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A systematic review and meta-analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child-bearing age with autoimmune rheumatic disease

Luong, S-N; Isaacs, A; Sin, FE; Giles, I; (2020) A systematic review and meta-analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child-bearing age with autoimmune rheumatic disease. Expert Review of Clinical Immunology , 16 (3) pp. 321-333. 10.1080/1744666X.2020.1724091. Green open access

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Abstract

Objectives: To systematically review the risk of sustained amenorrhoea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate the efficacy of gonadotropin releasing hormone agonists (GnRHa) to reduce this risk. / Methods: Systematic search for papers reporting the incidence of sustained amenorrhoea ≥ 12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide compared to IV cyclophosphamide alone. / Results: From 31 articles and 1388 patients with a mean age of 27.7 years, sustained amenorrhoea occurred in 273 patients (19.7%). Of 56 patients (mean age range 23.9-25.6 years) receiving GnRHa and IV cyclophosphamide, and 37 controls (mean age range 25-30.1 years) given IV cyclophosphamide only, sustained amenorrhoea occurred in 2/56 (3.6%) patients treated with GnRHa, compared to 15/37 (40.5%) controls. Pooled odds ratio of sustained amenorrhoea with GnRHa and cyclophosphamide versus cyclophosphamide alone was 0.054 (95% CI 0.0115-0.2576 p<0.001), corresponding to a number needed to treat of 2.7 (95% CI 1.955-4.388) and absolute risk reduction of 36.95% (95% CI 35.6-38.4%). / Conclusion: Sustained amenorrhoea with IV cyclophosphamide was observed in patients with ARD, especially with increasing age and cumulative doses >5g. GnRHa reduced this risk and should be considered with IV cyclophosphamide in women of childbearing age with ARD.

Type: Article
Title: A systematic review and meta-analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child-bearing age with autoimmune rheumatic disease
Event: Annual Conference of the British-Soceity-for-Rheumatology
Location: Birmingham, ENGLAND
Dates: 30 April 2019 - 02 May 2019
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/1744666X.2020.1724091
Publisher version: https://doi.org/10.1080/1744666X.2020.1724091
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Sustained amenorrhea, cyclophosphamide, gonadotropin-releasing hormone agonists, rheumatic disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10091188
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