Background: Adding ovarian function suppression to adjuvant endocrine therapy (AET) lowers the disease recurrence rates among premenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). However, a detrimental effect on endocrine symptoms burden (ESB) is expected. Therefore, this study aimed to investigate differences in Quality of life (QoL) and endocrine symptoms in premenopausal women prescribed AET, with/without gonadotropin-releasing hormone agonist (GnRH). Methods: This cross-sectional study included women, with HR+ EBC, premenopausal at diagnosis, treated with AET for more than 3 months, with and without GnRH. The research was conducted with institutional Ethics Committee approval at the University Hospital Centre Zagreb, General Hospital Šibenik, and with online survey. A validated instrument, the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES), was used. The collected data were analysed using SPSS v. 29 (p≤0.05). Results: Overall, 314 eligible BC survivors with a median age of 45 years (22-65) and a median duration of AET of 2 years (3 months -12 years) responded to FACT-ES and were included in the analysis. Altogether 45.2% (n=142) of participants were prescribed tamoxifen (TAM), 25.8% (n=81) GnRH+TAM, and 29% (n=91) GnRH+aromatase inhibitor (AI); exemestane (9%), letrozole (13.6%) and anastrozole (6.4%). The total QoL (FACT-ES) score was higher in patients treated with TAM as opposed to patients treated with AI+GnRH (p=0.01). Adding GnRH to TAM did not significantly change QoL when compared to TAM alone or AI+GnRH. In addition, patients on AI+GnRH had lower physical well-being (PWB) score than patients on TAM+GnRH (p=0.03) or TAM alone (p=0.05) and lower endocrine subscale score (ESS-19) than patients on TAM (p=0.01), indicating more endocrine symptoms in premenopausal women treated with AI+GnRH. Among patients treated with AI+GnRH letrozole had lower PWB (p=0.03) and ESS-19 score (p=0.01) than exemestane. Conclusions: This study showed that GnRH+AI in premenopausal women with HR+ EBC results in greater ESB and lower QoL compared to patients treated with TAM or GnRH+TAM. Therefore, interventions helping decrease the ESB in patients treated with AI+GnRH should be explored and developed to help patients adhere to and persist in AET.

*One-way ANOVA.

Social well-being (SW), emotional well-being (EWB), functional well-being (FWB).