From Saliva to Serum: Comprehensive Testing for Men's Hormonal Health

Hormones, chemical messengers traveling throughout our bloodstream, are crucial in regulating bodily functions like mood, energy, muscle growth, and sexual health. Due to the vast array of processes they influence, they are a fundamental aspect of men's overall well-being and help. A significant number of men will grapple with hormone imbalances and related health conditions. For instance, 39% of men over the age of 45 experience low testosterone levels. Chronic health conditions such as obesity, diabetes, cardiovascular disease, and osteoporosis are all associated with underlying hormonal imbalances such as low testosterone. Functional medicine tests allow men to take a proactive approach to their hormone health, preventing severe health conditions and optimizing their overall well-being. This article will explore essential hormones in men's health and the array of testing options available for those seeking to assess their hormone balance.

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Essential Hormones in Men's Health

Over 50 hormones have been identified in the human body, but we will introduce some key players in men’s health here.

Testosterone

Androgens are a class of sex hormones more abundant in men. Testosterone, produced primarily in the testes, is often considered the predominant androgen. It plays a role in the development of primary sexual characteristics, including the growth of genitalia, sperm production, and libido, as well as secondary sexual characteristics, including musculoskeletal growth, voice changes, and hair patterns. 

Testosterone has other far-reaching effects on men’s well-being beyond its essential role in sexual development. It contributes to the maintenance of healthy bone density and muscle mass while also influencing mood and cognitive functions. Low testosterone levels are often associated with symptoms such as fatigue, depression, low libido, and cognitive decline. (22, 33)

Testosterone can be metabolized into other hormones in the body. The enzyme 5-alpha-reductase converts testosterone into a more potent androgen, known as dihydrotestosterone DHT, that is associated with some conditions like alopecia and benign prostatic hyperplasia (BPH). The aromatase enzyme, in exceptionally high concentration in fat tissue, can convert testosterone into estradiol. Disturbances in the activity of these enzymes can influence men’s overall hormone balance.

As men age, testosterone levels gradually diminish, giving rise to a condition known as andropause. This transition puts them at risk for various health concerns, particularly obesity and type 2 diabetes.

DHEA

Dehydroepiandrosterone (DHEA) is a hormone produced predominantly by the adrenal glands. It can be converted in the body into other hormones, such as testosterone and estrogen. The body uses DHEA to produce other hormones, like testosterone and estrogen. It is a hormone in its own right, modulating multiple biological processes, including endothelial function, reducing inflammation, insulin sensitivity, immunity, body composition, bone metabolism, sexual function, and neuroprotection. DHEA levels peak around age 25 and then steadily decline with age. By the time individuals are over 70, their DHEA levels are only 10-20% of what they were at a younger age (35). Low DHEA levels are associated with conditions such as osteoporosis, heart disease, memory changes, burnout, mood and anxiety disorders, and low libido. (7, 9, 20, 27)

Thyroid

Thyroid hormones’ primary responsibility is regulating the body's metabolism, the reactions in which cells turn food into energy. The primary thyroid hormones are thyroxine (T4) and triiodothyronine (T3). T4 is the primary hormone produced and released by the thyroid gland. The other organs in the body then convert T4 into T3, which is more biologically active. Thyroid hormones act on all organs and cells, including other endocrine glands. When the thyroid is underactive (hypothyroidism) or overactive (hyperthyroidism), it can lead to a cascade of health issues, including fatigue, weight fluctuations, mood disturbances, and other hormone imbalances. (19, 34)

Cortisol

Cortisol is a hormone released by the adrenal glands in response to a variety of stressors, both physical and emotional. Its functions are diverse, encompassing regulation of metabolism, the sleep-wake cycle, immune responses, blood pressure, and the activation of the body's "fight or flight” response. While cortisol is essential for the body to adapt and respond to stress, chronic or prolonged stress can disrupt its delicate balance. In men, imbalanced cortisol levels are associated with numerous health issues, including decreased libido, reduced muscle mass, weight gain, fatigue, reduced cognitive function, mood changes like anxiety and depression, and even other hormone imbalances like low testosterone. (5) 

Insulin

Insulin is a hormone produced in the pancreas that maintains blood glucose levels, facilitates glucose uptake, and regulates carbohydrate, protein, and fat metabolism. In individuals with insulin resistance (IR), the cells become less responsive to insulin signals. To compensate, the pancreas often produces more insulin, resulting in higher-than-normal insulin levels in the blood. Insulin resistance is associated with other hormone imbalances in men, like low testosterone. Insulin resistance can result in decreased muscle mass, increased abdominal fat, and decreased libido and may contribute to conditions like metabolic syndrome, cardiovascular disease, and type 2 diabetes. (25)

Serum Hormonal Testing in Men 

A blood or serum test is collected through a blood draw taken by a phlebotomist and determines the total concentration of hormone(s) in the bloodstream. Total hormone levels include both the active, bioavailable hormone and the hormone that is bound to carrier proteins (unavailable) in the bloodstream. (10) In some cases, specialized tests can measure the free hormone fraction in the blood. Blood testing is considered the diagnostic standard for diagnosing hormone-related conditions such as hypogonadism or hypothyroidism. Serum tests allow for assessing a large number of hormones together with a single collection with high degrees of precision and accuracy. One of the primary drawbacks of blood tests is that they only offer a single point-in-time snapshot of hormone levels at the moment of collection. 

Hormones fluctuate throughout the day and, therefore, may not be fully represented in one serum collection (2, 26). Furthermore, obtaining blood samples can be invasive and uncomfortable for some patients. 

The Thyroid Panel by BostonHeart Diagnostics measures not only thyroid stimulating hormone (TSH) but also T4, T3, and thyroid antibodies to provide a complete picture of thyroid function. Like testosterone, thyroid labs should be drawn in the morning. (21, 28)

A fasting insulin level is an effective way to screen for insulin resistance. Increasing fasting insulin levels, with or without normal fasting glucose levels, correspond to insulin resistance. The HOMA-IR, or Homeostatic Model Assessment of Insulin Resistance, is a mathematical formula that calculates insulin resistance based on fasting blood glucose and fasting insulin levels. Generally, numbers under one are considered insulin sensitive, while numbers 2.9 or higher are insulin resistant. The HOMA-IR test by BostonHeart Diagnostics measures fasting insulin and fasting blood sugar to calculate this number. (14, 15)

Saliva Testing For Men's Hormones 

Saliva tests for men’s hormones measure the free, bioavailable hormone levels instead of the total amount of hormones in your bloodstream. Salivary testing provides a non-invasive and convenient option, as samples can be collected at home. This is particularly appealing when multiple samples are needed, enabling a comprehensive evaluation of diurnal hormonal fluctuations and responses to stressors. Salivary tests thus provide a valuable tool for obtaining a more detailed and dynamic picture of an individual's hormonal health. (1, 11, 17) 

The Salivary Hormone Profile III test by ZRT Laboratory measures the primary reproductive and adrenal hormones, including the diurnal rhythm of cortisol. Cortisol exhibits a significant variation in levels throughout the day, increasing in the morning, peaking at approximately 30 min after awakening in the morning, and gradually decreasing throughout the day. Changes to this pattern are associated with poor health outcomes.

Other Testing Modalities: Urine and Dried Blood Spots For Men’s Hormones 

Like salivary testing, urine testing allows for multiple, non-invasive sample collections in the privacy of one's own home, capturing complete pictures of hormone fluctuations throughout the day. Its advantage over other forms of testing is that it also measures hormone metabolites (23). The DUTCH Complete test by Precision Analytical measures the primary reproductive and adrenal hormones, including a diurnal cortisol rhythm. It also includes hormone metabolites, which can provide additional insight into the activity of enzymes like 5-alpha-reductase and aromatase, which we discussed earlier. (31) 

Dried blood spot (DBS) tests offer a minimally invasive and home-friendly option for collecting blood samples. The blood is dropped directly onto a filter card in multiple spots and left to dry. The sample is then rehydrated once it is received by the lab for analysis (38). While DBS testing provides convenience, it cannot measure quite as many hormones as are available through serum testing. The Male Blood Profile II by ZRT Laboratory measures testosterone, DHEA, cortisol, estrogen, and thyroid hormones using a dried blood spot collection. They also offer a Cardiometabolic Profile that includes an insulin measurement. This is an ideal option for patients who want to measure a broader range of hormones but avoid phlebotomy visits and fees.

Integrating Test Results for Holistic Analysis 

When interpreting hormone analysis results, it’s vital to consider the consequences both in the context of a complete hormone profile as well as in the context of the individual's medical and social history.

Hormones do not act in isolation; they interact with and influence one another. Therefore, analyzing the level of a single hormone in isolation may not provide a complete picture. For instance, a low testosterone level may raise concerns, but when evaluated alongside an elevated cortisol level, an underlying cause, such as chronic stress, becomes evident. For this reason, when investigating the root causes of men's hormone imbalances, it is essential to look at a comprehensive hormonal analysis. 

Several other factors also affect hormone levels. Age is a significant determinant, as hormone levels naturally fluctuate over a man’s lifespan. What is considered normal testosterone or DHEA level for a man in his 20s will differ significantly from what is normal for a man in his 70s. Social history (such as diet, physical activity, stressors, and environmental exposures), as well as medical history (such as diagnosed health conditions, past surgeries, or medications), can all impact hormone levels and function. Interpreting hormone results in the context of each individual’s unique history facilitates a deeper understanding of the underlying causes of imbalances and the creation of more personalized and effective treatment recommendations.

Tailoring Treatments Based on Test Results 

Utilizing comprehensive hormone profiles in men's health offers several distinct advantages. Firstly, they can identify imbalances before noticeable symptoms manifest. This early detection is crucial for initiating proactive treatment and preventing the development of more serious health conditions. Additionally, these profiles facilitate the creation of personalized treatment plans tailored to address specific imbalances and individual health factors. Treatment recommendations can include various interventions, including lifestyle modifications, dietary changes, stress management, and, in some cases, hormone replacement therapy. Reviewing the results of hormone tests with patients increases engagement and fosters a deeper understanding of their own health.

The utility of hormone tests extends beyond initial diagnosis and treatment. They provide an ongoing opportunity to monitor the efficacy of treatments and make any necessary adjustments. Periodic retesting allows healthcare providers to track the progress of personalized hormonal health interventions, ensuring the treatment plans remain aligned with the patient's evolving hormone profile. This not only minimizes the risk of potential side effects but also increases patient compliance, fostering optimal results.

Future Trends in Hormonal Testing for Men

The rapid growth of technology in recent decades, particularly in the fields of Artificial Intelligence (AI) and Machine Learning (ML), has the potential to optimize men's hormonal testing. AI refers to the development of computer systems or machines that use algorithms and data to perform tasks and make decisions that typically require human intelligence. These tasks may include problem-solving, learning from data, recognizing patterns, and adapting to new situations. ML is a subset of AI that focuses on the development of algorithms and statistical models, enabling computer systems to improve their performance on a specific task through learning from data and experiences without being explicitly programmed. AI/ML technologies can compute and analyze complex datasets, identify risk factors, and predict clinical outcomes more effectively than traditional methods. Utilizing such technologies can increase affordability and access to hormone testing for patients. (13, 24)

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Summary 

Essential hormones, such as testosterone, DHEA, thyroid hormones, cortisol, and insulin, play significant roles in men's well-being. Embracing comprehensive hormonal testing in men's health assessments uncovers how hormones interact with one another in response to lifestyle choices and stressors, facilitating the creation of personalized treatment plans to fit each individual’s unique needs. Multiple testing methods, such as blood, saliva, and urine tests, are available, offering patients options based on their needs and preferences.