Genitourinary syndrome of menopause (GSM) is a highly prevalent, not self-limiting condition displaying a major negative impact on sexual function and emotional well-being. Various non-hormonal and hormonal treatment options are available. Many women consider GSM treatment to be a short-term interval cure rather than a long-term or lifelong treatment. The aim of this systematic literature search was to assess the sustainability of vaginal estrogens for GSM treatment after treatment cessation. We found that objective GSM signs mostly deteriorated within approximately 4 weeks after vaginal estrogen treatment cessation, while vaginal estrogens had a more sustainable impact on subjective GSM symptoms up to 3-6 months. However, overall, scientific evidence on sustainability of vaginal estrogens was low. Thus, GSM treatment should not be considered a short-term interval cure but long-term therapy. Further studies in an internationally harmonized setting (Core Outcomes in Menopause [COMMA]) are needed.