Understand Hormones; You Are Not Linear
When your car breaks down, replacing or repairing the part often fixes the issue. The same goes with your computer or household appliances. These are often linear issues - something breaks, you fix it and move on with life. People mistakenly think this way with their health but rarely are pathologies in the human body this simple. When you have a symptom, several factors are at play - your level and exposure to chronic inflammation, stress, and toxicity, genetic expression, nutritional absorption capability, and even other organ system’s influence all have a strong impact on your pathology. This is far from linear.
We don’t fix the body the same way you fix your car. This is especially true for hormone management. Often, we get a blood test and start assessing if estrogen, testosterone, or progesterone are high or low. If low or high, you get a script of something. But, this linear take on hormones is not that simple.
For example, testosterone converts to estradiol and dihydrotestosterone (a potent form of testosterone implicated in prostate cancer and hair loss). If you have low testosterone, and simply give testosterone, you can overload the estradiol and dihydrotestosterone pathways. In addition, progesterone converts to estrone, so giving progesterone can increase your estrogen levels. Likewise, estradiol can convert to testosterone. You see, these are not linear pathways and circumstances like genetics, insulin resistance and inflammation up and down regulate these enzyme routes.
To start out the non-linear understanding of hormones, let's begin with knowing there are actually three different forms of estrogen, estrone (E1), estradiol (E2), and estriol (E3). Estradiol is the most biologically active estrogen that, in excess, causes heavy menstrual bleeding, cramping, irregular cycle length, long menses, breast tenderness, bloating, and mood changes. E1 is less biologically active, but still converts to E2 when needed.
Early on, E1 was thought of as the “bad estrogen” but new research and understanding have redefined it. Now, it is considered a "reservoir" for estrogen, being that it easily converts to the active E2. In addition, E1 is a dominant estrogen in menopause because it is secreted from the aromatase enzymes in fat cells. This can be a reason for weight gain around menopause. As the estrogen levels produced from the ovaries cease, the body utilizes secondary areas to stabilize estrogen, namely fat cells. You can stabilize estrogen production from a healthy, non-fatigued adrenal system, but if that is suppressed, thanks to chronic stress, then fat metabolism takes over.
Estriol is the weakest and most gentle of all the estrogens and is the dominant estrogen in pregnancy. E3 is also responsible for skin elasticity and vaginal and urogenital tissue health. People often get a “black-or-white” idea of estrogen thinking it is bad due to breast cancer risk factors. However, estrogen levels actually go up 50-100x in pregnancy. Why, then, does pregnancy not cause breast cancer? Because estriol is the dominant form of estrogen. In addition, estrogen levels themselves are not the sole risk factor for cancer, estrogen metabolism is.
Hormones do not last forever in the body, they have a life cycle and are metabolized by the liver and eliminated via your bowel movement. Hence, digestion is a big factor to hormone balance. Your hormones have to be essentially detoxed from the body. When the body detoxes something it makes it water-soluble by adding a hydroxy group to the molecule.
Any good chemistry student at one time had to calculate charges on a molecule and how that would change when you add a chemical side-group. Water is H2O, so attaching an -OH (hydroxy) group on a molecule is the first step towards water-solubility. The position of the -OH group matters because of the overall charge on the entire molecule. The body can do the right thing, but get the wrong result by inadvertently oxidizing or radicalizing estrogen through this process. The 4-OH estrogen metabolite is the most “geno-toxic” metabolite. With poor elimination, 4-OH estradiol can cause DNA damage and increase risks for breast cancer.
The 16-OH estrogen metabolite is not great - it is an estrogenic phase 1 metabolite that can potentially worsen estrogen excess. It is associated with endometriosis and estrogen dominance. The best estrogen metabolite is the 2-OH estradiol, in non-excessive amounts it poses the least oxidative stress on the system. The second route of estrogen elimination is the COMT (Catechol-o-Methyl Transferase) pathway, which requires a methyl donor from methylfolate. This is why people with methylation issues have a harder time with estrogen elimination.
The final step in estrogen elimination is the glucuronidation pathway. This pathway utilizes the bile and digestive system. The methylated 2OH metabolite is hooked to glucuronic acid and pitched into the bile and out the intestines. This is why bowel inflammation can mess up your hormone elimination. Hitting patches of inflammation, bacterial or yeast overgrowth can undo this package as can slow transit time (constipation). The estrogen metabolite can actually recirculate off the bowel.
As you can see, understanding hormone metabolism in the body is also a big help. In fact, I truly believe knowing estrogen metabolism is one of the most important tests in women’s health. This can only be performed through urinary analysis of hormones, which is not a conventional medical test.
I urge you to understand why hormone imbalances exist rather than just observing that they exist. Know that hormones can convert, they must be metabolized well, and digestion must be healthy. Problems with these pathways imbalance hormones and merely giving hormones does not solve these problems. Knowing these details can help you on the road to being well and staying well.
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Warm regards,
Dr. Amy Nelson
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