At the core of men's well-being lies the intricate interplay of endocrine glands and hormones, orchestrating an array of essential functions. Within this intricate orchestra, the adrenal, thyroid, and testicular glands assume pivotal roles. Evidence indicates a rising prevalence of hormone imbalances among men. Notably, estimates suggest that approximately 20% of adolescents and young adults, along with 39% of men above the age of 45, experience low testosterone. Understanding the interconnectedness of these glands and their respective hormones is crucial for comprehending and optimizing men's well-being and preventing chronic health issues. In this article, we will explain the relationships between these hormones and how to navigate the hormonal orchestra in men using functional medicine tests.
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Fundamentals of Male Endocrine Function
The endocrine system consists of various glands distributed throughout the body and the hormones they are responsible for producing and releasing. Hormones are chemical messengers that travel through the bloodstream to reach other organs and tissues, facilitating the coordination of critical bodily functions. There are eight (8) major glands and over 50 hormones comprising the human endocrine system, but three glands that are fundamental to male endocrine function include the adrenals, thyroid, and testes.
Adrenals
The adrenal glands are two triangular-shaped glands located on top of the kidneys. They produce and release hormones, including cortisol, DHEA, aldosterone, adrenaline, and noradrenaline, that are responsible for regulating functions such as blood pressure, blood sugar, sleep-wake cycle, “flight or fight” response, and immune responses.
Thyroid
The thyroid gland is a butterfly-shaped gland situated in the front of the neck. It produces hormones such as thyroxine (T4), triiodothyronine (T3), and calcitonin. T4 and T3 influence the rate at which the body's cells turn food into energy, essentially acting as the body’s metabolic thermostat. T4 and T3 regulate body temperature, heart rate, and overall energy levels. Calcitonin regulates the amount of calcium in the blood.
Testes
The testes are a pair of oval-shaped reproductive organs in men that produce sperm and hormones, most notably testosterone. Testosterone is involved in the development of both primary sexual characteristics, such as the growth of genitalia, sperm production, and sexual desire, and secondary sexual characteristics, including musculoskeletal growth, alterations in voice pitch, and patterns of hair growth. Furthermore, it plays a crucial role in sustaining proper bone density and muscle mass while also exerting an influence on mood and cognitive functions (49).
Adrenal Function in Male Health
A few of the most significant imbalances related to adrenal gland function include hypothalamic-pituitary-adrenal (HPA) axis dysfunction, Cushing syndrome, and adrenal insufficiency. The body's response to stress is coordinated through the hypothalamic-pituitary-adrenal axis. Under pressure, the brain's hypothalamus releases corticotropin-releasing hormone (CRH), prompting the pituitary gland to release adrenocorticotropic hormone (ACTH). This hormone signals the adrenal glands to produce cortisol. The HPA axis is regulated by a negative feedback mechanism to lower cortisol levels once the stressor subsides. Under normal circumstances, cortisol levels follow a circadian rhythm, peaking in the morning and gradually declining throughout the day.
Chronic exposure to stress, however, can lead to health issues due to prolonged activation of this system, often referred to as HPA axis dysfunction. It disrupts the standard feedback system the rhythm of cortisol secretion, and lowers DHEA production (1, 21). There are additional pathologies associated with the adrenal glands in which there is too much or too little cortisol produced. Cushing's syndrome is a medical condition characterized by an excessive level of the hormone cortisol in the body. This can result from several different causes, including endocrine tumors and long-term steroid use. In adrenal insufficiency, there is inadequate production of cortisol, most often caused by Addison's disease, destruction of the adrenal gland, or insufficient stimulation of the adrenal glands by the hypothalamus or pituitary (known as secondary insufficiency).
The imbalances in DHEA and cortisol, secondary to chronic stress or adrenal dysfunction, are associated with a spectrum of health conditions. Specifically, lowered DHEA levels compromise immune function and increase susceptibility to infections. DHEA is also thought to play a role in cognition, mood regulation, and sexual function, with deficiencies in DHEA linked to an increased risk of mood disorders, decreased feelings of well-being, memory loss, and erectile dysfunction. Elevated cortisol levels are associated with a risk of cardiovascular disease due to high blood pressure and cholesterol levels, disrupted sleep patterns, and weight gain. Furthermore, chronic stress and cortisol imbalances are linked to reduced bone density, impairments in cognitive function, mood disorders, and even a heightened risk of metabolic disorders, such as diabetes.
Understanding Thyroid Function is Men
The thyroid gland, similar to the adrenal glands, receives signals for hormone production from the brain. This hormone axis is called the hypothalamic-pituitary-thyroid (HPT) axis. If the body needs more thyroid hormone, it is sensed by the hypothalamus, which releases thyroid-releasing hormone (TRH). This hormone travels to the pituitary, stimulating the release of thyroid-stimulating hormone (TSH). TSH then directly signals the thyroid gland to start producing thyroid hormone. The majority of hormone produced by the thyroid is in the form of T4, which can then be converted to T3, a more biologically active hormone, by other tissues in the body.
Thyroid hormones are essential for the function of all of our cells. Therefore, thyroid imbalances, whether hypothyroidism or hyperthyroidism, are associated with a range of symptoms and chronic health conditions. In men with hypothyroidism, the metabolism slows down, making it challenging to maintain healthy muscle mass and weight and causing low energy. Additionally, hypothyroidism is associated with a higher risk of heart disease, as it can lead to elevated cholesterol levels and high blood pressure. It can also result in cognitive impairments, affecting memory and mental sharpness, and changes in mood like depression.
Conversely, in men with hyperthyroidism, the elevated levels of thyroid hormones rev up the body’s metabolic rate. This can lead to unexpected weight loss as the body expends more energy rapidly. While weight loss may seem beneficial in some cases, it often includes the loss of both fat and muscle mass, which can lead to weakness. The increased metabolic demands also placed added stress on the cardiovascular system. The heart must work harder and beat faster, which results in palpitations and irregular heart rhythms. Over time, this continuous strain on the heart can lead to a higher risk of developing cardiovascular conditions, such as hypertension, arrhythmias, and in severe cases, even heart failure. Excessive thyroid hormones can accelerate bone turnover, causing bones to lose density and increasing the risk of osteoporosis and fractures.
The Role of the Testes: Beyond Reproduction
The hypothalamic-pituitary-gonadal (HPG) axis is the hormonal feedback system in the body that regulates the function of the gonads and production of sex hormones. When testosterone levels are low, the hypothalamus and pituitary gland increase the release of gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to stimulate the testes to produce more sex hormones. Conversely, when hormone levels are too high, the system slows down hormone production.
Impaired function in testicular function can lead to hypogonadism, characterized by low testosterone levels and infertility in men. Hypogonadism is often caused by factors such as injury, genetic conditions, obesity, hypothyroidism, and aging. Infertility, on the other hand, can result from genetic diseases, structural blockages, and certain environmental factors that increase oxidative stress, like drug use, alcohol, smoking, and chemical exposures.
Certain enzymes in the body play a pivotal role in metabolizing testosterone. 5-alpha-reductase, for instance, converts testosterone into a more potent androgen, known as dihydrotestosterone DHT, that is associated with some conditions like alopecia and benign prostatic hyperplasia (BPH). Another enzyme, aromatase, found in higher concentrations in fat tissue, converts testosterone into estradiol. Disturbances in the activity of these enzymes can impact levels of testosterone and the overall balance of sex hormones in men.
Testosterone plays a role in men’s overall health beyond just sexual and reproductive function. It also helps in maintaining bone density, muscle mass, and metabolism. Moreover, testosterone impacts cognitive functions and mood. Low testosterone levels have been linked to a range of health conditions, including osteoporosis, weakness, fatigue, reduced libido, erectile dysfunction, mood disorders, metabolic syndrome, and cardiovascular disease (28).
The Harmonious Interplay: How Adrenals, Thyroid, and Testes Work Together
Rather than operating in isolation, hormones often work together to maintain a delicate balance in the body. Some hormones work synergistically, achieving more potent outcomes than they would individually, while others oppose each other's actions. The HPT, HPA, and HPG axes interact with each other, and imbalances in one can cascade into imbalances in the others, leading to a web of interrelated health issues.
The HPA axis impacts both the HPT and HPG axes. Activation of the HPA axis due to exposure to physical or emotional stressors leads to cortisol release. Cortisol suppresses the release of TRH and TSH from the hypothalamus and pituitary glands, ultimately resulting in decreased thyroid hormone production. It can also negatively impact the conversion of T4 into T3.
In the HPG axis, cortisol suppresses the release of GnRH from the hypothalamus, which is necessary to regulate the secretion of LH from the pituitary. When the HPA axis is over-stimulated, the decreased secretion of GnRH and LH leads to reduced testosterone production in the testes. A chronically overactive stress response can ultimately lead to low DHEA production, further reducing the pool of androgen hormones.
Decreased metabolic activity caused by low thyroid hormones inhibits the hypothalamus and pituitary's ability to release GnRH and LH. It can also trigger the pituitary to release higher levels of prolactin. Both low LH and high prolactin levels can lead to lower testosterone levels in men (30). Thyroid hormones also impact the amount of sex hormone binding globulin (SHBG), which binds to sex hormones like testosterone. This determines the amount of free and bioavailable testosterone in circulation (22). High TSH levels seen in hypothyroidism are associated with higher cortisol levels. This is thought to occur due to reduced metabolism and clearance of cortisol, as well as interfering with the negative feedback mechanism that usually exists in the HPA axis (53).
The intricate interplay between adrenal, thyroid, and sex hormones creates a complex web of interactions that significantly impact metabolic function. As these hormones are not isolated entities but rather components of a finely tuned system, slight dysregulation in one or all axes can lead to various health issues. Hormonal imbalances, such as elevated cortisol, diminished DHEA, suboptimal thyroid activity, and reduced testosterone levels, collectively contribute to an impaired metabolic state. Consequently, a holistic approach that considers the combined effects of these interconnected hormonal systems is essential for a comprehensive understanding of men's hormonal health and its impact on overall well-being.
Functional Medicine Lab Testing: Decoding the Male Hormonal Symphony
Due to the interconnectedness of the HPA, HPT, and HPG axes, all of these axes should be assessed together to optimize men's hormonal health.
Adrenal Testing
Adrenal hormones can be measured using blood, saliva, and urine testing. Genova’s Adrenal Stress Profile with Cortisol Awakening Response measures the diurnal rhythm of cortisol using four salivary measurements throughout the day. It also measures the Cortisol Awakening Response (CAR), which can provide more information on how the body is responding to stress. The DUTCH Adrenal test uses dried urine to assess for the daily free cortisol and cortisone patterns as well as the cortisol and cortisone metabolites. Measuring the metabolites can serve as an indicator of the total adrenal output. A serum cortisol level is useful in diagnosing Addison’s disease and Cushing's syndrome because blood levels indicate total hormones.
Sex Hormone Testing
Like adrenal hormones, sex hormones can be measured using blood, saliva, and urine testing. The Male Hormone Panel, by Precision Point, measures the primary reproductive hormones in the blood. The Salivary Profile III by ZRT Laboratory measures the free, bioavailable levels of these primary reproductive hormones in the saliva. Testosterone levels are highest in the morning, so these tests should be collected then to capture peak levels.
The DUTCH Sex Hormone Metabolites test by Precision Analytical measures the primary reproductive hormone in urine. Collecting the urine throughout the day helps to account for hormone fluctuations that can be missed in single collections. Furthermore, it includes hormone metabolites, which can provide additional insight into the activity of enzymes like 5-alpha-reductase and aromatase and how testosterone is metabolized.
Thyroid Testing
Thyroid hormones should be measured in a blood test. The Thyroid Health Panel by Ayumetrix offers a blood spot test.
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Summary
As the incidence of hormone imbalances and chronic health conditions grows, it becomes increasingly important to fully comprehend the pivotal roles of the adrenal, thyroid, and testicular glands and their associated hormones in men's health. Functional medicine tests serve as invaluable tools in unveiling the intricacies of this hormonal network, enabling the optimization of men's hormonal health and their overall well-being. In an era marked by multifaceted health challenges, this holistic understanding and diagnostic approach are crucial for improving men's quality of life.
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