Hormone APM Flashcards
1
Q
Which glands along HPATG axis are solely endocrine function?
A
Pituitary, Thyroid, and Adrenal
2
Q
Which glands along HPATG axis are mixed function?
A
Hypothalamus, Ovaries and Testes
3
Q
How does thyroid affect progesterone?
A
Thyroid hormones stimulate FSH mediated LH/hcg receptors to stimulate granulosa cells to produce progesterone. If progesterone is low, then can get menstrual problems.
4
Q
How does IR affect androgens?
A
Insulin Resistance causes increased androgen production which increases more insulin and decreases SHBG which allow more androgen to be free and creates this cycle. Disrupts LH signaling.
5
Q
How is thermoregulatory zone affected in menopause?
A
Decrease in estrogen causes increase in norepinephrine and serotonin which narrows hypothalamic thermoneutral zone so body thinks its too hot/cold and causes hot flashes/sweats to cool body down.
6
Q
Where in cell are the steroid hormones produced?
A
MItochondria
7
Q
What is acronym STAINS stand for?
A
In regards to hormone imblance causes: Stressors, Toxins, Antigens-allergens-adverse food reactions, Infections, Nutrition, Sleep.
8
Q
What is mechanism/effects of IR in PCOS?
A
Genetics, endocrine disruptors or diet/lifestyle causes IR which leads to hyperinsulinemia which causes the liver to make less SHBG and decreased IGFBP-1 which increases androgens; increased insulin increases pituitary LH which cause ovaries to make more androgens from theca cells. Increased androgens then increases FFA and VAT. More androgens make more insulin making it a vicious cycle.
9
Q
How is the mental, emotional and spiritual part of matrix affected by hormones?
A
Sex hormones have neuro-steroid metabolites that affect mood. Depression is associated with elevated TSH(20% or higher vs upper limit), hypothyroidism, anti-TPO ab, estrogen level fluctuations, low levels of testosterone(high testosterone associated with depression and mania).
10
Q
What mitigates effects of stress on hormones: cortisol, growth hormone, testosterone
A
Meditation
11
Q
How is defense and repair mode of matrix affected by stress?
A
1) Cortisol can suppress NK cell cytotoxicity. Acute stress can be beneficial as it upregulates natural immunity. Brief naturalistic stress can suppress cellular immunity but preserve humoral immunity. However, chronic stress suppresses both cellular and humoral immunity which is not beneficial.
2) Prolonged cortisol can downregulate cortisol receptors which leads to reduced response to anti-inflammatory signaling which leads to nonspecific inflammation which increases disease risk. Elevated cortisol slows wound healing.
3) Maternal elevated cortisol levels influences intrauterine programming of HPA Axis.
12
Q
How do hormones affect Energy mode of matrix?
A
Thyroid hormones, epinephrine, norepinephrine, cortisol, estrogens, testosterone affect ATP production and fatigue thru various mechanisms. Thyroid and steroid hormones target mitochondrial genes for transcription and biosynthesis of respiratory enzymes.
13
Q
Which estrogen metabolites are protective of cancer risks?
A
2-OH-E1
14
Q
Which estrogen metabolites increase cancer risks?
A
Quinones from 4-OH-E1, 16alpha-OH-E1
15
Q
Which SNPs affect the metabolism of estrogen?
A
COMT, GST
16
Q
What are some effects of elevated DHT?
A
Alopecia, BPH
17
Q
How is transport mode affected by hormones?
A
High urinary cortisol predicts CVD mortality across 6 years.
Suboptimal thyroid function associated with dyslipidemia, atherogenesis, MetSyn, obesity and cardiovascular dysfunction. Low testosterone associated with arterial stiffness. Estradiol but not CEE improves arterial stiffness.
18
Q
How is Communication node affected by hormones?
A
1) Hyperactivity of HPA axis leads to prolonged and excessive cortisol exposure, Cushing like effects, increased VAT, increased intramyocellular lipids, increased IR and increased MetSyn risk.
2) Hypothyroidism associated with MetSyn, IR, CV risk.
3) Prolonged cortisol exposure downregulates cortisol receptors.
19
Q
How do hormones affect bone health(structural integrity mode)?
A
HRT reduces PM osteoporotic fractures of hip, spine, non-spine even in women without osteoporosis; low doses effective in maintaining or improving BMD.
20
Q
How does intestinal permeability affect ovaries?
A
Causes inflammation of ovaries and impairs progesterone synthesis.
21
Q
How does assimilation affect estrogen?
A
Microbiome impacts 2-/4- estrogen ratios.
22
Q
What are steroid hormones derived from?
A
Cholesterol
23
Q
Where are steroid hormones made?
A
Mitochondria and/or endoplasmic reticulum, so mitochondrial health important.
24
Q
What are 5 takeaways in regards to hormones in general?
A
- Steroids are derived from cholesterol so low calorie/low fat diet, statin use can affect production.
- All the action occurs in the mitochondria and/or endoplasmic reticulum; therefore, mitochondrial health can be a cause of hormone dysfunction.
- All steroid hormones need water soluble carrier proteins - like SHBG to travel into the hydrophilic environment. Binding matter. \
- Steroid hormones are transformed from one to another via enzymatic modification. (eg: aromatase, COMT, Cytochrome P450)
- ATMs(chronic stress, toxins, nutrient insufficiencies, etc) modulate these enzymes(upregulate or downregulate). Therefore, modulating ATMs can lead to changes in hormones without giving hormone replacement.
25
What is the rate limiting step in hormone synthesis?
Getting cholesterol to the inner membrane of the mitochondria
26
What does cholesterol get broken down into and by what enzyme in the Steroidogenic Pathway?
to Pregnenolone via P450cc enzyme on the inner membrane of the mitochondria
27
Once Pregnenolone is formed what 2 pathways does it go down to?
1) To form DHEA via delta 5 pathway(17-OH-Pregnenolone)
| 2) To form Progesterone via Delta 4 pathway and enzyme 3 BHSD(beta hydroxysteroid dehydrogenase, isomerase)
28
What happens to progesterone once it is formed?
It is hydroxylated to form 17-hydroxyprogesterone the immediate precursors to 19 C androgens and ultimately the 18 C estrogens.
29
Which hormones do androstenedione form into?
Testosterone(17 BHSD) and E1 (aromatase)
30
What form of estrogen is made from testosterone
E2 via aromatase
31
What is the 2 immediate precursors to cortisol in the Steroidogenic Pathway?
17-OH-progesterone to 11-deoxycortisol to cortisol
32
What is the stress response/stress cascade?
Stressor induced activation of the HPA axis and SNS results in a series of neural and endocrine adaptations. Associated with changes in glucocorticoirds and catecholamines, etc. Met by 2 systems - HPA axis and SNS(sympathetic nervous system - fight or flight)
33
What is the stress response/stress cascade?
Perception of stress leads to release of Epi from adrenal medulla in acute response. Chronic stress results in release of cortisol from adrenal cortex. Cortisol can cause PNMT induction that crosses over to acute response and more adrenaline is released.
34
Ventral stress response involves which autonomic NS?
Sympathetic in Chest area
35
What is freeze response?
When there is too much PS stimulation.
36
What are some functions of cortisol?
Stimulates liver to convert amino acids to glucose
Stimulates increased glycogen in the liver
Mobilizes fatty acids into the blood
Increases coagulation
Suppresses parts of the inflammatory response
Prevents sodium loss in urine
Maintains resistance to stress
Maintains mood and emotional stability
37
What are some clinical sympathetic responses?
Dilated pupils, decreased saliva, tears, constriction blood vessels, relaxes airways, increased heart rate, stimulates glucose production and release, inhibits digestion, increase epi and norepi from adrenal medulla, affects large intestine, relaxes urinary bladder, stimulates orgasm. Predominantly Nepi neurons.
38
What are some clinical sympathetic responses?
Dilated pupils, Senses sharpen, sweating, increased heart rate and BP, digestion stops, empty bowels and bladder, increased coagulation, blood flow to muscles increases, breathe more rapidly, airways relax
39
What are effects of chronic stimulation with catecholamines?
Brain fog, anxiety, depression, increased visceral fat, increases CV risk factors - HTN, myocardial dysfunction
40
What are effects of chronic stimulation with cortisol?
Stimulation of fat deposits, suppression of immune system, increases in BP, Memory loss(hippocampus), Increase in protein breakdown, Depression, Demineralization of bone, increases in blood sugar
41
What part of the adrenals does Norepi and Epi get secreted from?
Medulla
42
What part of the adrenals does cortisol get secreted from?
Cortex
43
What is POMC
Proopiomelanocortin protein. It is a precursor to other hormones such as ACTH and Beta lipotrophin and Endorphin.
44
What happens in the acute response to stress on the immune function?
minutes to hours - enhanced dendritic, neutrophil, macrophage, lymphocyte trafficking and maturation, cytokine production
45
What happens in the chronic response to stress on the immune function?
alteration of Type 1 and 2 cytokine balance, low grade chronic inflammation, suppressingimmune cell numbers and trafficking.
46
What happens in the chronic response to stress on the immune function?
alteration of Type 1 and 2 cytokine balance, low grade chronic inflammation, suppressing immune cell numbers and trafficking.
47
How does chronic stress affect the Prefrontal Cortex?
It reduces the size and lose decision making capacity.
48
What is eustress?
Manageable levels of stress.
49
What is allostasis?
Maintaining homeostasis/stability thru physiological and biological change. It is positive and necessary to life. It is different from homeostasis in that it supports homeostasis. It supports physiological parameters essential for life as environments and/or life history stages change. It allows for a change in the set points of the various physiological systems so that the body can respond adequately to environmental changes.
50
What is allostasis?
Maintaining homeostasis/stability thru physiological and biological change; the ability to maintain homeostasis in response to stresses
51
How does multitasking affect brain?
It causes mental fog as multitasking increases cortisol and adrenaline which overstimulates the brain. Attention gets easily hijacked. It leads to dopamine-addiction feedback loop, rewarding the brain for losing focus and seeking external stimulation. Also decreases prefrontal cortex which is responsible for task management.
52
STAINS stands for
Stressors, Toxins, Antigens/allergens/adverse food reactions, Inflammation/Infections, Nutrition and Sleep (Acronym of what can affect hormone imbalance)
53
What is the HPATGIG axis?
Hypothalamic-Pituitary-Adrenal-Thyroid-Gut-Immune-Gonadal axis(Its your psycho-neuro-immuno-gastro-endocrine system.
54
What type of stress has capacity to elevate and maintain the stress response chronically causing disease consequences?
Psychological(opposed to physiological) but there are plenty of ATMs of chronic stress.
55
How do major life stressors impact you?
Increases in cortisol and DHEA after undesirable life events is predictive of major depression. High Cortisol low DHEA is predictive of persistence of major depression. Stress related cortisol secretion is associated with endocrine metabolic abnormalities and abdominal obesity.
56
How do toxins affect adrenals?
PCBs and dioxins accumulate in adrenal glands. Interferes with steroidogenic pathways(androgen, cortisol and aldosterone biosynthesis), Interferes with ACTH receptor sensitization, Associated with increased diabetes and cardiovascular risk among highly exposed people. Iatrogenic - etomindate causes adrenal suppression for example.
57
What is the hazard ratio between celiac and adrenal insufficiency?
11.4
58
The prevalence of celiac disease in patients with ___________ is significantly increased when compared with general population.
Autoimmune thyroid disease. In some cases, gluten withdrawal may single handedly reverse autoimmune thyroid abnormalities.
59
How does inflammation affect Adrenals?
It alters the adrenal response, results in the HPA stress response causing inappropriately low cortisol secretion in relation to ACTH secretion(ex RA) and lowers DHEA sulfate as shown in patients with chronic inflammatory disease.
60
How does vitamin C affect adrenals?
Is needed in organs that make catecholamines(Epi, Norepi and dopamine) such as in the brain and adrenal glands.
61
Is EFA deficiency associated with high or low plasma cortisol?
Low
62
When adrenaline goes up after a period of stress, zinc levels go _____.
Down
63
What nutritional insufficiencies affect adrenals?
Vitamin C, zinc, EFA, Pantothenic acid, magnesium
64
How does pantothenic acid insufficiency affect adrenal?
Causes impaired adrenocortical function and abnormal stress response.
65
How does magnesium deficiency affect adrenals?
Causes elevated HPA set point(increases CRH and ACTH). Stress increases requirement for magnesium.
66
Which type of diet helps lower levels of HPA axis disturbance?
Mediterranean Diet
67
What type of fat distribution is a disturbed HPA axis associated with?
Abdominal fat distribution, higher content of fat and saturated fatty acids in diet
68
Define disturbed HPA axis
Lower morning cortisol and post prandial cortisol secretion with low diurnal variability of cortisol
69
Is abdominal fat or peripheral fat associated with increased urinary cortisol?And why?
Abdominal Fat which may be result of increased CRF or ACTH, secondary to a state of functional cortisol resistance. Stress/inflammation leads to increased CRH/ACTH which leads to functional cortisol resistance which leads to abdominal obesity and to more stress and inflammation.
70
Does meal timing play a role in diurnal pattern of cortisol?
Yes, mid-day meal is seen to have a synchronizing role for normal plasma cortisol fluctuations
71
Which amino acid is likely to cause elevations in cortisol?
Tryptophan. All can but particularly tryptophan. Only with naso gastric feeds, not IV, therefore amino acid stimulation of adrenal glands is via gut mucosa and not due to increased serum levels of amino acids.
72
How soon after sleep deprivation can you see a reduced cortisol?
Next day
73
What are the effects of sleep deprivation over 1 day and 8 days?
After 1 day, no effect. After 8 days, decreased ACTH response to stress
74
What happens with sleep debt?
Decreased Glucose tolerance
Decreased Thyrotropin
Increased Evening cortisol
Increased Sympathetic nervous system activity
Effects are similiar to those seen in aging
Sleep can help restore adrenals
75
How can you help restore adrenals?
Removal and rebalance the triggers and mediators within modifiable LS factors - sleep, exercise/movement, nutrition, stress and relationships.
76
What is the physiological effect of Cortisol Steal?
Stress leads to increased cortisol formation. Stress and inflammation and simple carbs etc inhibits sex steroid hormone production directly and indirectly. (i.e. 17,20 lyase). Stress can increase cholesterol as endocrine system signals brain we need to make more cortisol.
77
When cortisol is increased, what downstream consequences are there?
Decreased progesterone, estrogens, DHEA, and testosterone. This is referred to as Cortisol Steal.
78
What are the functions of DHEA?
- Precursor for testosterone and estrogen
- Reverses immune suppression caused by excess cortisol levels
- Stimulate bone deposition and remodeling
- Lowers total cholesterol and LDL
- Increases muscle mass
- Improves body composition
- Involved in conversion of T4 to T3Accelerates recovery from acute stress
- Reverses many of the unfavorable effects of excess cortisol.
79
How does cortisol steal lead to other issues?
Have less progesterone an initially and estrogen dominant state. More cortisol production and stimulation of aromatase which leads to estrogen dominant conditions(breast cancer, fibroids, endometriosis). Long term decreased formation of androgens and estrogens(inhibition of DHEA pathway to form androgens and estrogens) - explains stress and hot flashes, stress and decreased libido.
80
How does cortisol steal lead to other issues?
Have less progesterone an initially an estrogen dominant state. More cortisol production and stimulation of aromatase which leads to estrogen dominant conditions(breast cancer, fibroids, endometriosis). Long term decreased formation of androgens and estrogens(inhibition of DHEA pathway to form androgens and estrogens) - explains stress and hot flashes, stress and decreased libido.
81
What happens in Stage 1 of Selye's General Adaptation Syndrome?
Both cortisol and DHEA increase with episodic stress, but recovery occurs to baseline. Asymptomatic, stimulated. Rapid increases in catecholamines and slower corticosteroid increase.
82
What happens in Stage 2 of Selye's General Adaptation Syndrome?
Cortisol chronically elevated, but DHEA declines. Alarm molecules elevated. Consequent alterations long term in glucose tolerance, blood pressure, thyroid and sex hormone metabolism. Stressed, anxiety attacks, mood swings, depression
83
What happens in Stage 3 of Selye's General Adaptation Syndrome?
Adrenal insufficiency - low cortisol and DHEA, Depression and Fatigue.
84
What happens in Stage 3 of Selye's General Adaptation Syndrome?
Degenerative disease characterized by adverse influence of corticosteroids and alarm molecules. Low cortisol and DHEA, Depression and Fatigue.
85
From a laboratory standpoint what changes do we see in Stage 1 Selye's Adaptation Syndrome?
Elevated Cortisol, elevated sum cortisol or normal depending on where on continuum patient is
Elevated cortisol/DHEA ratio
Elevated cortisol at one time point
Elevated cortisol sum over the day
Normal DHEA or low DHEA(occasionally elevated DHEA)
86
What are symptoms of elevated cortisol (Stage 1)?
```
Irritability/anxiety
Fatigue/low energy
Night sweats/muscular tremors
Insomnia
Poor sleep/sleep disturbance/hot flashes
Increased susceptibility to infection(cortisol effect on immune suppresion)
Shakiness between meals/sugar cravings(cortisol and blood sugar)
Weight gain - around the middle
```
87
What are possible exam findings with elevated cortisol?
```
Postural hypotension
Pupil contraction
Sergant's white lines
Positive Rogoff's sign
Chloasma(Melasma)
Swollen ankles
```
88
What is pupil contraction?
Iris cannot hold contraction when light is shone into eye
89
True or False: Higher urinary cortisol in persons with depression is associated with lower bone density.
True. It is also significantly associated with incident fractures. (Higher baseline UFC is an independent predictor of future fracture)
90
How does chronic stress affect the immune system?
It impairs the response to antiinflammatory signals: The capapcit tot suppress production of proinflammatory cytokines IL-6 was diminished.
91
From a laboratory standpoint what changes do we see in Stage 3 Selye's Adaptation Syndrome?
Diminution of corticosteroids over time and continued advance of many degenerative diseases.
Depressed cortisol over 2-4 time points.
Depressed cortisol sum.
Depressed DHEA
Generally, the cortisol/DHEA ratio is no longer useful
92
What are signs of depressed cortisol (Stage 3)?
Low BP
FM
Dizziness on standing or bending
Easy bruising/slow healing of cuts
93
What are symptoms of depressed cortisol (Stage 3)?
Fatigue, apathy, unmotivated
Absent minded/poor concentration
Increased excessive sleep but poor quality
Increased susceptibility to inflammation and allergies(not infections)
Depression, worse in evening
Early onset perimenopause or menopause
Muscle pains
Craving salty foods, pickles, etc
Inability to handle even slight stresses
Low blood sugar symptoms(dizzy, irritable, symptoms relieved by food)
Unstable body temperatures
94
What conditions are associated with depressed HPA axis and depressed cortisol?
```
Atypical depression
Seasonal affective disorder
Postpartum depression
Panic attacks/generalized anxiety disorder
Bipolar II disorder
PTSD
CFIDS(Chronic fatigue immune dysfunction syndrome)
FM
```
95
What are problems with measuring plasma cortisol?
Hard to measure free cortisol as most is bound by plasma protein corticosteroid binding globulin(CBG). CBG levels are affected by estrogen, progesterone, aldosterone, exogenous steroids, stress and other factors. Levels also fluctuate rapidly. Blood draw itself elevates cortisol. Can be artificially elevated by factors including drugs, pregnancy and congenital alterations.
96
What are issues with measuring urinary cortisol?
Represents urinary free cortisol over last 24 hours, no diurnal measurement, not well researched(but may be available now), inconvenient
97
What are advantages of measuring salivary cortisol?
Avoids issues that come with plasma cortisol and it still reflects the instant cortisol secretion, easy to collect, noninvasive and thus can do multiple sampling. Multiple sampling allow for diurnal variations to be plotted.
98
Should you measure DHEA or DHEA-S in blood?
DHEA-S as most is found in its sulfated form which has levels 100-1000 times higher than those of free DHEA. DHEA-S shows little diurnal variations whereas free DHEA does. DHEA-S does not fluctuate in short term in blood. Salivary DHEA-S is related to serum levels but dependant on PH of saliva and flow rate so levels may fluctuate. Overall the literature seems to suggest saliva is useful and reliable indicator for DHEA. DHEA fluctuates daily and is affected by factors that affect HPA axis. Baseline levels change over lifetime. DHEA-S levels change slowly and are a readout of overall balance in the system. They also change with age, peaking in mid 20's and declining thereafter. Serum DHEA-S and salivary DHEA correlate well. However, the use of Cortisol/DHEA ratio can be useful and best done thru saliva. In summary - order salivary cortisol and DHEA to assess HPA axis. If pt cannot afford saliva testing or if testing other hormones thru blood, then get serum DHEA-S.
99
What time should you measure morning cortisol?
Within 30 minutes of wakening.
100
What is a big picture approach to fixing hormones?
Removal of triggers and mediators, lifestyle modification, diet modification(Elimination diet, CM diet), supplements, botanicals, hormone replacement.
101
Long term overexposure to stress hormones accounts for ____% of all primary care visits in the US.
75-90%.
102
What is the number 1 reason why people eat poorly, quit healthy lifestyle programs and practice substance abuse?
Long term over exposure to stress hormones.
103
What are some Lifestyle tools to address stress?
1)CBT(relaxation training, progressive muscle relaxation)
2)Primary Care interventions:
Teach relaxation techniques(mindfulness, breathing,
meditation)
Promote self awareness with compassion
Promote connectedness with family and friends
Promote movement/exercise to tolerance
3)Biofeedback-based intervention
4)Dial UP the self care one step at a time
104
What are key aspects of dietary approach to Hormonal balance?
1) Glucose and insulin balance(avoid skipping meals and include protein at every meal)
2) Low glycemic load(CM or Elimination food plans)
3) Unrefined carbohydrates(increase veggies/low glycemic index fruits) with good -quality protein and fats(nuts, seeds) at all meals.
4) Avoid stimulants- caffeine, refined CHO's(sugar, flour, bread, fruit juice and chocolate)
5) Consider if any part of the SAD is contributing to allostatic load by adding to inflammation, metabolic burdens(eg. high glycemic load).
105
What are nutritional supplements that can help with stress?
High quality multivitamin with special attention to:
1) B Complex(co-factors in hormone production)
a) B5- pantothetic acid(100-150 mg)
b) B6 - pyridoxine (50-100 mg)
c) Biotin (1000 mcg)
d) Folate (400-800 mcg)
2) Vitamin C (1-2 grams) and antioxidant blend
3) Magnesium (400-600 mg)
4) Phosphatidylserine (600-800 mg) - give 30 minutes before bed if cortisol is high at night.
106
What supplement lowers cortisol?
Phosphatidyl Serine has been shown to attenuate the serum cortisol response to acute exercise stress, increase performance, improve mood and lower feelings of stress.
107
What are adaptogens?
Are botanicals that are non-toxic, produce a non-specific response in the body, and have a normalizing influence on physiology, regardless of the direction of change from normal caused by the stressor. In general, they work on the whole body rather than a specific organ system.
108
How do adaptogens affect HPA axis?
Overall, they have a balancing effect on HPA axis by:
1) Appropriate stimulation of adrenocortico-tropic hormone(ACTH) in the pituitary gland during times of acute stress
2) Improving cortisol sensitivity by increasing HPA sensitivity to glucocorticoids.
3) Possibly by promoting diffusion of corticosteroids across cell membranes in the hypothalamus
109
What are some adaptogenic herbs for hyper-adrenal states?
```
Rhodiola rosea(Russian Golden Root)
Hypericum perforatum (St John's Wort)
```
110
How does Rhodiola rosea help with hyper-adrenal states?
Has an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome. Some stress chemicals like cortisol, act as excitotoxins and damage cells via cell membrane effects. Salidroside, a constituent in Rhodiola rosea, has been shown to prevent excessive calcium channel activity induced by KCL and glutamate.
111
What happens to HPA axis in depression?
Patients with major depression tend to have an excessive activation of the HPA axis manifested as hypersecretion of ACTH and cortisol.
112
How does St John's wort(Hypericum Perforatum) help for depression?
SJW and hypericin have effects on the expression of genes that are involved in the regulation of the HPA axis. Individual flavonoids from SJW reduced plasma ACTH and Corticosterone after 2 weeks.
113
What are some adaptogens for the exhausted hypo-adrenal state?
```
Panax quinquefolius(Panax Ginseng)
Glycyrrhiza glabra(Licorice)
```
114
True or False: Several human trials have shown Panax Ginseng to have anti anxiety effects without any adverse side effects reported.
True.
115
How does Panax Ginseng help adrenal glands recover from chronic stress?
Improves corticoid response and the corticotropin feedback loops with the HPA axis(upregulates). Animal studies have shown Panax administration to enhance energy metabolism during exercise.
116
What happened when mice undergoing stress were treated with Panax ginseng and Withania somniferum?
Corticosterone levels were higher in all the herb supplemented groups. Physical endurance of swimming mice also increased in all the groups receiving Panax.
117
How does Glycyrrhiza glabra spare cortisol?
It inhibits 11-beta hydroxysteroid DH which blocks conversion of cortisol into cortisone.
118
What are side effects of glycyrrhizin?
Can cause pseudoaldosteronism leading to increased BP and alterned potassium levels. Licorice should not be used long term and interact s with multiple drugs.
119
What are the functions of DHEA?
1) Precursor to estrogen and testosterone
2) Reverses immune suppresion caused by excess cortisol
3) Stimulates bone deposition and remodeling
4) Lowers total cholesterol and LDL levels
5) Increases muscle mass
6) Improves body composition
7) Involved in conversion T4 to T3
8) Accelerates recovery from acute stress
9) Reverses many of the unfavorable effects of excess cortisol
120
What have clinical trials suggested in regards to dosage of DHEA for young adults with primary and secondary adrenal insufficiency?
Dosages of 50 mg oral DHEA but not <30 mg can increase serum androgen levels to within the physiologic range for young adults with primary and secondary adrenal insufficiency, possibly improve sexual function, improve mood and self-esteem(depression) and decrease fatigue.
121
What are dosages for DHEA in men and women and what consideration, side effects should you consider?
Females 5-25 mg bid
Males 10-50 mg bid
Side effects can include acne, facial hair in women and aggressiveness/irritability in men
Positive safety record up to 1 year at these dosages. But always test, don't guess.
122
What are side effects of DHEA?
Acne, facial hair - women
Irritability, aggressiveness - men
Positive safety record up to 1 year at safe doses.
123
How does childhood trauma lead to an average decrease in life expectancy of 20 years?
Chronic stress increases glucocorticoid receptor resistance which results in failure to downregulate the inflammatory response which leads to increased risk of CVD.
124
How is depression and cortisol related?
Patients with acute depression had 25% more cortisol than controls. However, within 60 minutes of wakening, the cortisol levels were same as controls. Thus, depressed patients tend to have increased early morning cortisol secretion but the demonstration of this effect requires control for time of waking.
125
Where and what points of leverage do you need to address with Cortisol/DHEA imbalances?
1) Production/synthesis and secretion of hormones - supply hormone precursors and co-factors to increase/decrease stimulation as needed.
2) Transport/conversion/distribution/interaction with other hormones
3) Sensitivity at the cellular level to the hormone signal - glucocorticoid receptor insensitivity
4) Detoxification/metabolism/excretion of the hormone - slow conversion of cortisol to cortisone
126
What is normal diurnal cortisol response?
Cortisol quickly peaks 30-45 minutes post awakening(about 50% increase). Gradual decline thru the day. The act of awakening causes cortisol response.
127
What are some facts about CAR?
1) It is one component of the circadian cortisol rhythm. It describes a salivary increase in cortisol within the first hour of awakening that is separate from the cortisol increase during the second half of the night.
2) Current evidence indicates that the CAR is independently regulated as it is mediated by an extra pituitary pathway to the adrenal from the supra-chiasmatic nucleus.
3) Can be influenced by stress anticipation as it serves to prepare to deal with demands of the day, therefore, the CAR is highly dynamic and reflects capacity to cope with an acute stressor.
4) In research setting, abnormalities of CAR have been associated with a number of health conditions including depression, T2DM, metabolic syndrome and central obesity.
128
How does thyroid supplementation affect the HPATG axis?
It increases the sensitivity of CRH to release ACTH, so patients who are initially put on thyroid supplementation get a hit to the adrenals and tend to feel good. Both hypothyroidism and subclinical hyperthyroidism tx with suppressive doses do this.
129
How does Cortisol affect the Thyroid?
It suppresses TSH conversion of T4 to RT3 and T3.
130
How does estrogen affect the Thyroid?
It increases TSH production.
131
What is the effect of synthetic estrogen/progestins on the defense and repair node?
It increases proinflammatory cytokines. Premarin - increases by 125%, Prempro - increases 150%
132
How is assimilation node affected in prenatal moms under stress?
It changes the infants microbiome.
133
How do antibiotics affect the metabolism of hormones?
They affect the metabolome and increase steroid metabolites from C21 pathway in the feces after abx tx
134
How does assimilation node affect the ovaries?
Metabolic endotoxins cross leaky gut into circulation, causing inflammation specifically in the ovaries, thus, decreasing progesterone production which causes luteal phase deficiency. So can affect fertility optimization and estrogen dominance as need progesterone to correct them.
135
What is the affect of phthalates on thyroid in children?
Early phthlate exposure reduces thyroid hormones and can cause cognitive dysfunction. There is an inverse relationship between phthlate metabolites measured in children age 3 and thyroid function in preschool children.
136
How does social support affect menopause?
It reduces symptoms
137
What is allostasis
It is how you cope with stresses to maintain homeostasis. The ability of an organism to maintain homestasis in response to stressors.
138
What is allostatic load?
All the stressors that affect you
139
How does stress affect immune function?
Increases susceptibility to infection
Increases severity of infection
Diminishes the strength of response to vaccines
Reactivates herpes virus
Delays wound healing
Increases release of proinflammatory cytokines that cause disease.
140
How does stress affect the steriodogenic pathway?
It directly stimulate the pituitary to increase release of ACTH to make more cortisol
It indirectly slows the anabolism of 17,20 lyase so doesn't go thru Test/Est pathway. It also stimulates aromatase to make more estrogen.
141
How does inflammation affect the steriodogenic pathway?
It inhibits 17,20 lyase and stimulates aromatase; It also increases 5 alpha reductase activity leading to increased DHT and hair loss. Insulin can also do this.
142
What is the rate limiting step in steroid synthesis?
Getting LDL cholesterol to the mitochondrial membrane
143
What types of sex steroids do ovaries produce?
Progestogens, estrogens and androgens
144
What enzyme does ovary lack and so what can't it produce?
21 hydroxylase, 11B hydroxylase, glucocorticoids, mineralcorticoids
145
How does steroid synthesis get cholesterol?
All steroid hormone producing cells can make it from acetate, but can't meet demand, thus, is required to get it from diet. Thus, think about hormone deficiency in undernourished or over athletic pts or those with too low cholesterol
146
What enzyme and where is it bound to transform cholesterol into prenenolone?
P450cc, mitochondria
147
What stimulates P450cc in the mitochondria of ovary?
FSH, LH
148
What stimulates P450cc in the mitochondria of the adrenals?
ACTH
149
What 2 substances does pregnenolone make?
DHEA(via 17OH pregnenolone with 17 a-hydroxylase)(delta 5 pathway)
Progesterone(directly)(delta 4 pathway)
150
Once progesterone is formed, what is it hydroxylated to and by which enzyme?
17 a-hydroxyprogesterone by 17 a-hydroxylase
151
What is 17-OHprogesterone a precursor to?
19C androgens(Androstenedione which goes to testosterone) and from there both can go to 18C estrogens via aromatase. It also is a precursor to cortisol.
152
What estrogen does testosterone form?
Estradiol
153
What estrogen does Androstenedione form?
Estrone which then can be converted to estradiol
154
What substances does progesterone produce?
17-OHprogesterone to cortisol or androgens(event to estrogens)
11 -deoxycorticosterone(eventually aldosterone)
155
What is cortisol steal?
If body needs cortisol or aldosterone, then less progesterone is circulated because it is shunted away; Also called pregnenolone steal.
156
What are physiological effects of cortisol steal?
Less progesterone and initially estrogen dominant state
More cortisol production and stimulation of aromatase which leads to estrogen dominant conditions
Longterm decreased formation of androgens/estrogens d/t inhibition of DHEA pathway to form androgens/estrogens which can explain stress, hot flashes and decreased libido
157
How does stress effect cortisol steal?
It increases cortisol formation which inhibits sex steroid directly and indirectly(17-20 lyase). Inflammation, simple carbs also do this.
158
What forms from DHEA?
Androstenedione and DHEA sulfate
159
What enzyme converts testosterone to estradiol?
Aromatase
160
What enzyme converts Androstenedione to estrone?
Aromatase
161
What does Androstenedione convert to and by which enzymes?
Testosterone via 17 B-OHsteroid dehydrogenase and estrone via aromatase
162
Why do you need to be careful in dosing DHEA supplement?
Too much can lead to increased estrogen and risk of breast cancer
163
What part of the adrenal is cortisol produced?
Cortex
164
What part of adrenal is adrenaline hormones produced?
Medulla
165
Why are androgens not produced in adrenal cortex?
No 17,20 lyase activity. Androgens are not produced in areas of cortisol activity.
166
Where is DHEA produced?
Ovarian theca cells, testicular leydig cells and adrenal reticularis
167
Where is progesterone made?
Corpus luteum
168
What decreases SHBG?
Obesity, inflammation, insulin resistance, hypothyroidism, androgens,IGF-1, corticoids, progestins. (Breast cancer risk)
169
What increases SHBG?
Vegetarian diet(so this can be a treatment in estrogen dominance)
Pregnancy
Hyperthyroidism
HRTs or OCPs
170
How are androgens formed in the ovary?
LH stimulates theca cell to produce androstenedione and testosterone via cAMP from cholesterol. This can go to granulosa cells via stimulation of FSH and via aromatase make estrone and estradiol.
171
What stimulates the ovary to make progesterone and in which cell of ovary and at what time?
LH, granulosa, after ovulation
172
How much of E2 and T are bound to SHBG once made? And where is rest bound to?
69% to SHBG
30% to Albumin
1% is free
173
What is transcortin?
Corticosteroid binding globulin; carries cortisol and progesterone.
174
What transport proteins carry progesterone?
Transcortin - 18%
Albumin - 80%
2% is free
175
What transport proteins carry cortisol?
Transcortin - 75%
Albumin - 15%
10% is free
176
Where is estriol made and from what?
in periphery, from estradiol(E2) and estrone(E1); Except in pregnancy it is formed by a detoxification. It is NOT made in the ovary.
177
Which biotransformation phase 2 process is important for excretion of estrogens?
Methylation
178
What is meant by perhipheral conversion of hormones?
Free circulating androgens from the adrenals are converted to free estrogens in the skin and adipose tissue. Therefore, women with more adipose produce more estrogens which can lead to vaginal bleeding in menopausal women and why estrogen depletion can be noticed in skin by some women.
179
Where does most of the estrogens come from in Men?
peripheral conversion of androgens
180
In women, what is the major source of circulating androgens, esp androstenedione?
Adrenal glands
181
What enzyme is missing in CAH and what is result?
21 hydroxylase, severe decrease in adrenal production of glucocorticoids; this leads to increased ACTH to make more cortisol d/t feedback loop. It also causes increased 17 OH progesterone/androgens so become virilized as 17OH P can't go down pathway to cortisol so it gets converted to androstenedione.
182
What is treatment for CAH?
Give cortisone to decrease ACTH stimulation
183
What hormone is not converted peripherally from steroids and why?
Progesteroneas it comes from ovary, almost nothing comes from adrenals. (Only exception is in pregnancy)
184
What level of progesterone will you see in CAH?
Higher levels up to 50x normal because of 21 hydroxylase deficiency
185
What are the major androgens from the ovary?
DHEA - 25% daily production
Androstenedione - 50% daily production
Testosterone - 25 % daily production
186
What are the major hormones from the adrenal cortex?
Glucocorticoids
Mineralcorticoids
Sex steroids(mostly all intermediates in the production of gluco and mineral corticoids) 50% DHEA and Androstenedione; 25% daily Testosterone
187
What is the percent of DHEA production from peripheral conversion?
25% daily production
188
What is the percent of Testosterone production from peripheral conversion?
50% daily production
189
Where is DHEA produced and in what percentage?
25% - Ovary
50% - Adrenal
25% - Peripheral conversion
190
Where is Testosterone produced and in what percentage?
25% - Ovary
25% - Adrenal
50% - Peripheral conversion
191
Where is Androstenedione produced and in what percentage?
50% - Ovary
| 50% - Adrenal
192
In hirsute women, should you look at total or free testosterone and why?
Free as Total may be normal d/t decreased SHBG; However, rarely are both total and free WNL in hirsute women.
193
What is total testosterone composed of?
Free T, T bound to albumin and T bound to SHBG
194
What is free testosterone composed of?
Free T, T bound to albumin. (T dissociates from albumin very easily so bioavailable).
195
What increases 5alpha reductase enzyme?
Insulin, inflammation, stress
196
What is active form of Testosterone and where is it found?
DHT, in all tissues except muscle
197
What are some characteristics of DHT?
Very potent
Can't be converted back to testosterone so irreversible pathway
Causes hair loss
Made from T via 5 a-reductase enzyme
198
What age does DHEA start diminishing?
30. In women, by the time they reach menopause it has decreased by 60%. In men 65-75 yo, adrenal DHEA contributes to 40% of total androgens, thus, age related decline in DHEA production is less important as T is continually produced
199
What is the feedback on DHEA?
There is no feedback loop, so once low will stay low unless we support adrenals or replace DHEA
200
What helps atrophic vaginitis without increasing estrogen levels?
DHEA
201
Where are DHEA receptors found?
Brain, Bone, Vagina
202
What is estrogen's effect on other hormone receptors?
Increases estrogen receptors, progesterone receptors and androgen receptors
203
What is progesterone's effect on other hormone receptors?
Blocks synthesis of estrogen receptors. This is why P is protective to the endometrium when added to HRT.
204
What are the 2 main estrogen receptors and describe their activity?
Alpha is stimulating and beta is anti-proliferative
205
Where are estrogen receptors located?
Alpha - breast, uterus
| Beta - breast, brain, CV system, granulosa cells ovary, colon(why 30% reduction in colon cancer in WHI)
206
Which estrogen receptor does phytoestrogens have an affinity for?
Beta
207
Which mineral is needed for activation of estrogen receptor?
Zinc
208
What type of cancers did they see a decreased expression of estrogen beta receptors?
Colon, uterine, ovarian, prostate
209
What stimulates ER-beta?
Phytoestrogens, estriol (S of PTSD)
210
What conditions does leptin increase risk for ?
DM, metsyn, CV dz, allergies, autoimmune
211
What do plasma leptin levels correlate with?
Fat stores and respond to changes in energy balance.
212
Why does leptin not always decrease appetite like it is supposed to?
D/t leptin resistance
213
Are levels of leptin high or low in obesity?
High d/t LR. Not leptin deficiency.
214
Describe mechanism of leptin resistance
Overnutrition leads to ER stress, hypothalmic inflammation and defective autophagy(Bidirectional), then thru SOCS3, PTP1B, IKKB-NFKB, leads to hypothalamic LR which leads to obesity
215
Which cancer is leptin resistance associated with?
Breast
216
What reverses ER stress induced impairment in leptin signalling?
PTP1B inhibitors - berberine, fish oil, curcumin
217
Why does maternal exposure to BPA, DES increase offsprings risk for obesity?
D/t leptin resistance
218
What tissue produces leptin?
Adipose(leptin is a protein)
219
What is glucocorticoids effect on leptin?
It stimulates it
220
What can contribute to increased hypothalamic pituitary adrenal adipose axis activity and hypercortisolism?
Dyfunctional leptin, insufficient leptin levels and LR
221
What salivary cortisol measurement changes first in adrenal dysfunction to indicate an impending problem?
CAR
222
What salivary cortisol measurement changes first in adrenal dysfunction to indicate an impending problem?
CAR
223
Should you order just a CAR in order to assess adrenals?
No, have to order the 4 point diurnal cortisol as well.
224
In stage 1 of Selye's GAS, what happens with cortisol and catecholamines?
Catecholamines are rapidly increased
| Cortisol is slowly increased
225
What is a preclinical biomarker of early stage adrenal dysfunction/dysregulation?
Elevated CAR(hyperactive cortisol response)
226
How is digestion affected by stress?
Stress dominated system shuts down appropriate functions of digestion. Thus, decreasing nutrition absorbed from our meals, causes erosion of our tissues which then creates IBS, ulcers, GERD, etc.
227
What should all women with IBS be screened for?
Childhood abuse
228
The gut brain axis is important for development of the newborn. T or F?
True. Changes in the commensal microbiota influence normal development of HPA axis, making microbial composition and important consideration for mom and newborn health.
229
How does early life stress affect cortisol pattern in adulthood?
Causes a reduction of cortisol output and blunted cortisol response.
230
What vitamins should you assess with Adrenal dysfunction?
B vitamins as this can affect methylation
231
What is android body type?
Central/truncal obesity - apple shaped.
| Can be associated with high cortisol and high insulin
232
What is gynoid body type?
Weight gain is in thighs/lower buttocks - pear shaped.
| Associated with estrogen dominance.
233
What are some biomarker patterns to recognize in android body shapes?
Increased inflammation thru adipocytokine communication
| IR/hyperinsulinemia and reduced adiponectin
234
What is the diurnal pattern in PCOS?
Lower morning cortisol and higher evening cortisol
235
What are signs/symptoms of high adrenaline?
```
Losing weight - low BMI
Anxious
Hot flashes
Cold(compensatory hypothyroidism)
Muscle wasting if not exercising to build muscles
Bone loss
```
236
What physical findings would you find with high cortisol?
```
Depression +/- anxiety
Any adrenaline symptoms
Weight around midsection
Elevated cholesterol
Body shape change
```
237
What are some manifestations of cortisol steal?
```
Low progesterone
Anxiety
PMDD/PMS
Hypoadrenalism
PCOS
```
238
What are some biomarkers to address in Gynoid body type?
Increased risk for HPATG dysfunction
Infection-obesity risks
Detoxification abnormalities - SNPs
GI and allergy concerns
239
What vitamin deficiencies can be associated with glossitis?
Protein under nutrition, iron, riboflavin, niacin, B6, folate, B12
240
What vitamin deficiencies can be associated with Burning mouth syndrome?
B1, B2, B6, B12, D, folate, zinc, elevated TSH, abnl fasting glucose
241
What vitamin deficiencies are associated with decreased taste?
Zinc
242
What vice is associated with leukoplakia?
Smoking
243
What can lead to hairy black tongue?
Smoking, abx use
244
What deficiency is keratosis pilaris associated with?
Omega 3 deficiency
245
What genetic classification is Keratosis pilaris?
autosomal dominant
246
What digestive issue could ridges of the nails be a sign of?
Hypochlorydria
247
What vitamin deficiency is white spots on nails a sign of?
Zinc
248
What vitamin deficiency is associated with taste bud atrophy?
B2, B12, niacin, iron
249
What is tongue fissuring a sign of?
Upregulated GALT
250
What is new onset abdominal girth a sign of?
Cortisol steal
251
What is a major comorbidity in hypercortisolism and what does it indicate?
Major depression. Glucocorticoid receptors typically regulate cortisol thru negative feedback system but chronic stress can desensitize GRs d/t HPA axis hyperactivity preventing them from returning to baseline conditions.
252
What type of depression is high cortisol associated with and what are the symptoms?
Melancholic - hyperactive stress response.
| Anxious, dread the future, insomnia, loss of appetite, diurnal variation - depression worse in morning.
253
What is the mechanism of Melancholic depression symptoms?
Activated HPA axis leads to increase CRH secretion which in turn activates brainstem noradrenergic nuclei. An increase in this feedback loop contributes to the hypernoradrenergic state associated with melancholic depression.
254
What is SSRIs effect on HPA axis?
Activates GR translocation, induces GR downregulation and decrease GR mediated effects in the presence of GR antagonists. Pretreatment with citalopram prior to cortisol administration inhibits consequences of the subsequent cortisol administration which leads to the decreased ability of cortisol to increase EEG alpha power and impair memory. (in melancholic depression)
255
What effects do SSRI have on cortisol levels?
Reduction in peak and total cortisol levels which led to improved anxiety
256
What happens in treatment resistant depression in regards to HPA axis?
They have reduced GR function and hyperactive HPA activity which both lead to higher levels of glucocorticoid hormones such as cortisol.
257
What are effects of chronic stress on the gut?
IP - increases immunomodulatory bacteral cell wall components(LPS)
Shifts the microbiome in relation to the level of pro-inflammatory cytokines
258
Which amino acid plays a role in communication between gut-brain axis?
Tryptophan
259
What substances are involved in communication of gut brain axis?
Vagus nerve, gut hormone signaling, immune system, tryptophan metabolism, microbial metabolites(SCFA)
260
What is cause of IBS in relation to HPA axis?
Hyperactive response to CRH
Alterations in ACTH and cortisol
Changes in catecholamine levels.
Has lower vagal tone and increased sympathetic activity
261
What polymorphisms are associated with increased susceptibility to stress?
Monoamine oxidase A, the serotonin transporter, and CRFR1.
| COMT - can't break down catecholamines so have trouble calming stress down.
262
Which IBS patients had higher levels of Norepi, epi and cortisol? IBS-C or IBS-D
IBS-C
263
What part of the brain is associated with dementia with chronic stress?
Hippocampus - becomes smaller
264
What levels of cortisol is associated with dementia?
Higher morning serum elevations in cortisol
265
What are signs of Atypical depression?
Lethargic, fatigued, hyperphasic, hypersomnic, diurnal variation - feels best in am
266
What cortisol and catecholamine levels are atypical depression associated with?
Low levels(Stage 3) but sometimes can be normal; low epi and norepi
267
What are the different HPA patterns with Melancholic and Atypical depression and PTSD
Melancholic - hyperactive CRH and overactivity of HPA axis
Atypical - hypoactive CRH and underactivity of HPA axis
PTSD - hyperactive central CRH and underactivity of HPA axis
268
What are some serum labs to order for adrenal dysfunction?
ACTH
DHEA-S
Prenenolone
Sex steroids to look for cortisol steal
269
What are some salivary labs to check for adrenal dysfunction?
```
Cortisol 4 or 6 pt
DHEA
Cortisol/DHEA ratio
Melatonin
Sex steroids
```
270
What are some issues with 24 hour urinary cortisol?
Doesn't give diurnal pattern.
| Can be influenced by high fluid intake so may not be reliable
271
Is DHEA catabolic or anabolic?
Anabolic - helps to counteract the catabolic effects of cortisol
272
What is a normal Cortisol:DHEA ratio?
5:1 to 6:1
273
What is the P in PTSD?
Production - what are the building blocks of the hormone? What affects synthesis-inflammation of the gland?
274
What is the T in PTSD?
Transport - Do the levels of one hormone affect the other? Does hormone's transport from its gland of origin to the target gland impact its effectiveness? Can we impact the level of free hormone? Is the hormone transformed and can we modulate that?
275
What is the S in PTSD?
Sensitivity - Are there nutritional or dietary factors that influence the cellular response to cortisol, thyroid, testosterone, estrogens, etc?
276
What is the D in PTSD?
Detoxification - Can we alter the metabolism of hormone? What can we do to affect the binding to and excretion of hormones?
277
What direct way does stress impact cortisol formation?
Causes pituitary increases in ACTH secretion
278
What indirect way does stress impact cortisol formation?
Decreases anabolism by slowing down 17, 20 lyase
279
How does stress/inflammation impact steroid hormone pathways?
Inhibits 17, 20 lyase
Stress if proinflammatory
Stimulates aromatase to increase estrogen formation
Increases 5 alpha reductase to increase DHT formation and causes hair loss
280
What are labs to get for Thyroid assessment?
TSH, Thyroid antibodies, FT3/FT4, TT3/RT3, RT3, Total T3, Total T4
Other labs: Serum Vitamin A, Zinc(RBC Zinc), Selenium(whole blood glutathione or RBC selenium),food sensitivities, celiac panel, toxic metals,
281
What are some factors that contribute to proper production of thyroid hormones?
Nutrients - iron, iodine, tyrosine, zinc, selenium, Vitamin E, B2, B3, B6, C, D
282
What are factors that increase conversion of T4 to RT3?
```
Stress
Trauma
Low calorie diet
Inflammation(cytokines, etc)
Toxins
Infections
Liver/Kidney dysfunction
Certain medications
```
283
What are factors that improve cellular sensitivity of thyroid hormones?
Vitamin A
Exercise
Zinc
284
What are factors that increase conversion of T4 to T3?
Zinc, Selenium
285
What are factors that inhibit proper production of thyroid hormones?
Stress
Infection, trauma, radiation, medications
Fluoride(antagonist to iodine)
Toxins: pesticides, mercury, cadmium, lead
Autoimmune disease: Celiac
286
What is estrogen dominance?
Increased Estrogen in relation to progesterone. (E&P may still be in normal range). No consensus on ideal ratio as varies between people and lifespan
287
What are some drivers of estrogen dominance?
Obesity, BMI, WHR, Inflammation, Aromatase activity, endocrine disruptors, POPs, caffeine, etoh, dysbiosis
288
In fibrocystic disease, how does ED cause these changes?
ED/inflammation leads to hyperproliferation of connective tissue which leads to fibrocystic breast
289
What is the effect of estrogen dominance on the endometrium?
high levels of estrogen vs low levels of progesterone lead to mitogenic proliferation of the endometrium which can lead to bleeding and increase endometrial cancer risks
290
Why does PMS happen in some with estrogen dominance?
Higher estrogen/prolonged exposure
291
What are symptoms of estrogen dominance?
Swollen/tender breasts, water retention, irritability, headaches, visual disturbance, memory difficulty, sweet craving
292
What are some associated conditions with estrogen dominance?
PCOS, PMDD/PMS, FC breast/breast pain, Menometrorrhagia, Fibroids, Endometriosis, Increased breast/endometrial cancer risk
293
What are potential diet causes of Estrogen dominance?
Phytoestrogen deficiency
| Sugar and refined starches
294
What are potential stress causes of EstD?
Cortisol
| Anovulatory cycle
295
What are iatrogenic causes of EstD?
OCPs, HRT
296
What are other nutritional causes of EstD?
Excess calories
Impaired liver function
Deficiencies that cause impair ovary or mitchondria
297
What are environmental causes of EstD?
Estrogen fed cattle
Xenoestrogen exposure during embryo pase of life
Chronic exposure to xenoestrogens
Toxicity
298
What are premenopausal etiologies of EstD?
Luteal phase dysfunctions
Estrogenic environmental toxins
Increased BMI/obesity
Stress
Perimenopausal elevation of FSH(increased E production in ovary)
Other proinflammatory states(increase aromatase leads to increased estrogen)
Gut dysbiosis(impaired detox, estrobolome)
299
What is the estrobolome?
How estrogen is metabolized in microbiome and whether or not it gets recirculated.
300
How does inflammation relate to estrogen?
Adipose tissue secretes proinflam cytokines
Obesity is chronic inflammatory state
Adipose tissue has aromatase that makes estrogen
PGE2 is a stimulator of aromatase.
PGE2 is produced by COX1 and COX2.(maybe why nsaids reduce risk of cancer)
Estrogen upregulates COX2 production of PGE2.
301
What are gut effects on estrogen potency?
Beta glucoronidase from abnormal bacteria
Fiber binds excreted estrogens
Dietary estrogens and factors that regulate CYP450
Alcohol inhibition of liver metabolism
Liver effects - SHBG, drug and toxin competition for CYP450 enzymes
302
What are interventions to improve gut interactions in regards to estrogen?
```
Improve gut dysbiosis(bacillus produces high BG)
Calcium d-glucarate
Ensure elimination
Treat yeast
Treat barrier function(with glutamine)
Assess HCL and protein absorption
5R intervention
```
303
What is a marker for enterohepatic circulation of estrogen?
Urinary E3-3G
304
What are causes of estD in postmenopausal women?
Genetics, obesity/inflammation with increase aromatase, alterations in est metabolism, stress induced lowering of adrenal progesterone
305
How does obesity and elevated BMI increase estrogen?
Increases aromatase and decrease SHBG
306
How do estrogen disruptors, POPs cause estD?
Binds to hormone receptors
Interference with steroidiogenic enzymes
Interaction with gene transcription/expression
307
What is luteal phase dysfunction?
Decreased progesterone by corpus luteum(<5 ng/ml)
Shorter luteal phase <11 days
Lack of endometrial maturity via histology
308
Which hormonal imbalance is associated with difficulty establishing pregnancy or miscarriage?
Luteal phase dysfunction
309
What are symptoms of LP dysfunction?
```
More frequent periods
Spotting before and after periods
Anxiety, mood, insomnia
May have low LH, FSH, altered FSH/LH ratio or abnormal FSH/LH pulsatility
Lower estradiol
```
310
What are associated conditions with LP dysfunction?
Obesity, infertility, early miscarriage, ovarian aging, metrorrhagia - more frequent periods, menorrhagia - heavy periods; anorexia, inadequately treated 21 hydroxylase deficiency, hyperprolactinemia, Thyroid dz, PCOS
311
What are causes of LP dysfunction?
Diet(SAD)
Excessive Exercise - low gonadotrophin and E2, delay in ovulatory LH peak
Stress(psych/physio)(d/t cortisol steal)
Endocrine abnormalities
Toxins
PCOS(anovulation and no corpus luteum)
312
What are some endocrine abnormalities assoc with LP dysfunction?
Hypothyroidism, Hyperprolactinemia(lactation), increased beta endorphin levels and other hypothalamic disruptions
313
What is relation with metabolic endotoxemia and LP dysfunction?
causes ovarian inflammation and impaired progesterone production; was positively correlated with plasma CRP and inflammation in ovary; negatively correlated with progesterone production
314
What is relation between diet and LP dysfunction?
Low fat diets assoc with low progesterone
| Low calorie diets show linear relationship with LP dysfunction severity; worse if augmented with exercise
315
What is relation between exercise and LP dysfunction?
Low gonadotropin and E2 levels delay in ovulatory LH peak; High estrogen levels in urine, low progesterone in urine
316
What is relation of stress and LP dysfunction?
3x's the increase cortisol within 4 hours of stress exposure
Prolonged follicular phase
Progesterone secretion drops by 52% in follicular phase, 31% if stress initiated in Luteal phase
Ovulation intact
317
How do you diagnose LP dysfunction?
No diagnostic gold standard - can't check progesterone thru serum at frequent intervals during luteal phase - not practical; single serum is of no value, so have to determine time of ovulation for single sample to mean anything
Alternatives:
Basal body temp (inaccurate)
Urinary LH surge detection kits(progesterone surges 6-8 days after ovulation)
Serum progesterone levels
Endometrial biopsy
318
How do you treat LP dysfunction?
Treat underlying other endocrine abnormality if any
Improve insulin sensitivity
80mg/day of progesterone cream as effective as 200mg/day oral (start after ovulation and stop on first day of bleeding)
Use oral when brain symptoms dictate but not fertility
Lower TSH levels
Weight loss which helps resume ovulation; lower body weight assoc with higher progesterone
Use organic meats w/o hormones
Vit B6,C, E
Black Cohosh 120 mg
Consider use of chasteberry prior to progesterone use
319
What vitamins are important for LP dysfunction?
Vitamin C, E, B6
320
What is fluctuations in hormone levels?
Changes in levels can cause signs and symptoms;
321
What are causes of fluctuations in hormone levels?
Perimenopause, major life stress, illness, sensitivity in changes to hormones during menstrual cycle - PMDD, PMS;
322
What is hormonal insufficiency?
Relative or absolute hormone insufficiency
323
What causes hormonal insufficiency?
Aging, POF, menopause, Nut'l deficiencies, chemo, oopherectomy
324
What is sub optimal hormone metabolism?
suboptimal 2, 4, 16 OH estrogen
325
What causes sub optimal hormone metabolism?
SNP(COMT, GST, CYP enzymes), poor diet, etoh, hrt, endocrine disruptors, PCOS
326
Why do you get salt retention, swelling, breast tenderness in PMS?
Increased aldosterone
327
Why do you get sweet cravings in PMS?
Decreased glucose tolerance, decreased RBC Mg, decreased PGE1
328
Why do you get anxiety, irritability in PMS?
Increased estrogen, decreased progesterone
329
Why do you get depression in PMDD?
Decreased estrogen, increased progesterone and androgens
330
Why do you get menstrual migraines in PMS?
Estrogen and progesterone interact with serotonin receptors; affect vasoconstriction/dilation
331
What enzyme converts 2-OH estrone to 2 methoxyestrone?
COMT
332
What enzyme neutralizes 4-OH quinone?
GSH
333
What enzyme neutralizes 16-OH estrone?
Reductase
334
Which estrogen metabolites are carcinogenic?
4-OH quinone and 16-OH estrone
335
Which estrogen metabolite is protective?
2-Methoxyestrone
336
What nutrition is associated with precocious puberty?
diet heavy in dessert, snacks, soft drinks and fried foods
337
What nutrition is associated with delayed menarche?
high fiber diet
338
What food consumption was associated with associated with earlier age of menarche?
Red meat >= 2 times/day compared to < 4 times a week
339
What toxins are associated with early menarche?
DDT, PBCEs, PCBs, Phthalates
340
What are some indications of abnormal cycles?
>3 months w/o cycle
No menarche 3 years after breast development
No menstrual cycle by age 14 with suspicion of eating d/o or excess exercise
Cycle shorter than 21 days or longer than 45 days
Menstrual flow >7 days
Changing tampon/pad every 1-2 hours
341
During what phase of menstrual cycle does PMS start?
luteal phase and normally subside 2-3 days after menses begins
342
Does estradiol or progesterone increase or decrease food intake?
Estradiol - decreases
| Progesterone - increases
343
Low levels of which vitamins/mineral were associated with PMS?
Vitamin D and calcium
344
What type of diet helps PMS and why?
Low fat vegetarian diet - increases SHBG so less free hormone, reduces weight, low fat reduce estrogen and fiber help fecal estrogen elimination decreasing enterohepatic recirculation
345
Why does low fat veg diet help fibroids, endometriosis?
Encourages fecal estrogen elimination
| Increased SHBG and low E so less proliferation of fibroid and decreases in PG production
346
What additional supplements/support can be useful in PMS?
```
MVI with minerals
B complex
Vit C
Mag citrate - reduces fluid retention
Progesterone cream on days 14-28 cycle
Chasteberry
Calcium
```
347
How does B6 help PMS?
Antianxiety - B6 cofactor for neurotransmitter synthesis
Antiinflammatory - cofactor for PgE1
Glucose regulation - cofactor using amino acids for gluconeogenesis
348
What botanicals might be beneficial in PMS?
Chasteberry(vitex) - dopaminergic effect, gingko, crocus sativus
349
What supplements did not have any effect on PMS?
Evening primrose oil and St Johns
350
What conditions should you be careful in using Chasteberry(vitex) and why?
Fibroids, breast cancer, endometriosis; linoleic acid found in the fruits of chasteberry can bind to estrogen receptors(beta) and turn on genes that are estrogen sensitive
351
What vitamin deficiency can be associated with menorrhagia?
Vitamin A
352
What is the AMH level in PCOS?
3 x's higher than non PCOS, but not in obese women. Obesity lowers AMH.
353
How does excess exercise affect hormones?
It lowers gonadotropin and E2 concentrations and get delay in ovulatory peak
354
What increases SHBG?
Vegetarian, low fat diet
Treating hypothyroidism
Treating obesity
355
What decreases SHBG?
Testosterone therapy
| Exercise - GH
356
What conditions would you want to decrease SHBG?
Osteoporosis
| Atrophic vaginitis
357
What conditions do you want to increase SHBG?
Breast, uterine cancer
| FC breast
358
When does menarche usually occur?
2-3 years after breast development
359
What are general principles of pharma approach to severe pms?
Targeting the HPA axis
| Targeting brain serotonergic synapses
360
What does PMS often reflect in terms of hormones?
EstD, progesterone deficiency, stress
361
What are some treatment strategies for PMS?
```
No sugar, caffeine, etoh
Small frequent meals with protein
Reg exercise, sleep
Stress reduction
Med diet
```
362
How does Vitex(chasteberry) help PMS?
binds to dopamine, possibly ach and opioid receptors
effective for physical symptoms esp compared to prozac(prozac better for mood)
phytoestrogen
363
What is menorrhagia?
Passing large clots with menses
Last longer than 7 days
Changing tampon or pad every hour
Has to change pad at night d/t bleeding
364
How does Curcumin help PMS?
modulates Nepi, dopamine and serotonin and affect inflammatory pathway(blocking PGE2)
365
How do you treat menorrhagia/fibroids?
Treat IR, EstD, inflammation, high levels of aromatase
Detox protocols
Optimize weight
Low does cyclical progesterone(day 12 until period starts)
366
What nutrients help tx menorrhagia?
Methylated B vitamins
Fish oil 2000 mg daily
Vitamin A, K
Iron supplementation if needed
367
What botanicals can you use to tx menorrhagia?
1. Hemostatic herbs - yarrow, shepherd's purse, cinnamon
| 2. Improve HPA axis - vitex, beth root, partridge berry
368
What is the pathophysiology of PCOS?
Elevated insulin which leads to altered HPA axis so LH and FSH not secreted properly. More LH is secreted which causes more androgens to be made and ovulation doesn't occur. Estrogens are not opposed by progesterone so this leads to estrogen excess.
High insulin also has decreased shbg which leads to increase in free testosterone which further decreases SHBG and increases estrogen d/t conversion.
Elevated insulin also alters enzymes in the ovaries to make more androgens;
Increased androgens may cause increase insulin.
369
What supplement was comparable to metformin in tx of PCOS?
NAC - reduced BMI and testosterone
370
What supplement may help fertility in PCOS?
Myoinositol - it improves the way ovaries use insulin and glucose and modulates FSH signaling; may alo improve by modulate steroid metab via noninsulin dep pathways
D-chiroinositol - mediates insulin on nonovarian tissue
371
What are risk factors for early perimenopause?
Smoking
Fam hx
Chemo or pelvic radiation
Hysterectomy without oopherectomy, if unilateral oopherectomy will go earlier
AI - PMOF
Toxins - mycotoxins and endocrine disruptors
372
Can you rely on FSH to dx menopause?
No, as it can fluctuate in perimenopausal period
373
What acronym helps you to remember what to address to balance hormones and what does it stand for?
GALS.
Gut - constipation/IBS/inflammation/microbiome
Adrenals - stress, cortisol steal, low P/DHEA
Liver - total body burden, detox, genetics, etoh
Sensitivity/sugar - receptor sensitivity, thyroid insulin, glucose
374
Why is it important to treat hot flashes?
People who have hot flashes have higher risks of CVD, stroke, poor endothelial fxn, sleep issues, anxiety/depression
375
What enzymes are involved in metabolism of estrogens?
COMT, MAO
376
What are benefits of black cohosh?
Nonhepatotoxic
Mild anti estrogenic properties
Helps prevent free radical damage
Has some activity against breast cancer proliferation
Can tx hot flashes as effective as transderm E2
Reduces sweating with tamoxifen and makes it work better
Helps with joint pain and doom and gloom
377
How does siberian rhubarb work?
It exerts serm like activities:estrogenic actions mediated by ERbeta. No action on ERalpha. Thus, reduces occurrence and severity of climacteric complaints in perimenopause.
378
How do isoflavones work?
They are phytoserms and act as SERM so bind to ERb and protects from overshooting of ERa effects on cell proliferation(high isoflavone assoc with reduced breast cancer risk)
379
What is red clover?
isoflavone
380
What are functions of progesterone?
```
Affect stem cells
Induction of enzymes important in estrogen metabolism
Priming of cellular cross talk
Down regulates estrogen receptor
Inhibits ER transcription at DNA
Effects on cellular adhesion
Increases cell differentation
Induces Apoptosis
Initiates ovulation
Inhibits uterine activity
```
381
What do you have to watch for when using progesterone?
Cortisol Steal
382
What are benefits of progesterone in perimenopause?
```
NOT PROGESTINS
Improves sleep
Improves VMS
Does not increase breast cancer proliferation
Increases bone formation
Beneficial CV effects
Can help with pms migraines
Decreases menorrhagia, dysmenorrhea
Improves mood
```
383
What botanical stimulates progesterone production?
Vitex chasteberry
384
What is a marker for adrenals being off if low?
Testosterone
385
How does marijuana affect libido?
THC is stimulatory
| CBD is inhibitory esp at neutral or higher doses
386
What has been well studied for vaginal dryness?
Estriol
387
What are root causes of endometriosis and fibroids per Fxn Med?
Inflammation
Detox
Blood sugar metabolism
388
Why do you need to be careful giving DHEA and testosterone to women with fibroids?
Fibroids make own estrogen d/t increased androgens and aromatization of androgens. So giving extra dhea and testosterone will make fibroids grow.
389
Do fibroids have only estrogen receptors?
No, they have both E and P receptors
390
What are the most potent stimulator of aromatase activity in fibroids?
IL1beta, PGE2 - inflammation
391
What is most potent stimulator of aromatase in cancerous breast?
PGE2
392
What vitamin can reduce growth of fibroid?
D; thus deficiency will cause growth
393
What enzyme is increased/decreased in endometriosis?
Increased - aromatase
Decreased - 17 B HSD
This results in increased estradiol and estradiol stimulates COX2 which causes PGE2 which stimulates aromatase further
394
Is there high level of aromatase in endometrium?
No
395
Is there high level of aromatase in endometriosis?
Yes
396
What are some molecular hallmarks of endometriosis?
1. Genetic predisposition
2. Estrogen dependance
3. Progesterone resistance
4. Inflammation
397
What conditions has there been shown a link to with endometriosis?
AI dz
398
What type of diet can help decrease symptoms of endometriosis after 12 months?
Gluten Free
399
How does metabolic endotoxemia affect progesterone production?
LPS was + correlated with plasma CRP and inflammation of ovary(follicular IL-6)
LPS negatively correlated with progesterone production
Endotoxin from gut lumen to circulation may interfere with progesterone production and result in luteal deficiency
400
What toxins are associated with endometriosis?
Heavy metals, PCBs, TCDD, Dioxin
401
Describe circle of fibroids and endometriosis
Gut issues are common and fuel inflammation.
Estrogen increases inflammation.
Inflammation increases estrogen and insulin.
Insulin causes more total and free estrogen
VAT causes more estrogen
VAT increases inflammation
402
What happens to adiponectin in obese?
If fat cell is too full of fat, then it makes less adiponectin which decreases insulin sensitivity and leads to more insulin and more estrogen.
403
What does adiponectin do?
increases insulin sensitivity
burns fatty acids,
decreases tgl and inflammation
404
What are natural aromatase inhibitors?
Dietary fiber and lignans(flax seed, not oil)
Soy
Resveratrol(blueberries, cocoa, grapes)
Grapeseed extract
Chrysin(passionflower tea, honey, propolis)
White button mushrooms
405
What are 4 main areas for Fxn Med Doctor to focus on in regards to cancer?
1. Prevention
2. Dx and eradication of tumor - conv med
3. Changing environment to prevent new tumors and reverse early tumors
4. Longterm health of cancer survivor
406
What are some common nutraceuticals with epigenetic effects on cancer stem cells?
Vitamin D, Iodine, Melatonin, Frankinsense, Myrrh, Mushrooms, turkeytail, cannaboids etc
407
What are some SEEMs?
Resveratrol, Genistein, Enterolactones, lignans, catechins, isoflavones, quercetin
408
How does insulin affect E2 in breast?
Mitogenic, antiapototic, proangiogenic, increase IGF-1, proinflammatory
409
What tissues have only ERa?
uterus, liver, kidney, heart
410
What tissues have only ERb?
ovary, prostate, lung, GI tract, bladder, hematopoietic, CNS
411
What tissues have both ERa and b?
breast, epididymis, thyroid, adrenal, bone, certan regions of brain, neurons and thymocytes
412
High dose of what supplement can help to prevent breast cancer?
Melatonin
413
What modulates estrogen metabolites?
DIM
414
What supplement can block effect of estrogen quinones?
Resveratrol
415
How does estrogen protect the cardiovascular system?
17 beta Estradiol inhibits expression of Crp and injured arteries. Estrogen also modulates oxidative stress and arteries and vascular smooth muscle.
416
What is estrogens action on the heart?
Increases vasodilation in vascular endothelium
Decreases cell migration and proliferation in smooth muscle
Decreases LDL oxidation, insulin resistance, cardiac hypertrophy and cardio myocytes
417
Describe metabolism of estradiol
Goes to estrone and then either gets sulfated or glucoronidated or
1) Converted to 2OHestrone via CYP1A1 then to 2Methoxyestrone via COMT methylation
2) Converted to 4OHestrone via 1B1 then to 4 methoxyestrone via COMT methylation or to quinones and then to mercaptuate via GST
3) Converted to 16OH estrone via 3A4 and then reduced to estriol
418
What are some characteristics of 2 OH estrone?
- Weak estrogenic activity
- high levels can increase risk for osteoporosis
- can be protective against breast cancer if methylated
- potent antiox and inverse relationship with atherosclerosis
419
What are some characteristics of 4 OH estrone?
can be carcinogenic thru oxidation of 3,4 quinones
levels parallel 16 OH estrone
Very bad metabolite
420
What are some characteristics of 16 OH estrone?
Full estrogenic activity
turns on estrogen receptor
little affinity for binding proteins
confers likelihood of estrogen dep conditions
421
Where do omnivores excrete most of their estrogens?
Kidneys
422
Where do vegetarians excrete most of their estrogens?
Gut
423
What is associated with craving for sweets, appetite in PMS?
glucose intolerance, low rbc magnesium, low PGE1
424
What are tx for PMS?
Progesterone cream
B6
Magnesium
Chaste berry(vitex)
425
How can you treat irregular periods?
Give progesterone on day 14-16 until day of cycle
426
How does estrogen affect thyroid?
It increases TSH secretion
427
How does Thyroid therapy affect adrenals?
Makes pts more sensitive to ACTH from CRH
428
How does cortsiol affect thyroid?
It reduces TSH response to TRH inhibiting thyroid hormone secretion. See same effect with Cushings, stress
429
How does stress impact steroid hormone pathway?
Directly by stimulating ACTH secretion forming more cortisol
Indirectly by decreasing anabolism and inhibiting 17,20 lyase
Stimulates aromatase to increase estrogen
Stimulates 5 alpha reductase
430
What stimulates CYP450 scc to cause cholesterol uptake by mito in ovary?
LH, FSH
431
What stimulates CYP450 scc to cause cholesterol uptake by mito in adrenals?
ACTH
432
What are the effects of cortisol steal?
1) Less progesterone and initially estrogen dominant state
2) More cortisol and stim of aromatase leads to est dom conditions - breast cancer, fibroids, endometriosis
3) Longterm decreased formation of androgens/estrogens which leads to hot flashes, decreased libido, stress
433
Where is DHEA made?
Ovarian theca cells, Testicular leydig cells, Adrenal reticularis
434
Where is progesterone made?
Corpus Luteum
435
What mineral is needed for activation of estrogen receptor?
Zinc
436
Which type of estrogen receptor do phytoestrogens bind to?
Beta
437
Which estrogen receptor does Estriol stimulate?
Beta
438
What conditions does adipokine leptin contribute to?
Type 2 DM, Metsyn, AI dz, Allergies, CVD
439
What is role of leptin in obesity?
Have high levels d/t leptin resistance(not deficiency); leptin in turn increases obesity and hyperphagia
440
What type of cancer is leptin associated with?
Breast
441
What is mechanism of leptin resistance/obesity?
Endoplasmic reticulum stress, Hypothalmic inflammation and defective autophagy from overnutrition leads to hypothalmic leptin resistance which leads to obesity
442
What is PTP1B?
cytoplasmic tyrosine phosphatase anchored to ER membrane that is increased in leptin resistant animals
443
What are PTP1B inhibitors?
Cucurmin, Berberine
444
What is leptin?
Protein hormone made and secreted by adipose tissue
445
What is glucocorticoids effect on leptin?
It increases it
446
What are estrogens actions on the heart(nonsynthetic)
Increases vasodilation
Decreases cell proliferation/migration in smooth muscle
Decreases LDL oxidation, IR, cardiac hypertrophy in cardiomyocytes
447
What is the timing hypothesis?
Early in atherosclerosis, estrogen is protective and retards plaque rupture. Late in disease estrogen causes plaque rupture, thrombosis and coronary events. Thus, if initiated within 6 years of menopause, can have reduced CVD.
448
How does estrogen affect bone?
Deficiency leads to more osteoclastic activity relative to osteoblastic activity. After 4-8 years of menopause, a second phase occurs due to reduced bone formation
Benefits bone by:
Lowers sensitivity of bone mass to PTH thus reducing bone resorption
Increases production of calcitonin inhibiting bone resorption
Accelerates calcium resorption by intestines
Reduces calcium excretion by kidneys
Direct binding to estrogen receptors on bone(bone also has DHEA receptors)
449
What is progesterone effect on bone?
Stimulates osteoblasts to form bone
450
What is testosterone's effect on bone?
Converted to DHT in osteoblasts and stimulates bone formation
451
What is cortisol's effect on bone?
in high levels increases bone resorption by inhibiting calcium absorption and decreasing estrogen levels. It also inhibits P and T so less osteoblastic activity.
452
Which is better for bones - hormones or meds?
Meds better for tx of severe osteoporosis
| Hormones better in tx of prevention of osteoporosis and tx of osteopenia
453
How does estrogen help brain?
Increases cerebral metabolic rate and blood flow
Reduces ROS
Increases expression of antiapoptotic Bcl-2 which sequesters calcium which makes neurons more resistnt to glutamic neurotoxicity
454
What is effect of progesterone on brain? medroxyprogesterone?
Progesterone - neuroprotective as activates MAP kinase which is antiapoptotic; promotes myelin.
MPA - not neuroprotective and negates estradiol neuroprotective effect
455
What blocks progesterone's promtion of myelin?
Mifepristone
456
What is adiponectin?
protein secreted by adipose tissue that is antiDM, increases insulin sensitivity, antiinflammatory and antiatherogenic
Crosses BBB
If adipose tissue too full of fat, it makes less adiponectin
457
What are risks of oopherectomy?
Increased carotid intimal media thickness
Increased risk of CAD death
Decreased bone density, osteoporosis and risk of hip fracture
Increased risk of cognitive impairment, PD, depression/anxiety
Increased risk of death from all causes
Increased risk of cancers except ovarian
458
What is yoga and meditation effect on aging?
Decreases 8OH2DG, ROS, cortisol, IL6
| Increases telemerase activity, Bendorphins, BDNF, and srituin-1
459
What food increases risk of hip fracture?
Dairy
460
When should you give vitamin K with vitamin D?
If treating bones
| If only tx vitamin D then only give if over 40
461
What is difference between vitamin K1 and K2?
K1-found in green veggies, predominant form in diet and works on coagulation
K2 - synthesized by microbiota and found in fermented foods and animal products
