Weight-loss interventions in endometrial cancer survivors


Endometrial or womb cancer is a common cancer in women and the number of cases is rising. This is due, in part, to increasing levels of obesity, which is a major risk factor for the disease. Whilst survival following endometrial cancer is generally excellent if diagnosed early, affected women are more likely to die early due to an increased risk of heart attack and stroke, and to have poorer quality of life. 

What did we want to find out?

We wanted to assess the evidence for weight-loss interventions in endometrial cancer survivors who are overweight or obese to determine whether they were of benefit compared with usual care.

What did we do?

We searched medical databases for well-designed clinical trials (called randomised controlled trials) of interventions (treatments) to facilitate weight loss in women with endometrial cancer who were overweight or obese undergoing treatment for, or previously treated for, endometrial cancer compared with any other intervention, usual care, or placebo (dummy treatment). 

 What did we find?

We found 12 randomised controlled trials where women were allocated at random to receive one of several interventions. They included 610 women with endometrial cancer who were overweight or obese. The trials were conducted in the US, Australia and New Zealand. All compared lifestyle advice (diet and exercise) plus self-help techniques (to encourage adherence to the advice) with usual care.

Key results
Within the limitations of the included studies, we found no benefit for endometrial cancer survivors who were overweight or obese from receiving lifestyle advice in terms of survival, cardiovascular events (for example, heart attacks or strokes) or quality of life, though such interventions were not associated with significant or serious harms to participants. It is unclear if these interventions increase musculoskeletal symptoms (for example, knee and leg pain and muscle weakness), as only one out of eight studies looking at these symptoms reported any events. Whilst some women lost weight with these interventions, others did not, meaning that overall there was little or no benefit.

What are the limitations of the evidence?
The quality of included studies was low or very low and all were small in terms of the number of participants with very short follow-up times, and not designed to specifically look at the effect of their intervention on survival or other longer-term outcomes. Additional high-quality studies, with appropriate durations of follow-up, are required in this field. There are seven ongoing trials that may add to our knowledge.

How up to date is this evidence?

The evidence is current to June 2022.

Authors' conclusions: 

The inclusion of new relevant studies has not changed the conclusions of this review.

There is currently insufficient high-quality evidence to determine the effect of combined lifestyle and behavioural interventions on survival, quality of life or significant weight loss in women with a history of endometrial cancer who are overweight or obese compared to those receiving usual care. The limited evidence suggests that there is little or no serious or life-threatening adverse effects due to these interventions, and it is uncertain if musculoskeletal problems were increased, as only one out of eight studies reporting this outcome had any events. Our conclusion is based on low- and very low-certainty evidence from a small number of trials and few women. Therefore, we have very little confidence in the evidence: the true effect of weight-loss interventions in women with endometrial cancer and obesity is currently unknown.

Further methodologically rigorous, adequately powered RCTs are required with follow-up of five to 10 years of duration. These should focus on the effects of varying dietary modification regimens, and pharmacological treatments associated with weight loss and bariatric surgery on survival, quality of life, weight loss and adverse events.

Read the full abstract...

This is an updated version of the original Cochrane Review published in Issue 2, 2018.

Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival, as well as a reduction in the risk of cardiovascular disease, which is a frequent cause of death in endometrial cancer survivors.


To evaluate the benefits and harm of weight-loss interventions, in addition to standard management, on overall survival and the frequency of adverse events in women with endometrial cancer who are overweight or obese compared with any other intervention, usual care, or placebo.

Search strategy: 

We used standard, extensive Cochrane search methods. The latest search date was from January 2018 to June 2022 (original review searched from inception to January 2018).

Selection criteria: 

We included randomised controlled trials (RCTs) of interventions to facilitate weight loss in women with endometrial cancer who are overweight or obese undergoing treatment for, or previously treated for, endometrial cancer compared with any other intervention, usual care, or placebo. 

Data collection and analysis: 

We used standard Cochrane methods. Our primary outcomes were 1. overall survival and 2. frequency of adverse events. Our secondary outcomes were 3. recurrence-free survival, 4. cancer-specific survival, 5. weight loss, 6. cardiovascular and metabolic event frequency and 7. quality of Life. We used GRADE to assess certainty of evidence. We contacted study authors to obtain missing data, including details of any adverse events.

Main results: 

We identified nine new RCTs and combined these with the three RCTs identified in the original review. Seven studies are ongoing. 

The 12 RCTs randomised 610 women with endometrial cancer who were overweight or obese. All studies compared combined behavioural and lifestyle interventions designed to facilitate weight loss through dietary modification and increased physical activity with usual care. Included RCTs were of low or very low quality, due to high risk of bias by failing to blind participants, personnel and outcome assessors, and significant loss to follow-up (withdrawal rate up to 28% and missing data up to 65%, largely due to the effects of the COVID-19 pandemic). Importantly, the short duration of follow-up limits the directness of the evidence in evaluating the impact of these interventions on any of the survival and other longer-term outcomes. 

Combined behaviour and lifestyle interventions were not associated with improved overall survival compared with usual care at 24 months (risk ratio (RR) mortality, 0.23, 95% confidence interval (CI) 0.01 to 4.55, P = 0.34; 1 RCT, 37 participants; very low-certainty evidence). There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as the studies reported no cancer-related deaths, myocardial infarctions or strokes, and there was only one episode of congestive heart failure at six months (RR 3.47, 95% CI 0.15 to 82.21; P = 0.44, 5 RCTs, 211 participants; low-certainty evidence). Only one RCT reported recurrence-free survival; however, there were no events. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six or 12 months compared with usual care (at six months: mean difference (MD) −1.39 kg, 95% CI −4.04 to 1.26; P = 0.30, I2 = 32%; 5 RCTs, 209 participants; low-certainty evidence). Combined behaviour and lifestyle interventions were not associated with increased quality of life, when measured using 12-item Short Form (SF-12) Physical Health questionnaire, SF-12 Mental Health questionnaire, Cancer-Related Body Image Scale, Patient Health Questionnaire 9-Item Version or Functional Assessment of Cancer Therapy – General (FACT-G) at 12 months when compared with usual care (FACT-G: MD 2.77, 95% CI −0.65 to 6.20; P = 0.11, I2 = 0%; 2 RCTs, 89 participants; very low-certainty evidence). The trials reported no serious adverse events related to weight loss interventions, for example hospitalisation or deaths. It is uncertain whether lifestyle and behavioural interventions were associated with a higher or lower risk of musculoskeletal symptoms (RR 19.03, 95% CI 1.17 to 310.52; P = 0.04; 8 RCTs, 315 participants; very low-certainty evidence; note: 7 studies reported musculoskeletal symptoms but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 8).