sierra health and life GnRH Analogs Coverage Update

Coverage Criteria and Indications

Central Precocious Puberty - Initial and Continuation

Covered when ALL of the following are met for initial therapy:

CPP initial therapy: Diagnosis of central precocious puberty (idiopathic or neurogenic)

CPP age criteria: Onset of secondary sexual characteristics in females ≤8 years of age or males ≤9 years of age

CPP diagnostic confirmation: Confirmation by one of: pubertal basal luteinizing hormone (per lab reference range), pubertal LH response to a GnRH stimulation test, or bone age advanced ≥1 year beyond chronological age

CPP initial authorization: Initial authorization limited to no more than 12 months≤ 12 months

CPP continuation: For continuation: patient currently receiving therapy; documentation of positive clinical response; patient remains younger than typical puberty onset (e.g., females <11 years, males <12 years)Reauthorization ≤12 months

Reauthorization limited to 12 months; discontinue at clinician discretion when appropriate age reached

Endometriosis - Initial and Retreatment

Covered when ALL of the following are met for initial therapy (Lupron Depot or Zoladex):

Endometriosis diagnosis: Diagnosis of endometriosis or suspected endometriosis

Endometriosis prior therapy OR surgery: Either (1) contraindication, intolerance, or failure of both oral contraceptives (or depot medroxyprogesterone) AND NSAIDs, OR (2) patient has had surgical ablation to prevent recurrence

Step therapy preferred: trial of OCs and NSAIDs prior to GnRH agonist unless post-surgical

Duration limits and retreatment: Initial treatment course limited to a maximum of 6 months; for retreatment (Lupron Depot only) recurrence of symptoms must be documented, therapy must be given with concurrent add-back therapy, and combined duration of initial plus recurrent courses must not exceed 12 months total6 months initial; combined ≤12 months

Lupron retreatment requires add-back therapy and limited total duration; Zoladex retreatment beyond 6 months not recommended due to lack of data

Endometrial Thinning prior to Ablation

Covered when ALL of the following are met:

Endometrial thinning prior to ablation: Use prior to endometrial ablation for dysfunctional uterine bleeding; other causes of bleeding ruled out; patient to receive Zoladex 3.6 mg implant; course limited to a maximum of two depotsMaximum two depots

Fertility Preservation - Initial and Continuation

Covered when ALL of the following are met for pre-menopausal women:

Fertility preservation initial: Patient is pre-menopausal and is receiving a cytotoxic agent associated with primary ovarian insufficiency (e.g., cyclophosphamide, procarbazine, vinblastine, cisplatin)

Initial authorization up to 12 months; discontinue after completion of cytotoxic therapy

Fertility preservation continuation: Continued GnRH therapy allowed only while the patient continues to receive the cytotoxic agent associated with ovarian insufficiencyReauthorization ≤12 months

Therapy should be discontinued upon completion of cytotoxic treatment

Uterine Leiomyomata (Lupron Depot) - Preoperative or anemia-related use

Covered when ONE of the following is met:

Fibroid-related anemia: Treatment for uterine leiomyomata–related anemia when patient did not respond to at least one month of iron therapy and therapy is used prior to surgeryFailure of 1 month of iron therapy

Preoperative size reduction: Use prior to surgery to reduce fibroid size to facilitate surgical procedure (e.g., myomectomy, hysterectomy); authorization limited to no more than 3 monthsAuthorization ≤3 months

Gender Dysphoria (Adolescents) - Initial and Continuation

Covered when ALL of the following are met for initial therapy:

DSM diagnosis and evaluator: Diagnosis of gender dysphoria per current DSM (DSM-5) by a mental health professional with expertise in child/adolescent psychiatry

Submission of medical records required

Endocrinology involvement: Medication prescribed by or in consultation with an endocrinologist or provider experienced in gender dysphoria hormone therapy

Pubertal status: Patient has experienced pubertal development to at least Tanner stage 2 (stage 2–4)Tanner stage ≥2

Laboratory confirmation: One of: pubertal estradiol in females, pubertal testosterone in males, pubertal basal LH, or pubertal LH response to GnRH stimulation

Adjunct GnRH for Transgender Adults - Initial and Continuation

Covered when ALL of the following are met for initial therapy in transgender adults:

DSM diagnosis and prescriber: Diagnosis of gender dysphoria per current DSM by a mental health professional; medication prescribed by or in consultation with an endocrinologist or provider experienced in transgender hormone therapy

Submission of medical records required

Gonadal status and hormone therapy: Gonads intact and functional; patient is currently receiving cross-sex hormone therapy to achieve desired gender; cross-sex hormones are insufficient to inhibit natal secondary sex characteristics or gonadotropins

Prescriber letter and psychosocial supports: Letter documenting treatment goals, addressed comorbidities, active psychosocial support enrollment and continuation, and patient understanding of expected outcomes

Initial authorization ≤12 months; continuation requires LH suppression documentation within last 6 months

Indications and supporting evidence

Clinical indications and evidence summaries present in this section:

Indications described: Central precocious puberty; endometriosis (pain relief and lesion reduction); uterine leiomyomata (preoperative hematologic improvement and size reduction to facilitate vaginal procedures)

Indications are supported by randomized trials and extension/long-term studies cited in the document

Indications supported by evidence/guidelines

Covered when supported by evidence and guideline recommendations for specific indications:

Uterine leiomyomata (fibroids) - preoperative use: GnRH agonists given for 2-3 months preoperatively to reduce uterine size, improve hemoglobin, decrease blood loss, and facilitate less invasive surgeryDuration: 2-3 months preoperatively

Benefits demonstrated in randomized trials and ACOG guidance

Endometriosis - empiric suppressive therapy: After pretreatment evaluation and failure of initial therapy with oral contraceptives and NSAIDs, a 3-month course of a GnRH agonist is appropriate; consider add-back therapy to reduce bone mineral loss if continuing therapyDuration: 3 months trial

Based on Cochrane review and ACOG practice bulletin

Fertility preservation during chemotherapy: GnRH agonists may be offered to reduce likelihood of chemotherapy-induced ovarian insufficiency when established fertility preservation methods are not feasible; evidence shows reduced amenorrhea and resumption of menses but limited evidence on pregnancy outcomes

Endometriosis — Initial and ongoing therapy

Endometriosis — recommended treatment sequencing and considerations

Endometriosis GnRH agonist use: After appropriate pretreatment evaluation to exclude other causes of chronic pelvic pain and failure of initial treatment with oral contraceptives and NSAIDs, empiric therapy with a three-month course of a GnRH agonist is appropriate3 months

If pain relief supports continued therapy, add-back therapy should be considered to reduce bone mineral loss

Leiomyomata — Preoperative use

Uterine leiomyomata (fibroids) — preoperative and anemia management

Preoperative GnRH agonist use for fibroids: GnRH agonists given for 2-3 months preoperatively can improve hemoglobin and reduce uterine/myoma volume to facilitate less invasive surgery; benefits should be weighed against cost and side effects2-3 months

Lupron Depot with iron demonstrated hematologic improvement; Lupron plus norethindrone acetate add-back is not indicated for preoperative hematologic improvement per labeling

Gender dysphoria — Pubertal suppression and hormone therapy

Gender dysphoria/gender incongruence — use of GnRH analogs for adolescents and adults

Adolescent pubertal suppression: Adolescents meeting diagnostic criteria who request treatment should undergo pubertal suppression with GnRH analogs after physical changes of puberty are present; initiation typically after multidisciplinary confirmation and when adolescent demonstrates capacity for informed consentTanner stage 2 for initiation

Monitor clinical pubertal development every 3-6 months and labs every 6-12 months during sex hormone treatment

Adult hormone therapy prerequisites: For adults, confirm diagnostic criteria and evaluate medical conditions that could be exacerbated by hormone depletion prior to treatment; measure hormone levels during treatment to ensure suppression/maintenance in physiologic range for affirmed gendern/a

WPATH and Endocrine Society guidance referenced

Approved oncology and pediatric indications

FDA-indicated oncology and pediatric uses

FDA oncology indications: Products (e.g., Camcevi, Eligard, Firmagon, Leuprolide Acetate Depot, Trelstar) are indicated for palliative treatment of advanced prostate cancer and other oncology indications as per product labelingPer product labeling

Oncology indications listed in NCCN Drugs & Biologics Compendium

Central precocious puberty (CPP): Fensolvi, Lupron Depot-Ped, Supprelin LA, and Triptodur are indicated for pediatric CPP per their labelingPediatric CPP diagnosis

Refer to individual product labeling for dosing and duration

Zoladex (goserelin) retreatment beyond a single 6‑month course for benign gynecologic indications such as endometriosis is not recommended. The policy notes that there are no clinical data supporting Zoladex use for periods in excess of 6 months for benign gynecologic conditions, and therefore retreatment with Zoladex for management of endometriosis cannot be recommended.

Listing of an HCPCS or diagnosis code in this policy is provided for reference only and does not by itself indicate that the associated service is a covered benefit. Coverage and reimbursement are determined by the member‑specific benefit plan document and applicable law; inclusion of a code in this document does not guarantee payment.

A Hayes Medical Technology Directory assessment assigned a rating of D2 for pubertal suppression therapy or cross‑sex hormone therapy in adolescents, indicating insufficient evidence to demonstrate benefit and/or safety. This reflects limited published evidence and uncertainty about long‑term outcomes for adolescent hormone therapies.

When using Lupron Depot (leuprolide acetate) with add‑back therapy for endometriosis or other gynecologic indications, the FDA‑labeled limitation is that the total duration of therapy (Lupron Depot plus add‑back) should not exceed 12 months because of concerns regarding adverse effects on bone mineral density. Providers should observe this duration caution when authorizing combined therapy.

Lupron Depot monotherapy is not recommended for retreatment of endometriosis. For recurrence after an initial course, Lupron retreatment should be given with concurrent add‑back therapy and prescribers should consider the impact on bone mineral density prior to retreatment; greater than one retreatment period is not recommended.

Medical suppressive therapies—including oral contraceptives and GnRH agonists—do not improve endometriosis‑associated infertility. ACOG and systematic reviews note that while medical suppression can improve pain, these therapies are ineffective for treating infertility related to endometriosis; surgical management is more likely to affect pregnancy outcomes.

More broadly, medical suppressive therapies for endometriosis are not indicated to treat infertility. Guideline statements and systematic reviews conclude that while medical treatment can reduce pain, it does not improve clinical pregnancy rates for women with endometriosis seeking fertility.

Initial Therapy Requirements and Evidence

Initial Therapy Requirements

Initial therapy requires indication-specific documentation and meets the detailed criteria for each indication (diagnosis, prior therapy failure where required, labs, prescriber qualifications, and psychosocial supports for gender-related indications).

CPP initial: Diagnosis of CPP, age criteria met, diagnostic confirmation as specified, initial authorization ≤12 months

Endometriosis initial: Diagnosis of endometriosis or suspected endometriosis and either failure/intolerance/contraindication to OCs and NSAIDs or prior surgical ablation; initial course ≤6 months6 months

Fertility preservation initial: Pre-menopausal woman receiving a cytotoxic agent associated with ovarian insufficiency; initial authorization ≤12 months

Continuation / Reauthorization Criteria

Continuation Therapy (by indication)

Continuation/reauthorization rules vary by indication and generally require documentation of clinical response and periodic lab monitoring (e.g., LH suppression); reauthorizations commonly limited to 12 months.

CPP continuation: Patient currently receiving therapy with documentation of positive clinical response and remains younger than typical puberty onset (e.g., females <11, males <12)Authorization ≤12 months

Fertility preservation continuation: Patient continues to receive the cytotoxic agent that threatens ovarian reserve; reauthorization ≤12 months; discontinue after cytotoxic therapy completeReauthorization ≤12 months

Gender dysphoria continuation (adolescents/adults): Ongoing DSM-based diagnosis, endocrinology involvement, documentation of LH suppression within the last 6 months, continued psychosocial supports and treatment goals; reauthorization ≤12 months

Step Therapy and Prior Treatment Requirements

Requirement	Detail
Step therapy requirement
Must have tried and failed, or be intolerant/contraindicated to BOTH: (1) oral contraceptives (or depot medroxyprogesterone) AND (2) non‑steroidal anti‑inflammatory drugs (NSAIDs), unless patient has had surgical ablation to prevent recurrence.

Note	Implication for Providers/Members
Benefit plan and state mandate variability
Member-specific benefit plan language and applicable state mandates may require additional step requirements or specific coverage conditions; consult the member's benefit document for final coverage determination.

First-line conservative therapies	Trial/Clinical rationale required before GnRH agonist
Oral contraceptives (OCs) or depot medroxyprogesterone (DMPA)
Documented failure, intolerance, or contraindication to OCs or DMPA; A 3‑month empiric trial of a GnRH agonist is appropriate only after failure of OCs and NSAIDs per ACOG guidance.

First-line options or preoperative rationale	Required documentation
Oral contraceptives and NSAIDs (first‑line) or documented clinical rationale for preoperative suppression (e.g., reduce uterine volume or improve hemoglobin prior to surgery)
Clinical notes documenting prior conservative therapy attempts (OCs and NSAIDs) or, for preoperative use, documentation of surgical plan and rationale for short‑term GnRH agonist (commonly 2–3 months) to optimize operative conditions or hematologic parameters.

Billing Codes and Diagnosis Lists

Applicable HCPCS/J codesHCPCS

J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J1951	Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg.
J1952	Injection, leuprolide, camcevi, 1 mg.
J1954	Injection, leuprolide acetate for depot suspension (lutrate depot), 7.5 mg.
J3315	Injection, triptorelin pamoate, 3.75 mg.
J3316	Injection, triptorelin, extended-release, 3.75 mg.
J9155	Injection, degarelix, 1 mg.
J9202	Goserelin acetate implant, per 3.6 mg.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.
J9226	Histrelin implant (Supprelin LA), 50 mg

Diagnosis codes referencedICD-10

D25.0	Submucous leiomyoma of uterus.
D25.1	Intramural leiomyoma of uterus.
D25.2	Subserosal leiomyoma of uterus.
D25.9	Leiomyoma of uterus, unspecified.
E22.8	Other hyperfunction of pituitary gland, central precocious puberty

HCPCS/J-codes listedHCPCS

J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J1951	Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg.
J1952	Injection, leuprolide, camcevi, 1 mg.
J1954	Injection, leuprolide acetate for depot suspension (lutrate depot), 7.5 mg.
J3315	Injection, triptorelin pamoate, 3.75 mg.
J3316	Injection, triptorelin, extended-release, 3.75 mg.
J9155	Injection, degarelix, 1 mg.
J9202	Goserelin acetate implant, per 3.6 mg.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.
J9226	Histrelin implant (Supprelin LA), 50 mg

Selected ICD-10 codes (leiomyoma, CPP)ICD-10

D25.0	Submucous leiomyoma of uterus.
D25.1	Intramural leiomyoma of uterus.
D25.2	Subserosal leiomyoma of uterus.
D25.9	Leiomyoma of uterus, unspecified.
E22.8	Other hyperfunction of pituitary gland, central precocious puberty

Extensive ICD-10 endometriosis and related codesICD-10

E30.1	Precocious puberty.
F64.0	Transsexualism.
F64.1	Dual role transvestism.
F64.2	Gender identity disorder of childhood.
F64.8	Other gender identity disorders.
F64.9	Gender identity disorder, unspecified.
N80.00	Endometriosis of uterus, unspecified.
N80.01	Superficial endometriosis of the uterus.
N80.02	Deep endometriosis of the uterus.
N80.03	Adenomyosis of the uterus.

1–10 of 41

1/5

Additional ICD-10 codesICD-10

N93.8	Other specified abnormal uterine and vaginal bleeding.
Z31.62	Encounter for fertility preservation counseling.
Z31.84	Encounter for fertility preservation procedure.
Z87.890	Personal history of sex reassignment

Coding notes / disorders to specify with gender dysphoriaICD-10

255.2	Example disorder of sex development (congenital adrenogenital disorder) — coding note
259.50	Example disorder of sex development (androgen insensitivity) — coding note

Age thresholds / authorization durations — summary

Precocious puberty age cutoffsFemales: onset ≤ 8 years; Males: onset ≤ 9 years

Initial authorization duration (CPP)Initial authorization up to 12 months

Reauthorization limitsReauthorization for CPP limited to no more than 12 months; continue only while patient remains younger than typical puberty onset (e.g., <11 yrs female, <12 yrs male)

Consideration for stopping therapyConsider discontinuing therapy before ~11 years in girls and ~12 years in boys at physician discretion

Prior Authorization, Documentation, and Provider Guidance

Prior Authorization

Prior Authorization Required

Prior authorization is required for GnRH drugs billed with the HCPCS J-codes listed in this policy. Obtain PA and submit clinical documentation supporting the indication prior to rendering service.

PA required for listed GnRH drug J-codes—submit clinical documentation supporting the indication.
When listed J-codes are billed, prior authorization is implied; verify member-specific benefit and obtain authorization as needed.

Prior Authorization

PA for Preoperative or Short Second‑Line Use

Prior authorization may be reasonable for preoperative GnRH agonist use (typically 2–3 months) or for short-term second‑line therapy (commonly 3 months) to reduce fibroid size or control symptoms. Approvals should consider expected benefit versus cost and side effects and require documentation of clinical need and duration.

PA may be appropriate for 2–3 month preoperative GnRH agonist therapy to reduce uterine/leiyomyoma size.
PA may be appropriate for up to 3 months of second-line GnRH agonist therapy when first‑line options are not tolerated or failed.

Administration Setting and Benefit Type

Billing Rule

Administer IM depot injections in outpatient/clinic (office) settings

Intramuscular depot GnRH injections are administered in outpatient/clinic (office) settings consistent with trial protocols; document site of administration where relevant to claims and authorization.

Trials and practice describe IM depot administration in outpatient settings.
Ensure billing reflects medical benefit drug administration site per member benefit.

Note

Policy applies to medical benefit drugs; follow member benefit for site‑of‑care

This policy is a Medical Benefit Drug Policy and interpretation of site‑of‑care follows the member’s benefit; site‑of‑care determinations (office vs infusion center) should follow the member‑specific benefit plan and applicable mandates.

Clinical Background and Rationale

Gonadotropin‑releasing hormone (GnRH) analogs act by suppressing pituitary gonadotropin secretion to reduce ovarian and testicular sex steroid production. Therapeutic uses include pediatric treatment of central precocious puberty to delay pubertal progression, gynecologic indications such as endometriosis and uterine fibroids to reduce estrogen‑driven pathology or to provide short‑term preoperative optimization, adjunctive use for fertility preservation during cytotoxic chemotherapy, and use in gender‑affirming care to achieve pubertal suppression or to augment adult hormone regimens when indicated.

Key Definitions

Central precocious puberty — definition and diagnostic confirmation

Onset age thresholdsOnset of secondary sexual characteristics before age 8 in females or before age 9 in males

Diagnostic confirmation methodsConfirmation by pubertal basal LH (lab reference ranges), pubertal LH response to GnRH stimulation test, or advanced bone age (bone age ≥ chronological age by ≥1 year)

Clinical documentation for coverageDiagnosis (idiopathic or neurogenic) and appropriate laboratory or bone age confirmation required for initial authorization

GnRH receptor antagonist — definition

DefinitionGnRH receptor antagonist: drug that binds reversibly to pituitary GnRH receptors to reduce gonadotropin release (example: degarelix/Firmagon)

Mechanism

Policy Revision History

2025-07-01HCPCS code update and prior policy archivedLatest

Updated list of applicable HCPCS codes (quarterly edits) and revised description for J1954; Benefit Considerations section updated; prior policy version 2024D0038V archived.

OpenPayer

Gonadotropin Releasing Hormone Analogs - Medical Benefit Drug Policy