Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China

Abstract

IMPORTANCEStudies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results.OBJECTIVE To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment.

Ovarian reserve in premenopausal women with breast cancer

“…This study showed that GnRHa treatment was an important factor affecting the incidence of POI: The risk of POI in patients with combined GnRHa was only 0.09 times that in those without combined GnRHa. Meanwhile, the probability of ovarian function recovery in patients with short-term ovarian function impairment after chemotherapy was 18.49 times higher in patients with GnRHa combination than in patients without GnRHa combination, which was consistent with the results of our own laboratory and clinical studies and with the results of most studies [ 3 , 9 , 10 , [20] , [21] , [22] , 30 ].…”

“…The trial was conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital in Shanghai and Zhejiang Cancer Hospital in Hangzhou, China. The trial protocol and all amendments that approved by an independent ethics committee or the institutional review board at each site were published [ 22 ]. Written informed consent was provided by all the patients.…”

“…Following the established criteria of the EGOFACT study, POI was still defined as AMH<0.5 ng/mL in this study [ 22 , 23 ]. Patients were divided into a high E2 group and a low E2 group, a high FSH group and a low FSH group with median baseline E2 (105.5 pg/mL) and FSH (5.67 mIU/mL) as cut-off values, respectively ( eTable 3 ).…”

“…We discovered that GnRHa protects granulosa cells from chemotherapeutic toxicity in vivo and in vitro, CTX-induced endoplasmic reticulum (ER) stress inhibits the secretion of AMH, and treatment with GnRHa relieves ER stress and the subsequent unfolded-protein response by modulating mTOR signaling to induce autophagy [ 21 ]. The EGOFACT study confirmed from a clinical perspective that administration of GnRHa with chemotherapy in premenopausal breast cancer patients reduces the risk of POI and promotes the recovery of ovarian function [ 22 ]. In this study we conducted an in-depth analysis of the data from the EGOFACT study to explore the changing characteristics of AMH levels in premenopausal women with breast cancer and various clinical factors affecting the ovarian reserve at different stages.…”

Analysis of the Benefit of Gonadotropin-Releasing Hormone Agonist in Premenopausal Women undergoing Hematopoietic Cell Transplantation

“…In recent years, the protective effect of GnRHa on ovary during chemotherapy has attracted attention. Several meta-analysises and prospective randomized studies (11,12) have shown that GnRHa signi cantly reduces the risk of POF in women undergoing gonadal toxic chemotherapy. Although these results seem promising, a paucity of data exists on similar use of GnRHa in the HSCT population, especially in China.…”