Background: Trastuzumab is a monoclonal antibody targeting HER2, overexpressed in approximately 25%–30% of breast cancers. While its survival benefit is well established, its impact on ovarian function and fertility preservation remains uncertain in premenopausal women.

Methods: A systematic literature review was conducted using MEDLINE and Biblioteca Virtual em Saúde databases, covering publications from 2010 to January 2025. Eligible studies included phase II–III clinical trials, prospective and retrospective observational studies and systematic reviews evaluating ovarian function outcomes – particularly amenorrhea rates and anti-Müllerian hormone (AMH) levels – in women with HER2-positive breast cancer treated with trastuzumab in the (neo)adjuvant setting.

Results: Eleven studies met the inclusion criteria: eight prospective, two retrospective and one descriptive. Four studies reported no association between trastuzumab and increased amenorrhea rates, one suggested higher amenorrhea when combined with chemotherapy and four demonstrated lower amenorrhea rates along with preservation of AMH levels, suggesting a potential protective effect on ovarian reserve. Two studies did not directly assess amenorrhea.

Conclusion: Current evidence does not demonstrate a consistent gonadotoxic effect of trastuzumab. Although some data suggest a possible protective role on ovarian function, findings remain heterogeneous. Prospective studies specifically designed to isolate the ovarian impact of trastuzumab are warranted. Comprehensive oncofertility counseling should be offered to all premenopausal women before treatment initiation.