Losing weight on purpose is associated with a significantly lower risk for endometrial cancer among postmenopausal women, according to a new analysis of data from the Women's Health Initiative (WHI) observational study.
The associated risk reduction was greatest among obese women who lost weight intentionally (as opposed to because of illness). In this group, purposely shedding pounds was tied to a 56% decreased risk compared with maintaining a stable weight (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25 - 0.78).
However, there was also a 29% risk reduction among all women in the study who lost weight — not just among the heaviest women (HR, 0.71; 95% CI, 0.54 - 0.95).
Weight loss was defined as a reduction of 5% or more of body weight between baseline enrollment and 3 years later. As part of the larger study, body weight was recorded during physical exams and participants were interviewed to determine whether weight loss was intentional.
During the subsequent 11.4 years of follow-up, there were 566 incident endometrial cancers among the 36,794 study participants, who were age 50 to 79 years at enrollment.
The new study is published online February 6 in the Journal of Clinical Oncology.
The quality of the evidence is high, even though the study is observational, suggested lead author Juhua Luo, PhD, from the Indiana University School of Public Health in Bloomington.
"Our study is a large and carefully conducted prospective observational study with a long follow-up period. Few randomized controlled trials could follow people for an average of more than 11 years," she told Medscape Medical News.
Weight loss is potentially an important intervention, suggests Jason D. Wright, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York City, in an accompanying editorial.
"It is estimated that nearly 60% of endometrial cancers in the United States are attributable to excess weight," writes Dr Wright.
He says that strategies to reduce endometrial cancer mortality have relied largely on early detection, which typically occurs when postmenopausal women present with vaginal bleeding, an early symptom when tumors are localized to the uterus.
Screening via endometrial sampling, transvaginal ultrasound, or experimental uterine lavage may also be considered in high-risk women, including those who are obese, says Dr Wright.
The situation has a growing urgency, he suggests, as the number of deaths from endometrial cancer in the United States in 2016 reached 10,170 — a 25% increase compared with 5 years earlier.
"This study tells us that weight loss, even later in life, is linked to a lower risk of endometrial cancer," said Jennifer Ligibel, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, and an American Society of Clinical Oncology expert in cancer prevention, in a press statement.
"The findings also support the development of weight loss programs as part of a cancer prevention strategy in overweight and obese adults,” said Dr Ligibel, who was not involved in the study.
The new study represents an under-researched topic, suggested Dr Ligibel. More than 1000 studies have linked obesity to an increased risk for cancer, but relatively few have examined the relationship between weight loss and risk, she said.
The study authors say that 4 other observational studies have tied self-reported weight loss during adult life with some degree of lower risk for endometrial cancer. However, none looked at intentionality, which is important because "unintentional weight loss is highly correlated with increased morbidity," they write.
Endometrial cancer is the most common gynecologic cancer in the United States, with most cases occurring in postmenopausal women, according to the American Cancer Society. About 2.8% of women will be diagnosed with endometrial cancer during their lifetime, according to the ACS.
That lifetime incidence rate would be higher in obese women, said Dr Luo.
In the new study, obesity was defined based on a body mass index (BMI) of 30 kg/m2 or greater, which is a widely used definition.
“Many older adults think it’s too late to benefit from weight loss or think that because they are overweight or obese, the damage has already been done. But our findings show that’s not true,” said Dr Luo.
"The findings should also motivate women to lose weight," she added.
Further Study Details
The WHI is a study of postmenopausal women with more than 160,000 participants. The current analysis involved less than 25% of the total because a long list of study exclusions, including a history of cancer or hysterectomy, and missing data related to the current study's design.
The study also provides a profile of the women who were more likely to achieve intentional weight loss.
These women, compared with women who had stable weight, were more likely to be less physically active, black, less educated, and heavier smokers and to have had a higher BMI. They were also more likely to have had no hormone therapy use, younger age at menarche, more term pregnancies, and younger age at first birth (all P < .05).
The investigators also found that women who gained 10 pounds or more had a 26% higher risk for endometrial cancer than women whose weight was stable (HR, 1.26; 95% CI, 1.00 - 1.57).
Notably, a second sensitivity analysis showed that women who intentionally lost weight and had a normal BMI at 3 years (ie, <25 kg="" m="" style="font-size: 0.85em; line-height: 0;" sup="">225>
The authors also reported no significant difference in risk between hormone users and nonusers. This was important because endometrial cancer is known to be highly hormone related, they say.
The WHI is funded by the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the US Department of Health and Human Services. Dr Luo and Dr Ligibel have disclosed no relevant financial relationships.