Hormone Metabolism, Detoxification, & Endocrine-Disruptors Flashcards
(200 cards)
1
Q
True or False: Once a message has been received and the task has been performed, there is still a need for that hormone
A
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.
2
Q
What can impair the proper detoxification of hormones, which can lead to an over-accumulation, causing problems?
A
- Blood sugar imbalances
- Gut dysfunction
- Systemic inflammation
- Inadequate nutrition
- Toxin exposure
3
Q
What is Estrogen?
A
A group term for specific hormones with estrogenic properties.
4
Q
What are the three main estrogens that facilitate women’s reproductive health?
A
- Estrone (E1)
- Estradiol (E2)
- Estriol (E3)
5
Q
What is Estradiol?
A
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
6
Q
What is Ethinyl Estradiol?
A
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.
7
Q
What is estrone?
A
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
8
Q
What is estriol?
A
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
9
Q
What is the liver responsible for?
A
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.
10
Q
Every toxin & hormone within the body eventually passes through the BLANK to be detoxified.
A
Liver
11
Q
What can lead to an over-accumulation of toxins, hormones, and eventually excess body and visceral fat stroage?
A
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.
12
Q
What are the 3 distinct phases of liver detoxification?
A
- 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
13
Q
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
A
Estrone; Estrone; Catechol Estrogens
14
Q
The three main metabolites that created (or catalyzed) during phase 1 detoxification are:
A
- 2-hydroxyestrone (2OH)
- 16-hydroxyestrone (16OH)
- 4-hydroxyestrone (4OH)
15
Q
If the three main metabolites that are catalyzed during phase 1 detoxification of the liver aren’t taken care of, what can happen?
A
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.
16
Q
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
A
2OH
17
Q
What is the most protective metabolite pathway, helping to mitigate damage from the others?
A
2OH
18
Q
Ideally, you want roughly BLANK % of your estrogen metabolites to be in 2OH form.
A
70%
19
Q
2OH is catalyzed predominantly through the BLANK enzyme
A
CYP1A1
20
Q
What is a metabolite?
A
A substance made or used when the body breaks down food, drugs, or chemicals, or its own tissue.
21
Q
Which metabolite is more problematic because it has proliferative effects?
A
16OH
22
Q
What metabolite has proliferative affects that can stimulate the build-up of estrogen-responsive tissues such as the endometrial lining, and breast tissues?
A
16OH
23
Q
Which metabolite increases in the presence of inflammation, especially within the gut?
A
16OH
24
Q
Which metabolite helps to contribute to some of estrogen’s beneficial roles, such as the proliferation of the uertine lining?
A
16PH
25
You want to have the 16OH metabolite in the BLANK% range.
20%
26
16OH is catalyzed predominatly through which enzyme?
CYP3aH
27
Which metabolite is highly reactive and can lead the accumulation of reactive oxygen species, resulting in the creation of carcinogens & DNA mutations?
4OH
28
4OH is catalyzed predominantly through the BLANK enzyme?
CYP1B1
29
Which metabolite pathway do you least want your estrogen to go down?
4OH
30
Which metabolite helps protect the brain and nervous system?
4OH
31
Ideally, you only want to have 4OH in the BLANK% range.
10%
32
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.
33
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.
34
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.
35
How can these metabolites and their percentiles be observed?
via a DUTCH test
36
What is a DUTCH test?
Dried Urine Test of Comprehensive Hormones
37
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
38
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
39
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
40
What are Quinones?
Quinones, which are considered free radicals or reactive oxygen species and lead to the formation of DNA Adducts
41
What are DNA Adducts?
Holes in the DNA that can turn into cancerous mutations
42
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;
43
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
44
What are free radicals?
Unstable atoms that can damage cells, causing illness and aging.
45
When overflowing, BLANK will still produce quinones, but instead of depurating adducts, they produce what are called Stable Adducts
2OH
46
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.
47
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
48
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
49
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
50
BLANK hormones are made up of cholesterol and other fat-soluble components, so they are not easily eliminated in those forms
Steroid
51
The process of conjugation neutralizes the BLANK and BLANK effects of the metabolites, rendering them less harmful
toxic and carcinogenic
## Footnote
This is where we put the broken shards into a box & tape it shut so that they can’t cause further damage
52
What are the 3 primary ways that phase 2 detoxification can take place?
* Methylation
* Sulfation
* Glucuronidation
53
What happens during methylation?
Methylation is where the liver attaches a methyl group to the estrogens via the COMT enzyme (catechol oxygen methyltransferase)
## Footnote
This happens in phase 2 detoxification
54
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.
## Footnote
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
55
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
56
Phase 2 methylation only happens to the BLANK and BLANK metabolites?
The 4OH and the 2OH and not the 16OH
57
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
58
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
59
What is sulfation?
Sulfation conjugates the estrogens via sulfate by the hepatic phase 2 enzymes, sulfotransferases (SULT1E1 or EST)
## Footnote
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.
60
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
61
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
62
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
63
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
64
Estrogen is primarily metabolized via BLANK
methylation
65
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
66
Lack of sufficient BLANK can also block the methylation process from happening properly
methyl donors
## Footnote
Methylation is where the liver attaches a methyl group to the estrogens via the COMT enzyme (catechol oxygen methyltransferase)
67
What do methyl donors consist of?
Nutrients such as Magnesium, B vitamins, Trimethylglycine, Choline, and Methionine.
68
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
69
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
70
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.
71
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
72
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
73
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
74
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
75
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
76
What is a cholecystectomy?
Gallbladder removal
77
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
## Footnote
The estrobolome is a collection of bacteria in the gut which is capable of metabolising and modulating the body's circulating estrogen.
78
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
## Footnote
The estrobolome is a collection of bacteria in the gut which is capable of metabolising and modulating the body's circulating estrogen.
79
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.
80
What androgens do we want to look at?
Total DHEA, which ncludes DHEA, DHEA-S (DHEA sulfate), and the DHEA metabolites, Etiocholanolone, and Androsterone
## Footnote
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.
81
Looking at these different forms of DHEA is important to understand how DHEA is BLANK
Being utilized by the body
## Footnote
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.
82
DHEA is a precursor to BLANK, which is DHEA with a sulfate group attached to it and is found in much higher circulating levels than DHEA within the system
DHEA-S
## Footnote
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.
83
DHEA-S, although more abundant, is technically considered BLANK. Why is this?
Inactive; The body stores and transports DHEA as DHEA-S until it is needed by tissues.
When DHEA is needed, it is then converted back into the usable form of DHEA within cell tissues through the help of sulfatase enzymes (enzymes that break the S off of DHEA-S)
Sulfatase enzymes are Cysteine dependent, so deficiencies in cysteine may result in high DHEA-S levels with low DHEA
## Footnote
This is the main protein in nails, skin, and hair. Cysteine is important for making collagen. It affects skin elasticity and texture. Cysteine has antioxidant properties.
84
What is DHEA important for?
Supporting insulin sensitivity, inflammation balance, bone mineral density, sexual function & libido, mood regulation, and heart healt
85
What is considered the "fountain of youth hormone" and when does it peak?
DHEA, known to peak between the ages of 20 and 30 and then decrease steadily after that point
86
Although BLANK decreases as we age, it should still be at a healthy, functional range for your client’s age group
DHEA
87
When we see low levels of DHEA-S, it can be indicative of BLANK?
* Increased inflammation within the body and on a cellular level
* It can also be a sign of adrenal insufficiency or cortisol dysfunction as DHEA plays an important role in modulating cortisol levels
*
88
When BLANK is produced in healthy amounts, DHEA comes in to help reduce some of the catabolic effects. But when there is excess BLANK due to increased stress or HPA-D, it can use up the available DHEA, leading to lower levels
cortisol; cortisol;
89
When there is excess cortisol due to increased stress or HPA-D, it can use up the available DHEA, leading to lower levels, which can also lead to issues with BLANK hormone production, as DHEA is a precuros to BLANK and BLANK, which are precursors to estrogen.
Sex hormone production; androstenedione and testosterone
## Footnote
A type of chemical known as an anabolic steroid. It is converted in the body to other sex hormones, including testosterone and estrogen. Androstenedione is naturally made in the body.
90
What is one the reasons why high stress can contribute to low hormone production and eventually amenorrhea if not corrected?
When there is excess cortisol due to increased stress or HPA-D, it can use up the available DHEA, leading to lower levels, which can also lead to issues with sex hormone production, as DHEA is a precursor to androstenedione and testosterone, which are precursors to estrogen.
91
High levels of DHEA are associated with BLANK, especially adrenal-driven BLANK?
PCOS; Adrenal-driven PCOS
92
What is the connection between cortisol and DHEA?
DHEA and cortisol are the most abundant hormones released by the adrenal glands, and both play a role in the stress response.
However, where cortisol is the hormone that causes high blood pressure, increased breathing, and other physiological responses, DHEA works to set things right. Essentially, DHEA opposes or offsets the effects of cortisol.
While DHEA is the more beneficial of the two hormones here, the key is mostly maintaining a balanced ratio.
93
What are the two pathways in which DHEA will be metabolized?
through the 5a-Reductase Pathway, which produces the metabolite Androsterone
or the 5b Reductase Pathway, which produces the metabolite Etiocholanolone
94
The 5a-Reductase Pathway produces which metabolite?
Androsterone
To remember: a = androsterone
95
The 5b-Reductase Pathway produces which metabolite?
Etiocholanolone
96
DHEA’s metabolites are important to look at as well to view a full picture of what’s going on with BLANK metabolism.
Androgen
## Footnote
Testosterone is the primary androgen, also include DHEA, DHEA-S, DHT
97
DHEA metabolism can favor either pathway, but ideally, we want the metabolism to be somwhere in BLANK?
The middle between the two, not favoring either side entirely.
98
The BLANK pathway is considered more androgenic, meaning when this pathway is favored, it is more likely that a woman will experience symptoms of high androgens such as BLANK
5a-reductase pathway
Hirsutism, which is the growth of male-pattern facial and body hair, as well as hair thinning and male-pattern balding, and is also associated with PCOS.
99
The 5a-reductase pathway is considered more BLANK meaning when this pathway is favored, it is more likely that a woman will experience symptoms of high androgens such as BLANK
Androgenic
Remember 5a = androgenic = alpha like amale
100
When the BLANK pathway is favored for DHEA metabolism, this pushes testosterone down the pathway that will produce more DHT (Dihydrotestosterone), which is incredibly more potent than Testosterone and contributes to facial hair production and male-pattern balding.
5a-reductase
101
Typically with PCOS, we see that the BLANK pathway is favored, and there is an elevation of BLANK contributing to symptoms
5a-reductase; DHT
## Footnote
DHT is incredibly more potent than Testosterone and contributes to these symptoms
102
Testosterone can also be metabolized into a metabolite from BLANK production, which is then excreted through the BLANK
etiocholanolone; urine
## Footnote
is an etiocholane (5β-androstane) steroid as well as an endogenous 17-ketosteroid that is produced from the metabolism of testosterone
103
Because BLANK is a precursor to estradiol production, that is another way in which it can be metabolized. However, systemic inflammation & excess body fat storage can increase the aromatization of BLANK, which can contribute to estrogen-excess-related issues.
Testosterone; testosterone
104
Steroid sex hormones must be carried through the blood via the help of binding globulins - specifically BLANK and BLANK
Sex Hormone Binding Globulin (SHBG) and albumin
## Footnote
Albumin is a protein made by your liver. Albumin enters your bloodstream and helps keep fluid from leaking out of your blood vessels into other tissues. It is also carries hormones, vitamins, and enzymes throughout your body.
105
What is albumin?
A protein made by your liver. Albumin enters your bloodstream and helps keep fluid from leaking out of your blood vessels into other tissues. It is also carries hormones, vitamins, and enzymes throughout your body.
106
With testosterone, roughly BLANK% is bound to SHBG, rendering it unavailable for usage by hormone receptors. From there, 2-3% is considered BLANK testosterone meaning it is unbound and highly available for usage by cells.
Finally, the remaining is weakly bound to the binding hormone BLANK, which is also fairly bioavailable and usable by tissues.
70%; free; albumin
| Sex Hormone Binding Globulin
107
What does "Free" testoserone mean?
it is unbound and highly available for usage by cells/the body
108
What is Total Testosterone (TT)?
The marker we would use to test levels of both bound and unbound testosterone
109
What is Bioavailable Testosterone?
The combination of Free Testosterone and Testosterone that is bound to Albumin
## Footnote
Albumin is a protein made by your liver. Albumin enters your bloodstream and helps keep fluid from leaking out of your blood vessels into other tissues. It is also carries hormones, vitamins, and enzymes throughout your body.
110
True or False: Total Testosterone (TT) isn't the best marker for testing testosterone.
True
111
Why isn't Total Testosterone (TT) the best marker for testing testosterone?
It is a measurement of all 3 forms of circulating testosterone, and doesn't provide specifics on how much is unbound and available (which is the most important factor!)
112
What can lead to false impressions that testosterone is high when it may not be?
It is highly influenced by SHBG and a lot can influence SHBG levels such as hyperthyroidism, insulin resistance, excess cortisol, excess estrogen, and hormonal birth control usage
113
To get a true assessment of testosterone, it's best to do BLANK?
Observe total testosterone in tandem with bioavailable and/or free testosterone
114
How is progesterone primarily metabolized?
Through the same CYP450 enzymes as Estorgen and then excreted into the urine.
115
What is the main metabolite for progesterone?
CYP3A4, which is the same as the 16OH pathway for estrogen
116
Similar to androgens, Progesterone is metabolized through what pathways?
Either the 5a-reductase or the 5b reductase pathways
117
What is the preferred pathway for progesterone?
The 5a-reductase pathway is preferred as it acts as a precursor to the metabolite Allopregnanolone, which easily passes the blood-brain barrier, promoting myelin sheath production and is said to be neuroprotective
118
With progesterone, whichever pathway is favored may be parallel with which pathway is favored for BLANK metabolism.
androgen metabolism
119
Those with PCOS or androgenic tendencies may favor which pathway for progesterone?
5a reductase pathway because that is the favored pathway for androgen metabolism
120
True or False: Although we may see parallel patterns within these reductase enzymes, they are not the exact same enzyme, rather, they are within the same set of reductase enzyme families. So for some, androgen and progesterone metabolism patterns may not line up perfectly, although, for many, they usually do
True
121
122
T or F: Most conventional testing tests for both the 5a-reductase pathway and the 5b-reductase pathway?
False.
Unfortunately, most conventional testing only tests for the 5b-reductase pathway, and typically only takes one measurement per day, in the morning when urine levels are the most concentrated.
123
BLANK has a relatively short half-life in the body, so only taking one measurement may be inconclusive
Progesterone
124
The DUTCH test takes BLANK measurements throughout the day to get a better assessment of where progesterone levels may rest
4
125
For those with PCOS who are testing their progesterone through conventional standards, they may show up as having a general BLANK level of progesterone, which may not be the case if they are favoring the BLANK pathway which was not tested.
“low”; 5a-reductase
126
What is the connection between PMDD and progesterone metabolism, specifically with the allopregnanolone metabolite?
Within the brain, allopregnanolone stimulates GABA receptors, resulting in a calm demeanor.
Some theories state that with those with PMDD, the opposite effect takes place where allopregnanolone irritates the GABA receptors which leads to heightened mood discrepancies within the luteal phase when progesterone is at its highest
127
In normal individuals, the allopregnanolone metabolite of progesterone is supportive of a healthy nervous system, sleep, and mood. So if one does not experience the severe symptoms of PMDD and they favor more of the BLANK pathway, this may result in similar symptoms of anxiety, depression, and sleep-related issues.
5b-reductase
128
When cortisol is produced, it flows through the bloodstream and is delivered to certain tissues such as the kidneys, colon, salivary glands, and sweat glands where it is deactivated into its inactive form, BLANK, via the BLANK enzyme
cortisone; 11b-HSD2 enzyme
129
The deactivation of cortisol takes place as a way to what?
To protect the cell’s mineralocorticoid receptors (receptors that respond to aldosterone) from the catabolic, damaging effects of cortisol
130
Where does the majority of the deactivation of cortisol take place?
Within the kidneys, which is the primary regulator of mineral balance.
When cortisol hits the kidneys, it up regulates the mineralocorticoid receptors, causing the kidneys to lose more potassium and retain more sodium. Thus, the deactivation takes place as a way to protect the kidney tissues and maintain mineral and electrolyte balance.
131
In a healthy individual, is the deactivation of cortisol a normal process?
Yes and it does not interfere with active cortisol levels as you may imagine. That’s because any cortisol that is deactivated into cortisone will enter back through the bloodstream where it is then reactivated back into cortisol within the liver via the 11b-HSD1 enzyme.
132
Where will any cortisol that is deactivated ito cortisone get reactivated back into cortisol?
Within the liver via the 11b-HSD1 enzyme. Reactivation also takes place within adipose tissue and the central nervous system for local utilization.
133
When cortisol is ready to be cleared, what happens next?
It is broken into metabolites via the liver.
134
Cortisol is metabolized through which pathways within the liver?
Similar to androgens and progesterone, cortisol is metabolized through the 5a-Reductase and 5b Reductase pathways, producing the metabolites 5b-tetrahydrocortisol (5B THF) and 5a-tetrahydrocortisol (5a-THF).
135
Which metabolites does cortisol produce as it is metabolized through the 5a-Reductase and 5b Reductase pathways within the liver?
5b-tetrahydrocortisol (5B THF) and 5a-tetrahydrocortisol (5a-THF)
These metabolites are often just referred to as THF metabolites. This process is irreversible, and once cortisol is broken into the THF metabolites, they are eliminated through the urine via the kidneys
136
Once cortisol is broken into the THF metabolites, what happens and is this process irreversible?
No, it's not irreversible and they are elimintaed through the urine via the kidneys.
137
Free cortisol may also be metabolized and eliminated directly within the BLANK and in terms of elimination, what metabolite is produced?
The kidneys.
In terms of elimination, some of which spills into the urine, producing the metabolite known as tetrahydrocortisone (THE)
138
When testing cortisol and cortisone metabolites via the DUTCH test, we can see both the BLANK and BLANK metabolites, which provide us with an overview of cortisol metabolism.
THE and THF metabolites
139
You can also see a "cortisone shadow" on the DUTCH test, what does that show?
This is where the diurnal pattern of cortisone and cortisol should ideally mimic each other due to the local deactivation within the kidney before elimination. Thus, the cortisone you see in urine testing actually reflects the free cortisol values. This makes free cortisone (THE) a great secondary and confirmatory marker for observing free cortisol levels.
| diurnal = daily, of each day
140
If you see excess cortisone over cortisol metabolites, it may be indicative of what?
An over-burdened liver, or 11b-HSD2 up-regulation due to inflammation, stress, or insulin resistance
141
Free cortisol and cortisone metabolites only make up roughly X% of total cortisol and cortisone, as the majority is bound to BLANK within the bloodstream
1%; CBG (cortisol binding globulin)
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In order to get a full assessment of cortisol metabolism, we need to observe both BLANK and BLANK, as well as the total measurement of BLANK.
free cortisol and cortisone metabolites; cortisol metabolites
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What are Xenoestrogens?
External estrogenic compounds that can mimic estrogen within the body and compete for estrogen receptors. They are often found in many common household & beauty products which many may think to be rather benign
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What is the problem with Xenoestrogens?
They can contribute to and exacerbate estrogen-dominant situations.
They also compete for the liver’s detoxification function, which can further increase estrogen excess.
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What are phytoestrogens?
External estrogenic compounds naturally found within plants such as soy, flax, black cohosh, red clover, dong quai, evening primrose, licorice, and ginseng
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What is the difference between xenoestrogens and phytoestrogens?
* Xenoestrogens are far more powerful and bind with a high affinity to estrogen receptors
* They can also bind to and/or interfere with other hormone receptors such as progesterone, androgens, and thyroid hormone.
* Neurotransmitter systems such as dopamine, norepinephrine, serotonin, and glutamate are sensitive to endocrine disruption via xenoestrogenic influence
* Phytoestrogens, on the other hand, have a weak affinity to estrogen receptors and may contribute to either stimulation or inhibition of internal estrogen levels, depending upon the phytoestrogen type
## Footnote
For example, a post-menopausal woman with low estrogen levels may benefit from moderate phytoestrogen consumption as it may help stimulate endogenous estrogen production. Whereas in those with estrogen excess, phytoestrogens (in moderate amounts) may mildly block estrogen receptors, helping to promote estrogen balance. Depends on the individual
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True or False: Just because a woman has low estrogen levels does not always mean she needs phytoestrogen suppor
True.
For example, vegans are often deficient in vital cofactors for hormone production, and in my experience, it is best to address this area of their hormone health before relying on phytoestrogen therapies.
This is a perfect example of why we need to take bioindividuality and assessment of lifestyle and additional factors into account when working with clients on their hormone balancing journeys.
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True or False: not all soy is created equal, and properly preparing it (fermenting and sprouting) may help to minimize some of its negative health benefits.
True!
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What are halogens?
Another subset of endocrine-disrupting chemicals commonly found within chlorine, bromide, and fluoride.
These compounds can displace and block iodine receptors within the thyroid, causing iodine-deficiency thyroid disease such as hypothyroidism.
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Where are chlorine and bormide usually found?
Often used as disinfectants and sterilizers, commonly used to treat pools and public tap water.
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Which compounds can displace and block iodine receptors within the thyroid, causing iodine-deficiency thyroid disease such as hypothyroidism?
Halogens
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Although iodine is technically included in the list of BLANK, iodine is a necessary component of thyroid health and thyroid hormone production.
Without enough iodine, the thyroid cannot make enough BLANK
Unfortunately, the thyroid’s iodine receptors easily latch onto endocrine-disrupting halogens over iodine as these compounds have a lighter atomic weight and are more reactive than iodine.
Halogens; thyroid hormone
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Those with thyroid concerns should ideally look to avoid contact with BLANK
Halogens
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What are menstrual sponges?
lso known as “sea sponge tampons”, are made from plant-like organisms similar to coral that grow within the ocean. They are incredibly absorbent and can be left in for 6-8 hours.
The advantage of menstrual sponges is that they are very comfortable and can conform to the shape of one’s vagina. However, they do require diligent upkeep & cleansing in-between uses and in-between cycles to avoid introducing bacteria to the vagina.
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What are reusable pads?
are typically made from fleece or flannel and come in a variety of shapes, sizes, colors, and patterns. They usually come with button clasps that you secure to your
underwear. After use, you simply wash in hot water, dry, and store for next usage. They can last up to 5-6 years with proper care. I recommend not using bleach to sanitize reusable pads and they are absorbent and directly touch your vulva. Hot water & soap does the trick just fine!
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What toxins can interfere with the liver's detoxification process and what should you ask about in regards to your client's history?
alcohol and drug use, both pharmaceutical and recreational and if they live near any conventional corps or an industrialized area where they may be subjected to toxins in the air
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Certain toxins, especially alcohol, compete for BLANK in the Phase X methylation process of liver detoxification.
Because these substances are seen as toxins by the liver, they wind up taking priority over hormone detoxification, which can factor into a variety of hormone imbalances, especially BLANK.
COMT; Phase 2
Estrogen dominance
## Footnote
COMT = An enzyme responsible for the degradation of catecholamines, such as dopamine and norepinephrine.
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Because toxins like alcohol compete for Phase 2 and often wins, this can be a major clog in the “drain” . Thus, they can drive up BLANK & BLANK production, further impairing one’s health & wellbeing.
quinone & adduct
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Alcohol can also increase BLANK, further factoring into issues with estrogen excess
Aromatization
If someone is dealing with a hormonal imbalance, specifically with estrogen, cutting alcohol may be an incredibly important step in the process that may very well make or break their success
## Footnote
Aromatization is the biochemical process in which aromatase catalyzes the conversion of testosterone into estradiol, the fundamental pathway for the synthesis of estrogens.
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What is aromatization?
Aromatization is the biochemical process in which aromatase catalyzes the conversion of testosterone into estradiol, the fundamental pathway for the synthesis of estrogens.
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Some studies have observed that lavender and tea tree essential oils have estrogenic and anti-androgenic effects, potentially contributing to BLANK?
Prepubertal gynecomastia, that is, prepubescent breast tissue development in children
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True or False: HBC works by intentionally disrupting the function of the endocrine system
True
The synthetic estrogens & progestin that are found within hormonal birth control directly disrupt natural hormonal fluctuations by interfering with GnRH, FSH & LH, thus, inhibiting ovulation
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True or False: It is a common misconception that the pill makes the body believe it is pregnant.
True
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How does HBC actually work?
It shuts down the menstrual cycle entirely and introduces a programmed withdrawal bleed each month, that occurs from the withdrawal of the synthetic hormones.
This makes one feel as though they are getting their period when the truth is, they absolutely are not, as true periods can only precede ovulation, which is what the pill is precisely designed to inhibit
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Are the synthetic hormones in HBC the same as the hormones our bodies produce?
No, although these synthetic hormones are said to be “molecularly similar” to our natural hormones, they are incredibly different from our own, even down to the molecule structure, which completely debunks that theory.
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Is Progestin similar to natural progesterone that's produced from ovulation?
No, progestin is nowhere near similar to natural progesterone that’s produced from ovulation, in fact, its molecule structure is more molecularly similar to Testosterone than it is to Progesterone.
Progestin may bind to progesterone receptors, similar to how xenoestrogens can bind to estrogen receptors, but the actions in which Progestin exhibits, are nowhere near the same, and cannot contribute to the vast amount of beneficial actions as Natural Progesterone.
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True or False: detoxification is constantly happening 24/7.
Yes, the liver is constantly at work metabolizing and detoxifying toxins, dead cells, pathogens, food wastes, hormones & more.
The truth is that many of those “detox” shakes, powders & pills can be more harmful than beneficial because they can potentially impair the liver from doing its thing.
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When it comes to juicing, it's important to remember that many vegetables also contain a significant amount of anti-nutrients such as oxalates, lectins, and goitrogens, which can negatively impair nutrient absorption & metabolism when over-consumed in their raw forms. What is better to do?
Eaten in their whole food forms, the anti-nutrient profile is minimal, especially if cooked
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What is the best first step for supporting detoxification naturally?
Remove the offenders, that is, the toxins that are placing a burden on the body in the first place such as endocrine-disrupting chemicals, alcohol, drugs, etc, as well as other liver burdens such as processed food, sugar & carbohydrates.
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What are some herbs & supplements that can gently support the liver at all phases?
Dandelion, milk thistle & artichoke
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Can the DUTCH test help determine how a client's liver is metabolizing their hormones?
Yes and you should check before introducting any phase 1 detoxification suppport
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What is DIM?
DIM contains phytonutrients called indoles that are found in cruciferous vegetables such as broccoli, cauliflower, kale, Brussel sprouts, and bok choy. Can recommend clients start consuming these vegetables, cooked, regularly to get indoles in
naturally.
However, some people find that taking them in the form of DIM is way more effective for their goals.
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What does DIM do and what is it an amazing supplement for?
Stimulates hydroxylation of the 2OH metabolite pathway, which is one of DIM’s is most famous properties. It also reduces the expression of 4OH & 16OH.
In this way, DIM is a truly amazing supplement for supporting the healthy metabolism of estrogen.
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DIM should not be supplemented with those who are low in BLANK?
Low in estrogen, as it tends to remove E1 & E2 from circulation
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DIM is not recommended to take with those who have poor BLANK and/or BLANK function.
Methylation and/or liver function
If phase 2 of estrogen metabolism (methylation) is not clear and working properly, this can lead to the build up of catechol estrogen metabolites which can induce oxidative stress and DNA damage. Taking DIM in this situation has the potential to increase metabolite production and up-regulate the amount of oxidative stress a person is exposed to.
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What is Indole 3 Carbinol, or I3C?
the raw, inactive version of DIM that is often found in certain cruciferous vegetables.
It can also be supplemented but requires sufficient stomach acid to convert to DIM in high quantities — which is why supplementation of I3C.
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What is Sulforaphane?
synthesized from glucoraphanin which is found highly concentrated within broccoli sprouts and other cruciferous vegetables.
When the enzyme, myrosinase (also found within cruciferous vegetables) is masticated or chewed, it chemically alters the glucoraphanin, turning it into Sulforaphane. From there, sulforaphane primarily supports the sulfation process of phase 2 detoxification.
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Sulforaphane also up-regulates certain enzymes such as BLANK and BLANK, that work to decrease DNA damage from the overproduction of quinones and depurating adducts produced in response to too many phase 1 metabolites.
Quinone Reductase and Glutathione-S-Transferase (GST)
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Some people respond better to sulforaphane for BLANK support as it does not lower estrogen out of circulation as DIM does. Thus, sulforaphane may be a better option for those with lower estrogen levels who tend to favor 4OH estrogen metabolism.
Phase 1
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What is NAC?
NAC is a precursor to glutathione production within the body and is usually a good way to support natural glutathione production. S
Since glutathione is the backbone of GST production, it can also be taken supplementally for those who have a more challenging time with conversion.
NAC and Liposomal Glutathione help to support the GST process by reducing quinones and depurinating adducts
## Footnote
Glutathione-S-Transferase (GST), that work to decrease DNA damage from the overproduction of quinones and depurating adducts produced in response to too many phase 1 metabolites
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Why is Iron is an important nutrient for supporting Phase 1 detoxification?
Because CYP is heme-dependent. This is one reason why iron absorption issues and anemia may lead to issues in Phase 1 detoxification.
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Before supplementing with iron, should your clients get tested?
Yes, they need to get tested to evaluate their iron levels, as too much iron can form free radicals within the body, and may offset copper and zinc levels.
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What can anemia issues stem from?
The result of nutrient deficiencies in B vitamins, copper, vitamin A, and zinc, as these nutrients are needed for the production and transportation of hemoglobin.
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Although selenium and iodine are not direct cofactors for Phase 1 metabolism, they are necessary nutrients for BLANK production
Thyroid hormone production and thyroid hormone is necessary for the function of CYP and estrogen metabolism
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High levels of estrogen will increase BLANK, causing an increase in BLANK as well. This can result in more bound thyroid hormone and less free hormone available for tissue usage.
SHBG; TBG
This can result in less thyroid hormone available to support estrogen elimination, further perpetuating excess estrogen and low thyroid issues
## Footnote
Sex hormone binding globulin; thyroxine-binding globulin (TBG minds thyroid hormones in circulation)
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What can result in less thyroid hormone available to support estrogen elimination, further perpetuating excess estrogen and low thyroid issues?
High levels of estrogen will increase SHBG, causing an increase in TBG as well. This can result in more bound thyroid hormone and less free hormone available for tissue usage
## Footnote
Sex hormone binding globulin; thyroxine-binding globulin (TBG minds thyroid hormones in circulation)
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What may a reason behind why women are more susceptible to hypothyroidism than are men?
Because they naturally produce more estrogen.
## Footnote
High levels of estrogen will increase SHBG, causing an increase in TBG as well. This can result in more bound thyroid hormone and less free hormone available for tissue usage. Unfortunately, this can result in less thyroid hormone available to support estrogen elimination, further perpetuating excess estrogen and low thyroid issues
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What is Calcium-D-Glucarate?
a form of calcium that promotes Phase 2 Glucuronidation.
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For methylation support, methyl donors are a necessary cofactor. However, keep in mind that some people can get BLANK when adding in methyl-donors, especially those with the BLANK genetic mutation.
Jittery; MTHFR genetic mutation
## Footnote
(MTHFR) is an enzyme that breaks down the amino acid homocysteine. If the MTHFR gene that codes for this enzyme mutates, it may contribute to a variety of health conditions ranging from depression to some cancers.
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Methyl donors consist of?
* Magnesium
* B Vitamins (especially those that are pre-methylated, such as folate instead of folic acid)
* Choline
* Methionine (SAMe)
* TMG (Trimethylglycine)
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Methyl donors are what?
Nutrients that play a role in one-carbon metabolism, which is a series of chemical pathways that are important for normal cellular functions.
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When it comes to methyl donors should someone take all of them at once?
No, that's not recommended. Start from the top down and first eat plenty of magnesium-rich foods in addition to foods that are rich in B vitamins.
Eggs are rich in choline, and methionine and TMG can be found in beets, quinoa, and spinach.
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What is the best support for Phase 3 detoxification?
The first step in this process is helping the water-soluble metabolites to get out of the cells, which means the best support for this process is to reduce inflammation and support healthy cell membranes by consuming healthy fats & oils to support proper cellular structure & permeability.
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BLANK health is also imperative for helping to facilitate the transport of estrogen metabolites into the intestines for elimination.
Gallbladder; compromised gallbladder with sluggish bile due to a low-fat or vegetable oil-rich diet can negatively impact hormone elimination.
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How can someone support their gallbladder heatlh?
By consuming healthy fats & cholesterol, and the occasional beet, as beets contain Betaine, which helps to stimulate the flow of bile & fat emulsion.
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Gut support is also imperative to this process?
Phase 3 detoxification; We need to make sure we are identifying and addressing any cases of dysbiosis, constipation, inflammation, leaky gut, and/or low stomach acid.
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A helpful supplement for supporting healthy estrogen elimination in the bowels is BLANK.
Calcium D-Glucarate (CDG)
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Why is Calcium D-Glucarate (CDG) a healthy supplement for supporting healthy estrogen elimination in the bowels?
Because CDG acts as a beta-glucuronidase inhibitor. This means that it can inhibit the effects of the bacteria that will deconjugate and recirculate estrogen metabolites.
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What are the contraindications for Calcium D-Glucarate (CDG)?
This must be taken in moderation and for extended periods, as it can have an estrogen-lowering effect if so. For those same reasons, it is not recommended for those with low estrogen.
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How does fiber help in facilitating estrogen's elimination?
It's important for binding to bile & estrogen, which helps facilitate this process.
