Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies

Ann Oncol. 2015 Dec;26(12):2408-19. doi: 10.1093/annonc/mdv374. Epub 2015 Sep 7.


Background: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS).

Methods: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models.

Results: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044).

Conclusion: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

Keywords: breast cancer; fertility preservation; luteinizing hormone-releasing hormone agonists; ovarian function preservation; premenopausal patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / adverse effects*
  • Female
  • Fertility / drug effects*
  • Fertility / physiology
  • Gonadotropin-Releasing Hormone / agonists*
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Ovary / drug effects*
  • Ovary / metabolism
  • Pregnancy
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / drug therapy*
  • Primary Ovarian Insufficiency / metabolism
  • Randomized Controlled Trials as Topic / methods*


  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone