The rate of chemotherapy-induced ovarian failure (CIOF) has been reported as 14-100% and is age- and agent-dependent. The role of GnRH analogs (GnRHa) and oral contraceptives (OC) in the prevention of CIOF is questionable. We performed a systematic review and a meta-analysis of studies assessing the efficacy of hormonal interventions in reducing CIOF in cancer or systemic lupus erythematosus (SLE) patients treated with chemotherapy. MEDLINE, EMBASE, and conference proceedings were searched until October 2009. From 504 potentially relevant references, 21 comparative studies were included for review and analysis. Data were collected to determine the risk ratio (RR) for amenorrhea, FSH levels, pregnancy rate, and biomarkers for ovarian reserve. Sixteen studies (SLE: 4 studies, 85 patients; malignancy: 12 studies, 596 patients) which assessed GnRHa for fertility preservation prior to chemotherapy were included in the meta-analysis. Five studies which evaluated the use of OC were systematically reviewed. Meta-analysis revealed that GnRHa are effective in reducing amenorrhea rates in all patients (RR 0.26, 95% CI 0.14-0.49). Pregnancy rate was higher in the GnRHa arm. The advantage of GnRHa was shown only in observational studies, but not in randomized controlled trials. Biomarkers for ovarian reserve were similar in both arms. Studies evaluating the efficacy of oral contraceptives in preserving ovarian function showed inconclusive results. GnRHa appears to improve menstruation resumption. Nevertheless, randomized prospective trials are less conclusive for their real value in conserving ovarian reserve and pregnancy. Large-scale prospective randomized trials are warranted to evaluate the role of GnRHa in preventing CIOF.