ModifiedCignaPolicy IP0109

Gonadotropin-Releasing Hormone Agonists - Lupron Depot

Defines prior authorization, coverage criteria, dosing, indications, and medical necessity determinations for Lupron Depot (leuprolide acetate) for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyGonadotropin-Releasing Hormone Agonists - Lupron Depot

Policy CodePolicy IP0109

Change TypeMaterial additions and coding updates

Effective Date

Next Review Date

Key ActionObtain prior authorization and submit appropriate covered HCPCS codes (e.g., J1950, J1954, J9217, J3490) when requesting coverage for Lupron Depot.

SourceLink

POLICY UPDATE CHANGES

Premenstrual Disorders, including Premenstrual Syndrome and Premenstrual Dysphoric Disorder, added as a new coverage condition for Lupron Depot 3.75 mg and 11.25 mg.

Removed requirement for a stimulation test to confirm central precocious puberty prior to initiation of treatment (leuprolide acetate only).

Added dosing information for all FDA approved indications.

Updated HCPCS coding: Added J3490, J1950, J1954, J9217.

Policy name updated multiple times, most recently to 'Gonadotropin-Releasing Hormone Agonists - Lupron Depot'.

Removed Lupaneta Pack (obsolete).

12distinct indication or use entries with approval criteria listed

3 monthsapproval duration for uterine leiomyomata (fibroids)

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

listed HCPCS/CPT drug codes

4listed dosing interval options (monthly → 6 months)

2025-05-15most recent annual revision date listed

Coverage Criteria and Indications

inv-01: Endometriosis — FDA-approved indication criteria

FDA-Approved Indications - Endometriosis

Endometriosis approval: Approve Lupron Depot 3.75 mg or 11.25 mg for 1 year if the patient has tried ONE of the following unless contraindicated: A) a contraceptive (e.g., combined oral contraceptives or levonorgestrel-releasing IUD), OR B) an oral progesterone (e.g., norethindrone), OR C) a depo‑medroxyprogesterone injection. Exception: prior use of a GnRH agonist or antagonist allows bypass of the trial requirement.duration 1 year

Dosing: 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months.

inv-02: Prostate Cancer — FDA-approved indication criteria

FDA-Approved Indications - Prostate Cancer

Prostate cancer approval: Approve Lupron Depot for 1 year if ALL of the following are met: A) prescribed by or in consultation with an oncologist; AND B) preferred product criteria is met (ONE of: patient has tried Eligard or Firmagon, OR patient is currently receiving Lupron Depot).duration 1 year

Dosing options include 7.5 mg IM monthly, 22.5 mg IM every 3 months, 30 mg IM every 4 months, or 45 mg IM every 6 months as applicable.

inv-03: Uterine Leiomyomata (Fibroids) — indication and criteria

Uterine Leiomyomata (Fibroids)

Fibroids approval: Approve Lupron Depot for up to 3 months for uterine leiomyomata when used for preoperative reduction/hematologic improvement.duration 3 months

Dosing: 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months. Combine with iron therapy as indicated.

inv-04: Other Supported Indications — selected examples with supportive evidence

Other Uses with Supportive Evidence (selected examples)

Abnormal uterine bleeding: Approve for 6 months when used for abnormal uterine bleeding as bridge or symptom control related to structural causes.duration 6 months

Dosing: 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months.

Breast cancer (ovarian suppression): Approve for 1 year if prescribed by or in consultation with an oncologist. Used for ovarian suppression per oncologic guidance.duration 1 year

Dosing: 3.75 mg or 7.5 mg IM once monthly OR 11.25 mg or 22.5 mg IM once every 3 months.

Gender dysphoria / transgender care: Approve for 1 year if prescribed by or in consultation with an endocrinologist or clinician who specializes in transgender care. Used for pubertal or adult hormone suppression per specialty guidance.

inv-05: Oncology-related Indications — oncology and supportive indications requiring oncology consult

Oncology and supportive indications requiring oncology consult

Head and neck salivary gland tumors: Approve for 1 year if ALL of the following are met: recurrent, unresectable, or metastatic disease; androgen receptor–positive disease; AND prescribed by or in consultation with an oncologist.duration 1 year

Dosing: 3.75 mg or 7.5 mg IM once monthly OR 11.25 mg or 22.5 mg IM once every 3 months.

Ovarian / fallopian tube / primary peritoneal cancer: Approve for 1 year if prescribed by or in consultation with an oncologist.duration 1 year

Dosing: 3.75 mg or 7.5 mg IM once monthly OR 11.25 mg or 22.5 mg IM once every 3 months.

Uterine cancer: Approve for 1 year if prescribed by or in consultation with an oncologist.

inv-06: General Dosing and Coverage Expectations — dosing and usage expectations when medically necessary

When coverage is available and medically necessary, the following dosing and usage expectations apply:

Dosing requirements: Use one of the specified depot dosing schedules: 7.5 mg IM once monthly OR 22.5 mg IM once every 3 months OR 30 mg IM once every 4 months OR 45 mg IM once every 6 months. Dosing should be reasonable, clinically appropriate, evidence-supported, and adjusted based on severity and prior response.

Documentation: Receipt of sample product does not satisfy any criteria requirements for coverage.

Lupron Depot (leuprolide acetate) is considered not medically necessary when prescribed for any indication that is not specifically listed as covered in this policy. The policy explicitly states that off‑label or other uses not enumerated in the Coverage Criteria are not covered and may be denied.

Examples of uses considered not medically necessary are provided to clarify common scenarios that will not meet coverage criteria. The policy lists menstrual migraine and polycystic ovarian syndrome (PCOS) as explicit examples; this list is not exhaustive and may be updated as new evidence emerges.

For menstrual migraine and PCOS, the policy explains why Lupron Depot is not covered: GnRH analogs can eliminate menstrual migraines but their use is limited by the significant adverse effects of estrogen deficiency (for example, severe vasomotor symptoms, sleep disruption, and marked reduction in bone density). Review articles and clinical guidelines do not recommend GnRH agonists for routine treatment of PCOS; they are mentioned only in the context of infertility and assisted reproductive procedures.

Although GnRH analogs may be efficacious for menstrual migraine, the policy highlights important risk and tolerability considerations that limit their use. Specifically, therapy is associated with estrogen‑deficiency adverse effects (severe vasomotor symptoms, sleep disruption, and significant bone density loss) that make these agents unsuitable as routine treatment for menstrual migraine, and therefore they are considered not medically necessary for this indication.

Billing and Code Lists

Considered Medically Necessary when criteria metHCPCSCovered

J3490	Unclassified drugs.
J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J1954	Injection, leuprolide acetate for depot suspension (Cipla), 7.5 mg.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.

Considered Medically Necessary when policy criteria are metHCPCSCovered

J3490	Unclassified drugs.
J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J1954	Injection, leuprolide acetate for depot suspension (Cipla), 7.5 mg.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.

Dosing interval options — Lupron Depot (selected depot formulations)

7.5 mgAdministered IM once every month (monthly dosing).

22.5 mgAdministered IM once every 3 months (q3 months).

30 mgAdministered IM once every 4 months (q4 months).

45 mgAdministered IM once every 6 months (q6 months).

Provider Requirements, Prior Authorization, and Billing Rules

Prior Authorization

Prior Authorization Required

Prior Authorization is recommended for prescription benefit coverage of Lupron Depot. Approval durations vary by indication; when authorized in months, 1 month = 30 days. Receipt of sample product does not satisfy any criteria requirements for coverage. Claims billed without a covered code listed in this policy will be denied as not covered.

Prior authorization requirement applies to prescription benefit claims for Lupron Depot.
Approval durations follow the criteria for each indication (e.g., 1 year for many oncologic indications; 3 months for uterine leiomyomata).
Samples do not fulfill prior therapy or documentation requirements.

Billing Rule

HCPCS Coding and Coverage

Background and Context

Lupron Depot is a depot formulation of leuprolide acetate administered at approved depot dosing intervals: 7.5 mg IM once monthly; 22.5 mg IM once every 3 months; 30 mg IM once every 4 months; or 45 mg IM once every 6 months. When coverage is available and medically necessary, dosing, frequency, and duration should be reasonable, clinically appropriate, evidence‑supported, and adjusted for severity and prior response. The policy also specifies that receipt of sample product does not satisfy coverage requirements and reiterates that uses not listed in the policy are considered not medically necessary.

Product Definitions and Dosing

Lupron Depot — depot formulations and available doses

Active ingredientLeuprolide acetate (Lupron Depot) depot suspension; GnRH agonist.

Depot formulations available7.5 mg (monthly), 22.5 mg (every 3 months), 30 mg (every 4 months), 45 mg (every 6 months), plus 3.75 mg and 11.25 mg formulations for gynecologic indications.

Indicated oncology usePalliative treatment of advanced prostate cancer (7.5 mg, 22.5 mg, 30 mg, 45 mg formulations).

Gynecologic indicationsEndometriosis and uterine leiomyomata (3.75 mg and 11.25 mg formulations typically used monthly or q3 months).

Lupron Depot dosing — depot formulation schedules

7.5 mg dosing7.5 mg IM administered once monthly (7.5 mg every month).

Policy Summary

PayerCigna

PolicyGonadotropin-Releasing Hormone Agonists - Lupron Depot

Policy CodePolicy IP0109

Change TypeMaterial additions and coding updates

Effective Date

Next Review Date

Key ActionObtain prior authorization and submit appropriate covered HCPCS codes (e.g., J1950, J1954, J9217, J3490) when requesting coverage for Lupron Depot.

SourceLink

On This Page

Dosing options include 3.75 or 7.5 mg IM once monthly; 11.25 or 22.5 mg IM once every 3 months; 30 mg IM once every 4 months; or 45 mg IM once every 6 months.

Preservation of ovarian function during chemotherapy: Approve for 1 year if prescribed by or in consultation with an oncologist for ovarian function preservation during cytotoxic therapy.duration 1 year

Dosing: 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months.

Dosing options: 7.5 mg IM once monthly OR 22.5 mg IM every 3 months OR 30 mg IM every 4 months OR 45 mg IM every 6 months.

When submitting claims, use one of the covered HCPCS codes for leuprolide depot products. Claims submitted without one of the covered codes listed in this policy will be denied.

Covered HCPCS codes: J3490 (Unclassified drugs) — may be used for Lupaneta Pack reporting when applicable; J1950 (leuprolide acetate per 3.75 mg); J1954 (leuprolide acetate for depot suspension (Cipla), 7.5 mg); J9217 (leuprolide acetate (for depot suspension), 7.5 mg).
Deleted or inactive codes at time of service may not be eligible for reimbursement — verify code currency at time of billing.

Denial Risk

Not Medically Necessary Uses

Lupron Depot is considered not medically necessary for uses not listed as covered in this policy. The list below is illustrative and not all-inclusive; additional not medically necessary uses will be updated as new data emerge.

Examples of not medically necessary uses include menstrual migraine and polycystic ovarian syndrome (PCOS).
Any other indication not explicitly listed as covered in this policy is considered not medically necessary and may be denied.

Documentation Required

Prescriber Specialty / Consultation Requirement

Certain approvals require the medication to be prescribed by or in consultation with a specialist appropriate to the condition being treated. For some oncology and other specialty indications, prescriber specialty or documented consultation is required for approval.

Prostate, breast, ovarian, head and neck (salivary gland tumors), and other oncologic indications: prescribed by or in consultation with an oncologist.
Gender dysphoria/gender-affirming treatment: prescribed by or in consultation with an endocrinologist or a physician who specializes in transgender care.
Some approvals specifically state 'prescribed by or in consultation with' a specialist — include consult notes or specialist prescriber information with the prior authorization request when required.

Step Therapy

Step Therapy for Selected Indications

Step therapy is required for certain FDA‑approved non-oncology indications such as endometriosis. A trial of specified alternative therapies is required prior to approval unless an exception applies.

Endometriosis: approve Lupron Depot 3.75 mg or 11.25 mg for up to 1 year only if the patient has tried ONE of the following unless contraindicated — A) a contraceptive (e.g., combination oral contraceptives, levonorgestrel-releasing IUD such as Mirena or Liletta), OR B) an oral progesterone (e.g., norethindrone tablets), OR C) a depo‑medroxyprogesterone injection. Exception: prior use of a GnRH agonist or antagonist (e.g., prior Lupron Depot or Orilissa) may satisfy the requirement.
Document prior trials (medication name, dates, reason for discontinuation) or a contraindication to the required step therapy when submitting a prior authorization request.

22.5 mg dosing22.5 mg IM administered once every 3 months (q3 months).

30 mg dosing30 mg IM administered once every 4 months (q4 months).

45 mg dosing45 mg IM administered once every 6 months (q6 months).