Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women With a History of Breast Cancer

Obstet Gynecol. 2023 Sep 1;142(3):660-668. doi: 10.1097/AOG.0000000000005294. Epub 2023 Aug 3.


Objective: To assess the risk of recurrence of breast cancer associated with vaginal estrogen therapy in women diagnosed with genitourinary syndrome of menopause with a history of breast cancer using a large U.S. claims database.

Methods: A U.S. health research network (TriNetX Diamond Network) was queried from January 2009 to June 2022. Our cohort consisted of women diagnosed with breast cancer within 5 years before the initial genitourinary syndrome of menopause diagnosis. Patients with active disease , defined as those undergoing mastectomy, radiation treatment, or chemotherapy within 3 months before diagnosis of genitourinary syndrome of menopause, were excluded. Recurrence was defined as mastectomy, radiation, chemotherapy, or secondary malignancy within 3 months to 5 years after the initiation of vaginal estrogen therapy for genitourinary syndrome of menopause. The study cohort included those with three or more vaginal estrogen prescriptions. The control cohort included women with breast cancer without any vaginal estrogen prescriptions after genitourinary syndrome of menopause diagnosis. Propensity matching was performed. A subanalysis by positive estrogen receptor status, when available, was performed.

Results: We identified 42,113 women with a diagnosis of genitourinary syndrome of menopause after breast cancer diagnosis with any estrogen receptor status, 5.0% of whom received vaginal estrogen. Of the initial cohort, 10,584 patients had a history of positive estrogen receptor breast cancer, and 3.9% of this group received vaginal estrogen. Risk of breast cancer recurrence was comparable between those who received vaginal estrogen and those who did not in both the any estrogen receptor (risk ratio 1.03, 95% CI 0.91-1.18) and positive estrogen receptor (risk ratio 0.94, 95% CI 0.77-1.15) status analyses.

Conclusion: In a large, claims-based analysis, we did not find an increased risk of breast cancer recurrence within 5 years in women with a personal history of breast cancer who were using vaginal estrogen for genitourinary syndrome of menopause.

MeSH terms

  • Breast Neoplasms* / complications
  • Estrogens / therapeutic use
  • Female
  • Female Urogenital Diseases* / drug therapy
  • Female Urogenital Diseases* / etiology
  • Humans
  • Mastectomy / adverse effects
  • Menopause
  • Neoplasm Recurrence, Local
  • Receptors, Estrogen / therapeutic use


  • Receptors, Estrogen
  • Estrogens