Dirty estrogen and the DUTCH test

Time to come clean

What is dirty estrogen?

Is the DUTCH test something I should do?

I have been told that my body favors the “bad” 4 HO pathway and that I should not be on menopausal hormone therapy?

I’ve had lots of questions like these about estrogen metabolism and menopausal hormone therapy (MHT) since I started this blog, so it seems appropriate to start the New Year with a post dedicated to debunking this latest wave of hormonal hokum.

Keep in mind that it is difficult to debunk something that isn’t a thing, but I’m going to do my best, so buckle up!

What is “Dirty Estrogen”?

It is a medically meaningless term. I could just as easily say there is something called candy estrogen, and tell people that while we love candy estrogen because it is the estrogen that makes us feel good, we shouldn’t have too much of it. And that I have developed a complicated and trade marked algorithm to detect levels of candy estrogen as well as supplements to correct the ratio of candy estrogen to non candy estrogen. But I have ethics, so that’s not going to happen.

What “dirty estrogen” appears to be is an attempt to describe some metabolites of estrogen, the implication being, if your body makes these metabolites in “excessive amounts”, then you are at risk for cancers that are influenced by estrogen, such as breast and endometrial cancer (cancer of the lining of the uterus) and shouldn’t take MHT. Also, if you have too much “dirty estrogen” then there are complicated and expensive, but thoroughly unnecessary, custom compounded hormones, diets and supplements and a never ending cycle of testing to see if these programs and pills and potions are working to lower you “dirty estrogen”.

The metabolite that is incorrectly referred to as “dirty” is 4-hydroxyestradiol (that is the 4-OH mentioned in the question above), but I’ve seen it used to describe estradiol and estrone. When you are making shit up, the sky is really the limit.

There are no quality studies telling us what levels of estrogen metabolites mean, so anyone telling you otherwise is making their pseudoscience up as they go. If there were tests to help us distinguish medically harmful estrogen metabolites, we would likely have heard about them from a reputable source because estrogen metabolism has been a very active area of research for breast and endometrial cancer as well as uterine fibroids. There would also be studies in peer-reviewed journals extolling the benefits of this testing, but those studies don’t exist.

I’m going to take a deep dive here and get pretty detailed. If you want the short answer up front, dirty estrogen is a made up word that is used to sell dangerous custom compounded hormones, unnecessary tests and worthless supplements and it is a way to get people to come back into the office over and over again under the guise of monitoring. Testing for estrogen metabolites, blood or urine or saliva, is not recommended by any reputable medical society. The DUTCH test uses dried urine to assess hormone levels including estrogen metabolites and there is no evidence to support it use in managing any medical condition, including menopausal hormone therapy. If it were indicated it would be found in medical guidelines, but it isn’t.

Interested in More? Read On.

Some Background on Estrogen.

The two main estrogens made by the body are 17-beta-estradiol, which we typically abbreviate to estradiol, and estrone. Estrone is a weaker estrone. Before menopause the levels of these hormones are higher because they are produced by the follicles in the ovaries in high enough amounts so that they can travel from the ovary to other tissues. For example, to the brain to trigger signaling for ovulation and to the uterus to stimulate the lining to grow each cycle. These two estrogens, estradiol and estrone, are also made in smaller amounts in other tissues, such as adipose tissue (fat), muscle, and the brain. By convention, when we say estrogen we typically mean estradiol and when we say estrogens we mean all the estrogens, including estradiol.

Estrogen production and how the body uses it is very complex. For example, the strength of an estrogen is determined by how well it binds to estrogen receptors on cells, but many factors can influence the activity of estrogen receptors. Meaning sometimes estrogen receptors are turned on and more receptive to estrogens and other times they are not. In addition, tissues can convert estradiol into estrone and estrone into estriol. Estrogens made tissues, such as muscle and adipose tissue, don’t make it into the bloodstream, but there are still present acting locally. All of this means that blood levels don’t tell us what is happening in the tissues as far as estrogen is concerned.

Hormones are constantly being made and so they must also be removed or they would accumulate. Estrogen and estrone must be metabolized to be removed, a good analogy here is packaging for disposal. This packaging can happen locally in tissues where the estrogens are made and also in the liver. Metabolism (the packaging) is accomplished by enzymes. Think of any hormone as a lego structure, metabolism in this situation means altering that lego structure in some way by adding bricks or taking some away so the lego structure fits in a box that you want to throw away.

Humans have two estrogen removing boxes, urine and bile. So all the estrogen made in the body or taken in as medication must be altered in some way so it can “fit” into these boxes for removal. I am using the term “fit” loosely here, because fit means things like being lipid soluble (being able to dissolve in fat) or having the right electric charge so it can pass through membranes.

What you need to know is the metabolism of estradiol and estrone is very complex and not not something that can be divined with a series of urine tests, which is the DUTCH test.

A Few Words on Metabolites

The process of metabolism, altering a chemical for removal, often involves intermediate chemicals that are harmful. This is because metabolism happens in steps. Going back to our lego block analogy, you can only remove one or a few blocks at a time and add one or a few at a time. Imagine you remove a block and that unleashes sunlight, which with prolonged or excessive exposure can cause cancer. But immediately after removing the block that exposed the sunlight, you put a different block back on and now the sunlight is contained once again. Your body was briefly exposed to a potentially harmful substance while you were packaging the lego for removal.

For example, acetaldehyde is produced by the body when it metabolizes alcohol. Acetaldehyde is harmful, but it is quickly broken down into acetate, so exposure is brief. However, the more you drink, the greater your acetaldehyde exposure and this is one of the ways that alcohol harms the body. Also, some people may be genetically more vulnerable to harm from acetaldehyde, or because of other illnesses be more at risk of consequences from acetaldehyde exposure. So whether a metabolite causes harm for a person depends on many factors.

Estrogen is Cancer Causing. But Don’t Freak Out

All estrogen can cause cancer. People who have never taken an estrogen product a day in their lives can get breast cancer or cancer of the lining of the uterus from the estrogen produced by their body. The reasons are very complex and can involve multiple pathways. One of the ways estrogen causes cancer is that it triggers growth of breast tissue and of the endometrium (lining of the uterus). The problem is that growth can lead to genetic mutations, or changes in the genetic code. Think of typing a given sentence 3 times versus 3000 times. You will have more typos writing it 3000 times because there are more opportunities for typos. And some of those typos code for cancerous cells.

So the body has multiple checks and balances for estrogen. For example, progesterone released during ovulation reduces the activity of estrogen receptors, basically stopping the estrogen from typing (in our typing analogy). Another mechanism is via the BRCA1 gene. It slows down the interactions between estrogen and the estrogen receptor, giving the repair mechanisms more time to check for typos and fix them. This is one of the reasons that BRCA1 mutations cause cancer, because that checking mechanism isn’t working as well.

So Now Let’s Look at the So-Called “Dirty Estrogen”, 4-hydoxyestradiol.

Another way that estrogen may cause cancer is via the metabolite, 4-hydroxyestradiol.

The major metabolic pathway for removing estradiol and estrone from the body is by converting it to 2-hydroxyestradiol (approximately 80% goes this route) and 4-hydroxyestradiol (20% goes via this route). This is called hydroxylation and it means tacking on an oxygen and a hydrogen molecule at a specific location (a different location for 2 versus 4).

4-hydroxyestradiol is then further metabolized by two pathways. One of these involves producing estradiol-3-4-semiquinone and estradiol-3.4-quinone. These 2 estrogens metabolites can be converted back and forth into each other, think of ice melting to water and water freezing to ice. The process of conversion back and forth between the semiquinone and quinone form releases free radicals, which can damage DNA.

There are animal studies that show giving 4-hydroxyestradiol causes endometrial cancer and higher levels of 4-hydroxyestradiol have been detected in benign uterine tumors (fibroids) and also in both benign and cancerous breast tumors. In addition, the enzyme CYP1B1 that produces 4-hydroxyestradiol is found in excessive amounts in some tumors. What this all means is 4-hydroxyestradiol may well be one of the reasons that some people develop cancers of the breast and the uterus, but the why and the how aren’t known.

What Does This Mean for Me?

Absolutely nothing. No guidelines recommend testing for 4-hydroxyestradiol levels. In addition, whether you have the MTHFR genetic variation does not affect whether you make more 4-hydroxyestradiol or not (this frequently comes up, so I thought I’d throw it in). If you want to read more about MTHFR check out this post and this one.

The only takeaway is that estrogen can cause cancer by multiple mechanisms, but that doesn’t make it unsafe. It means that estrogen therapies need to be studied so that they can be given safely. If you have a uterus, this is the reason that you must also take a progestin (progesterone or a progesterone-like medication) so the estrogen in menopausal hormone therapy (MHT) doesn’t cause cancer (as we reviewed earlier, progestins counteract the effect of estrogen on the lining of the uterus). From a breast cancer perspective, the risk of developing cancer from MHT is in the rare to very rare range, for women who are otherwise at a low risk of breast cancer:

• About 1 per 1,000 women per year for those taking estrogen plus a progestin and that risk doesn’t start until after three years.

• The risk seems slightly lower when estrogen is taken alone

So Let’s Get Back to the Original Questions.

What is dirty estrogen?

Dirty estrogen is a made up term that comes from naturopaths and/or functional medicine that has no medical meaning. Avoid anyone who uses that term.

Is the DUTCH test something I should do?

The DUTCH test or dried urine test for comprehensive hormones is not someone that anyone should do to understand what is happening in menopause or to guide their MHT. This test claims to measure and provide results about estradiol, estrone, and multiple estrogen metabolites. There is no indication for testing for estrogen metabolites for any reason. When we do recommend hormone testing in menopause, and that is uncommon, the gold standard is a blood test.

The DUTCH test is also advertised to providers by its manufacturer as a way for providers to grow their hormone replacement therapy practice. That is always a major red flag for me. “Here, you can make more money if you use our test”.

Estrogen metabolism is a complex biodynamic process and levels of different metabolites are constantly sending signals that fine tune pathways by a multitude of complex mechanisms. A single or even several blood levels or dried urine samples (the DUTCH test) cannot tell you what is happening.

I have been told that my body favors the “bad” 4 HO pathway and that I should not be on menopausal hormone therapy?

You have been misled by your provider. I would get another doctor. There is no guideline that recommends testing for estrogen metabolites to determine who should not take MHT. The main reasons not to start menopausal hormone therapy (this does not mean vaginal therapy that stays in the vagina) are as follows:

• A personal history of breast cancer or endometrial cancer

• High risk for cardiovascular disease (you can read what that means here)

• 60 years or older or more than 10 years from the last menstrual period

Might we one day find clinical use for tests for estrogen metabolites? Possibly. But this requires studies and they don’t exist.

Why are tests like the DUTCH and genetic testing like MTHFR so popular if they are not indicated?

My guess is because they are well-advertised and they help some providers make money. And many providers sadly don’t understand estrogen metabolism.

Many people equate testing with caring. It feels like tangible evidence that they were listened to, but the answer to medical disenfranchisement is not the illusion of caring (and care) with unnecessary tests.

In medicine, a test should answer a question. For example, the question with HPV testing is “Am I at higher risk for cancer or not?” If you have irregular periods and get your thyroid hormone tested, the question is, “Is a thyroid abnormality a potential cause of my irregular periods?” There is currently no question about MHT for women approaching menopause or who are in menopause that the DUTCH test can answer… and that is okay. We have clinical studies to guide us.

And one final word about “dirty” estrogen. Using dirty is a common way to scare women into different tests or therapies or away from therapies. It ties into purity culture and the binary of being good or bad, which are sadly effective marketing tropes.

So here is my detox advice for the New Year. Unfollow anyone on social media who mentions “dirty estrogen” or recommends urine testing for hormones. And if your provider suggests a DUTCH test or uses the words “dirty estrogen”, get a different provider.