Send to

Choose Destination
Reprod Sci. 2018 Oct 1:1933719118799203. doi: 10.1177/1933719118799203. [Epub ahead of print]

Gonadotropin-Releasing Hormone Analogs for Gonadal Protection During Gonadotoxic Chemotherapy: A Systematic Review and Meta-Analysis.

Author information

1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT, USA.
2 Division of Health Care Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany.
3 Department of Neurology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany.
4 Department of Obstetrics and Gynecology, Koc University, School of Medicine, Istanbul, Turkey.



A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents.


Major databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017. Methods and Study Selection Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs).


The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials [RCTs] and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I2 = 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment.


Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy. Capsule: The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents.


alkylating agents; chemotherapy; gonadotropin-releasing hormone analogs; meta-analysis; ovarian protection


Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center