CurrentCignaPolicy IP0109

Gonadotropin-Releasing Hormone Agonists - Lupron Depot

Cigna coverage policy for Lupron Depot (long-acting leuprolide acetate depot injections) describing prior authorization recommendations, FDA-approved and supported non‑FDA indications, dosing regimens, duration limits, specialty prescriber requirements, and coding for medical-benefit coverage under applicable Cigna plans.

Policy Summary

PayerCigna

PolicyGonadotropin-Releasing Hormone Agonists - Lupron Depot

Policy CodePolicy IP0109

Change TypeAnnual and selected revisions (coding, indications, criteria)

Effective Date

Next Review Date

Key ActionSubmit prior authorization documentation that demonstrates required prior therapy and specialist consultation where specified.

POLICY UPDATE CHANGES

Policy name updated to 'Gonadotropin-Releasing Hormone Agonists - Lupron Depot'.

Premenstrual Disorders (including PMS and PMDD) added as a new coverage condition for Lupron Depot 3.75 mg and 11.25 mg.

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

Added dosing information for all FDA-approved indications.

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

Added criteria for multiple oncology and supportive indications (prostate cancer, breast cancer, head & neck salivary gland tumors, ovarian cancer, preservation of ovarian function, prophylaxis/treatment of uterine bleeding in hematologic malignancy/BMT/SCT, uterine cancer).

12Approved / Supported Indications

4Dosing regimens (distinct)

HCPCS/J-codes listed

Coverage Summary

Lupron Depot (leuprolide acetate depot) is a long‑acting GnRH agonist with multiple FDA‑approved indications: treatment of endometriosis (3.75 mg monthly or 11.25 mg every 3 months) and short‑term management of anemia caused by uterine leiomyomata (fibroids) as preoperative hematologic improvement; and palliative treatment of advanced prostate cancer using longer‑acting formulations (7.5 mg monthly, 22.5 mg q3 months, 30 mg q4 months, or 45 mg q6 months).

Labeling specifies duration limits for the 3.75 mg and 11.25 mg products: endometriosis total treatment is limited to 12 months (initial 6 months, retreatment only with add‑back norethindrone acetate for an additional 6 months when needed) and uterine leiomyomata (fibroids) is recommended for up to 3 months. The longer‑acting prostate cancer formulations' labeling does not specify a treatment duration.

Because GnRH agonists cause hypoestrogenic effects, add‑back hormonal therapy (for example low‑dose estrogen and/or progestin such as norethindrone acetate) may be used to mitigate adverse effects, including decreased bone mineral density; the need for specialist prescribing/consultation and prior authorization is noted for many indications.

Policy summary & metadata

Scope SummaryCigna coverage policy for Lupron Depot describing prior authorization recommendations, FDA‑approved and supported non‑FDA indications, dosing regimens, duration limits, specialty prescriber requirements, and coding for medical‑benefit coverage under applicable Cigna plans.

Policy NumberIP0109

Coverage Stancecovered_with_criteria

Policy StatusCURRENT

Last Review Date2025-05-15

Approved / Supported Indications12

Dosing regimens (distinct)4

HCPCS/J-codes listed4

Medical Necessity Criteria (by indication)

Prior Authorization and General Requirements

Prior Authorization is recommended. Approvals provided for specified durations. Some indications require specialist prescribing or consultation.

ALL of the following

Prior Authorization is required/recommended for prescription benefit coverage of Lupron Depot.
Approvals are provided for the duration noted in each indication; when authorized in months, 1 month = 30 days.
Some conditions require the medication to be prescribed by or in consultation with a physician who specializes in the condition being treated (specified per indication).
Receipt of sample product does not satisfy criteria requirements for coverage.

Coding

Covered HCPCS / J-codes for Lupron Depot and related reportingHCPCSCovered

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
J3490	Unclassified drugs (may be considered for coverage when used to report Lupaneta Pack)

Provider Actions & Billing Impact

Prior Authorization

Prior authorization required/recommended

Prior authorization is recommended for Lupron Depot. Approvals are provided for the duration noted for each indication and PA submission must document that criteria are met (such as prior therapy or required specialty consult). Affected HCPCS/J‑codes: J1950, J1954, J9217, J3490.

J1950
J1954
J9217
J3490

Documentation Required

Specialist prescribing/consultation requirements

For many oncology and supportive oncology indications (breast, prostate, ovarian, uterine, head & neck salivary gland tumors, preservation of ovarian function, prophylaxis/treatment of uterine bleeding in hematologic malignancy/BMT/SCT) the medication must be prescribed by or in consultation with an oncologist. For gender dysphoria/gender reassignment, prescribe by or in consultation with an endocrinologist or clinician who specializes in transgender care. Documentation of specialist involvement must be available with the PA or medical record.

Background, Evidence & Definitions

ACOG (leiomyomas): The 2021 ACOG practice bulletin recommends GnRH agonists (with or without add‑back therapy) for bleeding associated with fibroids, uterine enlargement, and as a bridge to other treatments; add‑back therapy may mitigate hypoestrogenic effects including decreased bone mineral density (supports short‑term use for fibroids and consideration of add‑back).

ACOG (endometriosis): ACOG guidance supports an empiric 3‑month course of a GnRH agonist after evaluation and failure of initial therapy (eg, oral contraceptives, NSAIDs) and notes benefit from at least 6 months of therapy with add‑back medicine for certain patients (reaffirmed guidance and committee opinions cited).

NCCN (oncology uses): NCCN guidelines across tumor types (adolescent/young adult oncology, breast, head & neck, ovarian, uterine neoplasms) support leuprolide use for specific cancer contexts (ovarian suppression in breast cancer, ovarian preservation during chemotherapy, androgen‑receptor positive salivary gland tumors, and options in ovarian/uterine cancers), with dosing ranges consistent with the policy (eg, 3.75–7.5 mg every 4 weeks; 11.25–22.5 mg every 12 weeks) and recommendation for oncologist involvement.

Additional context: Lupron Depot has multiple FDA‑approved formulations and dosing regimens (3.75 mg and 11.25 mg for gynecologic indications; 7.5 mg, 22.5 mg, 30 mg, 45 mg for prostate cancer) and is also used in supported non‑FDA (oncology and other) indications such as ovarian suppression in breast cancer, preservation of ovarian function during chemotherapy, suppression for gender‑dysphoria care, and menstrual suppression in patients undergoing cancer treatment.

Policy revisions added premenstrual disorders (PMS/PMDD) as a coverage condition for 3.75 mg and 11.25 mg with requirements for prior SSRI or combined oral contraceptive trial in adults and updated medically necessary dosing and duration criteria across indications.

Because of hypoestrogenic risks (notably effects on bone density), add‑back therapy is recommended/considered in guidance and labeling for retreatment or longer courses, and many oncology/supportive uses require prescription by or consultation with an oncologist or relevant specialist.

Revision History

2024-06-15Annual Revision

Premenstrual Disorders (including PMS and PMDD) added as a new coverage condition for Lupron Depot 3.75 mg and 11.25 mg. Medical necessity criteria: removed requirement for a stimulation test to confirm diagnosis of central precocious puberty (leuprolide acetate only). Added dosing information for all FDA-approved indications. Conditions 'Hirsutism' and 'Premenstrual Syndrome (PMS)' removed from Conditions Not Covered.

2024-12-01Selected Revision

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

2025-05-15Annual RevisionLatest

Policy Summary

PayerCigna

PolicyGonadotropin-Releasing Hormone Agonists - Lupron Depot

Policy CodePolicy IP0109

Change TypeAnnual and selected revisions (coding, indications, criteria)

Effective Date

Next Review Date

Key ActionSubmit prior authorization documentation that demonstrates required prior therapy and specialist consultation where specified.

On This Page

1. Endometriosis (FDA-approved)

Approve Lupron Depot 3.75 mg or 11.25 mg for 1 year if the patient has tried ONE of the following, unless contraindicated:

ALL of the following

Trial requirement
- A contraceptive (e.g., combination oral contraceptives, levonorgestrel-releasing IUD such as Mirena or Liletta)
- An oral progesterone (e.g., norethindrone tablets)
- A depo-medroxyprogesterone injection
Exception: No trial required if patient has previously used a GnRH agonist (e.g., Lupron Depot) or antagonist (e.g., Orilissa).
Dosing (choose one)
- 3.75 mg IM once every month
- 11.25 mg IM once every 3 months

2. Prostate Cancer (FDA-approved)

Approve for 1 year if the patient meets ALL of the following:

ALL of the following

Prescribed by or in consultation with an oncologist.
Preferred product criteria is met for the product(s) as listed in the product-specific tables (see plan-specific criteria).
Dosing options per plan
- 7.5 mg IM once every month
- 22.5 mg IM once every 3 months
- 30 mg IM once every 4 months
- 45 mg IM once every 6 months

3. Uterine Leiomyomata (fibroids) / Abnormal Uterine Bleeding (AUB)

Approved durations and dosing:

ALL of the following

Uterine leiomyomata (fibroids): Approve for up to 3 months.
Dosing for fibroids
- 3.75 mg IM once every month
- 11.25 mg IM once every 3 months
Abnormal uterine bleeding: Approve for 6 months.
Dosing for AUB
- 3.75 mg IM once every month
- 11.25 mg IM once every 3 months

4. Breast Cancer (supported use)

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

ALL of the following

Prescribed by or in consultation with an oncologist.
Dosing
- 3.75 mg or 7.5 mg IM once every month
- 11.25 mg or 22.5 mg IM once every 3 months

5. Gender Dysphoria / Gender Reassignment

Approve for 1 year if prescribed by or in consultation with an endocrinologist or physician specializing in transgender care.

ALL of the following

Prescribed by or in consultation with an endocrinologist or a physician who specializes in the treatment of transgender patients.
Dosing
- 3.75 or 7.5 mg IM once every month
- 11.25 or 22.5 mg IM once every 3 months
- 30 mg IM once every 4 months
- 45 mg IM once every 6 months

6. Head & Neck Cancer - Salivary Gland Tumors

Approve for 1 year if all criteria are met:

ALL of the following

Patient has recurrent, unresectable, or metastatic disease.
Patient has androgen receptor-positive disease.
Medication is prescribed by or in consultation with an oncologist.
Dosing
- 3.75 mg or 7.5 mg IM every month
- 11.25 mg or 22.5 mg IM once every 3 months

7. Ovarian Cancer / Fallopian Tube / Primary Peritoneal Cancer

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

ALL of the following

Prescribed by or in consultation with an oncologist.
Dosing
- 3.75 mg or 7.5 mg IM once every month
- 11.25 mg or 22.5 mg IM once every 3 months

8. Premenstrual Disorders (PMS/PMDD)

Approve for 1 year if ALL of the following are met:

ALL of the following

Patient is ≥ 18 years of age.
Per prescriber, patient has severe, refractory premenstrual symptoms.
Prior therapy requirement
- A selective serotonin reuptake inhibitor (SSRI) (examples include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
- A combined oral contraceptive
Dosing
- 3.75 mg IM once every month
- 11.25 mg IM once every 3 months

9. Preservation of Ovarian Function/Fertility During Chemotherapy

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

ALL of the following

Prescribed by or in consultation with an oncologist.
Dosing
- 3.75 mg IM once every month
- 11.25 mg IM once every 3 months

10. Prophylaxis/Treatment of Uterine Bleeding or Menstrual Suppression in Hematologic Malignancy / BMT/SCT

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

ALL of the following

Prescribed by or in consultation with an oncologist.
Dosing
- 3.75 mg IM once every month
- 11.25 mg IM once every 3 months

11. Uterine Cancer

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

ALL of the following

Prescribed by or in consultation with an oncologist.
Dosing
- 7.5 mg IM once every month
- 22.5 mg IM once every 3 months
- 30 mg IM once every 4 months
- 45 mg IM once every 6 months

Not Medically Necessary / Exclusions

Lupron Depot for any other use is considered not medically necessary. Specific previously listed conditions removed from exclusions are noted.

ANY of the following

Use for indications not listed as approved or supported above is considered not medically necessary.
Policy previously listed 'Hirsutism' and 'Premenstrual Syndrome (PMS)' as not covered; these conditions were removed from the 'Conditions Not Covered' list per revision history.
Menstrual Migraine and Polycystic Ovarian Syndrome (PCOS) are noted as not recommended or limited by evidence and thus are not covered indications.

Oncology indications: prescribe by or in consultation with an oncologist (document specialty involvement).
Gender dysphoria: prescribe by or in consultation with an endocrinologist or clinician specializing in transgender care (document specialty involvement).

Documentation Required

Prior therapy documentation

Endometriosis: approve 3.75 mg or 11.25 mg for up to 1 year provided the patient has tried one contraceptive, an oral progesterone (e.g., norethindrone), or depo‑medroxyprogesterone, unless the patient previously used a GnRH agonist or antagonist (exception). Premenstrual disorders (PMS/PMDD): approve for 1 year in adults with severe, refractory symptoms who have tried an SSRI or a combined oral contraceptive. Document prior therapy trials or note exception for prior GnRH agonist/antagonist use.

Endometriosis prior therapy: one trial of a contraceptive, oral progesterone, or depo‑medroxyprogesterone required; exception if prior GnRH agonist/antagonist use.
Premenstrual disorders prior therapy: trial of an SSRI or a combined oral contraceptive required.

Billing Rule

Duration and dosing must match approved regimen

When coverage is authorized, approvals are limited to the durations stated for each indication (for example: endometriosis up to 1 year; fibroids up to 3 months; abnormal uterine bleeding up to 6 months; many oncology/supportive uses up to 1 year). Dosage, frequency, duration, and site of care must be clinically appropriate and supported by evidence and the medical record; approvals should not exceed the specified durations or dosing regimens listed in the policy.

Endometriosis: total duration limited to 12 months (3.75 mg monthly or 11.25 mg q3 months).
Fibroids: approve up to 3 months (3.75 mg monthly or 11.25 mg q3 months).
Abnormal uterine bleeding: approve up to 6 months (3.75 mg monthly or 11.25 mg q3 months).
Oncology/supportive uses: commonly approved for 1 year with specified dosing options per indication.

Definitions

MonthWhen approval is authorized in months, 1 month is equal to 30 days.

Policy name changed to 'Gonadotropin-Releasing Hormone Agonists - Lupron Depot'; Lupaneta Pack removed. Added criteria for multiple oncology and supportive indications including prostate cancer, breast cancer, head & neck salivary gland tumors, ovarian cancer, preservation of ovarian function, prophylaxis/treatment of uterine bleeding in hematologic malignancy/BMT/SCT, and uterine cancer.

Administrative

Multiple prior names consolidated; Lupaneta Pack removed.