General Flashcards
What is the HPO axis and what does it do?
Hypothalamus-Pituitary-Ovarian Axis. Maintains hormonal balance within the reproductive system
What stimulates the anterior pituitary gland to produce LH and FSH?
GnRH
Raised oestogen and testosterone exert _______ feedback over FSH and LH secretion
negative
What hormone is synthesised from cholesterol in steriodogenic tissues such as the adrenal glands, gonads, and brain by mitochondrial enzymes CYP11A1?
Pregnenolone
Pregnenolone is synthesised from …?
Cholesterol
What enzyme synthesises pregnenolone?
CYP11A1
Where is pregnenolone synthesised?
Gonads,
Adrenal glands
Brain
By the mitochondrial enzyme CYP11A1
Pregnenolone is a precursor of… ?
DHEA Testosterone Oestrogen Progesterone Cortisol
Name 2 benefits of pregnenolone?
Anti-inflammatory
Neuroprotective
Low levels of pregnenolone are caused by…?
Age (>30)
Statins
Name some symptoms of low pregnenolone…?
Poor memory Declining concerntration and attention Fatigue Dry skin Joint and muscle pain Decreased libido
What does DHT stand for?
Dihydrotestosterone
What does DHEA stand for?
Dehydroepiandrosterone
What can support healthy pregnenolone levels?
Sleep quality Stress management Healthyfats - avocado, flaz, chia, olive oil, walnuts B vitamins Vitamin K D3
What can help balance DHEA
Maca Rhodiola Magnolia Perilla oil Tribulus
High stress increases the use of pregnenolone for cortisol production, reducing the total amount of pregnenolone available for sex homrone production, what is this called?
Pregnenolone steal theory
What is the pregnenolone steal theory?
High stress = Increases pregnenolone to cortisol conversion = reduced pregenolone for sex homrones
Where is progesterone produced?
corpus luteum after ovulation
Adrenal cortex
Placenta during pregnancy
Name the functions of progesterone
Maintains the endometirum for implantion and pregnancy
Increases cervical mucus
Relaxes smooth muscle
Supports bone and mammary development
What conditions can see an imbalance in progesterone?
Perimenopause
PCOS
infertility
Low progesterone leads to what?
Oestrogen dominance
What are the causes of low progesterone?
Chronic stress
Synthetic progesterones
xenoestrogens
What are the sings and symptoms of low progesterone?
Irritability
mood swings
insomnia
Low progesterone can increase the risk of what condition?
breast cancer in perimenopausal women
Name ways in which progesterone can be balanced?
Supporting oestrogen detoxification Increase fibre 3 balanced meals a day No snacking avoid alcohol Mg Vitamin C B6 Zn Vitex Angus castus Exercise Box breathing
Name the 3 types of oestrogen
E1 - Oestrone
E2 - Oestrodoil
E3 - Oestriol
How are oestogens produced?
Conversion of androgens via aromatase
Which oestrogen is ost active during the reproductive years?
E2 - oestrodiol
What are the functions of oestrogen?
Reproductive tract development Menstural cycle Promotes cell proliferation Glucose homeostasis Immune robustness Bone and cardiovascular health
Name 3 oestrogen receptors that oestrogen binds to…
Er(alpha)
ER(beta)
GPER
What does GPER stand for?
G-protein coupled oestrogen receptor
What is aromatase?
CYP450 enzyme
What is oestrogen dominace?
A state of excess oestrogenix activity encompassing some or all of;
elevated oestrogen relative to progesterone (HIGH O:P despite normal oestrogen)
Elevated specifc types of oestrogen or metabolites due to poor detoxificatin and elimination
Exceess oestrogen induces overexpression of ERa and ERb
Oestrogen dominance is assocaited with;
firboids endometriosis PMS firbocystic breasts dysmenorrhea infertility miscarrigaes perimenopause breast/ovarian/endo cancers insulin resistance thyroid dysfunction brain fog anxiety depression
What can cause/affect oestrogen dominance?
Syntehtic HRT OCP Xenoestrogens Heavy metals Obesity Poor liver detoxification Constipation SNPs - COMT Intestinal dysbiosis Chronic srtress
Dicuss the phase 1 oestogen biotransformation…
CYP450 enzymes convert E1 into 1 of 3 metabolittes;
2-OH-E (CYP1A1)
4-OH-E (CYP1b1)
16a-OH-E (CYP3A4)
What is 2-OH-E and what CPY450 enzyme metabolises it?
CYP1A1
weakest form
Protective
COMT deactivates 1-OH-E1 to protective 2-MeOE1
What is 4-OH-E and what is the CYP450 enzyme that metabolises it?
CYP1B1
pro-carcinogenic
Neautralised by COMT into proetcitve 4-MeOE1 metabolites
What is 16a-OH-E and the CYP450 enzyme that metabolises it?
highest binding affinity for oestrogen receptors with high proliferative effects. High = higher risk of esteigen dependant conditions such as breast cancer, fibroids and endo
What are quinones?
Organix aromatic-derived compounds
Describe phase 1 oestrogen
Biotransfomration using CYP450 enzymes
Describe phase 2 oestrogen metabolism
Uses sulphation, methylation and glucuronidation pathways
Which pathway do 2-OH-E and 4-OH-E undergo during phase 2 of oestrogen metabolism?
Methylation via COMT
Poor methylation increases conversion of 4-OH-E to WHAT which will increase oxidative damage to DNA?
quinones
What increase in oranic aromatic-derives compound is assocaited with cancer when thinking about oestogen metabolism?
quinones
16a-Oh-E metabolises E3 which undergos metabolism on which pathway?
Sulphation
2-OH-E and 4-OH-E undergo which pathways?
Methylation
Sulphation
Glucoronidation
What nutritional support can be given to phase 1 oestogen metabolism?
I3C cruciferious veg antioxidants glutathione turmeric resveratrol berries roobios tea celery
When supporting phase 1 oestrogen metabolism, what should be avoided?
CYP450 inducers; paracetamol
PCBs
smoking]
grapefruit
How can phase 2 oestrogen metabolism be supported?
Conjugation pathway support - cruciferious veg, allium veg, Mg, antioxidants
Methylation support - folate, B12, B6 SAMe, choline
What should be avoided when supoprting phase 2 oestogen metabolism?
OCP
high alcohol
high cortisol
mould exposure
What is the oestrobolome?
collectio of microbes capable of metabilisng oestrogens
the oestrobolome bacteria produce which enzyme?
Beta-glucuronidase
What is beta-glucoronidase?
an enzyme which deconjugates (reactivates) oestrogen that were conjugated for elimation
deconjugated oestrogens can be reabsorbed via the…
enterohepatic circulation
What can increase chances of enterotoxigenic circulation of oestrogens?
Dysbiosis
low fibre
poor bile flow
Imbalances in beta-glucuronidase can promote conditions such as;
endo breast cancer ovarian cancer PCOS Endo cancer Endometrial hyperplasia
Discuss the obersvations seen with beta-glucuronidase in endo andPCOS;
Endo = larger numbers of beta-glucuronidase (high circ. oestrogen - oestogen dominace) PCOS = low beta-glucuronidase = reduced oestrogen and higher andrgoens
How to maintain healthy beta-glucuronidase levels;
High levels =
Low levels =
High levels =
increase fibre
calcium D-glucarate
glucaric acid-rish foods such as mung bean sprouts, apples, crucierfous veg, milk thistle, Lactobacilli and bifidum bacertia
LOW =
probiotics and/or probiotic foods
Where is testosterone produced in women?
Ovaries and adrenal cortex
What is testosterone converted to?
E2 and DHT
What are the functions of testosterone in women?
Ovarian density
Libido
Bpnoe strengthmood
cognition
List 2 testosterone imbalances
Andrgoen dominace in PCOS
Low testosterone
What is the more potent form of testosterone?
DHT
converts testosterone to DHT?
5a-reductase
List ways in which the testosterone to DHT pathway is upregulated;
insulin
Inflammation
obesity
List ways in which the testosterone to DHT pathway is downregulated;
Nettle Saw palmetoo Lycopene Turmeric Green tea Zn GLA and EPA
How do sex hormones travel around the body?
in the blood bound to SHBG
Where is SHBG produced?
Ine the liver
What are the functions of SHBG?
to oestadoil, testosterone, DHT
only unbound hormones are biologically active
Only ____________ sexx ormones are bilogically active
unbound
Low levels of SHBG are assciated with which conditions?
Hypoinsulinemia Metabolic syndrom T2DM hypothyroidism PCOS
High levels of SHBG are asscoaited with;
anorexia Pregnany Androgen deficiency hyperthyroidism liver disease
What is prolactin?
Key hormone controlled by oestrogen and dopamine
what 2 hormones control prolactin?
oestrogen and dopamine
What are the functions of prolactin?
lactation
breastmaturation
inhibitsmenstruation
What is hyperprolactinaemia?
Occurs naturally in pregnancy and lactiation but can also occue in non-pregnant women
What is hyperprolactinaemia asscoatied with?
Pregnancy Lactation Infertility Menstural irregularities low libido
osteopenia
breast pain
vaginal dryness
What increases Prolactin?
High cortisol Circadian rythmn disruption Pituitary tumours Renal failure vitamin D deficiency drugs - dopamine antagonists
What are EDCs?
Endocrine disrupting Chemicals
Exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of bodily hormones
List ways in which EDCs can affect hormones
binding metabolism elimination production release transportation action
List some EDCs
BPAs PCBs Phthalats heavy metals pesticides herbicides fire retardants dioxins drugs tap water
What can alter homrone receptor signalling, production, secretion and metabolism of homrones and well as induce oxidative stress, mitochondrial damamge and epigentic alterations?
EDCs
What adverse health effects are associated with EDCs?
Cancer PCOS Early puberty Gynaecomastia infertility cognitive defects obesity
What is the critical window of susceptibility of EDCs becoming an issue?
in utero
neonatally
childhood
puberty
What are xenoestrogens?
sub-category of EDCs. Structually similar to oestoogen and can bind to oestrogen receptor sites
Name some examples of xenoestrogens
Pesticides herbicides dioxins parabens phthalates BPAs preservatives tap water
When can xenoestrogens build up?
Fat of meat, fish, dairy and human fat cells with age
How can someone be exposed to xenoestrogens?
Ingesting via food and drink
inhaled
skin or mucus membranes
Why is dairy considered an endocrine disruptor?
It contains E1,E2 and E3 steroid hormones
Includes IGF, PCBs, dioxins insecticides, bovine growth hormone
What are phytoestogens?
NAturally occuring palnt compunds strcutually similar to 17beta oestradiol (E2)
Produce weak anti-oestoengic effect on high or low endogenous oestrogen
reduces circulating bioavailability of E2
Disrupts aromatase - favours 2-OH pathway
Oestrogen modulators
List some benefits of phytoestrogens
lower risk of; menopausal symptoms CVD obesity metabolic syndrome T2DM breast cancer
List some naturally occuring phytoestrogens
flavinoids
lignans
flavones
What phytoestrogen has been shown to inhibit breast cancer cell growth and is neuroprotective?
Apigenin
List soybean products;
Tempeh
soy paste
miso
natto
Is soy products are consumed they should be…
fermented
Why is consumption of soyban in western societies deemed as unhealthy?
include soya oil
flour
GMOs
What is necessary for fermentation of phytoestrogens?
a healthy microbiome
List some herbs which are considered good forms of tea/tinctures which contain phytoestrogens;
black Cohosh
agnus castus
red clover
dong qui
List ways in which hormone imbalance can be driven by;
blood glucose dysregulation high or low body weight/fat percentage chronic low-grade inflammation poor digestion Microbiome health detoxification and eliination thyroid and adrenal health High toxic load Chronic stress disrupted sleep Nutritional deficincies - B vitamins, Mg, Zn
List ways which can support hormone balancing from a Naturopathic perspective;
avoid; processed and microwaved foods stimulants refined sugars table salt artifical sweeteners cow's dairy Focus on; local, seasonal, while, fresh and organic foods - vegetables, fruit, legumes, whole grains, nuts, seeds, water, herbal teas, oily fish and meat Make sure food combining principles are followed Consider energetics Appropriate digestion - chew foods well, keep fluids away from meals, avoid snacking
List ways to imrpove blood glucose and weight management;
avoid processed foods
