Understanding Perimenopause, Stress Hormones and the HPA Axis


Perimenopause, Stress & the HPA Axis

Every day, your body is subjected to a wide range of physical and psychological situations that it perceives as stressful.

Typically, we think of work, finances, or relationships when it comes to stress. But the list is much longer. Lack of sleep, dieting, and winning the lottery are also stressful! Why? Because all of these situations signal your body to produce cortisol.

This is helpful up to a point (because it helps you get your to-do list done), but when your adrenals are required to crank out cortisol chronically, the communication between your brain and your adrenals (the HPA axis) goes haywire. The resulting adrenal imbalance zaps your mojo in a big way and affects your body’s ability to produce and balance other feel-good hormones like DHEA, estrogen, progesterone, and testosterone. This throws your hormone symphony way off-key!

More About the HPA Axis

The hypothalamic-pituitary-adrenal axis, or HPA axis as it is commonly called, describes the interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus and pituitary gland are located just above the brainstem, while the adrenal glands are found on top of the kidneys

The main function of the HPA axis is to control the body’s reaction to stress. When something stressful happens to us, our initial response is mediated by the sympathetic nervous system. This is called your “fight/flight/freeze” reaction. This response occurs almost immediately, and results in the secretion of epinephrine and norepinephrine, both of which work to create changes that you would generally expect if you felt stressed or frightened, like increased heart rate and perspiration.

About 10 seconds later, the HPA axis is stimulated. This creates a cascade of neurotransmitters and hormones that ultimately results in the adrenal glands secreting cortisol. Cortisol has a number of effects on the body that are carried out to help the body deal with a stressor that lasts longer than a few minutes. 

For example;

Cortisol increases blood pressure and cardiac output, providing more blood to your skeletal muscles in case the stressor you’re dealing with involves some sort of physical exertion (like running for your life). It also acts to increase circulating levels of glucose in your blood since glucose is a crucial energy source for your cells. This provides your body with extra energy to deal with the stressor.

Cortisol also acts to inhibit processes that are deemed to be of lesser importance at times of serious stress. These include lowering your immune system responses, suppressing the digestive system, the reproductive system, and any growth processes. Once your body relaxes and flips into the parasympathetic nervous system (rest and digest), these functions return.

While proper functioning of the HPA axis is essential for dealing with stress, when the HPA axis is stimulated too much (for example in someone who faces extreme stress on a daily basis), it can lead to physical and psychiatric problems. Repeated HPA axis activation has been linked to type 2 diabetes, obesity, and cardiovascular disease. Cortisol has also been demonstrated to have detrimental effects on memory and thinking and high cortisol levels are implicated in mood disorders like depression. 

Unfortunately, the way your HPA axis responds isn’t just dependent on what’s happening in the present. Baseline activity of the HPA axis can be affected by early life experiences, and some studies suggest that early-life trauma may lead to an over-reactive HPA axis later in life. This may contribute to increased anxiety and potential metabolic effects, including excess fat deposition and insulin resistance.

How Does Perimenopause Fit Into the Equation?

As you enter perimenopause, you may find you don’t cope as well with stress. It happens because losing progesterone during perimenopause can destabilize the HPA (adrenal) axis or stress response system.

This recalibration of the nervous system is why perimenopause is associated with an increased risk of anxiety, depression, and insomnia. Progesterone is not just a reproductive hormone. It’s also a brain and nervous system hormone. 

Progesterone does two important things in the brain: 
  • It promotes neurogenesis (new nerve growth) in a part of the brain called the hippocampus which is the main regulator of the HPA (adrenal) axis.
  • It converts to the beneficial neurosteroid allopregnanolone (ALLO), which calms GABA receptors. 

The end result is that progesterone promotes neurogenesis, GABA, and increased capacity to cope with stress. Losing progesterone will make it harder to cope with stress but only until your HPA axis can recalibrate. After that, you should recover your ability to cope with stress.

The HPA Axis is a Complex System

Hopefully, you now have an understanding of the basics of how it works and how progesterone plays into its function. There’s more to it, and I’ll cover that in upcoming posts.


Dr. Anna Garrett is a menopause expert and Doctor of Pharmacy. She helps women who are struggling with symptoms of perimenopause and menopause find natural hormone-balancing solutions so they can rock their mojo through midlife and beyond. Dr. Anna is the author of Perimenopause: The Savvy Sister’s Guide to Hormone Harmony. Order your copy at www.perimenopausebook.com.

Dr. Anna is available for 1-1 consultation. Find out more at www.drannagarrett.com/lets-talk

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Perimenopause: The Savvy Sister’s Guide to Hormone Harmony

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