Table 1.

Selected randomized controlled trials evaluating the use of GnRHa before and during chemotherapy in breast cancer patients

Study (year)	Participants	Intervention	Main Outcome	Findings
Badawy [32] (2009)	80 premenopausal women (< 40 years) with breast cancer	Goserelin co- treatment during cyclophosphamide based chemotherapy	Return of spontaneous menstruation and ovulation. Hormonal changes during and after the course of treatment	The use of goserelin during chemotherapy in these patients protects ovarian function *
Leonard [39] (2010) (preliminary report)	227 premenopausal women with breast cancer	Goserelin co- treatment during cyclophosphamide and/or anthracycline chemotherapy	Incidence of premature ovarian failure	No difference in menstruation resumption rates
Gerber [36] (2011)	60 premenopausal women (< 46 years) with hormone- insensitive breas cancer	Goserelin co- treatment during anthracycline / cyclophosphamide- based (with or without taxane) chemotherapy	Resumption of menses at 6 months after end of chemotherapy	No difference in menstruation resumption rates
Del Mastro [38] (2011)	281 premenopausal women with stage I through stage III breast cancer	Triptorelin co- treatment during different regimens of chemotherapy	Incidence of early menopause at 12 months after the last cycle of chemotherapy	The use of triptorelin during chemotherapy in these patients reduced the occurrence of early menopause *
Munster [40] (2012)	49 premenopausal women (≤ 44 years) with breast cancer	Triptorelin co- treatment during cyclophosphamide- based chemotherapy	Resumption of menses and changes in hormonal markers	No difference in menstruation resumption rates / FSH, Inhibin A and B levels correlated with menstrual status
Elgindy [41] (2013)	100 premenopausal women (18-40 years) with hormone- insensitive breast cancer	GnRH analogue (Triptorelin with or without GnRH antagonist) co- treatment during cyclophosphamide- based chemotherapy	Resumption of menses at 12 months after end of chemotherapy and change in hormonal and ultrasound markers	No differences in menstruation resumption rates / No differences in FSH, LH, E2 and AMH levels and antral follicle count

^*Important limitations were highlighted in the “Clinical Studies Evaluating Gonadal Suppression” section.