Active Voice: Physical Activity, Sedentary Behavior and Estrogen Metabolism — Where Do We Stand?

By Cher M. Dallal, Ph.D. and Gretchen L. Gierach, Ph.D.
Cher M. Dallal, Ph.D. Gretchen L. Gierach, Ph.D.

Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.

Cher Dallal, Ph.D., is an assistant professor in the Department of Epidemiology and Biostatistics at the University of Maryland School of Public Health in College Park, Maryland. Her research focuses on biobehavioral associations of hormones and lifestyle factors, including physical activity and obesity and their role in cancer risk and survival.

Gretchen Gierach, Ph.D., is an investigator in the Metabolic Epidemiology Branch of the Division of Cancer Epidemiology and Genetics at the U.S. National Cancer Institute in Bethesda, Maryland. Dr. Gierach is interested in the study of the etiology of hormonally-related female cancers, particularly in the molecular mechanisms underlying breast carcinogenesis.

This commentary presents Dr. Dallal’s and Dr. Gierach’s views on the topic of a research article which they had published with their colleagues in the March 2016 issue of
Medicine & Science in Sports & Exercise® (MSSE).

Physical activity has many benefits for health, including lowering risk of heart disease, obesity, and, more recently, specific cancers such as breast cancer. Accumulating evidence also points to sedentary behavior as a potential risk factor for cancer and other chronic diseases - and, this risk is independent of time spent in physical activities! However, the biological mechanisms by which these potentially modifiable lifestyle factors affect cancer risk remain unclear. Prior research has supported an association between increased physical activity and lower estrogen levels among women, one avenue whereby physical activity may reduce breast cancer risk. However, less is known regarding the relationships between physical activity, sedentary behavior and the metabolism of estrogen. Consideration of how women metabolize estrogen may be important, particularly given the recent findings from studies of breast cancer risk among postmenopausal women, which suggest that breast cancer risk differs by estrogen metabolism profiles measured in serum and urine.

Metabolites are produced when the body breaks down food, drugs and chemicals or, in this case, estrogen. Hydroxylation is the first step in estrogen metabolism and this involves the irreversible addition of a hydroxyl group (OH), at one of the three carbon sites (that is, the C-2, C-4, or C-16 position of the steroid ring) of the parent estrogens (estradiol or estrone); this results in numerous estrogen metabolites along these pathways. Previous laboratory studies have shown that estrogen metabolites within these pathways may be differentially related to DNA damage, cell division and cell growth. Thus, these pathway differences may play an important role in the development of cancer.

Prior studies of estrogen metabolites have mainly focused on two individual metabolites, 2-hydroxyestrone and 16-hydroxyestrone, and have relied upon self-reported measures of physical activity. In our study, as reported in the March 2016 issue of MSSE, we quantified urinary estrogen profiles among 540 postmenopausal women who were healthy participants in the National Cancer Institute’s Polish Breast Cancer Study. To accomplish this, 15 estrogens and estrogen metabolites were measured within three pathways of estrogen metabolism. We aimed to characterize relationships between objective measures of physical activity, sedentary behavior and urinary estrogen metabolite profiles among these women. This provided us with a means of improving understanding of biological mechanisms underlying previously reported associations between physical activity and cancer risk.

Our study participants wore the Actigraph accelerometer on the waist during waking hours. They wore the device over the span of a week and also underwent anthropometric assessment and donated a 12-hour urine specimen. Accelerometers capture a range of behaviors, including time spent active and sedentary. The device provides an objective assessment, without the potential bias associated with recalling one’s behaviors.

Results from our cross-sectional analyses, adjusted for age and body mass index, suggest that increased overall activity was associated with a higher urinary ratio of the 2-, 4-, and 16-pathway metabolites relative to parent estrogens. In contrast, increased time spent sedentary, independent of overall activity, was associated with a lower ratio of 16-pathway metabolites to parent estrogens. These findings suggest that physical activity may increase the breakdown and subsequent release of estrogen, whereas, sedentary behavior may reduce estrogen metabolism. As this is the first study of physical activity and sedentary behavior among postmenopausal women to measure estrogen metabolites in all three pathways, our findings require replication in different populations of women and ideally within prospective studies. Understanding relationships between physical activity, sedentary behavior and estrogen metabolism is critical - given that, at present, we have few known modifiable risk factors for breast cancer.