Study Shows Cancer-Related Fatigue & Depression Hits Female Survivors Harder

A retrospective study reveals that female cancer survivors are more likely to report cancer-related fatigue or depression than their male counterparts, and that those who reported fatigue or depression were more likely to reduce their activity level (Cancer Research 2025; doi.org/10.1158/1538-7445.AM2025-4989). The findings were presented at the American Association for Cancer Research (AACR) Annual Meeting 2025. “During my residency, I saw a lot of cancer patients both in the clinic and inpatient settings, and cancer-related fatigue was one of the most frequent complaints they brought up,” said lead author Simo Du, MD, MHS, a resident at NYC Health + Hospitals/Jacobi and Albert Einstein College of Medicine. “It impacts not just their daily activities but also their quality of life and mental health, making tasks like climbing stairs, getting groceries, or doing laundry overwhelming.” Du also clarified that cancer-related fatigue doesn't resolve with rest, the way general fatigue does. What's more, it can persist for weeks, months, or even years after treatment. Sex-related differences in cancer-related fatigue have been well established in other research—Du and her colleagues wanted to understand these differences and, perhaps more importantly, how they impact quality of life in cancer survivors. The researchers analyzed data collected by the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2022. These annual surveys collect health and nutrition information from adults and children in the U.S. and include a section on depression and anxiety. Du and her team pulled NHANES data for 1,555 cancer survivors who, based on a sampling methodology that adjusted for age, race, socioeconomic status, and comorbidities, represented the 25 million cancer survivors in the U.S. They discovered that female cancer survivors were 69% more likely to experience cancer-related fatigue and 58% more likely to experience depression than male survivors. But, while women had higher scores across most indicators of depression, more men reported thinking that they would be better off dead. This suggests male cancer survivors may face an increased risk of suicide, Du said. A limitation of the study is that it relies on self-reported data from cancer survivors—it's possible that women were more likely to report their fatigue and depression symptoms than men. However, the NHANES is careful to minimize biases through standardized research protocols, Du said. Understanding the Findings There may be several factors that play into these differences between male and female cancer survivors. First, research shows that women face a 1.5- to 2-fold greater risk for adverse effects from drugs, including those used in chemotherapy and radiation (Endocrinology 2022; doi.org/10.1210/endocr/bqac058). This may be due to differences in sex hormones and how hormones impact various therapies and a greater risk of drug interactions (women tend to use more medications). In addition, it often takes longer for drugs to clear from women's bodies, leading to higher rates of toxicity (ESMO Open 2020; doi.org/10.1136/esmoopen-2020-000770). Treatment for some types of cancer that are more common in women, including breast cancer, has also been shown to cause sleep-disrupting side effects, such as hot flashes (Sleep Medicine Reviews 2006; doi.org/10.1016/j.smrv.2006.03.005). This may exacerbate fatigue. Du suggested that social roles may also contribute. Women may be more likely to continue caregiving responsibilities—and take on a greater share of those responsibilities—during and after treatment. The added strain may amplify cancer-related fatigue and depression. Survivors' experiences of fatigue and depression often reduce quality of life, which Du's team measured by assessing their ability to perform work-related or recreational activities. They discovered that people who reported fatigue were 86% more likely to cut back on activities, such as brisk walking, cycling, golfing, and light gardening or yard work. Meanwhile, those who were depressed were 65% more likely to limit physical activity. Work-related activities weren't significantly impacted by fatigue or depression. Performing physical activity during and after cancer treatment may actually improve side effects. Moderate-intensity physical activity can cut the incidence of cancer-related fatigue by half, while “both moderate and vigorous physical activity are associated with a 2- to 5-fold reduction in depression,” Du said. Conversely, limiting physical activity can lower quality of life. Du and her colleagues are planning future studies to evaluate potential solutions. “Our findings highlight the importance of providing special attention and tailored interventions such as exercise programs, support groups, and mind-body behavioral techniques for vulnerable groups to help effectively manage fatigue and improve participation in recreational activities as they are an essential aspect of quality of life,” Du said. She and her team also plan to further study the connection between cancer-related fatigue and sex. Lauren Bedosky is a contributing writer.