title: Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women.
abstract: BACKGROUND
  Chemotherapy has significantly improved prognosis for patients with malignant and some non-malignant conditions. This treatment, however, is associated with ovarian toxicity and gonadotropin-releasing hormone (GnRH) analogues may have a protective effect on the ovaries. The mechanism of action of GnRH is based on suppression of the gonadotropin levels to simulate pre-pubertal hormonal milieu and decrease utero-ovarian perfusion.
  
  
  OBJECTIVE
  To assess the efficacy and safety of GnRH analogues given before or in parallel to chemotherapy to prevent chemotherapy-related ovarian damage in premenopausal women with malignant or non-malignant conditions.
  
  
  METHODS
  We searched the Cochrane Gynaecological Cancer Group Specialized Register (up to July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2011); MEDLINE (1950 to July 2011); EMBASE (1980 to July 2011); and the Chinese Biomedicine Database (CBM) (1976 to July 2011).
  
  
  METHODS
  Randomized controlled trials (RCTs), in all languages, which examined the effect of GnRH analogues for chemotherapy-induced ovarian failure in premenopausal women, were eligible for inclusion in the review.
  
  
  METHODS
  The review authors independently extracted data and assessed trial quality using the Cochrane risk of bias tool. We analyzed binary data using risk ratios (RRs) with 95% confidence intervals (CI) and for continuous data, we used the standardized mean difference (SMD) to combine trials. As there was substantial difference in the types of chemotherapy used, we applied the random-effects model in our analyses. We contacted study authors for additional information.
  
  
  RESULTS
  Included studies in this review showed that intramuscular/subcutaneous administration of GnRH agonists was effective in protecting menstruation and ovulation after chemotherapy (resumed menses: RR 1.90, 95% CI 1.30 to 2.79; amenorrhoea: RR 0.08, 95% CI 0.01 to 0.58; ovulation: RR 2.70, 95% CI 1.52 to 4.79), whereas intranasal administration of GnRH agonists had no protective effect on ovaries (resumed menses: RR 0.75, 95% CI 0.33 to 1.72; ovulation: RR 1.13, 95% CI 0.20 to 6.24). Pregnancy rates were not significantly different between groups (intramuscular/subcutaneous GnRH agonist: RR 0.21, 95% CI 0.01 to 4.09; intranasal GnRH agonist: RR 0.41, 95% CI 0.02 to 8.84). Ultrasound antral follicular count (AFC) was not significantly different between groups (SMD 1.11, 95% CI 0.32 to 1.90).
  
  
  CONCLUSIONS
  The use of GnRH agonists should be considered in women of reproductive age receiving chemotherapy. Intramuscular or subcutaneous GnRH analogues seem to be effective in protecting ovaries during chemotherapy and should be given before or during treatment, although no significant difference in pregnancy rates was seen.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, West China Women’s and Children’s Hospital,Chengdu, China. cqhulina@126.com.
authors.forename: Hengxi
authors.initials: H
authors.lastname: Chen
authors.forename: Jinke
authors.initials: J
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Cui
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
mesh_terms: D000281:Administration, Intranasal; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives*; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008598:Menstruation / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects; D017697:Premenopause; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic
chemical_list: D007987:Gonadotropin-Releasing Hormone