Liver Speed Date #2: Urine Steroid Hormone Testing

By George Gillson MD PhD CCFP

If you partner with an Integrative/Functional Medicine practitioner to improve your health, sooner or later (probably sooner) you are going to wind up talking a lot about steroid hormones. There is just no getting around that.

Steroid hormones are called that because they are all made from cholesterol. I like to use the below image when I talk about steroid hormones. It’s a picture of the Mississippi River flowing into the Gulf of Mexico. It’s often referred to as the Crow’s Foot. At the top left you start with cholesterol which then “flows” or is converted into the members of various hormone families: estrogens, glucocorticoids (cortisol et al), testosterone, progesterone and so forth. Each of those families has its own branched structure. The liver enzymes are responsible for many of the biochemical transformations that build the branches/Crow’s Foot. Ultimately the hormones flow into wastewater although some may be recycled along the way.

The following diagram called a heat map, looks at the steroid hormone “Crow’s Foot” from the biochemical standpoint. Each arrow in the diagram is an enzyme, with most of them living primarily in the liver although some are replicated in other tissues as well. If you’re so inclined, you can trace the paths from cholesterol to the tip of every “branch”.

Each oval in the heat map is a steroid hormone and the colors of the oval endcaps reflect the urine levels measured in one 24-hour period: low, below average, average, above average, high.  If a “parent” steroid is high (hotter color) and the “child” steroid at the other end of the arrow is relatively low (having a “cooler” color then the parent) then the activity of the enzyme linking child hormone to the parent hormone is reduced.

All the things we talked about in the previous post apply in determining the relative steroid hormone levels: genetics regulating the inherent activity of the enzymes, availability of enzyme cofactors, enzyme upregulators (also called inducers) and enzyme inhibitors. It is becoming more common for a person struggling to balance hormones to have a genetic assessment to determine if pathway blockages are “hard-wired” i.e. genetic in origin or temporary. The EvolveWell practitioners can do the genetic assessment if indicated.

There are at least six laboratories in North America measuring steroid hormones in urine. The test used by EvolveWell practitioners is from Precision Analytical in Oregon. The heat map displayed above comes from a hormone test that is no longer available but it gives a good overall picture of what is going on with hormones. (Full disclosure: I designed it.)

Labs also display findings with dials that resemble speedometers as well as with pie charts, bar graphs and tables. Here’s an example from a Precision Analytical report, showing the primary estrogens: Estrone and Estradiol are low while Estriol is average.

Your Integrative/Functional Medicine practitioner can still point out the patterns I’m going to talk about, even if the results are not presented as heat maps.

When we measure steroid hormones, we aren’t concerned so much with every individual result in isolation; we’re concerned with the overall patterns and relationships between results. If we consider the heat map above as a snapshot of traffic on city streets, we want to focus on what roads are blocked, roads where traffic is sped up and where traffic is just inching along. We can also identify “dead-ends” or special places that can only be gotten to by one road.

I’m now going to run through some examples of common patterns seen via urine steroid hormone testing. It might all seem completely obvious to you or it might be a bit opaque, but keep the traffic flow analogy in mind, no matter what.

First of all, we can tell how the adrenal glands are functioning if we look at the cortisol family. The adrenal glands make a lot of cortisol and cortisone. (Cortisone is basically an inactive storage form of cortisol.) Cortisol and cortisone are very rapidly converted to three inactive metabolites called alpha-THF, beta-THF and beta-THE. (I’ll just call them A, B and C.) These metabolite levels are 10 to 20 times higher than the parent cortisol and cortisone and have been shown to be quite representative of the daily production of cortisol for the adrenals.

If you look at the metabolite levels in aggregate, i.e. look at their sum, that can tell you whether the adrenal glands are working overtime or are on permanent vacation. Urine is actually the best way to determine the total amount of cortisol that is made in a 24-hour period. Blood and saliva tests only reflect snapshots taken at one point in time.

In the following figure, the cortisol (and cortisone) metabolite levels are all high: the adrenal glands are working overtime. You might see this in someone who is morbidly obese or has an adrenal tumor that produces excess cortisol.

Increased adrenal output of cortisol

Here is the flip side of that pattern where the adrenals aren’t making very much cortisol: you might see this in someone whose thyroid gland isn’t working well:

Diminished adrenal output of cortisol

Either way, it’s a key thing to know: how much cortisol is being produced.

The enzyme which converts testosterone to estradiol is called aromatase. When we supplement testosterone in men, aromatase can sometimes be too enthusiastic about converting testosterone to estradiol in abdominal fat, resulting in breast enlargement, prostate issues and crying while watching romantic comedies. Interestingly, along with excess abdominal fat, grapefruit juice is one of the agents that will increase the activity of aromatase. In any event, excess conversion of testosterone to estradiol might show up with estradiol relatively “hotter” than testosterone. I added extra arrows to indicate that the enzyme is working harder than usual:

Person converting too much testosterone to estrogen

There are prescription medications and natural products that will inhibit the function of the aromatase enzyme. These aromatase inhibitors are often prescribed for women with breast cancer, to reduce stimulation of the cancer by estrogens. They can also be given in much smaller doses, to men making too much estrogen. This might be what you see upon testing: a higher than average testosterone giving rise to a cooler than average estradiol. I added the X to indicate that the aromatase enzyme is inhibited or at least, slowed down:

Person taking an aromatase inhibitor

Via an enzyme called 5-alpha reductase, testosterone can be converted to a more potent form, dihydrotestosterone, in tissues like the prostate and in hair follicles. Prescription medications and natural products can be given to block 5-alpha reductase to treat prostate problems and hair loss.

Effect of a 5-alpha reductase inhibitor

You might see this pattern in a man taking a medication to reduce symptoms of an enlarged prostate.

This next example is an example of a growing problem which is that men in their 20’s to 40’s are experiencing low testosterone in the absence of obvious problems such as obesity, low thyroid activity and difficulty with insulin/glucose regulation.

There are two ways in which testosterone can be made from its precursor, DHEA. Both pathways involve the same enzymes: they are simply activated in a different order. In any event, if enzyme B is inhibited for some reason, this will decrease the amount of testosterone that is made.

It turns out that Enzyme B can be inhibited by many different environmental pollutants including herbicides, pesticides, plasticizers, fungal toxins and commonly-prescribed antifungal medications. We know this is real because we are seeing the same effects in male fish and other male animals who, increasingly are born with deformities of their sexual organs and other signs of impaired testosterone.

Blocked pathway due to inhibition of enzyme B

Whether they are supplementing with estrogen or not, many women can complain of excess estrogen effects such as breast tenderness and migraines. This can be due to a blockage or inhibition of a pathway that converts potent estrogens to less-potent forms via a chemical transformation called 2-hydroxylation. It would show up like this, with the “heat” from the estrogen unable to dissipate through the 2-hydroxylation pathway:

If this pattern is identified, it may be a sign of low thyroid activity. Rectification of a thyroid problem and/or supplementation with progesterone can help to open the 2-hydroxylation channel. This is one of the ways that progesterone helps balance estrogens. Natural products containing extracts of cruciferous vegetables can also help reduce the accumulation of the potent parent estrogens.

Speaking of thyroid hormone activity, it can influence the way a parent hormone is broken down. In the example below, high thyroid activity leads to an excess of one hormone “sibling” over the other. With low thyroid hormone activity, the opposite pattern is observed.

I sincerely hope that all this isn’t too confusing for you. If nothing else, once again, the take-home message is that via a urine steroid hormone test, you and your Integrative/Functional Medicine practitioner can now appreciate how important the liver is when it comes to understanding your steroid hormones.

There are basic supplements that might be recommended to you to support the liver and these include n-acetyl cysteine (NAC), MSM, betaine hydrochloride, alpha lipoic acid, dried extract of beef liver, beet root powder and so forth. Moderate alcohol exposure and attention to a clean diet minimizing highly-processed foods are also great ways to be kind to your liver when it comes to hormone balance. Your Integrative/Functional Medicine practitioner will be well-versed in making these recommendations.

Although I’m repeating myself, if your Integrative/Functional Medicine practitioner asks you to do a urine steroid hormone test, it will be easier for both of you when you look at the report if you always think of the liver enzymes as streets which can be widened, narrowed or blocked completely, changing the traffic “flow” through the entire hormone “city.”

May all your hormone-balancing navigation this summer, be smooth and stress-free! A urine steroid hormone test can help!