What Is the Hypothalamic-Pituitary-Adrenal (HPA) Axis

Yoga Anatomy Jun 18, 2025 0 18 Add to Reading List

If you’ve ever talked about stress, cortisol, energy, or fatigue, chances are you've heard of the Hypothalamic-Pituitary-Adrenal (HPA) Axis—the body’s central command center for regulating stress, hormones, and immune responses.

When the HPA axis is repeatedly over- or under-stimulated, the body reacts through a cascade of hormonal fluctuations, inflammatory responses, neurotransmitter imbalances, and shifts in energy levels. This axis plays a critical role in the optimal functioning of several glands and organs, including the thyroid, ovaries, testes, brain, and adrenal glands. At its core, the HPA axis helps maintain physiological homeostasis—a stable internal environment vital for health and wellbeing.

The HPA axis consists of three main components:

Hypothalamus
Pituitary gland
Adrenal glands

Together, these parts form a bridge between the central nervous system and the endocrine system, working closely to regulate hormone balance and coordinate the body's stress response. This includes physical reactions like increased heart rate, heightened alertness, and sweating when faced with a perceived threat.

What is the hypothalamic-pituitary-adrenal (HPA) axis?

The hypothalamic-pituitary-adrenal (HPA) axis is a complex communication network between three key organs—the hypothalamus, pituitary gland, and adrenal glands. It plays a central role in regulating the body’s response to stress.

This axis functions as a neuroendocrine system, meaning it connects the nervous system and endocrine system. When the body perceives stress, the nervous system stimulates specific cells within these organs to release hormones into the bloodstream. These hormones create a feedback loop that helps initiate, regulate, and eventually shut down the stress response, maintaining balance and protecting the body from the harmful effects of chronic stress.

In short, the HPA axis is essential for managing both acute and long-term stress while also influencing mood, immunity, digestion, energy levels, and more.

Which organs comprise the HPA axis?

Your HPA Axis is Made Up of Three Key Components:

Hypothalamus:
Located deep within the brain, the hypothalamus helps maintain the body's internal balance (homeostasis). It regulates functions such as temperature, hunger, mood, and more—either by directly influencing the autonomic nervous system or by managing hormone release.
Pituitary Gland:
About the size of a pea, this gland sits just below the hypothalamus. It produces several important hormones and controls other endocrine glands. The anterior part of the pituitary is especially important in the HPA axis.
Adrenal Glands:
These small, triangular-shaped glands rest on top of each kidney. They produce hormones essential for regulating metabolism, immune function, blood pressure, and the stress response. The outer layer, known as the adrenal cortex, is the part involved in the HPA axis.

Function

What is the role of the HPA axis?

The primary role of the hypothalamic-pituitary-adrenal (HPA) axis is to regulate the body’s response to stress by releasing cortisol, a glucocorticoid (steroid hormone). This hormone initiates a series of short-term physiological changes that prepare the body to handle perceived threats or challenges.

In stressful situations, the adrenal medulla—closely associated with the HPA axis—also releases adrenaline (epinephrine) to trigger the body’s “fight-or-flight” response.

The stress response is a natural and essential survival mechanism. When you face a stressor, your body reacts with increased alertness, energy, and readiness to respond. In short bursts, this response is helpful—it keeps you focused, motivated, and safe from danger.

However, when stress becomes chronic, this constant activation of the HPA axis can have harmful effects on physical and mental health, contributing to issues such as fatigue, anxiety, hormonal imbalance, and weakened immunity.

How does the HPA axis function?

The HPA axis operates through a hormonal chain reaction that ultimately results in the release of cortisol, the body’s primary stress hormone. Here's how the process works:

Stress Trigger: When you encounter a stressful event, your autonomic nervous system activates the hypothalamus.
Hormonal Cascade Begins: In response, the hypothalamus releases corticotropin-releasing hormone (CRH).
Pituitary Activation: CRH signals the anterior pituitary gland to release adrenocorticotropic hormone (ACTH).
Adrenal Response: ACTH then travels through the bloodstream to the adrenal cortex (part of your adrenal glands), prompting it to release cortisol.
Negative Feedback Loop: As cortisol levels rise, they signal the hypothalamus and pituitary gland to reduce CRH and ACTH production—effectively shutting down the stress response once the threat has passed.

This negative feedback loop is finely tuned to maintain balance. However, chronic or intense stress can disrupt this regulation, leading to HPA axis dysfunction—a condition linked with fatigue, anxiety, depression, and hormonal imbalances.

Role of Cortisol and Other Hormones

To help the body respond to stress, the HPA axis regulates and releases several vital hormones—the most significant being cortisol. During stressful situations, cortisol plays a central role in managing mood, immune function, and metabolism. However, cortisol production is part of a larger hormonal cascade involving corticotropin-releasing hormone (CRH) from the hypothalamus and adrenocorticotropic hormone (ACTH) from the pituitary gland.

Other important hormones also contribute to the body’s stress response, including:

Epinephrine and norepinephrine – which increase heart rate, blood pressure, and alertness
DHEA – which supports stress resilience and mood stability
Aldosterone – which helps regulate blood pressure and fluid balance

Together, these hormones create a coordinated and adaptive response, enabling the body to meet physical and emotional challenges more effectively.

The HPA Axis and Stress

Stress is closely linked to the development of several mental health conditions, such as major depression and posttraumatic stress disorder (PTSD), which occur more frequently in women than in men. The hypothalamic–pituitary–adrenal (HPA) axis is a central component of the neuroendocrine system, regulating the body’s response to both internal and external stressors. Proper HPA axis function is crucial for maintaining both mental and physical health, as dysregulation of this system has been implicated in a wide range of psychological and physiological disorders.

Research has revealed sex-based differences in how the HPA axis responds to stress. Preclinical studies have shown that females often exhibit a faster and more robust hormonal response to stress compared to males. These biological differences may partly explain the higher prevalence of stress-related mental disorders in women.

However, human studies have yielded inconsistent findings, likely due to variables such as differences in the type of stressors used, hormonal contraceptive use, and varying phases of the menstrual cycle among female participants.

The HPA Axis & Mental Health

Your body’s stress response system — the HPA axis — plays a crucial role in your mental well-being. When functioning properly, it supports emotional stability, focus, and effective stress management. However, chronic stress or trauma can disrupt this system, leading to imbalances.

Conditions such as burnout and PTSD are often associated with low cortisol levels, whereas anxiety and depression tend to correlate with elevated cortisol. Dysregulation of the HPA axis may manifest as mood swings, sleep disturbances, and mental fog.

Supporting the HPA axis through adequate rest, therapy, and positive lifestyle changes can help restore emotional balance, improve resilience, and enhance overall mental health.

Conditions and Disorders: What Affects the HPA Axis?

The HPA axis can become either overactive or underactive, leading to what’s known as HPA axis dysfunction.

What Causes HPA Axis Dysfunction?

Chronic or prolonged stress is a key trigger. When cortisol levels remain elevated for extended periods, it can impair the proper functioning of the HPA axis and disrupt the body's internal balance.

Health Conditions Linked to HPA Axis Dysfunction:

Immune System Disorders
Chronic inflammation and autoimmune diseases can arise due to impaired immune regulation.
Mental Health Disorders
Mood disorders, anxiety, and post-traumatic stress disorder (PTSD) are commonly associated with HPA imbalance.
Metabolic Disorders
Conditions like obesity, insulin resistance, diabetes, and even cancer can be linked to cortisol dysregulation.
Cardiovascular Conditions
Long-term stress and elevated cortisol can contribute to high blood pressure and vascular damage.
Cognitive and Neurological Issues
Dysfunction may lead to memory problems and increase the risk of neurodegenerative diseases like Alzheimer’s.

Symptoms of HPA Axis Dysfunction

HPA axis dysfunction can manifest in many ways, often overlapping with symptoms of chronic stress, hormonal imbalances, and fatigue-related disorders. Common signs include:

Persistent fatigue and exhaustion — feeling tired all the time, even after rest
“Tired but wired” sensation — feeling physically drained but mentally overstimulated
Unexplained weight changes — especially weight gain in the hips and abdominal region
Poor sleep quality — waking up unrefreshed despite sleeping for several hours
Difficulty falling or staying asleep — frequent nighttime awakenings or insomnia
Weakened immune function — frequent colds, infections, or slow recovery
Cognitive issues — brain fog, trouble concentrating, poor memory, and mood swings (including anxiety and depression)
Cravings — frequent urges for sugar or salty foods
Inflammation and puffiness — signs like poor circulation, swelling, or fluid retention
Hair and nail issues — thinning hair, bald spots, brittle nails
Hormonal imbalances — irregular menstrual cycles, missed periods, or shifts in cycle length

What Triggers HPA Axis Dysfunction?

The HPA axis is sensitive to both acute (immediate) and chronic (long-term) stress. While it’s designed to help you cope with temporary challenges, persistent stress can disrupt its optimal function—unless supported through lifestyle and nutritional changes.

Because HPA axis dysfunction can result from various types of stressors, it's helpful to identify all the cumulative factors that may be contributing to its imbalance, including the following:

1. Stress (Physical, Mental & Emotional)

Stress is a broad term encompassing any internal or external factor that disrupts your body’s balance. This can include:

Mental and emotional stress (e.g., financial worries, relationship issues, major life changes like a breakup, loss, or relocation)
Physical stress (e.g., overtraining, lack of rest)
Chemical or biochemical stress (e.g., poor sleep hygiene, shift work disrupting the circadian rhythm)
Environmental stress (e.g., exposure to mold, air pollution, pesticides, or endocrine-disrupting plastics)
Unresolved infections or chronic illness

All these stressors can cumulatively impair the HPA axis’s ability to regulate hormones, immunity, and energy levels.

2. Inflammation

A maladaptive inflammatory response can significantly impact the HPA axis. Excessive or prolonged stress can over activate the HPA axis, which in turn fuels chronic inflammation.

Inflammatory mediators can overstimulate cortisol production.
Chronic inflammation can disrupt the HPA axis's normal feedback loop, impairing how your brain regulates stress and hormonal balance.
This creates a vicious cycle: stress triggers inflammation, and inflammation continues to stimulate the stress response.

3. Nutritional Deficiencies

When the body is under stress, its nutritional needs increase—especially for:

B vitamins
Magnesium
Vitamin C
Zinc
Digestive enzymes and hydrochloric acid (HCL)

If these nutrients are depleted, the body’s ability to respond to stress and maintain HPA axis balance weakens. Consuming processed, high-sugar, and nutrient-poor foods only worsens the dysfunction by further straining your adrenal and immune systems.

What Is HPA Axis Suppression?

HPA axis suppression occurs when your body’s natural production of cortisol is reduced, often as a result of long-term use of synthetic glucocorticoids (corticosteroids). These medications are commonly prescribed for conditions such as:

Asthma
Organ transplant recovery
Cancer treatment
Rheumatologic disorders
Chronic pain conditions

When the HPA axis is suppressed, your body produces a weakened cortisol response. This can lead to:

Impaired stress response
Increased vulnerability to infections
A reduced ability to recover from illness

In severe cases, suppression can result in adrenal crisis, a potentially life-threatening condition due to dangerously low cortisol levels.

It’s important to note that not everyone who takes glucocorticoids will develop HPA axis suppression. However, if you're undergoing long-term steroid therapy, you should regularly consult your healthcare provider to discuss potential risks and explore strategies to safely taper medications when appropriate.

Functional Medicine Labs to Test the Root Cause of HPA Axis Dysfunction

To uncover the underlying causes of HPA axis dysfunction, several specialized functional medicine lab tests are available. These tests provide insight into hormonal balance, adrenal function, and nervous system health:

1. HPA Profile

This test measures both hormones and neurotransmitters to assess adrenal gland and nervous system activity. It's ideal for individuals experiencing stress-related quality-of-life issues such as:

Poor sleep
Anxiety
Fatigue
Mood swings

Key biomarkers analyzed:

DHEA-S
GABA
Epinephrine
Norepinephrine

2. DUTCH Complete / DUTCH Plus

The DUTCH Complete test offers a comprehensive assessment of sex and adrenal hormones, along with their metabolites. It also provides a detailed pattern of free cortisol levels throughout the day.

The DUTCH Plus goes further by including the Cortisol Awakening Response (CAR), offering deeper insight into HPA axis regulation.

Best suited for individuals with symptoms of low cortisol, such as:

Chronic fatigue
Depression
Insomnia
Fibromyalgia
Anxiety
Chronic inflammation

3. Adrenocortex Stress Profile

This test evaluates cortisol and DHEA levels using precisely timed saliva samples throughout the day. It helps determine:

Your natural diurnal cortisol rhythm
Underlying HPA axis imbalances

It is often used for diagnosing adrenal fatigue or stress-related dysfunction.

4. HPA-G Complete Profile

A comprehensive test that analyzes both hormones and neurotransmitters, offering a broad view of nervous system and endocrine health. It provides valuable data to identify imbalances that may be contributing to HPA axis dysfunction.

Caring for Your HPA Axis

Your Hypothalamic-Pituitary-Adrenal (HPA) axis plays a vital role in managing stress, energy, hormone balance, and immune function. While you can’t eliminate stress completely, you can support the health of your HPA axis through consistent lifestyle choices and targeted care.

Daily Stress Management for a Healthy HPA Axis

Simple, sustainable practices can go a long way in preventing stress from overwhelming your system:

Practice relaxation techniques like meditation, yoga, deep breathing, or progressive muscle relaxation.
Nourish your body with whole foods, regular exercise, and adequate rest.
Cultivate optimism and gratitude to shift your mindset and reduce reactivity to stress.
Let go of what you can’t control. Accepting limitations can reduce mental load and anxiety.
Say “no” when needed. Avoid overcommitting yourself when you're already overwhelmed.
Stay connected. Maintain relationships with people who bring calm, joy, and practical support into your life.

When to Seek Medical Help

If your symptoms become persistent, worsen over time, or begin to interfere with your daily life, consider consulting:

A primary care provider – for hormone testing, referrals, or an initial evaluation.
An endocrinologist – for a thorough assessment of adrenal function and hormone regulation.
A mental health specialist – for support with stress, trauma, anxiety, or burnout.
An integrative or functional medicine practitioner – for a holistic approach to HPA axis imbalance.

Functional Medicine Support for the HPA Axis

Functional medicine offers powerful tools to restore HPA axis function, focusing on adaptogens and nervines—herbal allies known for their support of the nervous and endocrine systems.

Adaptogens

Adaptogens are natural substances that enhance your body's resilience to stress and promote balance across multiple systems. These include:

Ashwagandha
Rhodiola
Cordyceps
Eleuthero (Siberian ginseng)
Schisandra
Tulsi (Holy Basil)

Adaptogens work best when used consistently and can be a long-term ally in restoring hormonal equilibrium.

Nervines

Nervines are herbs that support the nervous system and help regulate stress responses. Some calm the nerves; others gently stimulate or nourish them:

Passionflower
Skullcap
Albizia
Milky Oats
Kava Kava

Depending on your specific symptoms—whether you're feeling wired, exhausted, anxious, or emotionally depleted—a functional medicine practitioner can guide you in selecting the most appropriate herbs and dosages.

Complementary and Alternative Medicine for HPA Axis Support

There are many effective ways to support the Hypothalamic-Pituitary-Adrenal (HPA) axis through lifestyle adjustments and complementary or alternative therapies. One of the most powerful strategies is learning to modulate—not eliminate—stress. This begins with building a personalized stress-reduction protocol that suits your life and needs.

Start by Addressing Your Primary Stressors

Are there pro-inflammatory relationships in your life that consistently drain your energy or trigger anxiety?
Is it possible to switch jobs, set better boundaries, or reduce workload?
Can you make more time for yourself—for rest, creativity, joy, or meaningful social connection?
Are you practicing self-compassion? Sometimes what we need most is simply to be kinder to ourselves.
Don’t underestimate the healing power of Vitamin R&R: Rest and Relaxation.

Nutritional Support for the HPA Axis

Balancing blood sugar and fueling your body with the right nutrients can significantly impact HPA axis health:

Eat whole foods rich in protein, fiber, and healthy fats to help stabilize blood glucose levels.
Prioritize nutrient-rich vegetables high in magnesium, folate, and sulfur—like spinach, kale, cauliflower, broccoli, and Brussels sprouts.
Boost your Vitamin D levels (through sun exposure, foods, or supplements) to support immune health and hormone regulation.

Supportive Therapies & Lifestyle Practices

Sleep: Aim for 7–9 hours of restful sleep per night. Try to be in bed by 10:00 PM to align with your natural circadian rhythm.
Acupuncture: This ancient practice may help calm the nervous system, reduce cortisol levels, and restore balance to the HPA axis.
Low-intensity exercise: Gentle movement like yoga, walking, stretching, or swimming helps reduce stress without overstimulating the system.
Nature therapy: Activities like forest bathing, grounding (barefoot walking on natural surfaces), or even sitting in a park can lower cortisol and increase overall calm.

The HPA Axis in Women's Health

The HPA axis plays a crucial role in maintaining hormonal balance and supporting women’s reproductive health. Elevated cortisol levels—often triggered by chronic stress—can interfere with the hypothalamic-pituitary-gonadal (HPG) axis, which governs the menstrual cycle and regulates reproductive hormones.

This hormonal cross-talk can disrupt the normal release of estrogen and progesterone, potentially leading to:

Irregular or missed ovulation
Skipped or irregular periods
Heightened PMS symptoms

Furthermore, chronic low-grade stress and elevated cortisol can exacerbate conditions like Polycystic Ovary Syndrome (PCOS) by contributing to:

Insulin resistance
Systemic inflammation
Overall hormonal imbalance

The HPA Axis in Modern Life

The human stress response system evolved to handle short bursts of acute stress, not the constant, low-level stressors of modern life. Today’s world often keeps us in a near-continuous “fight or flight” state, which can lead to HPA axis dysfunction, burnout, and hormone imbalances.

Common lifestyle triggers include:

Digital overload & poor sleep hygiene: Constant screen exposure disrupts circadian rhythms and melatonin production, negatively affecting sleep and recovery.
Workplace pressure & overproductivity culture: Being constantly “on” or reachable can leave little space for mental rest and hormonal reset.
Excess caffeine consumption: Often used to mask fatigue, excessive caffeine can overstimulate the nervous system and elevate cortisol levels.
Overtraining: Intense exercise without adequate recovery may signal to the body that it’s under physical threat, perpetuating stress hormone release.

Final Thoughts

Stress is an unavoidable part of life—but how we manage it can make all the difference. The HPA axis is the body's built-in defense against stress, designed to protect us in moments of danger. However, chronic or unrelenting stress can disrupt this finely tuned system, affecting everything from mood and sleep to reproductive and immune health.

While research on the HPA axis continues to evolve, one thing is clear: proactive stress management is essential for long-term health.

If you’re feeling overwhelmed, speak with your healthcare provider. They can guide you toward effective lifestyle interventions, support strategies, or professional help when needed. Your body is built for resilience—sometimes, it just needs the right support.

Frequently Asked Questions

1. What is the HPA axis and why is it important?
The hypothalamic-pituitary-adrenal (HPA) axis is the body’s central stress response system. It regulates the production of hormones like cortisol, which influence your immune function, mood, metabolism, energy levels, and overall homeostasis.

2. What happens to the HPA axis under chronic stress?
Chronic stress can lead to HPA axis dysregulation, where the body produces either too much or too little cortisol. This imbalance may result in fatigue, hormonal imbalances, weakened immunity, anxiety, and other long-term health conditions.

3. What are common signs of HPA axis dysfunction?
Typical symptoms include:

Chronic fatigue
Mood swings
Brain fog or poor concentration
Sleep disturbances
Cravings for sugar or salt
Difficulty handling stress

4. Can the HPA axis be tested?
Yes. Healthcare providers can evaluate HPA axis function using cortisol level tests (via saliva, blood, or urine). Additional hormone tests, such as ACTH or DHEA, may also be used to assess adrenal and pituitary activity.

5. How can I naturally support my HPA axis?
You can support healthy HPA function through: