Hypothalamic-Pituitary-Adrenal (HPA) Axis

The hypothalamic-pituitary-adrenal (HPA) axis is your body’s main way of responding to stress. It consists of three organs that each release hormones to eventually raise cortisol levels in your body.


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

The hypothalamic-pituitary-adrenal (HPA) axis is a communication system between three organs. It’s crucial for your body’s stress management. These endocrine system organs create a feedback loop of hormones to enact and regulate your body’s stress reaction.

More specifically, the HPA axis is a neuroendocrine system. It consists of cells that release hormones into your blood (via your endocrine system) in response to nervous system stimulation.

Which organs make up the HPA axis?

The HPA axis consists of your:

  • Hypothalamus: The hypothalamus is a structure deep within your brain. Your hypothalamus keeps your body in a balanced state with regard to body temperature, hunger, mood and many other functions. It does this by directly influencing your autonomic nervous system or managing hormones.
  • Pituitary gland: The pituitary gland is a small, pea-sized gland located at the base of your brain below your hypothalamus. It makes several essential hormones and regulates other endocrine glands. The anterior pituitary, specifically, is part of the HPA axis.
  • Adrenal glands: Adrenal glands are small, triangle-shaped glands on top of each of your kidneys. They produce certain hormones that help regulate several important bodily functions. The adrenal cortex, specifically, is part of the HPA axis.


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What is the purpose of the HPA axis?

The main function of your HPA axis is to release cortisol (a glucocorticoid, or steroid hormone). This kicks off short-term bodily changes that allow you to respond to stress. The stress response is an automatic and instinctual process.

Your adrenomedullary system is also tightly connected to your HPA axis and stress response. Your adrenal medulla releases adrenaline (epinephrine) in times of stress to trigger your “fight-or-flight” response.

The human body is designed to experience stress and react to it. When you face changes or challenges (stressors), your body makes short-term physical and mental responses to adjust. The stress response can be positive, keeping us alert, motivated and ready to avoid danger. But chronic (long-term) stress can damage our bodies.

How does the HPA axis work?

The HPA axis produces a chain reaction of hormones that eventually triggers the release of cortisol. The steps are:

  1. In response to a stressful situation, your autonomic nervous system triggers your hypothalamus to release corticotrophin-releasing hormone (CRH).
  2. CRH triggers your anterior pituitary to release adrenocorticotropic hormone (ACTH).
  3. ACTH then triggers your adrenal glands, specifically your adrenal cortex, to release cortisol.

The HPA axis is meant to have a fine-tuned negative feedback loop: the cortisol in your body then triggers your hypothalamus to stop making CRH, ending the stress response. But experiencing frequent or intense stress and other issues can cause dysfunction with your HPA axis.

Conditions and Disorders

What conditions affect the HPA axis?

Your HPA axis can become overactive (typically called HPA axis dysfunction). It can also become underactive (HPA axis suppression).

What is HPA axis dysfunction?

Chronic stress can lead to HPA axis dysfunction and cause consistently increased cortisol levels in your body. This increases your risk for a variety of health conditions, like:

HPA axis dysfunction may also play a role in memory loss and neurodegenerative conditions like Alzheimer’s disease.

HPA axis dysfunction is a complex physiological concept. Researchers are still studying its causes and health impacts.

What is the treatment for HPA axis dysfunction?

So far, there’s no direct treatment for HPA axis dysfunction. But researchers are actively studying how to target it for certain conditions.

What is HPA axis suppression?

Taking manufactured forms of glucocorticoids (corticosteroids) for certain conditions may increase your risk of HPA axis suppression. This can include treatments for conditions like:

HPA axis suppression results in a reduced cortisol response. This can cause an impaired stress response and an inadequate defense against infection. Low levels of cortisol can increase your risk of frequent — and potentially severe — infections. In severe cases, HPA axis suppression can lead to adrenal crisis, which is life-threatening.

HPA axis suppression doesn’t always happen when you take glucocorticoid treatments. But you should talk to your healthcare provider about the possible side effects and risks of these treatments.



How can I take care of my HPA axis?

Researchers are still learning about the HPA axis and what we can do to protect it. Managing stress can be a big help with keeping your HPA axis working as it should.

Of course, you can’t avoid stress completely. But you can stop it from becoming overwhelming. Daily strategies to help reduce stress include:

  • Trying relaxation activities, like meditation, yoga, breathing exercises and muscle relaxation.
  • Taking good care of your body by eating nutritious foods, exercising and getting enough sleep.
  • Staying positive and practicing gratitude.
  • Accepting that you can’t control everything. Find ways to let go of worry about situations you can’t change.
  • Learning to say “no” to additional responsibilities when you’re too busy or stressed.
  • Staying connected with people who keep you calm, make you happy, provide emotional support and help you with practical things.

If you’re concerned about your stress level, don’t hesitate to ask your healthcare provider for help and guidance.

A note from Cleveland Clinic

Stress is part of the human experience. Thankfully, our body has a specific mechanism for responding to threats to protect us from potential danger: the HPA axis. But experiencing intense or chronic stress can cause an imbalance in your HPA axis, leading to health issues. Researchers are actively studying the ins and outs of the HPA axis. Until they know more, the best thing you can do to protect it is to manage and limit stressors. If you’re feeling overwhelmed by life, talk to your healthcare provider about how to manage stress. They’re available to help.

Medically Reviewed

Last reviewed on 04/12/2024.

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