Understanding Chronic Fatigue in Perimenopause: The Role of Cortisol and Thyroid Testing
Written and edited by Sarah Bonza MD, MPH, FAAFP, DipABLM, NBC-HWC
Woman in perimenopause reading about her fatigue
Chronic fatigue is a common complaint among perimenopausal women, often exacerbated by hormonal fluctuations. As a physician who trained and practiced for 20 years in hospital medicine and primary care, I found limitations in our training to help women overcome burdensome fatigue. Fatigue can have a significant impact on women’s quality of life. Feeling fatigued can influence performance on the job, family relationships and friendships. It’s also difficult to even think about exercise or eating right when you’re having trouble simply dragging yourself through the day.
I recently cared for one such patient who was dealing with the sudden onset of high blood pressure, weight gain and fatigue as she entered perimenopause. We started her on estrogen and progesterone, but she continued to have fatigue. Our next step is to evaluate her cortisol curve which led to a closer look at her thyroid studies. This blog post will explore the importance of functional cortisol curve testing and interpreting thyroid studies to provide a comprehensive approach to managing chronic fatigue in perimenopausal women.
Cortisol and the Diurnal Rhythm
Cortisol, often termed the "stress hormone," plays a pivotal role in regulating various physiological processes, including metabolism, immune function, and the body's response to stressors. The diurnal rhythm of cortisol typically follows a pattern where levels peak shortly after waking and gradually decline throughout the day, reaching their lowest point at bedtime [1,2]. However, in the context of perimenopause, this normal diurnal rhythm can become disrupted, leading to a variety of symptoms, including chronic fatigue. Perimenopausal women may experience dysregulation of the hypothalamic-pituitary-adrenal axis, leading to altered cortisol secretion patterns.
Precision Analytical’s DUTCH Cortisol Awakening Response (CAR) Test
One of the most comprehensive methods for assessing cortisol patterns is the DUTCH Cortisol Awakening Response (CAR) test by Precision Analytical. This test involves collecting five salivary samples over a 24-hour period
Immediately upon waking
30 minutes after waking
60 minutes after waking
In the afternoon
At bedtime
This detailed assessment provides valuable insights into the body's stress response dynamics and the natural diurnal rhythm of cortisol secretion. The DUTCH CAR test also measures cortisone levels, which helps in understanding the overall adrenal function and the activity of the enzyme 11β-HSD2 that converts cortisol to cortisone [4,5].
Interpreting Cortisol Test Results
When interpreting salivary cortisol results, it’s essential to consider the diurnal variations and overall pattern:
Elevated Morning Levels: Can suggest chronic stress or conditions like Cushing's syndrome.
Low Levels Throughout the Day: Could indicate adrenal fatigue or Addison's disease.
Elevated Nighttime Levels: Often associated with poor sleep quality and chronic fatigue [6,7].
My patient had elevated nighttime cortisol, improving sleep hygiene can be beneficial. Supplements like L-theanine, ashwagandha, and phosphatidylserine can help lower cortisol levels in the evening, promoting better sleep quality and reducing fatigue. Once we identified her elevated nighttime cortisol, we decided to take a closer look at her thyroid function, which by traditional medicine standards falls within normal levels.
Thyroid Function and Chronic Fatigue
Thyroid dysfunction is another critical factor to consider in perimenopausal women with chronic fatigue. The following thyroid tests are essential:
TSH (Thyroid Stimulating Hormone)
Free T4
Free T3
Reverse T3 (rT3)
Thyroid Antibodies
Interpreting Thyroid Test Results
TSH Above 2.0 mIU/L: May indicate subclinical hypothyroidism.
Reverse T3/ Free T3 Ratio Less than 10: Suggests poor T4 to T3 conversion.
Positive Thyroid Antibodies: Indicate autoimmune thyroid disease [8,9].
Subclinical hypothyroidism is not typically recognized by allopathic medical training, but it is appreciated in functional medicine. In the absence of other root causes, natural thyroid supplements or low-dose thyroid hormones may provide significant benefit [10].
Addressing Elevated Reverse T3 (rT3)
While my patient’s thyroid studies all fell within normal ranges per traditional medical guidelines, she did have TSH level slightly higher than 2.0 and elevated reverse T3. An elevated rT3/T3 ratio, such as 8.4, indicates an issue with thyroid hormone conversion. This can be due to several factors, including chronic illness, inflammation, nutrient deficiencies, liver or kidney dysfunction, uncontrolled diabetes, and chronic stress [10]. Addressing these underlying causes is crucial for improving thyroid function and overall well-being.
She has been screened for diabetes and her cortisol curve follows a normal pattern save for higher nighttime levels. For this reason, her next step is to analyze her sleep hygiene, and we will consider testing for sleep apnea. Supplements that may help lower reverse T3 include selenium, zinc, vitamin B6, vitamin E, and monolaurin.
Conclusion
For perimenopausal women experiencing intractable chronic fatigue with otherwise normal lab values, a thorough evaluation of cortisol patterns and thyroid function is essential. Precision Analytical’s DUTCH CAR test provides a comprehensive assessment of cortisol dynamics, while detailed thyroid testing helps identify and address potential subclinical dysfunctions. By integrating these insights into clinical practice, we can develop more targeted and effective treatment plans, ultimately improving the quality of life for our patients.
References
Adam, E. K., & Kumari, M. (2009). Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology, 34(10), 1423-1436. PMID: 19647372
Miller, G. E., Chen, E., & Zhou, E. S. (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychological Bulletin, 133(1), 25-45. PMID: 17201569
Kudielka, B. M., & Kirschbaum, C. (2005). Sex differences in HPA axis responses to stress: a review. Biological Psychology, 69(1), 113-132. PMID: 15740829
Hellhammer, D. H., Wüst, S., & Kudielka, B. M. (2009). Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology, 34(2), 163-171. PMID: 19095358
Kirschbaum, C., & Hellhammer, D. H. (1994). Salivary cortisol in psychobiological research: an overview. Neuropsychobiology, 22(3), 150-169. PMID: 7521429
Stalder, T., & Kirschbaum, C. (2012). Analysis of cortisol in hair--state of the art and future directions. Brain, Behavior, and Immunity, 26(7), 1019-1029. PMID: 22465166
Wüst, S., Federenko, I., Hellhammer, D. H., & Kirschbaum, C. (2000). Genetic factors, perceived chronic stress, and the free cortisol response to awakening. Psychoneuroendocrinology, 25(7), 707-720. PMID: 10938450
Biondi, B., & Cooper, D. S. (2008). The clinical significance of subclinical thyroid dysfunction. Endocrine Reviews, 29(1), 76-131. PMID: 17991805
Pearce, S. H. S., & Brabant, G. (2007). Thyroid hormone replacement for subclinical hypothyroidism. New England Journal of Medicine, 357(26), 2722-2729. PMID: 18160688
Buitelaar, J.K. The role of the HPA-axis in understanding psychopathology: cause, consequence, mediator, or moderator?. Eur Child Adolesc Psychiatry 22, 387–389 (2013). https://doi.org/10.1007/s00787-013-0441-7
Fliers, E., & Kalsbeek, A. (2016). Hypothalamic control of thyroid hormone metabolism. Nature Reviews Endocrinology, 12(11), 633-645. PMID: 27534699
