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. (3rd March 2020)

• Record Type: Journal Article
• Authors: Luong, Shi-Nan; Isaacs, Anthony; Liu, Zhixin; Sin, Fang E; Giles, Ian
• Is Part Of: Expert review of clinical immunology. Volume 16:Number 3(2020)
• Page Start: 321
• Page End: 333
• Publication Date: 2020-03-03
• Subjects: Sustained amenorrhea -- cyclophosphamide -- gonadotropin-releasing hormone agonists -- rheumatic disease; Clinical immunology -- Periodicals; 616.079
• DOI: 10.1080/1744666X.2020.1724091
• Languages: English
• ISSNs: 1744-666X

Abstract

ABSTRACT: Objectives : To systematically review risk of sustained amenorrhea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate efficacy of gonadotropin-releasing hormone agonists (GnRHa) to reduce this risk. Methods : Systematic search for papers reporting incidence of sustained amenorrhea ≥12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide compared to IV cyclophosphamide alone. Results : From 31 articles and 1388 patients (mean age 27.7 years) sustained amenorrhea 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 amenorrhea occurred in 2/56 (3.6%) patients treated with GnRHa, compared to 15/37 (40.5%) controls. Pooled odds ratio of sustained amenorrhea 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 amenorrhea with IV cyclophosphamide was observed in patients with ARD, especially with increasing age and cumulative doses >5 g. GnRHa reduced this risk and should be considered with IV cyclophosphamide in women of childbearing age with ARD.