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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.

AbstractBACKGROUND:
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.
AuthorsM Lambertini, M Ceppi, F Poggio, F A Peccatori, H A Azim Jr, D Ugolini, P Pronzato, S Loibl, H C F Moore, A H Partridge, P Bruzzi, L Del Mastro
JournalAnnals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 26 Issue 12 Pg. 2408-19 (Dec 2015) ISSN: 1569-8041 [Electronic] England
PMID26347105 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review)
Copyright© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Chemical References
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
Topics
  • Antineoplastic Agents, Hormonal (adverse effects)
  • Female
  • Fertility (drug effects, physiology)
  • Gonadotropin-Releasing Hormone (agonists, metabolism)
  • Humans
  • Ovary (drug effects, metabolism)
  • Pregnancy
  • Primary Ovarian Insufficiency (chemically induced, drug therapy, metabolism)
  • Randomized Controlled Trials as Topic (methods)

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