GnRH analogues protect ovarian function in women undergoing chemotherapy for breast cancer

January 2022 Cancer trials Willem van Altena
Breast cancer. 3d illustration

A clinical study in per-menopausal Asian women with early breast cancer has found that administering gonadotropin-releasing hormone analogues (GnRHa) with chemotherapy (CT) protects against ovarian insufficiency.

The primary concern with the use of CT in pre-menopausal women is that CT tends to induce menopause. Therefore, to address this issue, a randomised clinical trial has evaluated the effect of GnRHa treatment on ovarian function in women undergoing CT. 

Study design

A multicenter, open-label, randomised clinical study enrolled 330 patients (18-49 years) who were randomly divided into two groups to receive either cyclophosphamide-containing CT with GnRHa (n=165) or CT alone (control group, n=165). GnRHa was subcutaneously (3.6 mg goserelin or 3.75 mg leuprorelin) administered once every 28 days from 1 to 2 weeks before the first cycle of CT to 4 weeks after the last cycle of CT. The study’s primary endpoint was the incidence of premature ovarian insufficiency (POI-defined as anti-mullerian hormone levels of <0.5 ng/mL).

Main findings

After a median follow up of 49 months (25-60 months), differences in 4-year overall survival (OS) and tumour-free survival (TFS) was not significant. However, after a year of CT, treatment with GnRHa resulted in a lower incidence of POI than CT alone (10.3% vs 44.5%, odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Additionally, the GnRHa group had a significantly better anti-mullerian hormone resumption versus the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). Finally, a post hoc analysis in patients aged  <35 showed that the GnRHa group had a higher four year TFS than the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03).


The randomised clinical study demonstrated that GnRHa treatment with CT reduces the risk of POI and promotes recovery of ovarian function in premenopausal patients with breast cancer.


Zong X, Yu Y, Yang H, et al. Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial. JAMA Oncol. Published online December 30, 2021. doi:10.1001/jamaoncol.2021.6214