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 hormone releasing hormone (GnRH) 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 GnRH 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 (FSH) 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% vs 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% vs 34.8% in the control group (P = 0.048). FSH 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 (AMH) 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.
Trial registration: EudraCT 2004-000133-11
- breast cancer
- GnRH analogue