GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial

Ann Oncol. 2017 Aug 1;28(8):1811-1816. doi: 10.1093/annonc/mdx184.


Background: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI.

Patients and methods: This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI.

Results: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.

Conclusion: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

Keywords: GnRH analogue; breast cancer; chemoprotection; ovary.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amenorrhea / chemically induced
  • Amenorrhea / prevention & control*
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Early Diagnosis
  • Female
  • Gonadotropin-Releasing Hormone / agonists*
  • Goserelin / administration & dosage
  • Goserelin / therapeutic use*
  • Humans
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / prevention & control*
  • Prospective Studies


  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Goserelin
  • Gonadotropin-Releasing Hormone