Luteinizing Hormone-Releasing Hormone (LHRH) Analogs are synthetic analogs of
the naturally occurring gonadotropin releasing hormone (GnRH) with greater
potency than the naturally occurring hormone, that when given inhibits
pituitary gonadotropin secretion and suppresses testicular and ovarian
steroidogenesis.

[Leuprolide acetate (Lupron
Depot)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020517s036_019732s041lbl.pdf),
[goserelin acetate
(Zoladex)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019726s059,020578s037lbl.pdf),
[triptorelin pamoate
(Trelstar](https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020715s040,021288s035,022427s015lbl.pdf)[](https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019726s059,020578s037lbl.pdf)[)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020715s040,021288s035,022427s015lbl.pdf),
[histrelin acetate
(Vantas](https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021732s018lbl.pdf)[](https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019726s059,020578s037lbl.pdf)[)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021732s018lbl.pdf)
are synthetic LHRH agonists, analogs of the naturally occurring GnRH, and
[leuprolide mesylate
(Camcevi](https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211488s000lbl.pdf)[](https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019726s059,020578s037lbl.pdf)[)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211488s000lbl.pdf).
They will be covered for Food and Drug Administration (FDA) approved
indications. The dose and frequency of administration should be consistent
with the FDA approved labeling.

**Covered Indications**

Leuprolide Acetate is covered for endometriosis, uterine fibroids, advanced
prostate cancer, head and neck cancer (salivary gland tumors), ovarian
cancer/fallopian tube cancer/primary peritoneal cancer, premenopausal breast
cancer, male breast cancer, central precocious puberty (CPP) and palliative
treatment of advanced prostate cancer.1 Leuprolide mesylate is covered for
advanced prostate cancer.12 The National Comprehensive Cancer Network (NCCN)
Clinical Practice Guidelines in Oncology for Breast Cancer14, the NCCN
Clinical Practice Guidelines in Oncology for Head and Neck Cancers15, the
NCCN Clinical Practice Guidelines in Oncology for Ovarian Cancer16, and the
NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer17 are
referenced for recommendations for coverage across each of these disease
settings.

Goserelin implant is covered for locally confined prostate cancer in
combination with flutamide; for stage T2b-T4 (Stage B2-C) flutamide is
recommended only with radiation in this disease setting. Goserelin implant is
covered for advanced breast cancer in premenopausal and perimenopausal women,
endometriosis, to thin the endometrial lining of the uterus prior to
endometrial ablation for dysfunctional uterine bleeding, and palliative
treatment of advanced prostate cancer.2 The NCCN Clinical Practice Guidelines
in Oncology for Breast Cancer, is cited to nationally recognized guidelines
to accommodate specific clinical scenarios.14 The NCCN Clinical Practice
Guidelines in Oncology for Prostate Cancer is cited to nationally recognized
guidelines to accommodate specific clinical scenarios for "advanced prostate
cancer."17

Triptorelin pamoate is covered for palliative treatment of advanced prostate
cancer.3 The NCCN Clinical Practice Guidelines in Oncology for Prostate
Cancer is cited to nationally recognized guidelines to accommodate specific
clinical scenarios for "advanced prostate cancer."17

Histrelin acetate implant is covered for CPP.

**Note** : The NCCN Clinical Practice Guidelines in Oncology for Prostate
Cancer is cited to nationally recognized guidelines to accommodate specific
clinical scenarios for "advanced prostate cancer."17

**Limitations**

Services that are not reasonable and necessary cannot be covered by Medicare
in the following:

****

  1. The dose and frequency of administration is not consistent with the FDA approved labeling. Doses and frequencies that exceed the FDA recommended dosage/frequency as per the prescribing information, are considered not reasonable and necessary and not covered by Medicare.
  2. It is contraindicated to administer these products if you have experienced any type of allergic reaction to these drugs or to any of its ingredients.

Lawrence, et al. (2020) conducted a systemic review to create the American
Urological Association/American Society for Therapeutic Radiology and
Oncology/Society of Urologic Oncology (AUA/ASTRO/SUO) Guideline to aid
clinicians in the management of patients with advanced prostate cancer.
Clinicians should offer ADT (androgen deprivation therapy) with either LHRH
agonists or antagonists or surgical castration in patients with mHSPC
(metastatic hormone sensitive prostate cancer) (strong recommendation;
evidence level: Grade B). The use of primary ADT for the management of mHSPC
has been the standard of care (SOC) since its discovery by Huggins and
colleagues in the 1940s.5

Conn, et al. (1991) review article reports the use of GnRH agonist analogues
therapy to induce biochemical castration. The suppression of the normal
pituitary-gonadal function is sought because physiologic levels of secretion
of gonadal steroids which exacerbate an underlying medical condition, such as
endometriosis, uterine fibroids, or prostate cancer.6

Guzick, et al. (2011) conducted a prospective, randomized, double-blind
controlled trial to compare the efficacy of leuprolide and continuous oral
contraceptives in the treatment of endometriosis associated pain. The major
findings of this trial is that both treatment arms provided a significant
reduction in pain from baseline and there was no significant difference in the
extent of pain relief between the 2 treatment regimens. The strengths of this
clinical trial include its study design (randomized, double-blind prospective,
multicenter) and the choice of contemporary medical regimens currently in
widespread clinical use in the United States. The greatest weakness of the
study is its limited sample size, a direct result of significant challenges in
subject recruitment.7

Kendzierski, et al. (2018) assessed the efficacy of leuprolide depot in
combination with an aromatase inhibitor delivered monthly compared to once
every 3 months in premenopausal women with estrogen receptor (ER)-positive
breast cancer in a single center retrospective study. The Suppression of
Ovarian Function Trial (SOFT)/Tamoxifen and Exemestane Trial (TEXT) trials
solidified GnRH agonists as a definitive option in adjuvant therapy for
premenopausal women with ER-positive breast cancer. They concluded leuprolide
acetate depot administered every 3 months is as efficacious and tolerable as a
monthly injection in combination with an aromatase inhibitor for premenopausal
patients with hormone receptor-positive breast cancer. The study's
retrospective design comes with inherent limitations. The patient population
was small, and they describe a single institution experience not a larger
randomized, multicenter trial of adjuvant hormone therapy in breast cancer
patients.9

Hassett, et al. (2020) convened an expert panel to develop clinical practice
guideline recommendations based on a systematic review of the medical
literature. To date, approaches to treating men with breast cancer have been
extrapolated largely from research conducted in women with breast cancer.
Guideline development involved a formal consensus process. The American
Society of Clinical Oncology (ASCO) guideline offers recommendations on
several key aspects of the management of male breast cancer.10

Francis, et al. (2018) reported the updated results from the SOFT and the
TEXT. They concluded that among premenopausal women with breast cancer, the
addition of ovarian suppression to tamoxifen resulted in significantly higher
8-year rates of both disease free and overall survival than tamoxifen alone.
The use of exemestane plus ovarian suppression resulted in even higher rates
of freedom from recurrence.11

The analysis of evidence reviewed for LHRH analogs included the AUA/ASTRO/SUO
Guideline, a prospective, randomized, double-blind controlled trial, a
retrospective study, and the ASCO Guideline.

The AUA/ASTRO/SUO Guideline has a strong recommendation for the use of primary
ADT for the management of mHSPC.5 The article by Conn reports the use of GnRH
agonist analogues therapy to suppress the normal pituitary gonadal function in
medical conditions such as endometriosis, uterine fibroids, and prostate
cancer.6 Kendzierski stated that the SOFT/TEXT trials solidified GnRH agonists
as a definitive option in adjuvant therapy for premenopausal women with ER-
positive breast cancer.9