ObjectiveAs the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. MethodsThe MarketScan Database was used to identify patients 18–49 years who underwent hysterectomy plus oophorectomy and those aged 50–75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. ResultsA total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was −37.1% (95% CI, −40.5 to −33.6%) for patients 18–49 years of age and − 10.4% (95% CI, −10.9 to −9.9%) for those 50–75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50–75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18–49 years of age (P = .02) and those 50–75 years of age (P < .001). ConclusionsThe use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.