geeking with charts: stress and your sex hormones

Hormone imbalances are one of the most common complaints people have when they first come to see, especially the so-called “sex hormones” like testosterone, estrogen and progesterone. (These do more for us than just manage reproduction, but let’s leave that aside for now.)

There are many reasons these can get out of balance, but one thing I commonly see affecting them is stress.

The short version: High stress means lower sex hormones. Your body prioritizes running from the erupting volcano over helping you reproduce. The idea is that you should live to make babies another day.

In most cases I don’t find it useful to test single hormones. Rather, I generally test at least six (usually eight) at a time. That’s because our endocrine system is connected like a web, and pulling on one string effects everything else. We need to look at the whole picture to get a sense of what’s going on.

To explain this, I’m breaking out a couple of charts to share with you.

The steroid hormone cascade

the steroid hormone cascade | Dr. Orna Izakson


The first thing to notice here is that the whole chart starts with cholesterol. We hear all the time that folks are running around with cholesterol that’s too high, and that may be true. But we make it because we need it, for functions including many of our hormones.

Cholesterol is converted to pregnenolone. Following the branches on the chart, you can see that pregnenolone is used in turn to make the more familiar progesterone, testosterone and three kinds of estrogen (E1, E2 and E3.) It’s also used to make cortisol, our primary stress hormone.

(You can find a much more nuanced version of this chart here. It’s great for geeking because it shows all the steps as well as herbs, nutrients, medications and toxins that influence the speed and direction of many steps. This is what I use when talking to patients about their hormone test results.)

The Pregnenolone Steal

Biochemistry isn’t everyone’s first love, but it sometimes comes up with beautiful things. One is the name for what happens when stress hijacks your hormones: In biochemistry, it’s called The Pregnenolone Steal.


sex hormones and the pregnenolone steal | stress and hormones | Dr. Orna Izakson


Going back to the running-from-the-volcano example: under stressful conditions our bodies prioritize making cortisol over everything else. That cortisol pulls (or steals) the pregnenolone, so there’s less raw material available to make testosterone and the estrogens.


sex hormones and the pregnenolone steal | stress and hormones | Dr. Orna Izakson


That’s all fine and evolutionarily reasonable when we’re dealing with short bursts of threats to our survival — the volcano, the saber-toothed tiger, etc. We survive the danger and the system resets.

Everyday volcanos

Modern living brings chronic challenges that our bodies can react to in the same way — but without the quick resolution we’re adapted to.

What kinds of stresses can cause Pregnenolone Steal?

  • Inadequate sleep
  • Family stress
  • Financial insecurity
  • Low blood sugar
  • Politics
  • Discrimination
  • Global pandemics
  • Work stress
  • Underemployment
  • Housing insecurity
  • Unsafe work or home environment
  • Chronic toxics exposure

You no doubt can think of more.

Pulling the right thread

Medical training is about understanding all these interconnections, and then figuring out which threads to pull to help folks heal. Addressing stress is helpful for all facets of health, so it’s a great and obvious place to start. (See how stress affects digestion here.)

For patients with hormone-related complaints, I generally recommend comprehensive hormone testing. This lets us see the whole web and figure out how to get the most traction. My favorites labs for this are Precision Analytical’s DUTCH Complete or Doctor’s Data’s Comprehensive Hormone panel.

When results come in, we take a whole appointment to thoroughly review them, using charts like the ones in this post (or here) to explain what’s going on.

This stuff does get complicated. If you’d like help geeking with charts about your own hormones, I have online appointments available for people in Oregon and Alaska (coming soon).


—Dr. Orna


Header photo by Omar Flores on Unsplash