yet available.
  • ET is the most effective treatment of vaginal atrophy; low-dose, local vaginal ET is advised when only vaginal symptoms are present.

This statement acknowledges that it is impossible to generate guidelines that can be used for all women.  The decision to use hormone therapy must be made on a case-by-case basis, where the clinician takes into consideration the severity of the woman’s symptoms and their effect on her quality of life, as well as her personal risk factors for complications associated with hormone therapy (i.e., venous thrombosis, cardiovascular disease, stroke, and breast cancer).  Overall, these findings are reassuring.  While some women, specifically older postmenopausal women and those with certain risk factors, may not be good candidates for hormone therapy, estrogen remains a viable treatment option for many women with bothersome menopausal symptoms.

The U.S. Food and Drug Administration has ruled that some compounding pharmacies have  made claims about the safety and effectiveness of  bioidentical hormone therapy (BHT) unsupported by clinical trial data and considered to be false and misleading.  Pharmacies have been instructed not to use estriol without an investigational new drug authorization.  The Food and Drug Administration also states that there is no scientific basis for using saliva testing to adjust hormone levels.

NAMS recommends that BHT products include a patient package insert identical to that required for products that have government approval.  In the absence of efficacy and safety data for BHT, the generalized benefit-risk ratio data of commercially available HT products should apply equally to BHT.  For most women, government-approved HT will provide appropriate therapy without the risks of custom preparations.  Therefore, NAMS does not generally recommend compounded EPT or ET unless necessary because of allergies to ingredients contained in government-approved products.

Coding

Disclaimer for coding information on Medical Policies         

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

86.05, 185, 194.3, 227.3, 253.0, 253.1, 253.2, 253.3, 253.4,253.5,253.6, 253.7, 253.8, 253.9, 256.2, 256.31, 256.39, 256.8, 256.9, 257.0, 257.1, 257.2, 257.8, 257.9, 259.0, 259.1, 259.50, 259.51, 259.52, 346.40, 346.41, 346.42, 346.43, 597.80, 604.90, 606.1, 608.20, 608.21, 608.22, 608.23, 608.24, 608.3, 627.0, 627.1, 627.2, 627.3, 627.4, 627.8, 627.9, 733.00, 733.01, 752.51, 752.52, 758.7,  V10.47, V45.77

ICD-10 Codes
C-61, C75.1-C75.2, D35.2 - D35.3,   E22.0 – E89.3, E89.40 - E89.41, E89.5 - E89.5,    G43.D09-G43.19, G43.D01, G43.D11, N34.1 - N34.2 , N44.00, N44.01, N44.02, N44.03, N44.04,  N45.1 - N45.3, N46.11 - N46.129, N50.0, N92.4, N95.0, N95.1, N95.2, N95.8, N95.9, M81.0,   Q53.00 - Q53.9, Q55.22, Q98.0 - Q98.4,  Z85.47, Z90.721 - Z90.79   
Procedural Codes: 11980, 11981, 11982, 11983, S0189
References
  1. F-D-C- Reports Inc.  Estrogen pellets availability under compassionate INDs should be discontinued as a last resort treatment for menopausal symptoms – Food and Drug Administration advisory committee.  The Pink Sheet (1988 January 25) 50(4).
  2. Uruena, M., Pantsiotou, S., et al.  Is testosterone therapy for boys with constitutional delay of growth and puberty associated with impaired final height and suppression of the hypothalamo-pituitary-gonadal axis?  European Journal of Pediatrics (1991 May) www.springerlink.com .  (accessed – 2010 April 6).
  3. Savvas, M., Bishop, J., et al.  Type III collagen content in the skin of postmenopausal women receiving estradiol and testosterone implants.  British Journal of Obstetrics and Gynaecology. (1993 Feb) 100(2):154-6.
  4. American Medical Association, Drugs Used for Gynecologic Indications.  Drug Evaluations Subscription, AMA (1993 Spring).
  5. Holland, E.F., Leather, A.T., et al.  The effect of 25-mg percutaneous estradiol implants on the bone mass of postmenopausal women.  Obstetrics and Gynecology (1994 Jan) 83(1):43-6.
  6. Tord, N.  Maintained Bone Density at Advanced Ages After Long-Term Treatment with Low-Dose Estradiol Implants.  Journal of Obstetrics and Gynecology (1993)100:454.
  7. Sasich, L.D.  Public citizen’s health research groups statement before the pharmacy compounding advisory committee.  Public Citizen Publications (1998 October 14).
  8. Llop, V.D., Vizmanos, L.B., et al.  Testosterone treatment of delayed puberty: a longitudinal study in relation to a control group. Pediatrics (1999 October) 51(4):346-52.
  9. Lichten, E.M.  Testosterone & Estradiol Pellets, Natural Estrogen and Testosterone Pellets.  usdoctor@usdoctor.com .
  10. Testosterone therapy in boys with delayed puberty.  American Family Physician (1999 April 1) www.shortsupport.org .  (accessed – 2010 April 5).
  11. Panay, N., Versi, E., et al.  A comparison of 25 mg and 50 mg oestradiol implants in the control of climacteric symptoms following hysterectomy and bilateral-salpingo-oophorectomy.  British Journal of Gynocology (2000 August) 107(8):1012-6.
  12. Worboys, S., Kotsopoulos, D., et al.  Evidence that parenteral testosterone therapy may improve endothelium-dependent and –independent vasodilation in postmenopausal women already receiving estrogen.  Journal of Clinical Endocrinology and Metabolism (2001 January) 86(1):158-61.
  13. Kenemans, P., van Unnik, G.A., et al.  Perspectives in hormone replacement therapy.  Maturitas (2001 June 15) 38(Supplement 1) 1:S41-8.
  14. Vogelvang, T.E., Mijatovac, V., et al.  Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in healthy postmenopausal women:  two randomized, placebo-controlled studies.  American Journal of Obstetrics and Gynecology (2002 April) 186(4):729-36.
  15. American Association of Clinical Endocrinologists.  AACE Medical guidelines for clinical practice for the evaluation and treatment of Hypogonadism in adult male patients. Endocrine Practice. (2002) 8:439-56.
  16. Young, D.  FDA states policy on pharmacy compounding.  Agency follows up on Supreme Court ruling. (2002 July 1) 59(13):1222-4.
  17. Van der Mooren, M.J., and P. Kenemans.  Postmenopausal hormone replacement therapy in the light of the women’s health initiative trial.  European Journal of Obstetrics and Gynecology Reproductive Biology (2003 April 25) 107(2):123-4. 
  18. FDA/Center for Drug Evaluation and Research.  Report: Limited FDA Survey of Compounded Drug Products. (2003 January 28).
  19. Smolders, R.G., de Meer, K., et al.  Hormone replacement influences homocysteine levels in the methionine-loading test:  a randomized placebo controlled trial in postmenopausal women.  European Journal of Obstetrics and Gynecology Reproductive Biology (2004 November 10) 117(1):55-9.
  20. NAMS—The role of testosterone therapy in postmenopausal women.  Position Statement of the North American Menopause Society.  Menopause (2005 September 5) 12(5):497-511.
  21. Theodorsson, A., Hilke, S., et al.  Serum concentrations of 17beta-estradiol in ovariectomized rats during two times six weeks crossover treatment by daily injections in comparison with slow release pellets.  Scandinavian Journal of Clinical and Laboratory Investigation (2005) 65(8):699-705.
  22. FDA – Electronic Orange Book.  Approved drug products with therapeutic equivalence evaluations.  Food and Drug Administration – Center for Devices and Radiologic Health (2002 June) http://www.fda.gov (Accessed 2006 January 2).
  23. Nieschlag, E.  Testosterone treatment comes of age:  New options for hypogonadal men.  Clinical Endocrinology (Oxf) (2006) 65(3):275-81.
  24. Seftel, A.  Testosterone replacement therapy for male Hypogonadism: Part III.  Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents.  Int. Journal of Impot Res.  (2007) 19(1):2-24.
  25. Edelstein, D., Sivanandy, M., et al.  The latest options and future agents for treating male Hypogonadism.  Expert Opinion Pharmacotherpy. (2007) 8(17): 2991-3008.
  26. AACE—Medical guidelines for clinical practice for the diagnosis and treatment of menopause.  American Association of Clinical Endocrinologists (2006) http://www.aace.com                  accessed 2009 June 22). 
  27. Filho, A.M., Barbosa, I.C., et al.  Effects of subdermal implants of Estradiol and testosterone on the endometrium of postmenopausal women.  Gynecology and Endocrinology (2007) 23(9):511-7.
  28. Braustein, G.D.  Safety of testosterone treatment in postmenopausal women.  Fertil Steril (2007 July) 88(1):1-17.
  29. FDA—Bio-Identicals:  Sorting myths from facts.  U.S. Food and Drug Administration (2008 April 8). www.fda.gov (accessed – 2009 June 22).
  30. Healthy Children. Org.  American Academy of Pediatrics (AAP).  Delayed Puberty.  http://www. healthychildren.org . (2010). (accessed - 2010 April 6).
  31. Position Statement: The 2012 Hormone Therapy Position Statement of The North American Menopause Society.  Menopause: The Journal of The North American Menopause Society. (2012) 19(3):257-271.
History
June 2013  New 2013 BCBSMT medical policy.
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Subcutaneous Hormone Implants