What is the peptide starting with L used in medical contexts, specifically in the treatment of hormone-responsive cancers?

Leuprolide Acetate (Leuprolide)

The peptide starting with "L" used in medical contexts for hormone-responsive cancers is leuprolide acetate (also called leuprolide or leuprorelin), a synthetic GnRH agonist that suppresses sex hormone production and is extensively used in prostate cancer, breast cancer, endometriosis, and other hormone-dependent conditions. 1, 2

Mechanism of Action

Leuprolide acetate functions as a gonadotropin-releasing hormone (GnRH) agonist that initially stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, causing a transient rise in sex hormones during the first 1-2 weeks of treatment 1, 2. However, continuous administration leads to pituitary desensitization and receptor downregulation, resulting in profound suppression of gonadotropins and subsequent reduction of testosterone to castrate levels in males (within 2-4 weeks) and estrogen to postmenopausal levels in premenopausal females 1, 2, 3.

Primary Clinical Applications

Prostate Cancer

• Leuprolide is a standard first-line hormonal therapy for advanced prostate cancer, offering equivalent efficacy to surgical castration (orchiectomy) but with significantly lower cardiovascular toxicity compared to diethylstilbestrol 1, 4
• The American Society of Clinical Oncology guidelines establish leuprolide as a primary androgen deprivation therapy option for metastatic, recurrent, or progressive androgen-sensitive prostate cancer 1
• Standard dosing includes leuprolide 3.75-7.5 mg intramuscularly every 4 weeks, or 11.25-22.5 mg every 12 weeks 1, 2
• Castrate testosterone levels are achieved and maintained for periods up to 5 years with continuous treatment 2, 4

Breast Cancer and Gynecologic Malignancies

• For premenopausal women with hormone receptor-positive breast cancer, leuprolide (combined with ovarian function suppression) is recommended as adjuvant endocrine therapy, particularly for higher-risk patients with young age, high-grade tumors, or lymph node involvement 1
• The NCCN guidelines recommend leuprolide acetate as ovarian function suppression for 5 years in combination with either tamoxifen or aromatase inhibitors for premenopausal breast cancer patients 1
• Leuprolide is also used for grade 1 (low-grade) serous/endometrioid and borderline epithelial ovarian carcinomas as hormone therapy 1
• In endometriosis, monthly depot leuprolide 3.75 mg demonstrates comparable efficacy to danazol or buserelin for achieving objective and subjective responses 3

Neuroendocrine Tumors

• While octreotide (another peptide) is the primary somatostatin analog for neuroendocrine tumors 1, 5, leuprolide has distinct applications in hormone-dependent conditions
• Leuprolide should not be confused with octreotide LAR, which is specifically indicated for carcinoid syndrome and neuroendocrine tumor growth control 5

Dosing Regimens by Indication

Standard Formulations

• Prostate cancer: 3.75 mg IM/SC monthly, 7.5 mg monthly, or 11.25-22.5 mg every 3 months 1, 2
• Breast cancer ovarian suppression: 3.75-7.5 mg every 4 weeks for 5 years 1
• Endometriosis: 3.75 mg IM monthly for up to 6 months (limited duration due to bone mineral density reduction) 3
• Therapeutic levels are not achieved until 10-14 days after initial injection 5

Critical Adverse Effects and Management

Testosterone/Estrogen Flare Phenomenon

• A major pitfall is the initial 1-2 week surge in sex hormones before suppression occurs, which can cause symptom flare in 4-29% of patients 1, 4
• In prostate cancer, this manifests as worsening bone pain or urinary obstruction 1, 4
• Antiandrogens (such as flutamide or bicalutamide) should be co-administered during the first 2-3 weeks to prevent flare reactions in patients with advanced disease 1

Hypoestrogenic/Hypotestosterone Effects

• Impotence and hot flashes occur in most male recipients 1, 4
• Women experience vasomotor symptoms, weight gain, mood changes, fatigue, and loss of libido 1
• Long-term castrate hormone levels induce osteopenia and hypercholesterolemia, requiring monitoring and potential bisphosphonate therapy 1
• Bone mineral density reduction limits endometriosis treatment duration to 6 months 3

Cardiovascular Safety

• Unlike diethylstilbestrol, leuprolide does not significantly increase cardiovascular events (myocardial infarction, stroke, thromboembolism), making it far safer than older estrogen-based therapies 1, 4, 6
• This improved safety profile allows earlier-stage disease treatment 6

Important Contraindications and Precautions

Absolute Contraindications

• Pregnancy and breastfeeding are absolute contraindications 1
• Patients must be continent and self-caring when receiving radiolabeled peptide therapies to minimize radiation exposure to caregivers 1

Hormone Receptor-Positive Breast Cancer

• Estrogen hormone replacement therapy is absolutely contraindicated in patients with ER-positive breast cancer history, as exogenous estrogen directly contradicts the goal of reducing estrogen stimulation 7
• Even after completing adjuvant therapy, HRT remains contraindicated because recurrence risk extends for many years 7
• Non-hormonal alternatives (SSRIs/SNRIs, gabapentin, clonidine) should be used for menopausal symptom management instead 7

Pharmacokinetics and Drug Interactions

• Leuprolide is not orally active and requires parenteral administration 2
• Bioavailability by subcutaneous administration is comparable to intravenous administration 2
• The terminal elimination half-life is approximately 3 hours, with metabolism to smaller inactive peptides 2
• Drug-drug interactions are not expected because leuprolide is degraded by peptidases rather than cytochrome P-450 enzymes, and only 43-49% is protein-bound 2
• Less than 5% is recovered unchanged in urine 2

Comparative Efficacy Evidence

Prostate Cancer

• Meta-analyses demonstrate equivalent survival outcomes between leuprolide and orchiectomy at 2 years 1
• Some studies suggest survival advantage when leuprolide is combined with antiandrogen flutamide (combined androgen blockade) 1, 4
• Neoadjuvant leuprolide with bicalutamide and goserelin for 3-6 months before radical prostatectomy significantly reduces positive surgical margins (from 48.7% to 75.6-81.0% for stage B disease) 1

Breast Cancer

• The SOFT and TEXT trials established that 5 years of ovarian function suppression with leuprolide plus either tamoxifen or aromatase inhibitors improves disease-free survival in premenopausal women with hormone receptor-positive breast cancer 1
• Eight-year disease-free survival was 85.4% with ovarian suppression plus tamoxifen versus 80.2% with tamoxifen alone 1

Practical Clinical Algorithms

Initiating Leuprolide in Prostate Cancer

1. Assess cardiovascular history and baseline testosterone levels 1
2. Begin antiandrogen (flutamide, bicalutamide) 1 week before first leuprolide injection if patient has symptomatic metastatic disease 1
3. Administer leuprolide 7.5 mg IM monthly or 22.5 mg every 3 months 1, 2
4. Continue antiandrogen for 2-3 weeks to prevent flare 1
5. Monitor testosterone levels at 4 weeks to confirm castrate levels (<50 ng/dL) 2, 4
6. Screen for osteopenia after 6-12 months of therapy 1

Initiating Ovarian Suppression in Breast Cancer

1. Confirm premenopausal status and ER/PR-positive tumor 1
2. Start leuprolide 3.75 mg IM every 4 weeks concurrently with or after chemotherapy 1
3. Monitor estradiol and FSH/LH levels if under 60 years and amenorrheic ≤12 months, particularly before next dose in women under 45 1
4. Continue for 5 years total duration 1
5. After stopping ovarian suppression, transition to tamoxifen if still premenopausal 1