Saliva Testing: Cortisol and Hormone Test Result Interpretation Guide

One aspect of a journey to optimal health is gaining a nuanced understanding of our body's endocrine system. Salivary hormone tests have emerged as invaluable instruments, offering a unique and non-invasive window into the delicate balance of hormones that govern our well-being.

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Why Use Saliva Testing for Hormones?

Salivary testing is a diagnostic method that analyzes various compounds in saliva to gain insights into an individual's health status. Unlike blood tests, which are more traditional methods of sample collection, saliva testing offers a non-invasive and convenient alternative. Saliva contains a diverse range of substances, including hormones, antibodies, enzymes, and nucleic acids, making it a valuable medium for assessing different physiological parameters. (29)

One of the primary advantages of salivary testing is its utility in measuring steroid hormone levels. Steroid hormones are a class of lipid-derived signaling molecules secreted by the adrenal glands, testes, ovaries, and (during pregnancy) placenta. These hormones play crucial roles in regulating various physiological functions, including metabolism, immune responses, and reproduction, and imbalances can contribute to various health issues. Salivary testing provides a dynamic and accurate assessment of hormone levels, as it reflects the bioactive fraction of hormones actively available to tissues. This contrasts with serum testing, which measures total hormone levels but may not represent the hormone's functional status within the body.

Saliva is a preferred hormone testing method due to its non-invasive nature, allowing for stress-free sample collection, which is especially relevant for patients. Additionally, saliva samples can be easily obtained multiple times throughout the day, enabling a more comprehensive understanding of hormone fluctuations and circadian rhythms. This temporal aspect is crucial for assessing conditions such as adrenal fatigue and hormonal imbalances, as it captures the natural variability in hormone secretion. (30)

Understanding Cortisol and Its Function

Cortisol, a steroid hormone produced by the adrenal glands, is a central player in the body's stress response system while exerting regulatory influences on numerous physiological functions. Its primary functions include modulating metabolism, regulating blood sugar levels, and aiding in immune response suppression during stress.

In the body's normal physiological state, cortisol follows a distinct circadian rhythm, typically peaking in the early morning to support the awakening process and gradually declining throughout the day. This circadian pattern is essential for maintaining energy balance, promoting alertness, and facilitating bodily functions that align with the demands of daily activities. Disruptions in the circadian rhythm of cortisol secretion, whether due to genetics, age, or shift work, may contribute to disordered sleep patterns, mood disorders, and impaired cognitive function.

Whether elevated or deficient, abnormal cortisol levels can have profound health implications. Elevations in cortisol levels can result from chronic stress, exogenous steroid use, and cortisol- or ACTH-secreting tumors. Chronic stress leading to consistently elevated cortisol levels may contribute to conditions such as adrenal fatigue, immune system suppression, and disruptions in sleep patterns. People with Cushing's syndrome commonly present with a round, red face, a hump on the back of the neck, purple stretch marks, and rapid centralized weight gain. Complications of Cushing's syndrome include muscle weakness, vision problems, frequent infections, osteoporosis, high blood pressure, diabetes, and changes in reproductive functions. 

Conversely, insufficient cortisol production, as seen in conditions like Addison's disease, can result in chronic fatigue, weight loss, darkened skin patches, and salt cravings. Over time, chronic stress can ultimately result in adrenal hypo-responsiveness, resulting in low cortisol production. Researcher Hans Selye termed this the Stage of Exhaustion in his stress response model. Colloquially, people often call this adrenal fatigue or burnout. 

Other Hormones Commonly Tested in Saliva

Other hormones are also commonly measured with salivary testing, including testosterone, estrogen, progesterone, and dehydroepiandrosterone (DHEA). 

Testosterone is an androgen hormone, primarily known as the principal male sex hormone synthesized in the testes. Females also produce small amounts of testosterone in the ovaries and adrenal glands. In males, it is crucial for developing male reproductive tissues and promoting secondary sexual characteristics such as facial and body hair growth, deepening of the voice, and increased muscle mass. Additionally, testosterone is essential for maintaining bone density, muscle mass, and overall energy levels. It is a key player in regulating libido and contributes to sperm production, influencing male fertility. In females, testosterone is converted to the primary female sex hormone, estrogen. It also maintains bone density, muscle mass, energy levels, mood, libido, and fertility. (3, 11)

Estrogen, a group of steroid hormones comprising estrone (E1), estradiol (E2), and estriol (E3), is primarily associated with the female reproductive system but is also present in males. Estradiol, the most potent form, regulates menstrual cycles, influences mood, and maintains bone density in females, and contributes to testicular function, libido regulation, bone health, and cardiovascular maintenance in men. Estrone is prevalent postmenopause, influencing bone density and overall well-being, and estriol predominates during pregnancy, which is crucial for the uterine environment and fetal development. Imbalances in estrogen levels may lead to menstrual irregularities, mood swings, and an increased risk of osteoporosis.

Progesterone, synthesized in the ovaries in females, is crucial for maintaining pregnancy, regulating the menstrual cycle, and supporting mood. In females, progesterone balances the effects of estrogen and prepares the uterus for pregnancy. Made in smaller amounts in men, progesterone facilitates androgen synthesis and sperm development. Progesterone imbalance may contribute to menstrual irregularities, mood disorders, and fertility issues.

DHEA, produced by the adrenal glands, is a precursor to testosterone and estrogen. DHEA levels peak around age 25 and then decline with age. In addition to being a precursory hormone, DHEA has other roles in endothelial function, modulating inflammation, promoting insulin sensitivity, immune function, bone metabolism, sexual function, and neuroprotection. Low DHEA levels can be associated with osteoporosis, heart disease, cognitive decline, chronic stress, mood disorders, and low libido. (11, 48) 

Interpreting Saliva Test Results for Cortisol

Salivary cortisol tests measure the unbound, biologically active fraction of cortisol, representing the free cortisol available to tissues. Research consistently affirms the reliability and non-invasiveness of salivary cortisol testing in assessing cortisol levels and diurnal variations, with studies highlighting a robust correlation between salivary cortisol and biologically active free cortisol in the blood. This method's advantages include convenience, ease of sample collection, and the ability to capture multiple samples throughout the day, making it particularly useful in studying conditions related to the hypothalamic-pituitary-adrenal (HPA) axis and cortisol dysregulation. Salivary cortisol testing has applications in studying the stress response, circadian rhythm, and adrenal disorders. It is a preferred tool in clinical and research settings for its correlation with biologically active cortisol and its ability to provide valuable insights into cortisol dynamics.

Interpreting salivary cortisol results involves considering several key factors. Firstly, understanding diurnal variations is crucial; cortisol typically peaks in the early morning and gradually decreases throughout the day. Values within the expected range for specific time points are considered normal. Elevated morning levels may suggest chronic stress or conditions like Cushing's syndrome, while consistently low levels may indicate adrenal fatigue or Addison's disease. Assessing the cortisol rhythm is also an important aspect of salivary cortisol interpretation; abnormal peaks or a flattened pattern can signify HPA axis or circadian dysregulation. 

Cortisol Test Options

The following are popular salivary cortisol test options ordered through the Rupa Health portal:

• Cortisol (C) by ZRT Laboratory
• Diurnal Cortisol by Ayumetrix
• ASP with CAR by Genova Diagnostics
• DUTCH Cortisol Awakening Response by Precision Analytical

Interpreting Saliva Test Results for Other Hormones

Salivary assessments of testosterone, estrogen, and progesterone correlate strongly to serum hormone levels, particularly in the context of dynamic hormonal changes. Studies indicate a strong agreement between salivary and serum measurements, supporting the use of saliva as a non-invasive and convenient medium for assessing sex hormones. Like salivary cortisol, measurable sex hormones reflect the biologically active, free fraction of hormones, providing a more accurate representation of the hormones available to tissues. The exception is conjugated hormones, such as DHEA-S, which cannot cross the phospholipid membrane of cells lining blood vessels into salivary glands. (29)

Salivary testing has significant implications for diagnosing and managing conditions related to hormonal imbalances, such as reproductive health issues and menopausal transitions. The reliability, ease of sample collection, and correlation with serum levels make salivary hormone testing a valuable tool in functional medicine for assessing cyclical variations in sex hormones and guiding targeted interventions. Accurate interpretation of hormone results requires consideration of absolute reference ranges and clinical context. For instance, when assessing testosterone levels, it is vital to recognize the inherent gender differences. In men, normal testosterone values fall within a specific range, while in women, the reference range is markedly lower. (3) Similarly, when interpreting estrogen and progesterone results, understanding the clinical context involves recognizing the impact of menstrual cycle phases and menopausal status in women. Normal estrogen and progesterone values vary across menstrual cycle stages. Furthermore, normal ranges differ between premenopausal and postmenopausal women due to the significant hormonal changes associated with menopause. (6) 

Hormonal imbalances, reflected in abnormal levels of testosterone, estrogen, and progesterone, are associated with a range of conditions, including andropause (low testosterone in men), menopause (low estrogen and progesterone in women), PCOS (elevated testosterone and DHEA in women), and irregular menstrual cycles (high and/or low estrogen and progesterone in women).

Sex Hormone Test Options

The following are popular salivary sex hormone test options ordered through the Rupa Health portal:

• Saliva Profile I by ZRT Laboratory
• Rhythm by Genova Diagnostics
• Menopause by Genova Diagnostics

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Functional Medicine Labs and Hormone Testing

In functional medicine, comprehensive hormone analysis is instrumental in understanding an individual's hormonal status and guiding personalized interventions. Collaborating with a knowledgeable functional medicine provider is important to interpret salivary hormone results within the context of clinical symptoms and an individual's medical history. These results aid in pinpointing underlying imbalances and potential triggers contributing to hormonal issues and symptoms. Treatment plans developed by functional medicine providers are tailored to address these specific imbalances, incorporating lifestyle modifications, stress management, nutrition, and targeted interventions as needed. The integration of hormonal testing within the broader framework of functional medicine supports a nuanced and individualized approach to healthcare.

Clinical Applications of Saliva Test Results

Clinical indications for ordering salivary hormone test panels are diverse and often align with conditions related to hormonal imbalances. Healthcare providers may recommend these tests for patients with the following health concerns:

Reproductive Health

For both men and women, salivary hormone testing helps evaluate reproductive health, identifying imbalances in testosterone, estrogen, and progesterone associated with fertility issues and sexual dysfunction. Salivary hormone testing is valuable for assessing hormonal fluctuations across menstrual cycles, aiding in the diagnosis of irregularities such as anovulation or luteal phase defects in women. Salivary hormone tests are also beneficial for women experiencing perimenopausal and menopausal symptoms, helping to understand changes in estrogen and progesterone levels and guiding appropriate interventions for managing symptoms.

Stress

Cortisol and DHEA are often measured in panels that evaluate adrenal function and the HPA axis, particularly for patients facing chronic stress and experiencing chronic fatigue and other symptoms of adrenal fatigue.

Thyroid Dysfunction

Hormonal imbalances can impact thyroid function. This is reflected in the increased incidence of thyroid disorders in postmenopausal women, for example. Salivary testing can complement thyroid assessments by providing insights into steroid hormone levels and their influence on thyroid hormones.

Mood Disorders

Hormonal imbalances can contribute to mood disorders. This is one of the reasons contributing to the higher rates of depression, anxiety, PTSD, eating disorders, and suicide attempts observed in the female population. Imbalances in cortisol and testosterone are linked to low mood and irritability in men. 

Metabolic Disorders

Sex hormones and cortisol play intricate roles in metabolic health, and imbalances in these hormones can contribute to the development or exacerbation of metabolic diseases. In men, low testosterone levels have been associated with an increased risk of metabolic syndrome. During menopause, the decline in estrogen levels is linked to an increased risk of abdominal obesity, insulin resistance, and metabolic syndrome in women. Chronic stress and elevated cortisol levels can contribute to abdominal obesity, insulin resistance, and dysregulation of appetite and energy balance.

Challenges and Considerations in Saliva Testing

Saliva testing, while valuable for assessing hormonal status, has inherent challenges and limitations that warrant consideration. This method primarily measures free, unbound hormones, limiting its applicability for hormones predominantly bound in the blood, such as DHEA-S and thyroid hormones. Lifestyle factors like diet, medications, and oral hygiene can influence hormone concentrations, necessitating standardized conditions for sample collection. Additionally, hormone stability in saliva is a concern, requiring meticulous sample handling and storage conditions. Population variability in reference ranges, limited availability of commercial tests for all hormones, and the complexity of result interpretation further highlight the challenges associated with saliva testing. While a valuable tool, the limitations underscore the need for careful consideration and interpretation by skilled healthcare professionals to ensure its effective use in comprehensive health assessments. (19) 

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Salivary Cortisol and Hormone Test Interpretation: Key Points

Saliva testing is a valuable diagnostic tool, providing insights into the dynamic interplay of hormones in the body. Understanding the nuances of sample collection times, lifestyle factors, and testing limitations is crucial for accurate interpretation. By incorporating salivary testing into regular clinical practice, clinicians can make informed, targeted treatment decisions for their patients more easily. Integrating saliva testing into clinical practice aligns precision healthcare strategies in addressing hormonal imbalances.