Medical Benefit Drug Policy governing coverage criteria for GnRH analog products (e.g., leuprolide, triptorelin, goserelin, histrelin, degarelix) for UnitedHealthcare Community Plan members; includes indications like central precocious puberty, endometriosis, fertility preservation, uterine fibroids, and gender dysphoria. Applies except where state-specific guidance supersedes.
Policy Summary
PayerUnitedHealthcare
PolicyGonadotropin Releasing Hormone Analogs
Policy CodePolicy CS2O25D0O38AD
Change TypeState applicability addedproduct list updated
Effective DateOct 1, 2025
Next Review Date
Key ActionSubmit prior authorization with indication-specific documentation (diagnosis, age/lab confirmation, prior therapy or counseling as required).
Added language to indicate the gender dysphoria and gender-affirming hormonal therapy criteria in this policy are not applicable for the state of Kentucky.
Revised list of applicable gonadotropin releasing hormone analog (GnRH analog) products and added Lutrate Depot (leuprolide acetate).
10/01/2025Policy updated
11+GnRH products listed
≤12 moInitial auth (typical)
≤6 moEndometriosis initial
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3+Major indications
Coverage Criteria
inv-01: Central Precocious Puberty (CPP) — Covered when ALL of the following are met
Central Precocious Puberty (CPP) — Covered when ALL of the following are met
Provider action: Diagnosis plus product required for authorization
Provider action: Prior authorization for GnRH analogs
inv-02: Endometriosis — Covered when ALL of the following are met
Endometriosis — Covered when ALL of the following are met
Provider action: Step therapy before GnRHa for endometriosis/fibroids
Provider action: Prior authorization for GnRH analogs
Provider action: Coding and Coverage
inv-03: Fertility Preservation — Covered when ALL of the following are met
Fertility Preservation — Covered when ALL of the following are met
Initial Therapy — General: Initial authorization requirements are indication-specific and generally limited in duration (commonly ≤ 12 months for CPP, gender dysphoria, and fertility preservation; endometriosis initial course limited to ≤ 6 months; leiomyomata preoperative use typically ≤ 3 months).Varies by indication (see specific criteria)
Follow product labeling for dosing; prior therapies may be required for endometriosis and fibroids
Initial therapy sequencing — Endometriosis: Before initiating GnRHa for endometriosis, document failure, intolerance, or contraindication to both an oral contraceptive or depot medroxyprogesterone and an NSAID; consider a 3-month empiric course with add-back therapy as appropriate.Failure of initial therapy required
ACOG guidance recommends empiric 3-month course after evaluation
Continuation and Reauthorization Criteria
Continuation Therapy
Continuation Therapy — requirements vary by indication; demonstration of response, age appropriateness, documentation required
Continuation — General: Continuation/reauthorization requirements vary by indication and generally require demonstration of response (clinical or laboratory), age appropriateness (e.g., still younger than pubertal milestones for CPP), and required documentation such as LH suppression within the last 6 months for gender-related indications; reauthorization periods are generally limited to ≤ 12 months.Reauth ≤ 12 months
Documentation requirements include chart notes, labs, prescriber letters as applicable
CPP Continuation: Patient currently receiving therapy with documented positive clinical response; female remains younger than ~11 years or male younger than ~12 years; reauthorization ≤ 12 months; monitor LH suppression and clinical signs.Reauth ≤ 12 months
Consider discontinuing at physician-determined appropriate age
Step Therapy Requirements
Required prior therapy
Details / documentation
Oral contraceptives or depot medroxyprogesterone (e.g., Depo‑Provera)
Documentation of contraindication, intolerance, or failure of oral contraceptives or depot medroxyprogesterone prior to GnRH agonist initiation
Non‑steroidal anti‑inflammatory drugs (NSAIDs)
Documentation of contraindication, intolerance, or failure of NSAID therapy prior to GnRH agonist initiation
Surgical ablation to prevent recurrence
Record of prior surgical ablation when used to prevent endometriosis recurrence
Initial treatment course limit
Initial GnRH agonist course for endometriosis limited to a maximum of 6 months per product labeling and policy
Requirement
Documentation needed
Fertility preservation counseling prior to GnRH agonist use
Documentation that patient received counseling about fertility risks of planned chemotherapy and available fertility preservation options (oocyte, embryo, ovarian tissue cryopreservation)
Chemotherapy regimen risk assessment
Documentation of planned chemotherapy agents/regimen with intermediate or high risk of ovarian toxicity (e.g., alkylating agents) to justify GnRHa for ovarian protection
Feasibility or declination of standard preservation methods
Record that standard fertility preservation methods were infeasible or declined by the patient when GnRHa is considered as adjunctive ovarian protection
Intent and timing relative to chemotherapy
Plan documenting timing of GnRHa administration relative to chemotherapy and intent for ovarian suppression during cytotoxic therapy
First‑line therapy
Failure / trial requirement
Oral contraceptives (OCs) or depot medroxyprogesterone (DMPA)
Documented trial with lack of adequate symptom control, intolerance, or contraindication before initiating GnRHa
Non‑steroidal anti‑inflammatory drugs (NSAIDs)
Documented trial with lack of adequate symptom control, intolerance, or contraindication before initiating GnRHa
Empiric 3‑month medical management option
ACOG supports an empiric 3‑month course of a GnRH agonist after failure of OCs and NSAIDs; policy requires documentation of prior first‑line therapy failure per sequencing rules
Step therapy item
Notes / policy context
No additional explicit step therapy requirements listed in excerpt
Policy revision notes include product list updates (added Lutrate Depot) and a state applicability change for Kentucky; refer to full policy for any product‑specific or formulary step edits
Coding
Provider Actions & Documentation
Prior Authorization
Prior authorization required for GnRH analogs
Prior authorization is required for GnRH analogs and must include documentation that meets the specific indication criteria (for example, diagnosis, age limits, laboratory confirmation, and prior therapy failure) associated with the requested HCPCS/J-code.
Include the requested HCPCS/J-code from the policy list (e.g., J1950, J9217).
Provide indication-specific documentation (diagnosis, age, labs, prior treatment history).
Prior Authorization
Include diagnosis code and drug product on authorization
Authorization requests must reference an applicable ICD-10 diagnosis from the policy and identify the specific GnRH product being requested (for example, N80.* for endometriosis or D25.* for leiomyoma and the leuprolide depot product).
List one of the policy's ICD-10 diagnosis codes on the request/claim.
Specify the exact product (e.g., Lupron Depot, Lutrate Depot, Fensolvi) being requested.
Site of Care & Administration
Billing Rule
Administration — clinic/office depot injections per labeling
Administer GnRH analogs per product labeling as intramuscular or subcutaneous depot injections in clinic or office settings; follow the specific administration instructions in the prescribing information.
Follow product-specific route and dosing (IM or SC depot) per prescribing information.
Administer in outpatient clinic or office consistent with trial administration.
Monthly depot injections (examples in trials include leuprolide acetate 3.75 mg every 4 weeks) are typically provided in outpatient or office settings; document administration site and dosing on claims.
Document dose and administration date (e.g., 3.75 mg IM every 4 weeks) on the claim.
Background
Gonadotropin-releasing hormone (GnRH) analogs include both agonists and antagonists that suppress gonadotropin secretion through pituitary receptor effects. Agonists such as leuprolide, goserelin, triptorelin, and histrelin act as synthetic peptide analogs that—when administered continuously—downregulate GnRH receptors and reduce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, thereby suppressing ovarian and testicular steroid production. Antagonists (for example, degarelix) bind reversibly to pituitary GnRH receptors and promptly reduce gonadotropin release without an initial stimulatory flare. Clinically, these mechanisms are the basis for use in conditions such as central precocious puberty, endometriosis, uterine fibroids, fertility preservation during gonadotoxic chemotherapy, and as adjuncts to gender-affirming hormone therapy.
Definitions
Central Precocious Puberty definition and diagnostic thresholds
CPP clinical definitionOnset of secondary sexual characteristics before age 8 in females or before age 9 in males with confirmation by pubertal basal LH, advanced bone age, or pubertal LH response to GnRH stimulation
Diagnostic confirmationsPubertal basal luteinizing hormone level, bone age advanced ≥1 year, or pubertal LH response to GnRH stimulation test
Typical initial authorizationInitial authorization will be for no more than 12 months
Initial therapy — CPP product dosing: Initiate CPP therapy per pediatric product labeling (examples: Lupron Depot-Ped, Fensolvi, Supprelin LA, Triptodur); initial authorization generally limited to 12 months and dosing follows FDA-approved pediatric formulations.Initial auth ≤ 12 months
Trials used depot leuprolide formulations with demonstrated LH suppression (see CPP criteria)
Initial therapy — dosing and trial-based evidence
Initial therapy — dosing and trial-based evidence
CPP initial therapy evidence: Pediatric trials of leuprolide depot (3-month formulations) demonstrated sustained LH suppression (peak-stimulated LH < 4 mIU/mL) and regression or no progression of secondary sexual characteristics over 36 months in extension studies; dosing and administration per product labeling used in trials.Peak-stimulated LH < 4 mIU/mL
No dose adjustments were permitted in the cited extension trial; monitor for injection-site pain
Endometriosis initial therapy evidence: Randomized trials of depot leuprolide demonstrated clinically and statistically significant reductions in pelvic pain versus placebo over 12 weeks; leuprolide suppresses menses and estradiol to menopausal levels in these trials.
Evidence supports empiric use for painful endometriosis when prior therapies fail
Initial therapy sequencing
Initial therapy sequencing — sequence considerations before initiating GnRHa
Sequence before GnRHa for endometriosis/fibroids: Document failure, intolerance, or contraindication to first-line medical therapies (oral contraceptives, depot progestogens, NSAIDs) prior to initiating GnRHa for endometriosis or consider short preoperative medical management for fibroids; document prior iron therapy for anemia indication in fibroids.Failure/intolerance of first-line therapies
ACOG practice bulletin and trial eligibility used similar sequencing
Fertility preservation sequencing: Prior to using GnRHa for ovarian protection, counsel regarding and consider proven fertility preservation methods (oocyte/embryo/ovarian tissue cryopreservation); when these methods are infeasible or declined, GnRHa may be considered alongside chemotherapy with documented plan and timing.
ASCO and NCCN guidance referenced
Initial therapy
Initial therapy — follow FDA-approved indications and product labeling
Initiation per labeling: Initiate GnRH analog therapy according to FDA-approved indications and product-specific dosing and administration guidance; FDA indications and labeling inform duration limits and add-back requirements (e.g., Lupron Depot add-back and 12-month total duration limit).Follow prescribing information
FDA labeling provides limitations and recommended concomitant therapies
Gender-related Continuation: For adolescents and adults receiving GnRHa for gender dysphoria or adjunctive therapy, require documentation (within last 6 months) of LH suppression or appropriate laboratory monitoring, continued endocrinology involvement, and ongoing psychosocial support; reauthorization ≤ 12 months.LH suppression documented within 6 months; Reauth ≤ 12 months
Continuation should document ongoing benefit and monitoring per guidelines
Continuation therapy
Continuation therapy — maintenance therapy considerations reflected in trials
CPP maintenance evidence: Extension trials of depot leuprolide maintained suppression over 36 months without dose adjustments and required ongoing monitoring of LH suppression and clinical signs to continue therapy.
Trial data support maintenance dosing schedules; monitor for adverse events
Endometriosis continuation limit: Do not exceed total duration of Lupron Depot plus add-back therapy beyond 12 months due to concerns about bone mineral density per prescribing information.<= 12 months total
Prescribing information limitation
Continuation therapy
Continuation therapy — reference to product labeling and duration limits
Label-based continuation rules: Continuation and total duration of therapy should follow product-specific labeling and limitations (for example, Lupron Depot add-back total duration ≤ 12 months); reauthorization should document adherence to labeled limitations and monitoring requirements.Follow product labeling
FDA prescribing information governs duration and add-back requirements
Prior Authorization
PA requirements for gender dysphoria (pubertal suppression/adjunct therapy)
For gender dysphoria indications, prior authorization must include confirmation of DSM‑based diagnosis by a qualified mental health professional, Tanner stage documentation for adolescents, a recommending mental health/provider letter, laboratory confirmation of pubertal hormones or LH response, and documentation of informed consent including fertility counseling.
DSM diagnosis by a mental health professional experienced in child/adolescent psychiatry (adolescents) or qualified mental health professional (adults).
Tanner stage ≥2 for pubertal suppression and relevant laboratory tests (testosterone, estradiol, basal LH, or GnRH stimulation test).
Prescriber letter documenting psychosocial supports, informed consent/assent, and fertility preservation discussion.
Prior Authorization
PA documentation for fertility preservation with GnRHa
Prior authorization for use of GnRH agonists as adjunctive ovarian protection during cytotoxic chemotherapy must document the patient is premenopausal, identify the planned chemotherapy regimen (agents with known gonadotoxic risk), state that standard fertility preservation methods are not feasible or were declined, and include a plan for timing of GnRHa relative to chemotherapy.
Document patient age (premenopausal) and the specific chemotherapy agents/regimen.
Document counseling about fertility preservation and reasons proven methods (oocyte/embryo/ovarian tissue cryopreservation) are infeasible or declined.
Provide the treatment plan including timing of GnRHa dosing relative to chemotherapy.
Prior Authorization
PA likely required for listed medical-benefit GnRH products
Prior authorization is likely required when billing medical-benefit GnRH products (examples listed in the policy include Camcevi, Eligard, Firmagon, Lupron Depot, Zoladex, Lutrate Depot); include product-specific supporting documentation per indication.
Confirm the product is one of the policy-listed GnRH agents.
Submit indication-specific documentation (see CPP, endometriosis, fertility preservation, GD criteria).
Step Therapy
Required prior treatments for endometriosis before GnRHa
For endometriosis, authorization must show contraindication, intolerance, or failure of both (1) oral contraceptives or depot medroxyprogesterone and (2) NSAIDs before initiating GnRH analog therapy.
Document trials of oral contraceptives or depot medroxyprogesterone and NSAIDs and the clinical reason for failure/intolerance/contraindication.
For retreatment with Lupron Depot, document concurrent add-back therapy and duration limits.
Prior Authorization
Evidence of gonadotoxic chemotherapy required for fertility-preservation PA
When GnRHa is requested for fertility preservation or menstrual suppression during chemotherapy, prior authorization should include evidence of an expected gonadotoxic chemotherapy regimen and documentation of counseling about fertility preservation options.
Provide the anticipated chemotherapy agents/regimen with known gonadotoxic risk.
Include documentation that fertility preservation counseling took place.
Step Therapy
Step therapy — trial of medical management before GnRHa
Initial therapy for endometriosis or fibroids should follow a stepwise medical management approach; documentation of failure of first-line medical therapy (OCs, NSAIDs, other options) is required prior to GnRHa in these indications.
Document prior use and failure/intolerance of oral contraceptives and NSAIDs for endometriosis.
For fibroids, document rationale for preoperative medical management and failure of conservative options when applicable.
Note
Documentation Required
Required clinical documentation for gender dysphoria
For gender dysphoria indications, submit medical records including chart notes, laboratory values, and prescriber letters that document DSM diagnosis, Tanner stage (if adolescent), hormone levels or LH suppression, and evidence of psychosocial support involvement.
Chart notes documenting DSM-5 diagnosis by qualified mental health professional.
Laboratory results (testosterone, estradiol, basal LH, or GnRH stimulation testing).
Prescriber letter documenting psychosocial supports and treatment goals.
Documentation Required
Supporting documentation for fibroid (preoperative/anemia) indication
For preoperative use of leuprolide in uterine leiomyomata, include baseline hemoglobin and hematocrit values and imaging documentation of uterine/fibroid volume; trials used thresholds such as hemoglobin ≤ 10.2 g/dL or hematocrit ≤ 30% to support benefit.
Provide pre-treatment hemoglobin and hematocrit (trial threshold: Hgb ≤ 10.2 g/dL or Hct ≤ 30%).
Include imaging or measurements documenting uterine and myoma volume if available.
Documentation Required
Formal mental health diagnosis required for GD treatment PA
Authorization for pubertal suppression or gender-affirming treatment must include a formal diagnosis of gender dysphoria/gender incongruence by a qualified mental health professional and documentation of persistence and readiness for endocrine treatment.
DSM-5–based diagnosis by a mental health professional experienced in gender dysphoria.
Evidence of persistence of gender incongruence and documentation of capacity for informed consent/assent.
Documentation Required
DSM-5 diagnosis, duration, and hormone-therapy documentation for GD
Document the clinical diagnosis of gender dysphoria according to DSM-5 criteria (symptom duration ≥ 6 months and manifestation criteria) and, when relevant for surgical planning, evidence of at least 12 months of gender-affirming hormone therapy or documentation that hormone therapy is not desired or contraindicated.
DSM-5 criteria documentation including duration (≥ 6 months) and symptom manifestations.
When required for surgery, document ≥ 12 months of gender-affirming hormone therapy or rationale if not applicable.
Billing Rule
Use correct HCPCS/J-code; listing does not guarantee payment
Inclusion of the correct HCPCS/J-code on claims is required for processing; listing of a code in this policy does not guarantee payment and absence of an appropriate code or unsupported service coding may affect coverage determination.
Use one of the policy-listed HCPCS/J-codes when submitting authorization/claims (e.g., J1950, J9217, J9226).
Verify that the billed code matches the service and product requested.
Denial Risk
Ensure diagnosis code matches a listed policy diagnosis
Claims lacking a listed applicable diagnosis code from the policy (for example, N80.* for endometriosis, D25.* for leiomyoma, E30.1/E22.8 for precocious puberty, or F64.* for gender dysphoria) may be at risk for denial.
Ensure the claim includes one of the policy-listed ICD-10 diagnosis codes that corresponds to the requested indication.
If coding a disorder of sex development, code both the disorder and gender dysphoria as indicated.
Denial Risk
Fertility preservation — document consideration of proven methods
When GnRHa is proposed for fertility preservation, prior authorization and claims should include documentation that proven fertility preservation methods (oocyte, embryo, or ovarian tissue cryopreservation) were considered and found infeasible or declined; absence of this documentation may lead to denial.
Document counseling about standard fertility preservation options and reasons they are not feasible or were declined.
Include evidence of the planned chemotherapy regimen and rationale for GnRHa adjunct use.
Note
Kentucky — gender dysphoria criteria not applicable
Gender dysphoria and gender-affirming hormonal therapy criteria in this policy are not applicable in Kentucky; do not rely on this policy language for coverage decisions for Kentucky members without checking state-specific guidance.
Use appropriate HCPCS/J-code corresponding to the product and dose administered.
Note
Follow product labeling and site-of-care best practices
Follow product labeling and site‑of‑care best practices for administration and implant products; the policy does not specify additional site‑of‑care restrictions but providers should follow administration instructions in prescribing information.
Adhere to manufacturer instructions for implants and depot formulations.
No additional site-of-care limitation is specified in this policy excerpt.
Adult adjunct requirementGonads intact and functional; inability of cross-sex hormones alone to inhibit natal secondary sex characteristics when used as adjunct
GnRH agonist — definition and examples
DefinitionGnRH agonists are synthetic peptide analogs of GnRH (examples: leuprolide, goserelin, triptorelin, histrelin) that, when given continuously, downregulate GnRH receptors and suppress gonadotropin secretion
Clinical effectChronic administration reduces LH/FSH release and suppresses ovarian/testicular steroid production
GnRH antagonist — definition and examples
DefinitionGnRH antagonist (example: degarelix) binds reversibly to pituitary GnRH receptors and immediately reduces gonadotropin release without an initial stimulatory phase
Example agentFirmagon (degarelix)
Clinical distinctionAntagonists avoid initial hormone flare seen with agonist initiation
DefinitionGnRH-a (GnRH agonist) refers to synthetic gonadotropin-releasing hormone analogs, including depot formulations (e.g., depot leuprolide acetate) administered to suppress ovarian or testicular function
Depot formulation examplesLeuprolide acetate depot products (e.g., Lupron Depot), 1‑month and 3‑month depot preparations referenced in trials
Therapeutic useUsed to induce temporary medical suppression of gonadal steroid production for indications such as CPP, endometriosis, fibroids, and fertility preservation
Gender dysphoria (adolescents) — DSM-5 snippet
Adolescent DSM-5 snippetMarked incongruence between experienced/expressed gender and assigned gender lasting at least 6 months with associated distress or impairment
ManifestationsExamples include strong desire for the primary/secondary sex characteristics of the other gender, strong preferences for cross-gender roles and activities, and dislike of one’s sexual anatomy
Clinical impactCondition is associated with clinically significant distress or impairment in social, school, or other important areas of functioning
DSM-5 criteria summaryMarked incongruence between experienced/expressed gender and assigned gender or primary/secondary sex characteristics, present for at least 6 months with clinically significant distress or impairment
Adult/adolescent common featuresDesire for removal of primary/secondary sex characteristics, desire to be of other gender, and strong conviction of typical feelings and reactions of other gender
Coding noteWhen present, also code any disorder of sex development if applicable (e.g., congenital adrenal hyperplasia, androgen insensitivity)
Post-transition definition
Post-transition definitionLiving full-time in the desired gender and has undergone or is preparing for at least one cross-sex medical procedure or regular cross-sex hormone treatment
Examples of cross-sex proceduresMay include penectomy, vaginoplasty, mastectomy, phalloplasty, or regular cross-sex hormone therapy
Documentation useUsed to support transition status in clinical records and procedural eligibility assessments