Gonadotropin-releasing Hormone Agonist for the Preservation of Ovarian Function in Survivors of Haematopoietic Stem Cell Transplantation for Haematological Diseases

Overview

Journal BMC Womens Health

Publisher Biomed Central

Specialty Gynecology & Obstetrics

Date 2022 Nov 8

PMID 36345026

Authors

Zhenhong Wang

Jian An

Chaohua Wang

Affiliations

Soon will be listed here.

Abstract

Objective: Administration of GnRH agonist (GnRHa) prior to chemotherapy may decreases the risk of gonadal dysfunction in patients with tumors. However, relevant data in haematopoietic stem cell transplantation (HSCT) recipients has not yet been established. Hence, the present study was designed to evaluate the clinical efficacy of GnRHa cotreatment prior to myeloablative regimens on ovarian protection in female survivors of HSCT for haematological diseases.

Patients And Methods: Eligible patients were divided into a GnRHa group and a control group. Medical records regarding age at HSCT; diagnosis/indication for HSCT; pre- and posttransplantation serum sex hormone levels; menstruation and perimenopausal symptoms after HSCT were collected and compared. The primary and secondary outcome was the incidence of premature ovarian insufficiency (POI) symptoms associated with hypoestrogenism.

Results: A total of 330 patients were enrolled in the study: 19 patients were lost to follow-up, and clinical information was obtained in 311 patients. There was no significant difference in the primary outcome of follow-up between the two groups (78.50% [84 of 107] for the GnRHa group versus 83.33% [170 of 204] for the control group). The adjusted relative risks (RR) and 95% confidence interval (CI) were 1.19 and 0.73-1.93 (P = 0.487). Among patients who received cotreatment with GnRHa, 62.62% (67 of 107) complained of perimenopausal symptoms, which was significantly lower than the 74.51% (152 of 204) in the control group (adjusted RR: 1.46, 95% CI: 1.04-2.06, P = 0.031).

Conclusion: GnRHa cotreatment may not decrease the POI rate in HSCT survivors. However, it may reduce perimenopausal symptoms in this population, suggesting a potential benefit of GnRHa in clinical practice and warrant further researches.

Citing Articles

Gonadotropin-Releasing Hormone (GnRH) Agonists Do Not Protect Ovarian Function in Patients Undergoing Stem Cell Transplants.

Benor A, Decherney A Cureus. 2024; 16(4):e58387.

PMID: 38756303 PMC: 11097921. DOI: 10.7759/cureus.58387.

References

Peccatori F, Azim Jr H, Orecchia R, Hoekstra H, Pavlidis N, Kesic V . Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 Suppl 6:vi160-70. DOI: 10.1093/annonc/mdt199. View

Demeestere I, Brice P, Peccatori F, Kentos A, Dupuis J, Zachee P . No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial. J Clin Oncol. 2016; 34(22):2568-74. DOI: 10.1200/JCO.2015.65.8864. View

Blumenfeld Z, Patel B, Leiba R, Zuckerman T . Gonadotropin-releasing hormone agonist may minimize premature ovarian failure in young women undergoing autologous stem cell transplantation. Fertil Steril. 2012; 98(5):1266-70.e1. DOI: 10.1016/j.fertnstert.2012.07.1144. View

Bedaiwy M, Abou-Setta A, Desai N, Hurd W, Starks D, El-Nashar S . Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril. 2010; 95(3):906-14.e1-4. DOI: 10.1016/j.fertnstert.2010.11.017. View

Phelan R, Mann E, Napurski C, DeFor T, Petryk A, Miller W . Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning. Bone Marrow Transplant. 2016; 51(10):1369-1375. PMC: 5299542. DOI: 10.1038/bmt.2016.150. View

Imai A, Sugiyama M, Furui T, Tamaya T, Ohno T . Direct protection by a gonadotropin-releasing hormone analog from doxorubicin-induced granulosa cell damage. Gynecol Obstet Invest. 2006; 63(2):102-6. DOI: 10.1159/000096062. View

Letourneau J, Ebbel E, Katz P, Katz A, Ai W, Jo Chien A . Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2011; 118(6):1710-7. PMC: 3235264. DOI: 10.1002/cncr.26459. View

Oktay K, Bedoschi G . Appraising the Biological Evidence for and Against the Utility of GnRHa for Preservation of Fertility in Patients With Cancer. J Clin Oncol. 2016; 34(22):2563-5. DOI: 10.1200/JCO.2016.67.1693. View

. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019; 112(6):1022-1033. DOI: 10.1016/j.fertnstert.2019.09.013. View

10.

Kim S, Kim S, Lee J, Woodruff T . Toward precision medicine for preserving fertility in cancer patients: existing and emerging fertility preservation options for women. J Gynecol Oncol. 2016; 27(2):e22. PMC: 4717227. DOI: 10.3802/jgo.2016.27.e22. View

11.

Kitajima Y, Endo T, Nagasawa K, Manase K, Honnma H, Baba T . Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5. Endocrinology. 2005; 147(2):694-9. DOI: 10.1210/en.2005-0700. View

12.

Pup L, Zanet E, Rupolo M, Talamini R, Tirelli U, Mazzucato M . Which tools may help physicians in female fertility prediction after autologous bone marrow transplantation for lymphoma? A pilot study. J Chemother. 2014; 26(5):293-9. DOI: 10.1179/1973947813Y.0000000162. View

13.

Joshi S, Savani B, Chow E, Gilleece M, Halter J, Jacobsohn D . Clinical guide to fertility preservation in hematopoietic cell transplant recipients. Bone Marrow Transplant. 2014; 49(4):477-84. PMC: 4071767. DOI: 10.1038/bmt.2013.211. View

14.

Cheng Y, Takagi M, Milbourne A, Champlin R, Ueno N . Phase II study of gonadotropin-releasing hormone analog for ovarian function preservation in hematopoietic stem cell transplantation patients. Oncologist. 2012; 17(2):233-8. PMC: 3286172. DOI: 10.1634/theoncologist.2011-0205. View

15.

Wallace W, Anderson R, Irvine D . Fertility preservation for young patients with cancer: who is at risk and what can be offered?. Lancet Oncol. 2005; 6(4):209-18. DOI: 10.1016/S1470-2045(05)70092-9. View

16.

Christin-Maitre S, Givony M, Albarel F, Bachelot A, Bidet M, Blanc J . Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome). Ann Endocrinol (Paris). 2021; 82(6):555-571. DOI: 10.1016/j.ando.2021.09.001. View

17.

Lambertini M, Ceppi M, Poggio F, Peccatori F, Azim Jr H, Ugolini D . Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann Oncol. 2015; 26(12):2408-19. DOI: 10.1093/annonc/mdv374. View

18.

Behringer K, Wildt L, Mueller H, Mattle V, Ganitis P, van den Hoonaard B . No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group. Ann Oncol. 2010; 21(10):2052-2060. DOI: 10.1093/annonc/mdq066. View

19.

Della Corte L, Barra F, Mercorio A, Evangelisti G, Rapisarda A, Ferrero S . Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis. Expert Opin Drug Metab Toxicol. 2020; 16(9):759-768. DOI: 10.1080/17425255.2020.1789591. View

20.

Soleimani R, Heytens E, Oktay K . Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One. 2011; 6(4):e19475. PMC: 3084884. DOI: 10.1371/journal.pone.0019475. View