A systematic review recently published in the journal Cancers found that considering measures of metabolic instability during the workup for endometrial cancer (EC) may improve diagnosis and prevention.
“From a clinical standpoint, the findings underscore the importance of incorporating markers of metabolic variability into endometrial cancer risk stratification models and developing preventive strategies aimed at stabilizing metabolic homeostasis in non-obese women,” the authors wrote.
EC has historically—and inaccurately—been referred to as a “disease of obesity,” the authors explained. Although EC is strongly associated with obesity, this description neglects the complex metabolic, inflammatory and hormonal fluctuations that may also contribute to EC risk.
In their review, the investigators evaluated 57 previously published studies that assessed EC risk factors in non-obese individuals.
Read more about EC causes and risk factors
Metabolic instability was defined as a dynamic state in which a person experiences frequent changes in their weight, glucose levels, hormone levels and signaling molecules. This can cause stress on the body’s tissues, promoting inflammation.
These changes in metabolic functioning may impede the normal process of endometrial regeneration, which can lead to uncontrolled cell growth. For patients with a normal or mildly increased body mass index (BMI), therefore, metabolic instability may be a useful tool for determining EC risk.
Several studies have demonstrated that metabolic dysfunction increases the risk of EC, regardless of BMI. “These findings challenge the traditional view of endometrial cancer as a ‘hormone-dependent obesity disease’ and highlight the need for a more comprehensive approach to assessing metabolic risk factors,” the authors explained.
Other studies have shown that fluctuations in weight over time may be a sign of metabolic dysfunction and systemic inflammation. The researchers advise that physicians collect detailed information on their patients’ history of weight changes when considering risk factors.
A number of biochemical pathways linking metabolic changes to EC have been suggested; it is likely that elements of many of these pathways are simultaneously at play. Even after losing weight, levels of some of these marker may remain abnormal in some patients, indicating sustained inflammation.
The study also cited past research showing that women with metabolic syndrome experience unique changes in hormone levels over time, which could elevate cancer risk. For example, some individuals may experience high estrogen levels and insulin resistance for a period of time, followed by low estrogen levels and insulin sensitivity.
In combination with inflammation, these hormonal changes may stimulate a cycle of endometrial activation, which could encourage carcinogenesis.
“The introduction of the concept of ‘metabolic instability’ provides a fresh perspective
on the relationship between metabolism and oncological processes,” the study concluded. “This approach focuses on the dynamic characteristics of metabolism, which helps to clarify the pathogenetic model of endometrial cancer.”
Sign up here to get the latest news, perspectives, and information about EC sent directly to your inbox. Registration is free and only takes a minute.
