Clinical Policy: Reference Number: CA.CP.MP.507 Effective Date: 1/12 Last Review Date: 7/17 Coding Implications Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Implantable hormone pellets have been investigated as an alternative to hormone replacement via other routes. The biodegradable pellets are implanted underneath the skin (e.g. abdomen, buttocks) and must be reimplanted at specific intervals depending on the hormone implanted, dosage, and rate of release. Policy/Criteria I. It is the policy of Health Net of California that implantable testosterone pellets (e.g. Testopel pellets) are medically necessary for the following indications: A. As a replacement therapy for males with conditions associated with a deficiency or absence of endogenous testosterone, specifically, for either of the following situations when there has been a failure or intolerance of topical (e.g. patch, gels) and injectable testosterone: 1. Congenital or acquired hypogonadism (i.e., testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, or orchidectomy); 4 OR 2. Congenital or acquired hypogonadotrophic hypogonadism (i.e., idiopathic or gonadotrophic luteinizing hormone-releasing hormone deficiency, or pituitaryhypothalamic injury from tumors, trauma or radiation). 4 **Note: If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment would be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty. 4 II. It is the policy of Health Net of California that implantable testosterone pellets are investigational for any other circumstances than those specified above, including for routine use in older men with low testosterone levels, due to inconclusive evidence in the peer reviewed studies regarding its potential benefits. 10 III. It is the policy of Health Net of California that implantable estradiol pellets are investigational. There are no U.S. FDA approved estradiol pellets for subcutaneous implantation available in the United States. 1 Background Testosterone Deficiency Testosterone deficiency has become a growing concern in the field of men's sexual health, with more men presenting for evaluation of this condition. This has caused increased use of subcutaneous testosterone pellets for the treatment of hypogonadism since the introduction of Page 1 of 6
Testopel in 2008 by Slate Pharmaceuticals (Durham, NC, USA). The dosage of Testopel is 3-6 (75 mg) pellets every 3-6 months. Adverse events include pellet extrusion, infection and fibrosis. 8 Androgens may be used cautiously to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder. Therefore, puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be taken every 6 months to assess the effect of treatment on epiphyseal centers. 2 Endocrine Society Recommends the following: Testosterone therapy for men with unequivocally low serum testosterone levels, symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. Against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 4 ng/ml or greater than 3 ng/ml in men at high risk for prostate cancer. This would include African Americans or men with first-degree relatives with prostate cancer without further urological evaluation, hematocrit > 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate SymptomScore > 19, or uncontrolled or poorly controlled heart failure. 9 Studies have noted that subcutaneous testosterone pellets are a viable treatment option for hypogonadal men seeking a convenient and efficacious alternative modality of testosterone replacement therapy. 3 Bioidentical hormones Menopausal therapy has been provided not only by commercially available products but also by compounding. This refers to creation of an individualized preparation in response to a health care provider s prescription to create a medication tailored to the specialized needs of an individual patient. This would include compounded bioidentical hormone therapy. 5 Bioidentical hormones are plant-derived hormones that are chemically similar or structurally identical to those produced by the body. Many compounding pharmacies use the term bioidentical hormone to imply that these preparations are natural or the same as endogenous substances and, thus, are safe. The phrase bioidentical hormone therapy has been recognized by the FDA and the Endocrine Society as a marketing term and not one based on scientific evidence. 1 Page 2 of 6
Subcutaneous implantable pellets made up of estradiol, estrogen, or testosterone in combination with estrogen or estradiol have been custom compounded 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. 1 The FDA requires manufacturers of FDA-approved products that contain estrogen and progesterone to use class labeling (i.e. the black box warning indicating a drug with special problems, particularly ones that may lead to death or serious injury) reflective of the findings of the Women s Health Initiative. 12 American College of Obstetricians and Gynecologists Evidence is lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy. Conventional hormone therapy is preferred over compounded hormone therapy given the available data. 1 Endocrine Society There is no rationale for routine prescribing of unregulated, untested, and potentially harmful custom compounded bioidentical hormone therapies. 7 Coding Implications This clinical policy references Current Procedural Terminology (CPT ). CPT is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2017, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. CPT Description Codes 11980 Subcutaneous hormone pellet implantation (implantation of estradiol and/or testosterone pellets beneath the skin) 11981 Insertion, non-biodegradable drug delivery implant 80414 Chorionic gonadotropin stimulation panel; testosterone response This panel must include the following: Testosterone (84403 x 2 on 3 pooled blood samples) 80415 Chorionic gonadotropin stimulation panel; estradiol response This panel must include the following: Estradiol (82670 x 2 on 3 pooled blood samples) 82670 Estradiol 84402 Testosterone; free 84403 Testosterone; total 84410 Testosterone; bioavailable, direct measurement (eg, differential precipitation) Page 3 of 6
HCPCS Description Codes S1089 Testosterone pellet, 75 mg ICD-10-CM Diagnosis Codes that Support Coverage Criteria ICD-10-CM Description Code E29.1-E29.1 Testicular hypofunction E30.0 Delayed puberty Q53.01-Q53.22 Undescended and ectopic testicles N44.0-N44.02 Torsion of testes N45.2 Orchitis Reviews, Revisions, and Approvals Date Approval Date Policy Adopted from Health Net NMP #507 7/17 References 1. American College of Obstetricians and Gynecologists (ACOG). Compounded Bioidentical Hormones. Number 322. Reaffirmed 2014. 2. Crowley WF, Pitteloud N. Diagnosis and treatment of delayed puberty. UpToDate. March 3, 2016. 3. Guo C, Gu W, Liu M, et al. Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials. Exp Ther Med. 2016 Mar;11(3):853-863. 4. Hayes. Search & Summary. Testopel Implantable Testosterone Pellets (Endo Pharmaceuticals Inc.) for Hypogonadism. June 1, 2017. 5. Hayes. Health Technology Brief. Subcutaneous Implantation of Estradiol Pellets for Postmenopausal Disorders. December 24, 2014. Archived January 26, 2016. 6. Martin KA, Barbieri RL. Treatment of menopausal symptoms with hormone therapy. UpToDate. April 19, 2017. 7. Santoro N, Braunstein GD, Butts CL, et al. Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement. J Clin Endocrinol Metab. 2016 Apr; 101(4): 1318-43. 8. Snyder P. Testosterone treatment of male hypogonadism. UpToDate. April 12, 2017. 9. The Endocrine Society Clinical Guideline. Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes. J Clin Endocrinol Metab, June 2010, 95(6):2536 2559. 10. U.S. FDA. 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. January 31. 2014. 11. U.S.. FDA. Drugs@FDA: FDA Approved Drug Products. Testopel. 2008. 12. U.S. FDA. Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women. May 31, 2002. Updated 2016. Page 4 of 6
Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members Page 5 of 6
and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services. Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy. Note: For Medicare members, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs, LCDs, and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional information. 2016 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 6 of 6