Abstract: We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumour recurrence in 2.3% of women in the oestrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.54 to 2.50; very low-certainty evidence). The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32 to 2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up. The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.

Plain-language summary: We searched clinical trial databases to look for any evidence of effectiveness and safety of HRT use in women who had had endometrial cancer up to May 2017. We only found one study that randomly allocated women to receive either HRT or a placebo (pretend treatment). This found no difference in the likelihood of the cancer regrowth between the two groups. They showed that HRT may or may not increase the risk of recurrence of developing a new cancer. They did not provide any information on survival or symptom relief. However, the study was not completed due to poor recruitment into the clinical trial, so was not large enough to definitively say whether the use of HRT could be recommended after treatment for early endometrial cancer. We are uncertain whether HRT increases the risk of recurrence after a diagnosis of endometrial cancer, as the certainty of the current evidence was very low. We identified only one randomised trial and this trial did not include enough women to definitely answer the question. This trial also had areas of potential bias that reduced our certainty in the results. Limited, very-low certainty, evidence suggests that HRT may have little or no effect on the risk of endometrial cancer returning for women who have been treated surgically for an early-stage endometrial cancer. There were no data to say whether HRT had an effect on overall survival after hysterectomy for endometrial cancer.