Cigna Lupron Depot Coverage Update

Coverage Criteria

FDA-Approved Indications

FDA-Approved Indications and requirements

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., combination oral contraceptives, levonorgestrel-releasing intrauterine systems), OR B) an oral progesterone (e.g., norethindrone), OR C) a depo‑medroxyprogesterone injection. Exception allowed if patient previously used a GnRH agonist or antagonist.1 trial

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

Prostate cancer approval: Approve for 1 year if BOTH of the following are met: A) prescribed by or in consultation with an oncologist; AND B) preferred product criteria is met per plan-specific product criteria (see employer/individual plan details).both required

Dosing varies by strength; employer/individual plan product-preference may require trial of Eligard or Firmagon or current receipt of Lupron Depot.

Uterine leiomyomata (fibroids): Approve for 3 months when indicated for preoperative hematologic improvement/anemia.duration limit

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

Other Supported Indications

Other uses with supportive evidence and coverage conditions

Abnormal uterine bleeding: Approve for 6 months.duration limit

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

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

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

Gender dysphoria/gender reassignment: Approve for 1 year if prescribed by or in consultation with an endocrinologist or a physician who specializes in transgender care.specialist consult

Ovarian Cancer (and related) - Initial therapy

Covered when ALL of the following are met for Ovarian Cancer (including fallopian tube and primary peritoneal cancer):

Ovarian Cancer coverage: Prescribed by or in consultation with an oncologist; approve for 1 year.

Dosing: choose ONE of the following regimens: A) 3.75 mg or 7.5 mg IM once every month OR B) 11.25 mg or 22.5 mg IM once every 3 months.

Premenstrual Disorders - Initial therapy

Covered when ALL of the following are met for Premenstrual Disorders:

Premenstrual Disorders coverage: Patient is ≥18 years of age; AND prescriber documents severe, refractory premenstrual symptoms; AND patient has tried ONE of: i) an SSRI OR ii) a combined oral contraceptive.

Dosing: 3.75 mg IM once every month OR 11.25 mg IM once every 3 months. Approve for 1 year. Examples of SSRIs are listed in the policy (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline).

Fertility preservation, Menstrual suppression in cancer, Uterine cancer

Covered when ALL of the following are met for Fertility preservation, Menstrual suppression in cancer contexts, and Uterine cancer:

Preservation of ovarian function/fertility: Prescribed by or in consultation with an oncologist; approve for 1 year.

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

Prophylaxis or treatment of uterine bleeding/menstrual suppression in hematologic malignancy or prior to BMT/SCT: Prescribed by or in consultation with an oncologist; approve for 1 year.

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

Uterine cancer: Prescribed by or in consultation with an oncologist; approve for 1 year.

Dosing: choose ONE of: 7.5 mg IM once every month 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.

Use of Lupron Depot for infertility is addressed under a separate Cigna coverage policy: Fertility Injectables - 1012. Refer to that policy for medical necessity criteria, prior‑authorization requirements, and coding when Lupron Depot is prescribed for infertility or assisted reproductive technology purposes.

Lupron Depot use for indications not listed as covered or supported in this policy is considered not medically necessary. The policy specifically notes that GnRH analogs are not recommended for the treatment of Polycystic Ovarian Syndrome (PCOS), and that other off‑label uses (for example, menstrual migraine) have limitations related to adverse effects and are not supported for routine coverage. Providers should consult the policy’s not‑medically‑necessary section before initiating therapy for indications outside those enumerated as covered.

The following conditions are considered not medically necessary under this policy: Polycystic Ovarian Syndrome (PCOS) and other uses not supported by evidence (this list is not exhaustive). The policy notes that GnRH agonists are not recommended for PCOS and that certain historically listed conditions (e.g., hirsutism, premorbid PMS in prior versions) were removed from the not‑covered list during revisions; always confirm current exclusions in the policy text before billing or authorizing treatment.

Initial Therapy

Initial therapy

Initial therapy — approval conditions and dosing for initiation

Endometriosis initial: Approve 3.75 mg IM once every month OR 11.25 mg IM once every 3 months for up to 1 year if patient has trialed a contraceptive OR an oral progesterone OR depo‑medroxyprogesterone unless prior GnRH agonist/antagonist use.

Uterine fibroids initial: Approve 3.75 mg IM once every month OR 11.25 mg IM once every 3 months for up to 3 months.

Prostate cancer initial: For employer/individual plans, approve per product‑preference rules when criteria met; dosing options include 45 mg IM every 6 months, 30 mg IM every 4 months, 22.5 mg IM every 3 months, or 7.5 mg IM monthly.

Initial Therapy and Dosing

Initial Therapy and Dosing — indication-specific dosing regimens

Continuation and Retreatment

Continuation/retreatment rules

Continuation/retreatment rules — duration limits and retreatment notes for select indications

Endometriosis retreatment: For the first 6 months, Lupron Depot may be used as monotherapy or with norethindrone acetate; if retreatment is needed, retreatment must be used in combination with norethindrone acetate for 6 months; total limited to 12 months.

Uterine leiomyomata duration: Recommended duration up to 3 months for uterine fibroids (preoperative use).

Continuation Therapy

Continuation Therapy — renewal/extension approval conditions and typical durations

Continuation approvals: Approvals are generally issued for up to 1 year when initial criteria are met; dosing regimens specified per indication and should be adjusted based on response and clinical appropriateness.

Step Therapy / Prior Trials

Step	Requirement	Notes
1
Prior trial of specified alternatives or current use of Lupron Depot
Employer and Individual plans: patient must have tried ONE of Eligard or Firmagon (may require prior authorization) OR be currently receiving Lupron Depot; applies to 7.5, 22.5, 30, 45 mg formulations. Dosing options vary by product and plan.

Step	Requirement	Notes
1
Trial of one of: an SSRI OR a combined oral contraceptive
Patient must be ≥18 years and prescriber must document severe, refractory premenstrual symptoms; examples of SSRIs listed include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline. Dosing: 3.75 mg IM monthly or 11.25 mg IM every 3 months; approve for 1 year when criteria met.

Provider Actions and Authorization

Prior Authorization

Prior Authorization and Prescriber Requirements

Prior Authorization is recommended for prescription benefit coverage of Lupron Depot. Approvals are provided for the duration specified in the criteria for each indication (when months are used, 1 month = 30 days). Some indications (particularly oncology and other severe conditions) are typically approved for 1 year. Approval for certain conditions requires the drug to be prescribed by or in consultation with a specialist (e.g., oncologist for prostate cancer, ovarian cancer, preservation of ovarian function, uterine cancer, and other cancer-related indications).

Prior authorization recommended for Lupron Depot; approvals provided for the duration noted in the indication-specific criteria (1 month = 30 days).
Approvals for oncology and other severe conditions are typically authorized for 1 year.
Some approvals require prescription by or consultation with a physician who specializes in the condition being treated (specialist-prescribing/consult requirement).

Step Therapy

Prostate Cancer — Prior Authorization and Product Preference

Coding and Billing

Covered CPT/HCPCS/ICD-10 codesmixed

No codes listed

Considered Medically Necessary codesHCPCSCovered

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

Authorization duration month conversion

Authorization duration conversion1 month = 30 days (use this conversion when approvals are issued in months)

Prior authorization requirementPrior Authorization is recommended for prescription benefit coverage of Lupron Depot; approvals are provided for the duration noted in the policy

Specialist prescribing noteSome approvals require Lupron Depot to be prescribed by or in consultation with a physician who specializes in the condition being treated

Site of Care

Note

Site of care: office or infusion center as clinically appropriate

Site of care should be reasonable and clinically appropriate; dosing frequency and duration should be adjusted based on severity, alternative treatments, and prior response to therapy.

Appropriate settings include office or infusion center as clinically indicated.

Background

Lupron Depot (leuprolide acetate) is a long‑acting gonadotropin‑releasing hormone (GnRH) agonist that suppresses gonadal steroid production. It is FDA‑indicated for conditions including endometriosis, anemia due to uterine fibroids (preoperative hematologic improvement), and palliative treatment of advanced prostate cancer, and it is used in several evidence‑supported non‑FDA contexts (eg, menstrual suppression in oncology, ovarian suppression in breast cancer, pubertal suppression in gender dysphoria). The 2024–2025 revisions updated the policy name and added dosing and indication details for multiple strengths and dosing intervals; prescribers should follow the indication‑specific dosing, duration, and specialist consultation requirements listed in this policy when seeking authorization.

Definitions

GnRH agonist — definition / key term

TermGnRH agonist

DefinitionA class of agents (eg, long-acting leuprolide) that suppress gonadal steroid production by agonizing the gonadotropin-releasing hormone receptor to achieve gonadal suppression

Clinical use examplesFDA-indicated uses include endometriosis and preoperative hematologic improvement for uterine fibroids; long-acting formulations used for pubertal suppression and various oncology indications

GnRH analogs — definition / key term

TermGnRH analogs

DefinitionGonadotropin-releasing hormone (GnRH) analogs (long-acting GnRH analogs) are agents used to suppress the hypothalamic-pituitary-gonadal axis and inhibit pubertal development or gonadal steroid production; they are the currently preferred option for pubertal suppression in gender-dysphoric adolescents

Revision History

2025-05-15Annual revisionLatest

Policy name updated to 'Gonadotropin-Releasing Hormone Agonists - Lupron Depot'; dosing information for all FDA‑approved indications added; Lupaneta Pack removed; criteria added for multiple oncology and fertility‑preservation indications (prostate, breast, head and neck salivary gland tumors, ovarian and related cancers, preservation of ovarian function, prophylaxis/treatment of uterine bleeding/menstrual suppression, and uterine cancer).

2024-12-01Selected revision (coding)

HCPCS coding updated: added J3490, J1950, J1954, and J9217 to support billing variations and generic/manufacturer codes.

2024-06-15Annual revision