Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: A meta-analysis of randomized controlled trials

Background: While chemotherapy significantly improves the prognosis of breast cancer patients, it also damages otherwise healthy organs, such as the ovaries. Gonadotropin-releasing hormone (GnRH) agonists may have a protective effect against chemotherapy-induced ovarian toxicity in premenopausal women being treated for breast cancer; however, studies of its clinical efficacy have reported conflicting results. Objectives: This meta-analysis was designed to assess the collective data from previous studies of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian toxicity in premenopausal women with breast cancer. Methods: Electronic literature databases (Cochrane Library, Medline, and Embase) were searched for relevant randomized controlled trials (RCTs) published prior to April 2012. Only RCTs that compared GnRH agonists plus chemotherapy to chemotherapy alone for premenopausal women with breast cancer were selected. A random-effects model was used to calculate the risk ratios (RRs) for premature ovarian failure (POF) within one year after chemotherapy treatment and rates of resumed menses and spontaneous pregnancy during the follow-up period after cessation of treatment. Results: Five RCTs composed of 528 patients (GnRH agonist combination, n = 274; chemotherapy alone, n = 254) were included in the meta-analysis. Significantly fewer women treated with GnRH agonist experienced post-chemotherapy POF, yielding a RR of 0.40 (vs. chemotherapy alone, 95% confidence interval [CI] 0.21-0.75). In contrast, both treatment groups experienced similar rates of resumed menses (RR = 131, 95% Cl 0.93-1.85) and spontaneous pregnancy (RR = 0.96, 95% CI 0.20-4.56). Conclusion: Concurrent administration of GnRH agonists during chemotherapy treatment of breast cancer in premenopausal women appears to protect against chemotherapy-related POF in the first year after treatment, but appears to have no effect on resumed menses or spontaneous pregnancy rates. (C) 2012 Elsevier Ltd. All rights reserved.