Leuprolide

Key Benefits#

• Medical: reduces testosterone in prostate cancer
• Medical: suppresses estrogen in endometriosis and uterine fibroids
• Medical: delays precocious puberty
• Research: testosterone rebound effect after short course
• Transgender care: hormone suppression in adolescents
• Research: hormonal re-sensitization protocols

Mechanism of Action#

Leuprolide is a GnRH analog with ~80x higher GnRH receptor affinity than native GnRH. Continuous (non-pulsatile) GnRH receptor stimulation causes receptor downregulation and desensitization, leading to paradoxical suppression of LH, FSH, and sex hormone production within 2-4 weeks. This is used therapeutically to create a 'chemical castration' state in prostate cancer (testosterone fuel cut-off) and endometriosis (estrogen suppression). An initial 'testosterone flare' occurs in the first week before suppression kicks in. Some researchers use short-course leuprolide in PCT protocols to 'reset' GnRH receptors.

Dosing Protocols#

Side Effects#

• Hot flashes (with testosterone suppression)
• Decreased libido and erectile dysfunction
• Initial testosterone flare (first 1–2 weeks)
• Bone density loss with long-term use
• Fatigue and depression
• Injection site reactions
• Rare: pituitary apoplexy at very high doses

Contraindications#

Not for use without medical supervision. Initial testosterone flare may worsen prostate cancer symptoms. Bone density loss with long-term use requires monitoring. Pregnancy: category X (teratogenic).

Storage#

Refrigerate vials at 2–8°C. Depot kits: room temperature for up to 24 months. Follow product-specific storage instructions.

1. 1.
   Apalutamide + Abiraterone acetate plus Prednisone (AAP) + Leuprolide with Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer: A Single Arm, Phase 2 Study

   McBride SM, Spratt DE, Kollmeier M, Abida W, Xiao H, Slovin SF et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · 2026PubMed Verified

2. 2.
   Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate Cancer: A Randomized Clinical Trial

   Patel SA, Yadalam AK, van Assen M, Cantu SM, Onnis C, Zheng B et al. · JAMA cardiology · 2026PubMed Verified

3. 3.
   Dydrogesterone and Letrozole Combination for the Treatment of Endometriosis: A Mechanism-Based Therapeutic Approach

   Rai SK, Kumar R, Khan MI, Kumar A · Obstetrics and gynecology international · 2026PubMed Verified

4. 4.
   A single biomarker may not yield a reliable binary clinical answer: B cell lymphoma 6 testing and resulting interventions for endometriosis in infertility care

   Taggar A, Ulrich A, Tan Y, Luciano DE, Sanders M, Courtois ET et al. · F&S reports · 2026PubMed Verified

5. 5.
   Long-term Safety, Efficacy, and PROs: Phase 3 Study of Leuprolide Acetate 6-month IM Depot in Central Precocious Puberty

   Klein KO, Mauras N, Nayak S, Sunil B, Soliman AM, Kansra AR · Journal of the Endocrine Society · 2026PubMed Verified

6. 6.
   The effect of tinzaparin sodium and leuprolide acetate in an experimental mouse model of endometriosis: The rol of the WNT/beta-catenin pathway

   Albak Y, Sönmez Ünal G, Yıldız Ç, Çetin M, Durna Daştan S, Gümüş E et al. · Turkish journal of obstetrics and gynecology · 2026PubMed Verified

7. 7.
   CT-Based Quantification of Prostate Volume Change After LHRH-Agonist Androgen Deprivation: A Prospective, Three-Reader Study for Radiotherapy Planning

   Feltes Benítez N, Galdeano-Rubio M, Muñoz-Rodriguez J, Domínguez A, Solé I Monné JM, Pérez Márquez M et al. · Life (Basel, Switzerland) · 2025PubMed Verified

8. 8.
   Rare phenotypic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency: case series from infancy to adolescence

   Sridhar S, Muthu AK, Palaniappan S, Nandini K, Chandrasekaran A, Kalavathy R · Journal of pediatric endocrinology & metabolism : JPEM · 2026Case ReportPubMed Verified

9. 9.
   Development of institutional guidelines for menstrual suppression and abnormal uterine bleeding in patients undergoing intensive chemotherapy for hematologic malignancies

   Roberts L, Stokvis K, Christianson M, Gojo I, Seraphin M, Newman M · Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026PubMed Verified

10. 10.
    Progestin-suppressed in vitro fertilization cycles yield similar outcomes to traditional protocols in patients with diminished ovarian reserve

    Pierpoint SC, Gonzalez AM, Peavey MC, Williams CD, Smith LP, Purcell SH et al. · F&S reports · 2025PubMed Verified

11. 11.
    Late-stage Tyrosine ortho-C(sp(2))-H Alkenylation for Macrocyclic Peptide SuFEx Proximity Labeling and Targeted Degradation

    Wang P, Wang K, Yin S, Liu X, Xie W, Li H et al. · Angewandte Chemie (International ed. in English) · 2026PubMed Verified

12. 12.
    Combination Hormonal Drug Therapy Inhibits In Vitro Growth of Adult Ovarian Granulosa Tumor Cells

    Summey RM, Iden M, Tsaih SW, Schmidt R, Parashar D, Wang S et al. · Cancer investigation · 2026PubMed Verified

13. 13.
    Cerebellar Hemangioblastoma Resection Complicated by Postoperative Vasogenic Edema in the Setting of Concurrent Immunotherapy Treatment

    Sheth A, Dietz N, Becerril-Gaitan A, Kasem R, Mistry A, Williams BJ et al. · Cureus · 2025Case ReportPubMed Verified

14. 14.
    Novel Combination of Metronomic Cyclophosphamide and Darolutamide Induces Sustained Clinical Response in Heavily Treated Prostate Cancer with Prostate-Specific Membrane Antigen-Negative Liver Metastases and Rapid Disease Progression

    Patel VM, Cai Q, Ahn R, Hill K, Wang J · Case reports in oncology · 2026Case ReportPubMed Verified

15. 15.
    Limosilactobacillus reuteri NCU-37 alleviates leuprorelin-induced perimenopausal syndrome in infertile women by modulating the gut microbiota: a randomized controlled trial

    Wu X, Chen W, Yong Q, Zeng Q, You J, Zeng K et al. · Food & function · 2026RCTPubMed Verified

16. 16.
    Success of Menstrual Suppression for Patients with Obstructive Müllerian Anomalies

    Isaacson EE, Richardson R, McCracken K, Rosen MW, Dendrinos M · Journal of pediatric and adolescent gynecology · 2025PubMed Verified

17. 17.
    Treatment of High-Risk Biochemically Recurrent Prostate Cancer With Enzalutamide in Combination With Leuprolide: Secondary Endpoints From the EMBARK Trial

    Shore ND, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Sridharan S et al. · The Journal of urology · 2025PubMed Verified

18. 18.
    Enzalutamide Monotherapy for the Treatment of Prostate Cancer With High-Risk Biochemical Recurrence: EMBARK Secondary End Points

    Shore ND, De Giorgi U, Tutrone RF, Bailen JL, Roos EPM, Kliment J et al. · The Journal of urology · 2025PubMed Verified

19. 19.
    Unresectable Desmoplastic Small Round Cell Tumor: A Case Report and Review of the Literature

    Rueda DA, Fernández Ugarte ML, Torressi N, Acevedo V, Lezcano FG, Moreira Grecco A et al. · Case reports in oncology · 2025Case ReportPubMed Verified

20. 20.
    Does gonadotropin-releasing hormone analogue treatment alter body mass index in boys with central precocious puberty?

    Unsal Y, Vuralli Karaoglan D, Gonc EN, Alikasifoglu A, Kandemir N, Ozon ZA · European journal of pediatrics · 2025PubMed Verified

21. 21.
    The effect of the magic glove technique on pain and anxiety in children during leuprolide injection: A quasi-experimental study

    Sadat Hosseini AS, Rostamian F, Haghani S · Journal of pediatric nursing · 2026RCTPubMed Verified

22. 22.
    Electroacupuncture for Refractory Chronic Pelvic Pain: A Case Report with 24-Month Follow-Up

    Gao S, Sun Y, Liu Z · International journal of women's health · 2025Case ReportPubMed Verified

23. 23.
    Enzalutamide with or without leuprolide in patients with high-risk biochemically recurrent prostate cancer: EMBARK post hoc analysis by age

    Shore ND, De Giorgi U, Kalac M, Tang Y, Croitoru R, Rosales M et al. · European journal of cancer (Oxford, England : 1990) · 2026RCTPubMed Verified

24. 24.
    The Ethics of Gender-Affirming Care: An Evaluation of the Research

    Cirucci CA · The Linacre quarterly · 2025PubMed Verified

25. 25.
    Clinical Effectiveness of Oral Relugolix in Advanced Prostate Cancer: A Structured Review of Current Primary Research

    Higgi A, Melvin C, Abdelrasheed A, Wilson K · Cureus · 2025ReviewPubMed Verified

26. 26.
    Impact of sleep fragmentation and estradiol suppression on positive and negative affect: Results of an experimental model of menopause

    Nathan MD, Spagnolo PA, Grant LK, Rahman SA, Gonsalvez I, Harder J et al. · Psychoneuroendocrinology · 2026PubMed Verified

27. 27.
    Upconverting Nanoparticle-Loaded Microneedles for Near-Infrared Responsive Delivery of Gonadotropins to Increase Success of In Vitro Fertilization

    Tam V, Trana R, Nieto-Arguello A, Olasubulumi OO, Babity S, Skripka A et al. · Small (Weinheim an der Bergstrasse, Germany) · 2026PubMed Verified

28. 28.
    Sterile Abscess Following Intramuscular Leuprolide Acetate Injection for Endometriosis: A Case Report

    Evans JR, Krishnan V, Hewitt G, Fei YF, Kebodeaux CA · Journal of pediatric and adolescent gynecology · 2025Case ReportPubMed Verified

29. 29.
    Racial Differences in Adverse Events After Androgen Deprivation in Veterans With Prostate Cancer

    Friedrich NA, Janes JL, Parrish J, De Hoedt AM, Josan K, Tatonetti NP et al. · JAMA network open · 2025PubMed Verified

30. 30.
    Therapeutic impact of leuprorelin acetate on spinal and bulbar muscular atrophy: pre- and post-marketing observational study

    Hashizume A, Hanazawa R, Yamada S, Ito D, Kishimoto Y, Komori S et al. · Journal of neurology · 2025PubMed Verified

31. 31.
    Relugolix in treatment of prostate cancer: a review

    Kyriazis I, Bellos T, Katsimperis S, Angelopoulos P, Neofytoy P, Varkarakis I et al. · Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica · 2025ReviewPubMed Verified

32. 32.
    Two cases of MACS due to PBMAH associated with an in vivo aberrant response to LHRH treated with leuprolide acetate

    Branchaud-Croisetière L, Maillet M, St-Jean M · Endocrinology, diabetes & metabolism case reports · 2025PubMed Verified

33. 33.
    Effective management of a diabetic patient with hormone-receptor-positive, HER2-negative metastatic breast cancer using nanosomal docetaxel lipid suspension for 12 cycles: A case report

    Rammohan P, Patel L, Bunger D, Chaturvedi A, Ahmad I · Molecular and clinical oncology · 2025Case ReportPubMed Verified

34. 34.
    Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer

    Shore ND, Luz MA, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM et al. · The New England journal of medicine · 2025PubMed Verified

35. 35.
    Peripheral Precocious Puberty Due to Autonomous Gonadal Activation: A Multicenter Experience

    Yewale S, Khadilkar V, Shah N, Mehta S, Prasad HK, Oza C et al. · Cureus · 2025PubMed Verified

36. 36.
    Prolonged oral GnRH-antagonist administration before euploid embryo transfer in patients with endometriosis: a prospective randomized pilot non-inferiority trial

    Surrey ES, Katz-Jaffe M, Kondapalli LA, Schoolcraft WB, Makloski R · Reproductive biomedicine online · 2025PubMed Verified

37. 37.
    Correction to: The Effect of Leuprolide Acetate 11.25 mg 3-Month Formulation in Children with Central Precocious Puberty: A Systematic Review and Meta-analysis

    Han L, Zhai C, Da L, Sun Y · Advances in therapy · 2025PubMed Verified

38. 38.
    Self-assembled leuprolide-oleic acid nanoparticles encapsulating docetaxel for synergistic drug delivery

    Lee J, Nguyen HD, Abdullah SS, Löbenberg R, Lee BJ · International journal of pharmaceutics · 2025PubMed Verified

39. 39.
    PubMed PMID 41474842

    2025ReviewPubMed Verified

40. 40.
    Differential Effects of Ovarian Steroids in Women With and Without Premenstrual Dysphoric Disorder: A Replication and Extension of Findings

    Wei SM, Wakim P, Martinez PE, Nieman LK, Rubinow DR, Schmidt PJ · The American journal of psychiatry · 2025PubMed Verified

41. 41.
    Effectiveness and Safety of Postoperative Medical Treatments Following Fertility-Preserving Surgery for Endometriosis: A Network Meta-Analysis

    Xiong Y, Huang W, Wang C, Ma W, Jin S, Lin J et al. · BJOG : an international journal of obstetrics and gynaecology · 2026Meta-AnalysisPubMed Verified

42. 42.
    Tolerability and Shared Decision-Making in the Hormonal Management of Endometriosis-Associated Pain

    Pinto da Costa Viana D, Jacobsen L, Padovesi I, Comin A, Correia ELS, Fernandes DDM et al. · Biomedicines · 2025ReviewPubMed Verified

43. 43.
    Optimization of aqueous remote loading of leuprolide in poly(lactic-co-glycolic acid) microspheres

    Giles MB, Walker J, Schwendeman SP · International journal of pharmaceutics · 2025PubMed Verified

44. 44.
    Multiplex Apolipoprotein Panel Improves Cardiovascular Event Prediction and Cardiovascular Outcome by Identifying Patients Who Benefit From Targeted PCSK9 Inhibitor Therapy

    Reijnders E, Bossuyt PM, Jukema JW, Ruhaak LR, Romijn FPHTM, Szarek M et al. · Arteriosclerosis, thrombosis, and vascular biology · 2025RCTPubMed Verified

45. 45.
    An 85-Year-Old Man With Dyspnea and a History of Hormone Therapy for Prostate Adenocarcinoma

    Nakashima K, Tomoi C, Kakiuchi T, Saikawa S, Igarashi K, Ishizuka T · Chest · 2025Case ReportPubMed Verified

46. 46.
    Impact of dietary patterns on body weight in girls with central precocious puberty treated with leuprolide during the COVID-19 pandemic

    Figueiredo FN, Ganen AP, Figueiredo CC, Evangelista NMA, Fernandes VFT, Pacheco LA et al. · Frontiers in pediatrics · 2025PubMed Verified

47. 47.
    Treatment of overweight and obese girls experiencing central precocious puberty: a comparison of the effectiveness of leuprolide acetate and triptorelin pamoate

    Thaneetrakool T, Aroonparkmongkol S, Chatdamrongsakool K, Numsriskulrat N, Supornsilchai V, Wacharasindhu S et al. · Annals of pediatric endocrinology & metabolism · 2025PubMed Verified

48. 48.
    Commentary on "Treatment of overweight and obese girls experiencing central precocious puberty: a comparison of the effectiveness of leuprolide acetate and triptorelin pamoate&quot

    Kim SH · Annals of pediatric endocrinology & metabolism · 2025PubMed Verified

49. 49.
    Late-onset Leber's hereditary optic neuropathy and antiandrogens for prostate cancer: is there a causative link?

    Amore G, Carbonelli M, D'Angeli D, Bonan L, Faustini-Fustini M, Maresca A et al. · Frontiers in neurology · 2025PubMed Verified

50. 50.
    Effect of PCSK9 Inhibition With Alirocumab in Patients With Probable Familial Hypercholesterolemia or Type III Hyperlipoproteinemia: Results From the ODYSSEY OUTCOMES Trial

    Geba GP, Mohammadi KA, Damask A, Paulding C, Lotta LA, Hindy G et al. · Journal of the American Heart Association · 2025RCTPubMed Verified