Hormone Metabolism, Detoxification, & Endocrine-Disruptors Flashcards
True or False: Once a message has been received and the task has been performed, there is still a need for that hormone
False; Once a message has been received and the task has been performed, there is no need for that hormone any longer. If it remains in the system, it could very well lead to hormonal miscommunication and havoc.
What can impair the proper detoxification of hormones, which can lead to an over-accumulation, causing problems?
- Blood sugar imbalances
- Gut dysfunction
- Systemic inflammation
- Inadequate nutrition
- Toxin exposure
What is Estrogen?
A group term for specific hormones with estrogenic properties.
What are the three main estrogens that facilitate women’s reproductive health?
- Estrone (E1)
- Estradiol (E2)
- Estriol (E3)
What is Estradiol?
The “most potent” estrogen, and is the primary estrogen in charge during a woman’s fertile years. This is the estrogen that is responsible for building up the endometrial lining each cycle.
Way to remember: diol = dialing up the endometrial lining
What is Ethinyl Estradiol?
A synthetic version of Estradiol that is used in hormone replacement therapy & oral contraceptive because it is thought to be the “most potent”, and therefore would take care of the job.
Just because it is the most potent estrogen does not mean we want to have this over-abundant within the system, as hormonal birth control does. In the end, this can only further drive estrogen-dominant issues.
What is estrone?
The second most potent estrogen, and is also quite abundant within the body.
However, it is primarily produced via aromatization of testosterone in adipose tissue, and from the conversion of estradiol for elimination purposes.
It is commonly found highest after menopause, where it acts as a resource for the bulk of estradiol production during that time.
strone = aromatization of testosterone (to remember), strone sounds like stone, old like a stone = commonly found after menopause
What is estriol?
The “weakest” of the estrogens, and is typically highest only during pregnancy
Although estriol may be considered weak, it is still a valuable player, contributing anti-inflammatory and antioxidative properties that support bone health, heart health & more.
Estriol can be made from the conversion of estrogen metabolites, but the majority of it is made in the placenta of pregnant women.
to remember = estriol sounds like stroll, taking a baby out in a stroller
What is the liver responsible for?
It is responsible for breaking down nutrients, storing excess glucose, producing bile, activating enzymes, as well as filtering just about every single substance that passes through the blood.
Every toxin & hormone within the body eventually passes through the BLANK to be detoxified.
Liver
What can lead to an over-accumulation of toxins, hormones, and eventually excess body and visceral fat stroage?
Dueto how much the liver has on its plate at any given time, if there are other things going on that it needs to take care of to keep you alive, detoxification gets placed on the back burner.
What are the 3 distinct phases of liver detoxification?
- Phase 1 takes the estrogen and cleaves it, meaning it breaks it into pieces or metabolites.
- Phase 2, this is a protective mechanism, which prevents the broken glass from being able to do any more damage. It neutralizes the estrogen metabolites, inhibiting them from causing further damage
- Phase 3 is the process of taking the box with the broken glass out to the trash to be eliminated. This is where the body removes the estrogen metabolites from the system via urine & feces
In the liver, estradiol is converted to BLANK and then Cytochrome P450 (CYP450) enzymes (specifically the CYP1A1, CYP1B1, or CYP3a4 enzyme) convert the BLANK into different forms of metabolites also known as BLANK
Estrone; Estrone; Catechol Estrogens
The three main metabolites that created (or catalyzed) during phase 1 detoxification are:
- 2-hydroxyestrone (2OH)
- 16-hydroxyestrone (16OH)
- 4-hydroxyestrone (4OH)
If the three main metabolites that are catalyzed during phase 1 detoxification of the liver aren’t taken care of, what can happen?
They will go on to bind to estrogen receptors within the cells, wreaking havoc on hormone balance and contributing to estrogen-dominant issues if not controlled.
If you’re going to be breaking down your estrogens into metabolites, the BLANK metabolite pathway you want to have favored as it doesn’t bind to estrogen receptors very easily, and is not considered highly proliferative
2OH
What is the most protective metabolite pathway, helping to mitigate damage from the others?
2OH
Ideally, you want roughly BLANK % of your estrogen metabolites to be in 2OH form.
70%
2OH is catalyzed predominantly through the BLANK enzyme
CYP1A1
What is a metabolite?
A substance made or used when the body breaks down food, drugs, or chemicals, or its own tissue.
Which metabolite is more problematic because it has proliferative effects?
16OH
What metabolite has proliferative affects that can stimulate the build-up of estrogen-responsive tissues such as the endometrial lining, and breast tissues?
16OH
Which metabolite increases in the presence of inflammation, especially within the gut?
16OH
Which metabolite helps to contribute to some of estrogen’s beneficial roles, such as the proliferation of the uertine lining?
16PH
You want to have the 16OH metabolite in the BLANK% range.
20%
16OH is catalyzed predominatly through which enzyme?
CYP3aH
Which metabolite is highly reactive and can lead the accumulation of reactive oxygen species, resulting in the creation of carcinogens & DNA mutations?
4OH
4OH is catalyzed predominantly through the BLANK enzyme?
CYP1B1
Which metabolite pathway do you least want your estrogen to go down?
4OH
Which metabolite helps protect the brain and nervous system?
4OH
Ideally, you only want to have 4OH in the BLANK% range.
10%
When you see 4OH percentages and absolutes elevated, it is often a good indication of BLANK and BLANK exposure, amongst other BLANKS.
PCB and PAH, amongst other xenoestrogens.
What are PCBs?
Polychlorinated biphenyls (PCBs) are a group of human-made chemicals that were commonly used in building materials and electrical equipment before 1980. Caulk, paint, glues, plastics, fluorescent lighting ballasts, transformers and capacitors are examples of products that may contain PCBs.
What are PAHs?
Polycyclic aromatic hydrocarbons (PAHs) are made whenever substances are burned. PAHs are also found at former coal-gasification sites. Breathing smoke or coming into contact with contaminated soil exposes people to PAHs.
How can these metabolites and their percentiles be observed?
via a DUTCH test
What is a DUTCH test?
Dried Urine Test of Comprehensive Hormones
Why is the DUTCH test one of the most comprehensive for observing hormone health?
It can tell you how the hormones are being used and metabolized
The BLANK metabolites, specifically the BLANK & BLANK metabolites need to move on to Phase 2 detoxification or else they can pose more damage than good
hydroxy; 4OH & 2OH
If there are issues with the metabolites moving onto Phase 2, they will instead form BLANK
Quinones, which are considered free radicals or reactive oxygen species and lead to the formation of DNA Adducts, which are holes in the DNA that can turn into cancerous mutations
What are Quinones?
Quinones, which are considered free radicals or reactive oxygen species and lead to the formation of DNA Adducts
What are DNA Adducts?
Holes in the DNA that can turn into cancerous mutations
Phase 2 needs to be clear enough in order to allow for the movement of BLANK metabolites. Otherwise, the metabolites can overflow and recirculate through the system causing havoc
Estrogen;
When 4OH overflows, it produces quinones, and then BLANK, which contain the holes that we just talked about a bit ago, that can go on to lead to DNA damage & mutations
Depurinating Adducts
What are free radicals?
Unstable atoms that can damage cells, causing illness and aging.
When overflowing, BLANK will still produce quinones, but instead of depurating adducts, they produce what are called Stable Adducts
2OH
What is the difference between Stable Adducts and Depurating Adducts?
Stable adducts still produce holes in the DNA, however, they tend to get cleared through the DNA repair processes that happen naturally.
BLANK metabolites do less damage, that is, unless the DNA repair process is overburdened due to too many quinones to process, or lack of cofactors, specifically magnesium
2OH
What can be done if too many quinones are produced?
Quinone reductase and Glutathione Sulfur Transferase (GST) have been shown to reverse the process, helping to regenerate cells after damage from quinone production. However, this is a redundant process if the Phase 2 pathway is blocked
What happens in Phase 2 Detoxification?
The liver takes the catechol estrogens and conjugates them — meaning it turns them into water-soluble forms making them easier for excretion
BLANK hormones are made up of cholesterol and other fat-soluble components, so they are not easily eliminated in those forms
Steroid
The process of conjugation neutralizes the BLANK and BLANK effects of the metabolites, rendering them less harmful
toxic and carcinogenic
This is where we put the broken shards into a box & tape it shut so that they can’t cause further damage
What are the 3 primary ways that phase 2 detoxification can take place?
- Methylation
- Sulfation
- Glucuronidation
What happens during methylation?
Methylation is where the liver attaches a methyl group to the estrogens via the COMT enzyme (catechol oxygen methyltransferase)
This happens in phase 2 detoxification
What happens when the liver attaches a methyl group to the estrogens via the COMT enzyme (during methylation)?
This creates 2-methoxy and 4-methoxy metabolites that are then eliminated through the urine.
These are the metabolites that can be observed on a DUTCH test, and are a wonderful indication of estrogen metabolism as the majority of estrogen is metabolized through methylation
What are the metabolites that can be observed on a DUTCH test, and are a wonderful indication of estrogen metabolism as the majority of estrogen is metabolized through methylation?
2-methoxy and 4-methoxy metabolites
Phase 2 methylation only happens to the BLANK and BLANK metabolites?
The 4OH and the 2OH and not the 16OH
BLANK metabolite can go on to bind to estrogen receptors unless it is either converted back to BLANK via BLANK enzymatic activity or is encouraged to convert back to the 2OH pathway instead
16OH; estradiol via via 16-hydroxylase enzymatic activity
How can 16OH be converted back to estradiol via 16-hyroxylase enzymatic activity or is encouraged to convert back to the 2OH pathway?
This can potentially be achieved by reducing gut inflammation & supporting Phase 1 and 2OH conversion
What is sulfation?
Sulfation conjugates the estrogens via sulfate by the hepatic phase 2 enzymes, sulfotransferases (SULT1E1 or EST)
During conjugation, one bacterium serves as the donor of the genetic material, and the other serves as the recipient. Sulfation happens in phase 2 detoxification.
What is conjugation?
The process by which one bacterium transfers genetic material to another through direct contact. During conjugation, one bacterium serves as the donor of the genetic material, and the other serves as the recipient
During sulfation, most of the conjugated estrogens are BLANK, however some may be re-converted to BLANK and then recirculated through the system via the BLANK enzyme.
eliminated; estradiol, steroid sulfatase (STS) enzyme
BLANK is not the most dominant phase 2 process, so the recirculation may not necessarily contribute to estrogen excess as you may imagine, but in some cases, it could potentially be a factor
Sulfation
What happens during Glucuronidation?
Glucuronidation conjugates estrogen via glucuronic acid by the hepatic phase 2 enzymes, UDP-glucuronosyltransferases (UGT), to be eliminated through the biliary system into the bowels
Estrogen is primarily metabolized via BLANK
methylation
Methylation can easily get blocked, especially in those with BLANK or BLANK, which is common in those with hypothyroidism and nutrient deficiencies
MTHFR gene mutation or methylation issues
Lack of sufficient BLANK can also block the methylation process from happening properly
methyl donors
Methylation is where the liver attaches a methyl group to the estrogens via the COMT enzyme (catechol oxygen methyltransferase)
What do methyl donors consist of?
Nutrients such as Magnesium, B vitamins, Trimethylglycine, Choline, and Methionine.
What happens in phase 3 detoxification?
Once the estrogen metabolites have been broken down and neutralized, they move onto phase 3 of the detoxification process
After phase 2, the now BLANK-soluble metabolites first need to get out of the cells before they can move on to be eliminated from the system
water
After phase 2, the now water-soluble metabolites first need to get out of the cells before they can move on to be eliminated from the system. Cell membranes are lipophilic, and won’t be able to pass the phospholipid bilayer without a little help. This is where BLANK comes into play
Phase 3 transporters such as ATP-Binding Cassettes, for example P Glycoprotein.
What do ATP-Binding Cassettes do?
Facilitate the transportation of the metabolites out of the cell and then into the kidneys & bile for elimination through the urine & feces, respectively
What do the Phase 3 transporters need to do their job effectively?
- We need to make sure we have healthy cell membranes. Inflammation of any kind can inhibit transporter function, so balancing essential fatty acid ratios may be important in helping to modulate levels of inflammation and support healthy cell membrane structure and permeability
- Certain drugs, especially proton pump inhibitors, and even some supplements, like Quercetin, can negatively affect these transporters from doing their job as well
Which phase does this happen in? Once the metabolites are out of the cells, they are then shuttled to the kidneys to be excreted through the urine, which are the metabolites that can be measured on the DUTCH test. Or, they are shuttled to the intestines via bile, which then binds to fiber and is eliminated through the feces.
Phase 3
When it comes to membrane health and inflammation, we also need to consider the health and function of what organs, as they play a major role in the detoxification process?
Kidneys as well as gallbladder
Those without which organ, may have a difficult time clearing out estrogens efficiently and this is one reason why one may want to forego a cholecystectomy?
Gallbladder
What is a cholecystectomy?
Gallbladder removal
An unhealthy BLANK can deconjugate the conjugated estrogens, reactivating them, and recirculating them through the system which can lead to a lot of estrogen-related complication
estrobolome.
Thus, lack of one healthy bowel movement per day can lead to estrogen re-absorption, which is why supporting healthy motility is imperative to estrogen balance
The estrobolome is a collection of bacteria in the gut which is capable of metabolising and modulating the body’s circulating estrogen.
Why can lack of one healthy bowel movement per day can lead to estrogen re-absorption?
Because an unhealthy estrobolome can deconjugate the conjugated estrogens, reactivating them, and recirculating them through the system which can lead to a lot of estrogen-related complication
The estrobolome is a collection of bacteria in the gut which is capable of metabolising and modulating the body’s circulating estrogen.
What is the Estrobolome?
The “aggregate of enteric bacterial genes whose products are capable of metabolizing estrogen.”
When the conjugated estrogen compounds enter the gut, they can be deconjugated (activated) by certain bacteria species that have beta-glucoronidase activity. Too much beta-glucoronidase activity can lead to estrogen resorption into circulation…leading to estrogen dominant symptoms: weight gain, breast tenderness, abdominal bloating, PMS, cramps.
What androgens do we want to look at?
Total DHEA, which ncludes DHEA, DHEA-S (DHEA sulfate), and the DHEA metabolites, Etiocholanolone, and Androsterone
Dehydroepiandrosterone (DHEA) is a hormone that your body naturally produces in the adrenal gland. DHEA helps produce other hormones, including testosterone and estrogen. Natural DHEA levels peak in early adulthood and then slowly fall as you age.
