CurrentHealth NetPolicy CP.PHAR.174

Nafarelin Acetate (Synarel)

Clinical policy defining medical necessity criteria, initial and continued approval criteria, dosing limits, covered indications (central precocious puberty, endometriosis, and select off-label use for gender dysphoria/gender transition), contraindications, and duration limits for Synarel for Centene-affiliated health plans (HIM/ICHRA, Medicaid).

Policy Summary

PayerHealth Net

PolicyNafarelin Acetate (Synarel)

Policy CodePolicy CP.PHAR.174

Change TypeMultiple revisions and additions (including off-label gender dysphoria criteria)

Effective DateOct 1, 2016

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

4Q 2022 annual review clarified endometriosis duration of therapy should not exceed 12 months and modified continued approval duration wording; template changes applied.

Added off-label use criteria for gender dysphoria or gender transition.

2Q 2024 annual review reduced total treatment duration for endometriosis from 12 to 6 months per prescribing information; clarified bone age requirement and corrected basal LH units to mIU/mL.

For gender dysphoria/gender transition, added requirement for provider attestation of understanding state regulations and that care is coverable under State regulations; Appendix D updated to reference Movement Advancement Project.

2Q 2025 annual review added example of positive response for gender dysphoria continuation: member continues to meet individual goals of therapy.

As result of Marketplace Integrity and Affordability rule, added requirement for HIM that requests be for members in states where gender dysphoria and gender transition treatment is covered (listed states excluded).

2Q 2026 annual review: added ICHRA line of business; references reviewed and updated.

4Q 2022 and later annual reviews: multiple template and reference updates; corrections to units and clarification of bone age phrasing.

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Coverage Summary

Scope: This clinical policy defines medical necessity criteria, initial and continued approval requirements, dosing limits, covered indications (central precocious puberty [CPP], endometriosis, and select off-label use for gender dysphoria/gender transition), contraindications, and duration limits for Synarel (nafarelin acetate) for Centene-affiliated health plans (HIM/ICHRA, Medicaid). Coverage stance: Synarel is covered with criteria when the indication-specific initial and continued therapy criteria in this policy are met, including the CPP, endometriosis (time-limited), and specified off-label use for gender dysphoria/gender transition; the policy aligns with Centene clinical coverage processes and references (prescribing information and professional guidelines) and notes state Medicaid precedence where applicable.

Key thresholds and limits

Max therapy duration (endometriosis)6 months total therapy

Max dose (CPP)1,800 micrograms per day

Max dose (Endometriosis)800 micrograms per day

Basal LH threshold> 0.2 - 0.3 mIU/mL (assay-dependent)

Leuprolide‑stimulated LH threshold> 3.3 - 5 IU/L (assay-dependent)

Bone age differenceBone age − chronological age > 1 year

CPP age limits (initial/continued) - femaleInitial: 2 to ≤ 11 years; Age at onset of secondary sex characteristics: < 8 years; Continued: ≤ 11 years

CPP age limits (initial/continued) - maleInitial: 2 to ≤ 12 years; Age at onset of secondary sex characteristics: < 9 years; Continued: ≤ 12 years

Initial Therapy Criteria

Initial Approval Criteria

Synarel is medically necessary when the following criteria are met:

Indication (ONE of)

A. Central Precocious Puberty (must meet all)
- Diagnosis of CPP confirmed by all of the following
  - Laboratory criteria: Elevated basal luteinizing hormone (LH) level > 0.2 - 0.3 mIU/mL (dependent on type of assay used) and/or elevated leuprolide-stimulated LH level > 3.3 - 5 IU/L (dependent on type of assay used)Basal LH > 0.2 - 0.3 mIU/mL; Leuprolide-stimulated LH > 3.3 - 5 IU/L
    Units depend on assay; use lab-specific cutoffs
  - Bone age: Difference between bone age and chronological age was > 1 year (bone age - chronological age)

Continuation Therapy Criteria

Continued Therapy

Continued therapy is authorized when the following indication-specific criteria are met:

Indication (ONE of)

A. Central Precocious Puberty (must meet all)
- Continuity of care or prior approval (ONE of)
  - Currently receiving or prior approval: Currently receiving medication via Centene benefit or member has previously met initial approval criteria
  - Continuity of care regulation pathway: Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state addendums CC.PHARM.03A and CC.PHARM.03B)

Unproven / Exclusions

Diagnoses/Indications Not Authorized

Uses not covered unless supported by off-label policy documentation:

Non-FDA approved indications which are not addressed in this policy are not authorized unless sufficient documentation of efficacy and safety per off-label use policies (HIM.PA.154 or CP.PMN.53) or evidence of coverage documents

Refer to off-label policies or evidence of coverage

Provider Actions / Prior Authorization

Documentation Required

Submit supporting documentation

Provider must submit supporting documentation such as office chart notes, laboratory results, and other clinical information demonstrating the member meets all approval criteria (for initial and continued requests). Include relevant data per indication (e.g., basal LH and/or leuprolide-stimulated LH values and bone age for CPP; documentation of surgical confirmation or trial of therapies for endometriosis; evidence of diagnosis, Tanner stage or prior hormone therapy response and provider attestations for gender dysphoria).

Office chart notes documenting diagnosis and clinical findings
Laboratory results (e.g., basal LH > 0.2–0.3 mIU/mL or leuprolide-stimulated LH > 3.3–5 IU/L for CPP)
Bone age assessment showing bone age > chronological age by > 1 year (CPP)
For endometriosis: surgical confirmation OR documentation of 3-month trial of NSAID, contraceptive, or progestin unless contraindicated
For gender dysphoria: documentation of Tanner stage or prior gender-affirming hormone therapy response and provider attestations as required

Applicable Codes

No procedure/drug codes listedmixed

No codes listed

Clinical Evidence and References

Evidence: Primary reference is the Synarel Prescribing Information (FDA) November 2025 which provides approved indications, dosing regimens, maximum doses, and endometriosis duration information. Guideline references include the Endocrine Society clinical practice guideline on endocrine treatment of gender-dysphoric persons and WPATH Standards of Care (versions cited in references). The policy aligns with the prescribing information for endometriosis duration and dosing limits and references Endocrine Society and WPATH guidance where cited for gender dysphoria/gender transition criteria and multidisciplinary care recommendations.

Background

Background: Nafarelin acetate (Synarel) is a GnRH receptor agonist indicated by the FDA for central precocious puberty and for management of endometriosis in adult women (experience limited to women ≥ 18 years treated for 6 months). This policy permits select off-label use for gender dysphoria/gender transition when all off-label criteria are met (including specialist prescribing/consultation, age/pubertal development criteria, psychosocial support and provider attestation regarding state regulations). The policy is implemented in alignment with Centene processes (documentation requirements, specialty prescriber requirements, continuity of care considerations) and cites the Synarel prescribing information and professional guidelines (Endocrine Society, WPATH) as references.

Definitions and policy reference

CPPCentral precocious puberty

LHLuteinizing hormone

Policy numberCP.PHAR.174

SubjectNafarelin acetate (Synarel)

Scope summary

Revision History

07.21.22revised

4Q 2022 annual review clarified endometriosis duration of therapy should not exceed 12 months and modified continued approval duration wording; template changes applied. (P&T Approval Date 11.22)

02.16.23addedLatest

Added off-label use criteria for gender dysphoria or gender transition. (P&T Approval Date 05.23) [Material change]

01.09.24revised

B. Endometriosis (must meet all)

Continuity/prior approval: Currently receiving medication via Centene benefit or member has previously met initial approval criteria
Positive response metrics: Member is responding positively to therapy as evidenced by improvement in any of: improvement in dysmenorrhea, dyspareunia, pelvic pain/induration/tenderness, size of endometrial lesions
Examples listed
Duration limit: Total duration of Synarel therapy has not exceeded 6 monthsNot to exceed 6 months total therapy
Dose increase limit: If request is for a dose increase, new dose does not exceed 800 micrograms per day≤ 800 micrograms per day

C. Gender Dysphoria, Gender Transition (off-label) (must meet all)

Continuity/prior approval (ONE of)
- Currently receiving or prior approval: Currently receiving medication via Centene benefit or member has previously met initial approval criteria
- Continuity of care pathway: Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to CC.PHARM.03A and CC.PHARM.03B)
Positive response: Member is responding positively to therapy (e.g., continues to meet their individual goals of therapy for gender dysphoria)
Example of positive response
HIM/ICHRA state exclusion: For HIM/ICHRA, request is for a member in a state other than AL, AZ, AR, FL, GA, IN, IA, KS, KY, LA, MS, MO, NE, NH, NC, OH, OK, SC, and TN
Requests from listed states where treatment is not a covered benefit are excluded
Dose increase support: If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Prescriber must supply supporting evidence when required

Prior Authorization

Specialty prescriber requirement

Prescriptions must be written by or in consultation with the specialist(s) required for the indicated diagnosis: pediatric endocrinologist for central precocious puberty; gynecologist for endometriosis; and for gender dysphoria/gender transition, an endocrinologist plus a provider with expertise in gender dysphoria and transgender medicine (based on certified training or affiliation with local transgender health services).

Central precocious puberty: pediatric endocrinologist (prescribe or consult)
Endometriosis: gynecologist (prescribe or consult)
Gender dysphoria/gender transition: endocrinologist AND provider with transgender expertise (certified training or local affiliation)

Prior Authorization

Off-label evidence requirement

For off‑label uses or when the requested dose/indication exceeds FDA‑approved limits, the prescriber must submit supporting evidence (practice guidelines or peer‑reviewed literature) showing the dose or indication is appropriate. Requests for gender dysphoria/gender transition that exceed FDA limits require prescriber-submitted evidence per the criteria.

If dose exceeds FDA maximum for any FDA-approved indication, submit guideline or peer-reviewed literature support
For off-label gender dysphoria/gender transition uses, include supporting evidence when required by criteria

Documentation Required

Provider attestation for state regulations

For HIM/ICHRA requests for gender dysphoria/gender transition, the provider must attest they understand current State regulations regarding transgender-related health care and that the requested care is coverable under those State regulations. The policy references resources (e.g., Movement Advancement Project) to confirm state coverage status.

Provider attests care is coverable under current State regulations for the member
Provider attests understanding of applicable State rules for transgender-related health care
Use Movement Advancement Project resources (Appendix D) as applicable to confirm coverage

Documentation Required

Continuity of care documentation

For continuity of care/continued therapy requests, submit documentation that the member is responding positively to therapy or evidence of prior approval/receipt. Examples of response metrics are indication-specific: for CPP — decreased growth velocity, cessation of menses, softening of breast tissue or testes, or arrested pubertal progression; for endometriosis — improvement in dysmenorrhea, dyspareunia, pelvic pain or reduction in size of endometrial lesions; for gender dysphoria — continuing to meet individual goals of therapy.

CPP response examples: decreased growth velocity; cessation of menses; softening of breast tissue or testes; arrested pubertal progression
Endometriosis response examples: improved dysmenorrhea, dyspareunia, pelvic pain/induration/tenderness, or reduced lesion size
Gender dysphoria response example: member continues to meet individual goals of therapy
Alternatively, documentation of prior approval or evidence of prior receipt via Centene benefit as applicable