Muted Morning Cortisol Response Linked to Chronic Fatigue in Women

By Charles Bankhead
ATLANTA, Jan. 17 -- Women with symptoms of chronic fatigue syndrome have a muted morning cortisol response that may represent an underlying mechanism of the condition, according to investigators here.The spike in cortisol levels that occurs during the first hour after awakening was significantly lower (P=0.037) in women with chronic fatigue symptoms compared with well women, William C. Reeves, M.D., of the CDC, and colleagues reported online in the Journal of Clinical Endocrinology and Metabolism. Print publication is slated for the March issue.There was no such disparity in morning cortisol response among men with chronic fatigue symptoms compared with well men, they added.
"Our results suggest that a sex difference in hypocortisolism may contribute to the increased risk of chronic fatigue syndrome in women," the authors concluded.
The findings support previous research implicating a faulty stress response in the etiology of chronic fatigue syndrome. However, Dr. Reeves and colleagues cautioned that "no statement on a causal relationship can be made at this point."
Although recognized for decades as a health issue, chronic fatigue syndrome still has no clear pathophysiologic correlates. A growing volume of research has implicated dysregulation of the hypothalamic-pituitary-adrenal axis, which encompasses the cortisol circadian response.
Elevated cortisol awakening response has been associated with a variety of mood and stress-related emotional disturbances, the authors noted. In contrast, an attenuated cortisol awakening response has been linked to chronic pain, general health complaints, and several psycho-emotional disorders.
Previously, Dr. Reeves and colleagues reported that patients with chronic fatigue symptoms have a flattened diurnal salivary cortisol curve. They have lower morning concentrations of cortisol and higher evening concentrations compared with matched controls.
Continuing their examination of a cortisol link to chronic fatigue, the investigators studied patterns of morning cortisol response in 75 patients and 110 controls. Study participants collected saliva samples immediately after awakening and again 30 minutes and 60 minutes afterward. Participants were instructed not to eat, drink, smoke, or brush their teeth until all three samples were collected.
Overall, salivary cortisol levels did not differ across the three time points between the two groups. However, the data revealed a significant interaction effect, indicating different cortisol profiles between patients and the healthy controls.
The investigators then performed separate analyses for men and women. The analyses showed that the morning cortisol curve was significantly attenuated in the 57 women with chronic fatigue symptoms but not in the 82 female controls. Comparison of awakening cortisol response in men showed no difference between the 18 patients and 18 male controls.
The authors acknowledged that prior studies of cortisol dynamics have yielded inconsistent results. Small sample size and the adequacy of chronic fatigue syndrome diagnostic criteria could account for the different findings, they stated.
Noting limitations of the investigation, Dr. Reeves and colleagues said their analyses did not account for all potential influences of the HPA axis, such as menstrual cycle and smoking. Additionally, the reliability of patient-collected saliva samples has been questioned. At-home measurements are subject to factors and activities that do not influence laboratory measurement. Unequal sample sizes for men and women might have contributed to the lack of difference observed between men with chronic fatigue symptoms and well controls.
Dr. Reeves declared no potential conflicts. Co-author Christine Heim acknowledged funding from Eli Lilly and Novartis, as well as from government agencies, professional groups, and charities.
Primary source: Journal of Clinical Endocrinology and MetabolismSource reference:Nater UM, et al "Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls" J Clin Endocrin Metab 2008: DOI: 10.1210/jc.2007-1747.