ModifiedUnitedHealthcarePolicy IEXD0038.12

Gonadotropin Releasing Hormone Analogs

Medical benefit drug policy governing coverage criteria for gonadotropin releasing hormone (GnRH) analogs for Individual Exchange plans (except MA, NV, NY). It affects prescribers and prior authorization reviewers for the listed GnRH products.

Policy Summary

PayerUnitedHealthcare

PolicyGonadotropin Releasing Hormone Analogs

Policy CodePolicy IEXD0038.12

Change TypeUpdated applicable HCPCS codes (quarterly edit)

Effective DateJul 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and use updated HCPCS codes (including revised J1954 description) when requesting GnRH agent coverage.

SourceLink

POLICY UPDATE CHANGES

Updated list of applicable HCPCS codes to reflect quarterly edits and revised description for J1954.

~11distinct indication sections

12 motypical auth max duration

3 mofibroid preop auth

3excluded states

9+HCPCS/J-codes listed

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.

Level AACOG recommendation level

Coverage Criteria for GnRH Analogs

Central Precocious Puberty — Initial and Continuation Therapy

Proven and medically necessary when ALL of the following are met

Initial therapy: Diagnosis of central precocious puberty (idiopathic or neurogenic); onset of secondary sexual characteristics in females ≤ 8 years or males ≤ 9 years; and confirmation by one of: pubertal basal LH (per lab reference range), pubertal LH response to a GnRH stimulation test, or bone age advanced ≥ 1 year beyond chronological ageage thresholds as listed

Initial authorization will be for no more than 12 months

Continuation therapy: Patient is currently receiving therapy for central precocious puberty; documentation of positive clinical response to therapy; patient remains younger than the appropriate timepoint for the onset of puberty (for example: females < 11 years; males < 12 years)reauthorization will be for no more than 12 months

Treatment should be discontinued at appropriate age of puberty onset; consider discontinuing before 11 years in girls and 12 years in boys

Endometriosis — Initial and Retreatment (Lupron Depot, Zoladex)

Proven and medically necessary when ALL of the following are met

Initial therapy: Diagnosis of endometriosis or suspected endometriosis; and either (1) contraindication, intolerance, or failure of initial treatment with both oral contraceptives or depot medroxyprogesterone AND NSAIDs, or (2) patient has had surgical ablation to prevent recurrenceinitial treatment course is limited to a maximum of 6 months

Prescribing information limits initial treatment to 6 months

Retreatment (Lupron Depot only): Diagnosis or suspected recurrence of endometriosis; recurrence of symptoms following an initial course of therapy; to be used concurrently with add-back therapy (e.g., progestin, estrogen, or bone-sparing agents); and total duration of initial plus recurrent therapy no longer than 12 monthstotal duration ≤ 12 months

Consider bone mineral density impact prior to retreatment; Lupron monotherapy not recommended for retreatment; Zoladex retreatment beyond 6 months not recommended due to lack of data

Endometrial Thinning for Dysfunctional Uterine Bleeding (Zoladex)

Medically necessary when ALL of the following are met

Pre-ablation use: Use prior to endometrial ablation; other causes of symptoms or bleeding ruled out; patient to receive Zoladex 3.6 mg implant; course of therapy limited to a maximum of two depotsmaximum two depots

Fertility Preservation

Proven and medically necessary when BOTH of the following are met

Initial therapy: Patient is a premenopausal woman receiving a cytotoxic agent associated with primary ovarian insufficiency (examples include cyclophosphamide, procarbazine, vinblastine, cisplatin); and intended use is for ovarian protection during cytotoxic treatmentinitial authorization will be for no more than 12 months

GnRH therapy should be discontinued upon completion of cytotoxic treatment

Continuation: Patient is currently receiving GnRH analog therapy for fertility preservation and continues to receive a cytotoxic agent associated with primary ovarian insufficiencyreauthorization will be for no more than 12 months

Uterine Leiomyomata (Fibroids) — Preoperative use

Proven and medically necessary when BOTH of the following are met

Indications for preoperative use: Either (1) treatment of fibroid-related anemia with failure to respond to one month of iron therapy and use prior to surgery; OR (2) use prior to surgery to reduce fibroid size to facilitate a surgical procedure (e.g., myomectomy, hysterectomy)authorization will be for no more than 3 months

Gender Dysphoria in Adolescents — Initial and Continuation Therapy

May be covered when ALL of the following are met

Initial therapy: Submission of medical records documenting DSM-5 diagnosis of gender dysphoria by a mental health professional with expertise in child/adolescent psychiatry; medication prescribed by or in consultation with an endocrinologist or provider experienced in gender dysphoria hormone therapy; patient has experienced pubertal development to at least Tanner stage 2 (stage 2–4); and one pubertal laboratory confirming pubertal estradiol (females) or testosterone (males) or pubertal basal LH or LH response to GnRH stimulation; plus a prescriber letter stating pubertal changes increased gender dysphoria with significant impairment, coexisting issues addressed, current enrollment and intent to continue psychological/social support, and patient understanding of expected outcomesinitial authorization will be for no longer than 12 months

Continuation therapy: Within last 6 months documentation of LH suppression or assessment for dosing change; continued DSM-5 diagnosis by an experienced mental health professional; medication prescribed by or in consultation with an endocrinologist; and a prescriber letter documenting ongoing benefit, continued goals of therapy, continued psychosocial support participation, and that discontinuation would impair functioningreauthorization will be for no longer than 12 months

Adjunct for Gender-Affirming Hormonal Therapy for Transgender Adults

May be covered when ALL of the following are met

Initial therapy: Submission of medical records documenting DSM-5 diagnosis of gender dysphoria by a mental health professional; medication prescribed by or in consultation with an endocrinologist or provider experienced in transgender hormone therapy; intact, functional gonads; patient currently receiving cross-sex hormone therapy; inability of cross-sex hormones to inhibit natal secondary sex characteristics or LH/gonadotropins; and a prescriber letter documenting identified goals, comorbidities addressed, current enrollment in psychological/social support, and patient understandinginitial authorization will be for no more than 12 months

Continuation therapy: Within last 6 months documentation of LH suppression assessment; continued DSM-5 diagnosis; endocrinology involvement; intact functional gonads; ongoing cross-sex hormones; inability of cross-sex hormones to suppress natal characteristics; and prescriber documentation of continued goals and psychosocial support participationreauthorization will be for no more than 12 months

Indication summaries and supporting evidence

Clinical indication summaries and supporting trial evidence included in policy:

Central Precocious Puberty (CPP): Lupron Depot-Ped is indicated for CPP; extension trials demonstrated maintenance of LH suppression (peak-stimulated LH < 4 mIU/mL) and suppression of physical signs of puberty over 36 monthspeak-stimulated LH < 4 mIU/mL

Phase III extension: 72 patients showed maintenance of LH suppression and sex steroid suppression

Endometriosis: Leuprolide acetate is indicated for management of endometriosis with demonstrated improvements in pain measures versus placebo and suppression of menses and estradiol to menopausal levelsclinical response in pain measures over 12 weeks

Randomized trials (e.g., Pelvic Pain Study Group, Lupron Study Group) showed statistically significant pain improvements vs placebo

Uterine Leiomyomata (Fibroids):

Uterine Leiomyomata (Fibroids) — preoperative adjuvant therapy

Covered when ALL of the following are met

Fibroid preoperative GnRH use: Patient has uterine leiomyomata and a GnRH agonist (e.g., depot leuprolide acetate) is used as a preoperative adjuvant to reduce uterine volume or improve hematologic/operative parameters2-3 months preoperative use referenced

Randomized trials and ACOG note 2–3 month preoperative benefit

Endometriosis — medical suppressive therapy

Covered when ALL of the following are met

Endometriosis GnRH use after initial therapy: Clinically diagnosed endometriosis with appropriate pretreatment evaluation and failure of initial treatment with oral contraceptives and NSAIDs; empiric GnRH agonist therapy considered following failure3 months of GnRH agonist therapy referenced

ACOG supports a 3-month course after pretreatment evaluation; add-back therapy recommended to mitigate bone loss

Fertility preservation during chemotherapy — ovarian protection

Covered when ALL of the following are met

GnRH agonist for ovarian protection: Premenopausal patient facing chemotherapy with substantial risk of ovarian insufficiency and GnRH agonist used prior to and/or concurrently with chemotherapy for ovarian protection when standard proven fertility preservation methods (oocyte/embryo/ovarian tissue cryopreservation) are not feasible or as an adjunctnot specified

Guidelines (ASCO) recognize conflicting evidence but permit offering GnRHa when proven methods are not feasible; meta-analyses show reduced amenorrhea rates but limited randomized evidence for pregnancy outcomes

Gender dysphoria — puberty suppression and hormone therapy

Covered when ALL of the following are met

Puberty suppression in adolescents: Adolescent meets diagnostic criteria for gender dysphoria/gender incongruence with multidisciplinary confirmation and informed consent; pubertal suppression with GnRH analogs is initiated after pubertal onset (clinically) and at Tanner stage 2 or greater, with clinical monitoring every 3–6 months and laboratory monitoring every 6–12 monthsmonitoring intervals as stated

Endocrine Society and WPATH recommend multidisciplinary confirmation and monitoring; observational studies show psychosocial functioning improvements when combined with psychological support

Hormone therapy in adults: Adult evaluated and meeting criteria for the endocrine phase of transition; medical contraindications addressed; hormone levels monitored to maintain physiologic ranges for affirmed genderlaboratory monitoring every 6–12 months referenced

Hayes assigned limited/uncertain ratings for adolescent pubertal suppression and cross-sex hormones due to insufficient evidence

Guideline-based Indications and Considerations

Clinical contexts and recommendations cited in the policy (guideline summaries):

Uterine Leiomyomata (Fibroids): ACOG (2008; reaffirmed 2019 & 2021) states GnRH agonists given for 2–3 months preoperatively improve hematologic parameters, shorten hospital stay, and decrease blood loss and operating time; benefits should be weighed against cost and side effects2-3 months preoperative use

Level A evidence cited

Endometriosis: Lupron Depot is indicated for management of endometriosis; when used with norethindrone acetate (add-back), total therapy should not exceed 12 months because of bone mineral density concerns<= 12 months with add-back

Prescribing information limitation reiterated

Central Precocious Puberty (CPP): Selected GnRH agonists (e.g., Fensolvi, Lupron Depot-Ped, Supprelin LA, Triptodur) are indicated for pediatric CPP per FDA labeling

Zoladex (goserelin) retreatment for management of endometriosis beyond 6 months is not recommended due to lack of clinical data supporting safety or effectiveness for treatment periods in excess of 6 months.

A listing of a procedure or diagnosis code in this policy is provided for reference only and does not imply coverage. Benefit coverage for a service is determined by the member-specific benefit plan document and applicable laws; inclusion of a code does not guarantee reimbursement or claim payment.

Hayes reviewed hormone therapy for gender dysphoria and assigned a D2 rating (no proven benefit and/or not safe) specifically for pubertal suppression and cross-sex hormone therapy in adolescents, reflecting insufficient published evidence to assess safety or impact on health outcomes.

Lupron Depot is not indicated to be used in combination with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by fibroids; the prescribing information specifies that add-back combination is intended for endometriosis management and limits total duration with add-back to no more than 12 months.

Lupron Depot monotherapy is not recommended for retreatment of endometriosis; when retreatment is considered the product should be used with add-back therapy (e.g., norethindrone acetate) and the combined duration of initial plus retreatment courses should not exceed 12 months. The prescribing information advises consideration of bone mineral density impact prior to retreatment and states that greater than one retreatment period is not recommended.

Some treatments described in this policy may be considered experimental, investigational, or unproven. Benefit coverage for such treatments depends on the member-specific benefit plan document and applicable state or federal mandates; consult the member’s plan document to determine whether coverage for an investigational therapy may be allowed under specific circumstances.

FDA approval or an FDA indication alone is not a basis for coverage. Coverage decisions must reference the member-specific benefit plan document and applicable mandates or laws; FDA labeling is provided for informational purposes and does not guarantee benefit coverage.

Initial Therapy Rules and Regimens

Initial Therapy Rules

Initial therapy coverage requires meeting specified diagnostic, age/pubertal, prior therapy, and documentation requirements depending on indication.

Central precocious puberty initial: Diagnosis of CPP plus age thresholds (females ≤ 8 years; males ≤ 9 years) and confirmation via pubertal basal LH, GnRH stimulation test response, or advanced bone age; initial authorization ≤ 12 months

Endometriosis initial: Diagnosis or suspected endometriosis and either failure/intolerance/contraindication to OC or depot medroxyprogesterone AND NSAIDs, or post-surgical ablation; initial course limited to 6 months

Fertility preservation initial: Premenopausal woman receiving a cytotoxic agent associated with ovarian insufficiency; initial authorization ≤ 12 months; therapy discontinued upon completion of cytotoxic treatment

Continuation and Reauthorization Rules

Continuation Therapy Rules

Continuation/reauthorization typically requires documentation of ongoing benefit and relevant labs; reauthorization durations commonly up to 12 months.

Central precocious puberty continuation: Patient currently receiving therapy; documentation of positive clinical response; patient younger than puberty onset thresholds (females <11, males <12); reauthorization ≤ 12 months

Fertility preservation continuation: Patient continues to receive cytotoxic agent associated with ovarian insufficiency and remains on GnRH analog therapy for fertility preservation; reauthorization ≤ 12 months

Gender dysphoria/adult adjunct continuation: Documentation within last 6 months of LH suppression assessment, continued DSM-5 diagnosis, endocrinology involvement, ongoing psychosocial support, intact gonads (adults adjunct), ongoing cross-sex hormones (adults adjunct), and prescriber documentation of continued benefit; reauthorization ≤ 12 months

Step Therapy Requirements

Requirement	Details
Prior trial of first-line therapies required
Initial therapy for endometriosis requires either: (1) contraindication, intolerance, or failure of both oral contraceptives or depot medroxyprogesterone AND non-steroidal anti-inflammatory drugs (NSAIDs), or (2) prior surgical ablation to prevent recurrence

Consideration	Policy Detail
Use of first-line therapies before GnRH agonist
ACOG and the policy indicate that after pretreatment evaluation and failure of initial treatment with oral contraceptives and NSAIDs, a 3‑month course of a GnRH agonist is appropriate; prior use/failure of these first-line therapies should be documented before initiating GnRH agonist therapy

Note	Action for Providers
Use of external utilization criteria (e.g., InterQual)
UnitedHealthcare may use third‑party tools such as InterQual to implement step therapy or other utilization management algorithms; confirm plan‑specific step therapy requirements in the member’s benefit document

Applicable Codes and Diagnosis Lists

Applicable HCPCS/J-codesHCPCS

J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J1951	Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg.
J1952	Injection, leuprolide, camcevi, 1 mg.
J1954	Injection, leuprolide acetate for depot suspension (lutrate depot), 7.5 mg.
J3315	Injection, triptorelin pamoate, 3.75 mg.
J3316	Injection, triptorelin, extended-release, 3.75 mg.
J9155	Injection, degarelix, 1 mg.
J9202	Goserelin acetate implant, per 3.6 mg.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.
J9226	Histrelin implant (Supprelin LA), 50 mg

Applicable ICD-10 Diagnosis Codes (part 1)ICD-10

D25.0	Submucous leiomyoma of uterus.
D25.1	Intramural leiomyoma of uterus.
D25.2	Subserosal leiomyoma of uterus
D25.9	Leiomyoma of uterus, unspecified.
E22.8	Other hyperfunction of pituitary gland, central precocious puberty.
E30.1	Precocious puberty.
F64.0	Transsexualism.
F64.1	Dual role transvestism.
F64.2	Gender identity disorder of childhood.
F64.8	Other gender identity disorders.

1–10 of 11

1/2

Applicable ICD-10 Diagnosis Codes (part 2)ICD-10

N80.00	Endometriosis of uterus, unspecified.
N80.01	Superficial endometriosis of the uterus.
N80.02	Deep endometriosis of the uterus.
N80.03	Adenomyosis of the uterus.
N80.101	Endometriosis of right ovary, unspecified depth.
N80.102	Endometriosis of left ovary, unspecified depth.
N80.103	Endometriosis of bilateral ovaries, unspecified depth.
N80.109	Endometriosis of ovary, unspecified side, unspecified depth.
N80.111	Superficial endometriosis of right ovary.
N80.112	Superficial endometriosis of left ovary.

Listed HCPCS/J-codes for GnRH agentsHCPCS

J1950	Injection, leuprolide acetate (for depot suspension), per 3.75 mg.
J1951	Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg.
J1952	Injection, leuprolide, camcevi, 1 mg.
J1954	Injection, leuprolide acetate for depot suspension (lutrate depot), 7.5 mg.
J3315	Injection, triptorelin pamoate, 3.75 mg.
J3316	Injection, triptorelin, extended-release, 3.75 mg.
J9155	Injection, degarelix, 1 mg.
J9202	Goserelin acetate implant, per 3.6 mg.
J9217	Leuprolide acetate (for depot suspension), 7.5 mg.
J9226	Histrelin implant (Supprelin LA), 50 mg

Uterine leiomyoma (fibroids) diagnosis codesICD-10

D25.0	Submucous leiomyoma of uterus.
D25.1	Intramural leiomyoma of uterus.
D25.2	Subserosal leiomyoma of uterus.
D25.9	Leiomyoma of uterus, unspecified.

Endometriosis diagnosis codes (partial listing shown in document)ICD-10

N80.00	Endometriosis of uterus, unspecified.
N80.01	Superficial endometriosis of the uterus.
N80.02	Deep endometriosis of the uterus.
N80.03	Adenomyosis of the uterus.
N80.111	Superficial endometriosis of right ovary.
N80.112	Superficial endometriosis of left ovary.
N80.113	Superficial endometriosis of bilateral ovaries.
N80.3A1	Superficial endometriosis of the right uterosacral ligament.
N80.5	Endometriosis of intestine.
N80.9	Endometriosis, unspecified.

CPP and fertility preservation codesICD-10

E30.1	Precocious puberty.
E22.8	Other hyperfunction of pituitary gland, central precocious puberty.
Z31.62	Encounter for fertility preservation counseling.
Z31.84	Encounter for fertility preservation procedure.

Gender dysphoria / related codesICD-10

F64.0	Transsexualism.
F64.9	Gender identity disorder, unspecified.
Z87.890	Personal history of sex reassignment

Updated HCPCS (example noted)HCPCS

J1954

Description for J1954 revised as of 07/01/2025 (see policy for exact billing descriptor)

Coding notes for gender dysphoria with disorder of sex developmentICD-10

255.2	E25.0 congenital adrenal hyperplasia (example disorder of sex development) — coding note referenced
259.50	E34.50 androgen insensitivity syndrome (example disorder of sex development) — coding note referenced

inv-31: Age criteria for central precocious puberty

Female age thresholdFemales ≤ 8 years of age

Male age thresholdMales ≤ 9 years of age

Diagnosis requirementDiagnosis of central precocious puberty (idiopathic or neurogenic)

inv-32: Age markers for continuation

Continuation age marker — femalesFemales younger than 11 years of age

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization and Duration Limits

Prior authorization is required for GnRH analogs and related products. Initial authorizations are limited in duration (commonly up to 3 months for some indications and up to 12 months for others) — confirm the appropriate initial and reauthorization limits for the specific indication. Verify member benefits for coverage and duration limits before initiating therapy.

Initial authorization durations vary by indication (e.g., up to 12 months for central precocious puberty and fertility preservation; up to 3 months in certain contexts as noted in policy source).
Reauthorization limits generally mirror initial limits (commonly up to 12 months when continued therapy criteria are met).
Prior authorization must reference the specific product and the diagnosis/indication being treated.

Prior Authorization

Prior authorization considerations

Prior authorization requests must include clinical documentation that supports the medical necessity criteria for the requested indication. Consideration should include prior trials of and intolerance to first-line therapies where required (for example, documentation of trial and failure of oral contraceptives and NSAIDs for endometriosis), confirmation of diagnostic testing (e.g., LH stimulation testing or basal pubertal LH, bone age), and clinician specialty (e.g., endocrinologist for CPP or gender‑affirming care when required).

Background and Therapeutic Context

Gonadotropin-releasing hormone (GnRH) analogs act by suppressing pituitary gonadotropin release and thereby reducing ovarian or testicular sex steroid production. These agents include both GnRH agonists (e.g., leuprolide formulations such as Lupron Depot, goserelin [Zoladex], histrelin implant) that initially stimulate then downregulate pituitary receptors with continuous dosing, and GnRH antagonists (e.g., degarelix) that reversibly block pituitary GnRH receptors. Clinically, GnRH analogs are used for indications that include central precocious puberty, endometriosis, preoperative reduction of fibroid-related uterine volume or anemia, fertility preservation during cytotoxic therapy, and pubertal suppression in gender dysphoria.

inv-55: GnRH analogs — examples listed

Examples — leuprolide productsCamcevi, Eligard, Fensolvi, Lupron Depot (including Lupron Depot-Ped)

Examples — histrelin implantSupprelin LA (histrelin acetate)

Examples — triptorelin and goserelinTrelstar, Triptodur (triptorelin) and Zoladex (goserelin acetate)

inv-56: Degarelix / Firmagon description

Site of Care

Note

No explicit site-of-care restrictions specified

The policy does not specify any site-of-care restrictions for GnRH analog administration; providers should follow standard clinical and payer site guidelines.

No explicit site-of-care restrictions are listed in this policy section.
Follow applicable plan or facility site-of-care requirements if present in the member's benefit plan.

Revision History and Policy Changes

2025-07-01codes_updatedLatest

Updated list of applicable HCPCS codes to reflect quarterly edits and revised the billing descriptor for J1954; archived previous policy version IEXD0038.11.

Policy Summary

PayerUnitedHealthcare

PolicyGonadotropin Releasing Hormone Analogs

Policy CodePolicy IEXD0038.12

Change TypeUpdated applicable HCPCS codes (quarterly edit)

Effective DateJul 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization and use updated HCPCS codes (including revised J1954 description) when requesting GnRH agent coverage.

SourceLink

On This Page

Leuprolide acetate indicated for preoperative hematologic improvement and to reduce fibroid size preoperatively; trials showed increased hemoglobin/hematocrit response and significant reductions in uterine and myoma volume versus placebo or iron alone

response defined in trials (e.g., Hb >= 12 g/dL and Hct >= 36%)

Multiple RCTs demonstrated uterine volume reductions and hematologic improvement

Fertility Preservation: Systematic reviews and guideline updates (Cochrane, ASCO) report that GnRH agonists administered prior to or during chemotherapy are associated with reduced amenorrhea and resumption of menses; evidence for preserved fertility (pregnancy outcomes) is mixedN/A

Meta-analyses identified reduced amenorrhea rates but insufficient randomized evidence for pregnancy outcomes

pediatric CPP per FDA labeling

Prescribing information references provided

Prostate Cancer: Multiple agents (Camcevi, Eligard, Firmagon, Lupron Depot, Trelstar, Zoladex) are indicated for palliative treatment of advanced prostate cancer per labelingoncology indications per FDA/NCCN

Oncology indications listed in NCCN Drugs & Biologics Compendium

Gender Dysphoria / Gender Incongruence: Endocrine Society (2017) and WPATH (v8, 2023) recommend pubertal suppression with GnRH analogs for adolescents meeting diagnostic criteria with multidisciplinary confirmation; monitoring recommendations include clinical assessment every 3–6 months and labs every 6–12 monthsdiagnostic criteria and maturity assessments per guidelines

Guideline-based monitoring and initiation recommendations included

Gender dysphoria adolescent initial: DSM-5 diagnosis by an experienced child/adolescent mental health professional; endocrinology involvement; Tanner stage ≥ 2; pubertal labs confirming status; prescriber letter documenting impairment, supports, and understanding; initial authorization ≤ 12 months

Transgender adult adjunct initial: DSM-5 diagnosis by a mental health professional; endocrinology involvement; intact, functional gonads; ongoing cross-sex hormones insufficient to suppress natal characteristics; prescriber letter documenting goals and supports; initial authorization ≤ 12 months

Initial therapy regimens

Initial courses and timing referenced in evidence and guidelines

Preoperative leiomyomata regimen: Depot leuprolide acetate 3.75 mg IM every 4 weeks for 2–3 months has been studied and is recommended by ACOG for preoperative use to improve hematologic and operative parameters3.75 mg every 4 weeks as studied

RCTs showed uterine volume reductions after 12 and 24 weeks

Endometriosis initial course: Empiric GnRH agonist therapy for endometriosis is appropriate following pretreatment evaluation and failure of oral contraceptives and NSAIDs; a 3-month course is described as appropriate3 months

Add-back therapy reduces bone mineral loss

Pubertal suppression initiation (gender dysphoria)

Guideline-based initiation criteria for pubertal suppression and gender-affirming hormone therapy.

Adolescents requesting pubertal suppression: Adolescents who meet diagnostic criteria and request treatment should undergo pubertal suppression after physical signs of puberty appear (Tanner stage ≥2); initiation should follow multidisciplinary confirmation and assessment of capacity for informed consentTanner stage >=2; diagnostic criteria met

Monitor clinical pubertal development every 3–6 months and labs every 6–12 months per guideline recommendations

Lupron Depot continuation limit

Duration and continuation considerations for Lupron Depot when used with add-back therapy.

Lupron Depot with norethindrone acetate: Total duration of therapy with Lupron Depot plus add-back (norethindrone acetate) should not exceed 12 months due to concerns about adverse impact on bone mineral density<= 12 months

Limitation of use stated in prescribing information

Continuation age marker — malesMales younger than 12 years of age

Reauthorization durationReauthorization will be for no more than 12 months

inv-33: Peak-stimulated LH for CPP suppression

Peak-stimulated LH thresholdPeak-stimulated LH < 4 mIU/mL

ContextDocumented in CPP trial showing maintenance of LH suppression after 6 months

Clinical outcomeLH suppression associated with regression or no progression of pubertal signs

inv-34: Hemoglobin response for preoperative anemia in fibroids trial

Hemoglobin response definitionResponse defined as hemoglobin ≥ 12 g/dL

Hematocrit response definitionHematocrit ≥ 36%

Study entry baselineStudy participants had hemoglobin ≤ 10.2 g/dL and/or hematocrit ≤ 30%

inv-35: Maximum duration for Lupron Depot with add-back therapy

Maximum total duration with add-backTotal duration of Lupron Depot plus add-back therapy should not exceed 12 months

Purpose of add-backAdd-back (norethindrone acetate) intended to reduce BMD loss and vasomotor symptoms

Limitation contextLimitation due to concerns about adverse impact on bone mineral density

Document prior conservative/first-line therapy attempts and outcomes when the policy requires failure/intolerance (e.g., endometriosis step requirement).
Include relevant laboratory or diagnostic test results (pubertal basal LH, LH response to GnRH stimulation, estradiol/testosterone levels, bone age) when cited by the coverage criteria.
Identify the prescribing provider specialty and any required consults (e.g., endocrinology or mental health specialist for gender dysphoria).
Check member benefit plan for any additional prior authorization rules or local/state mandates that modify coverage.

Documentation Required

Central Precocious Puberty Documentation

For central precocious puberty (CPP), prior authorization submissions must document the diagnosis and confirmatory testing. Initial and continuation authorizations are time-limited and require documentation of clinical response and age criteria for ongoing therapy.

Document a diagnosis of central precocious puberty (idiopathic or neurogenic).
Document onset of secondary sexual characteristics at or before: females ≤ 8 years, males ≤ 9 years.
Provide confirmatory evidence by one of: pubertal basal LH (per lab reference range), pubertal LH response to a GnRH stimulation test, or bone age advanced ≥ 1 year beyond chronological age.
Initial authorization length: up to 12 months; continuation/reauthorization: patient must show positive clinical response and remain younger than the policy’s pubertal age thresholds (examples: females <11 years, males <12 years) — reauthorization generally for up to 12 months.
Note: Treatment should be discontinued when appropriate age of pubertal onset is reached; consider discontinuing before 11 years (girls) or 12 years (boys) at physician discretion.

Step Therapy

Endometriosis Step Requirement

Endometriosis coverage commonly requires demonstration of prior failure or intolerance to first-line medical therapy before a GnRH agonist will be authorized, or documentation of prior surgical ablation to prevent recurrence. A time-limited empiric trial (e.g., a 3-month course) may be appropriate following failure of initial therapy per guideline recommendations.

Document diagnosis of endometriosis or suspected endometriosis.
Document failure, contraindication, or intolerance to both: oral contraceptives or depot medroxyprogesterone AND NSAIDs, prior to GnRH agonist authorization.
Alternatively, provide documentation of prior surgical ablation if that is the reason for GnRH therapy.
Policy/guideline note: A 3-month empiric course of a GnRH agonist after failure of initial treatment is consistent with ACOG guidance; when clinically effective, consider add-back therapy to mitigate bone mineral loss.
Initial authorization will reflect the applicable duration (see Prior Authorization and Duration Limits).

Prior Authorization

Endometriosis preauthorization context

When requesting authorization for GnRH analogs in the context of endometriosis, include prior treatment history and objective evidence that initial treatments were tried and failed or were contraindicated. Specify planned duration (e.g., 3-month empiric trial) and whether add-back therapy will be used.

Provide documentation of trials of OCs or depot medroxyprogesterone and NSAIDs with dates and outcomes.
If requesting beyond an initial empiric course, include evidence of clinical benefit from the GnRH agonist and plans for add-back therapy if continued therapy is requested.
Confirm planned authorization length and request reauthorization only when continuation criteria are documented.

Documentation Required

Gender-Affirming Adjunct Documentation

For gender‑affirming and gender dysphoria related requests, include required letters, mental health assessment documentation, and evidence of multidisciplinary management as specified in the policy. For transgender adults receiving GnRH analogs as adjunctive therapy, document prior hormone use, retained gonadal function, and rationale for adjunctive GnRH therapy.

Adolescents: include DSM-based diagnosis by a mental health professional with pediatric/adolescent expertise, endocrinology involvement, Tanner staging (≥ stage 2 required), and relevant laboratory confirmation (pubertal estradiol/testosterone or LH measures).
Include a prescriber letter documenting how pubertal changes have increased gender dysphoria and that psychosocial/psychiatric barriers have been addressed. Document current engagement in psychological/social support and plan for ongoing participation.
Adults (adjunct use): document diagnosis, prescriber specialty, retained functional gonads, current gender-affirming hormone therapy, failure/inability of cross-sex hormones to suppress natal sex characteristics or gonadotropins, and a prescriber letter outlining goals and supports.

Documentation Required

Benefit documentation requirement — consult member benefit plan

Always consult the member specific benefit plan document for coverage determinations. Benefit limits, prior authorization processes, and required documentation may vary by contract and by state mandates; the plan document governs in the event of conflict.

Confirm whether the member’s certificate of coverage allows the requested indication (some plans may restrict experimental/investigational uses).
Check for state or federal mandates that may require coverage for off‑label uses or gender‑affirming care.
If the member plan includes additional required forms or prior authorization portals, follow those instructions.

Documentation Required

Required supporting documentation for fertility preservation / chemotherapy context

When fertility preservation is the indication, include documentation that the patient is pre‑menopausal, receiving a specified cytotoxic agent associated with ovarian insufficiency, and that GnRH therapy is intended solely for preservation during cytotoxic treatment. Authorization lengths are limited and reauthorization requires ongoing cytotoxic therapy.

Provide name and schedule of cytotoxic agent(s) associated with primary ovarian insufficiency and dates of therapy.
Document patient menopausal status (pre‑menopausal) and intent to undergo cytotoxic therapy.
Initial authorization: up to 12 months; reauthorization: contingent on continued cytotoxic therapy and typically up to 12 months.
State that GnRH therapy will be discontinued upon completion of cytotoxic treatment.

Note

Benefit plan and documentation note

Reminder: the member specific benefit plan controls coverage. This policy is an interpretive guide and UnitedHealthcare may use external utilization criteria (e.g., InterQual) or other tools when administering benefits.

Use the member’s benefit plan to confirm covered services and any exceptions.
UnitedHealthcare may apply external criteria (InterQual) to support utilization review decisions.
Check the updated applicable HCPCS/HCPCS code lists and billing guidance prior to claim submission.

Pharmacologic classGnRH receptor antagonist

MechanismBinds reversibly to pituitary GnRH receptors, reducing gonadotropin release and consequently testosterone

Example productFirmagon (degarelix)

inv-57: Leuprolide, histrelin, triptorelin, goserelin — agonist description

Agent typesSynthetic peptide analogs of GnRH (nonapeptide or decapeptide)

Mechanism with continuous dosingChronic administration downregulates GnRH receptors, reducing LH/FSH release and suppressing estradiol/testosterone

Representative agentsLeuprolide, histrelin, triptorelin, goserelin (e.g., Lupron Depot, Supprelin LA, Trelstar, Zoladex)

inv-58: GnRH agonists / analogs summary

DefinitionDrugs that initially stimulate then suppress pituitary gonadotropin release when given continuously, used to suppress ovarian or testicular hormone production

Common clinical usesCPP, endometriosis, fibroid preoperative therapy, fertility preservation, pubertal suppression for gender dysphoria

Representative formulationsDepot injections and implants (e.g., depot leuprolide acetate, goserelin implant, histrelin implant)

inv-59: Pubertal suppression definition

DefinitionUse of GnRH analogs to suppress pubertal hormone development in adolescents with gender dysphoria

Initiation criteriaBegin after physical signs of puberty; typically when patient has reached Tanner stage 2

MonitoringClinical monitoring every 3–6 months and laboratory monitoring every 6–12 months while on therapy

inv-60: Add-back therapy definition

DefinitionConcomitant use of norethindrone acetate with Lupron Depot to reduce bone mineral density loss and vasomotor symptoms

Indication contextUsed in management of endometriosis and recurrence when combined with Lupron Depot per labeling

Duration limitTotal duration with Lupron Depot plus add-back should not exceed 12 months