Women's Health Flashcards
What axis maintains hormonal balance within the female reproductive system?
HPO (or HPG) axis
Hypothalamic-pituitary-ovarian (or gonadal)
Key female hormones and their roles
GNRH - stimulates anterior pituitary to produce and release LH and FSH
LH and FHS - support follicle development, ovulation, corpus luteum maintenance, progesterone, oestrogen and inhibin production
Progesterone and oestrogen regulate target organs e.g uterus, mammary glands
What is the impact of raised oestrogen and testosterone on FSH and LH?
Negative feedback loop to the hyperthalamus.
How is pregnenolone synthesised and what is it a precursor to (x6)?
Pregnenolone - grandmother / base hormone
Synthesised from cholesterol in steroidogenic tissues (adrenans, gonads and brain) by CYP11A1
Precursor to:
DHEA (dehydroepiandrosterone)
Testosterone
DHT (dihydrotestosterone)
Oestradiol
Progesterone
Cortisol
What causes low pregnenolone and what are the symptoms?
(similar to menopause / hypothyroid)
Advancing age and statins
Poor memory
Declining concentration and attention
Fatigue
Dry Skin
Joint and muscle pain
Decreased libido
How to support healthy pregnenolone?
Think Chris Newbold
Think good fats, B vits, D and adaptogens
Avocado
Flax
Chia seeds
EVOO
Walnuts
B vitamins
Vit K
BD
Maca
rhodiola
Key points about ‘pregnenolone steal theory’
High stress increases = more pregnenolone for cortisol reducing sex hormones
However,
- no giant pregnenolone pool
- Stress down regulates LH and FSH to reduce ovulation
Progesterone synthesis & functions
Made in corpus luteum after ovulation, in the adrenals and placenta during pregnancy
Lack of ovulation = lack of progesterone
Functions:
Maintains the endometrium for pregnancy
Increased cervical mucus
Promotes GABA by modulating receptors to relax smooth muscle
Bone health
Mammary development
What causes progesterone imbalance or low progesterone?
Imbalance: perimenopause, PCOS and infertility
Low: stress, synthetic progesterone (OCP and some MHT (menopause hormone therapy, updated term for HRT)), xenoestrogens.
Signs and symptoms of low progesterone and how to balance
(low GABA symptoms) Irritability, mood swings, insomnia, increases breast cancer risk
Balance - support oestrogen detox (fibre, balanced meals, avoid snacking and alcohol)
Magnesium, vitamin C, B6, Zn, vitex agnus castus, Australian Bush Flower essence She Oak, exercise and box breathing.
What are the three types of oestrogen?
Oestrone (E1) - post menopause
Oestradiol (E2) - most active during reproductive years
Oestriol (E3) - produced in pregnancy by placenta
How is oestrogen produced and what receptors does it bind to?
Conversion of androgens via aromatase (aromatisation) in the ovaries, bone, breasts and adipose tissue.
note: tamoxifen is an aromatase inhibitor.
Binds to ER alpha
ER beta
GPER (oestradiol) E2
Key functions of oestrogen?
Reproductive tract development
Menstrual cycle
Cell proliferation (esp breasts)
glucose homeostasis
Immune, bone and cardiovascular health
What is oestrogen dominance and how is it characterised?
Excess oestrogenic activity
Elevated oestrogen to progesterone (so oestrogen can be normal)
Elevated oestrogen due to poor detox/elimination
Overexpression of alpha and beta receptors
What conditions is oestrogen dominance associated with?
Fibroids
Endometriosis
PMS
Fibrocystic breasts
Breast/ovarian and endometrial cancers
Insulin resistance
Thyroid dysfunction
Brain fog
Anxiety and depression
Factors that can cause oestrogen dominance (aetiology on the slide)
Synthetic hormones - HRT/MHT OCP
Xenoestrogens
Heavy metals
Obesity - increased aromatisation of testosterone to oestrogen
Poor liver detox / methylation
Constipation
Genetic - COMP SNP
Dysbiosis
Stress (downregulates LH and FSH)
What 3 metabolites is E1 converted to by CYP450 enzymes?
PHASE 1 Oestrogen ‘biotransformation’
2-OH-E (CYP1A1) - weakest, protective form.
4-OH-E (CYP1B1) - pro-carcinogenic / neutralised by COMT
16a-OH-E (CYP3a4) - highest binding affinity / high proliferative effect. High levels associated with oestrogen dependent conditions (breast cancer/fibroids
More detail on slide 11.
Describe Phase II oestrogen metabolism?
2-OH-E and 4-OH-E - methylation via COMT to become less reactive
undergo sulphation and *glucuronidation”
Excreted in urine or bile.
16a-OH-E - metabolises to E3 then sulphation
What SNPs can impact Phase II oestrogen metabolism
Methylation SNPs - COMT SNP
Poor methylation increases conversion of 4-OH-E to quiones - oxidative damage to DNA.
How do you support phase I oestrogen metabolism?
CYP3A4, CYP1A1, CYP1B1
I3C
Cruciferous veg
Antioxidants - turmeric, resveratrol, berries, tea, celery
Glutathione - also neuralises reactive quinones)
Support microbiome
AVOID
CYP450 inducers = paracetamol, PCBs, smoking, grapefruit
How do you support phase II oestrogen metabolism?
Conjugation pathway support - cruciferous
Alliums
Magnesium
Antioxidants
Methylation support - folate, B12, SAMe, Choline
AVOID
OCP, high alcohol, high cortisol, mould
What is the oestrobolome and what bacteria can it produce?
A collection of microbes that can metabolise oestrogens.
These bacteria produce beta-glucuronidase, bacteroides fragilis, bacteroides vulgatus, escherichia coli, clostridium perfringens
What is beta-glucuronidase and what is its role in oestrogen metaboism?
A enzyme which deconjugates oestrogens that were already conjugated for elimination.
These oestrogens can be reabsorbed via enterohepatic circulation
A healthy gut produces the right amount of beta-glucuronidase to maintain oestrogen homeostasis. Too low or too high can be a problem.
What other factors also negatively impact the oestrobolome?
Dysbiotic microbiome
Low fibre
Poor bile flow
What conditions are imbalances in oestrobolome associated with?
Endometriosis - may have larger numbers of beta-glucuronidase producing bacteria
PCOS - lower beta-glucuronidase
Also - oestrogen associated cancers
How do you maintain healthy beta-glucuronidase levels?
Optimise the micro-biome - probiotics / prebiotics
If high - increase fibre,
calcium D-glucarate (inhibitor)
Glucaric acid-rich foods - mung bean sprouts, apples, cruciferous veg, milk thistle
Consider 5R protocal
If low - focus on commensal support e.g. probiotics
How is testosterone produced and what are its key functions in women?
In the ovaries and adrenal cortex
Converted to E2 via aromatase and DHT
Functions: ovarian density, libido, bone strength, mood, cognition.
What is the impact of androgen dominance in PCOS?
Anovulation
hirsutism
Acne vulgaris
Driven by insulin resistance
What is the impact of 5a-reductase on testosterone? What upregulates and down regulates?
It converts testosterone into more potent DHT
Upregulated - insulin, inflammation, obesity
Downregulated: nettle (esp root), saw palmetto, lycopene, zinc (shortened list)
What is SHBG role, what is it and where is it produced?
Sex homones are not water-soluble so need to be transported in blood bound to SHBG
Glycoprotein synthesised by the liver
When do you see lower and high levels of SHBG?
Lower - higher circulating free/ active hormone levels - hyperinsulinemia, obesity, metabolic syndrome, T2DM, hypothyroidism, PCOS
High - anorexia, pregnancy, androgen deficiency, hyperthyroidism
Which hormones control prolactin and what are its functions?
Oestrogen (increases prolactin) and dopamine (reduces prolactin)
Functions:
Lactation
Breast maturation
Inhibits menstruation
What is increased prolactin associated with? (think what happens post childbirth)
Infertility
Menstrual irregularities
Low libido
Breast pain and vaginal dryness
Hyperprolactinaemia - occurs naturally in pregnancy and lactation but can also occur in non-pregnant women.
What increases prolactin?
Cortisol
Pituitary tumours
Circadian disruption
Renal failure
Vitamin D deficiency
Dopamine antagonist drugs (domperidone)
What are endocrine disrupting chemicals (EDC) and give some examples?
Exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of hormones
Examples: BPA
Phthalates
Heavy metals
Perticides
Herbicides
Fire retardants
Some drugs (NSAIDs)
Tap water (contains many of the above)
Mechanism for endocrine disrupting chemicals, what health effects are they linked to and what are the critical windows of susceptibility?
Alter hormone receptor signalling, sex hormone production, secretion and metabolism
Induce oxidative stress, mitochondrial damage and epigentic alterations
Increased risk of: cancer, PCOS, early puberty, infertility, cognitive deficits.
Window of susceptibility - in utero, neonatally, childhood and puberty.
What are xenoestrongers, where to they bioaccumulate and typical sources of exposure?
Sub-category of EDC (endocrine disrupting chemicals), structurally similar to oestrogen that can bind to oestrogen receptors.
E.g. pesticides, herbicides, dioxins, parabens, BPAs, tap water (chlorine, pharmaceuticals)
Build up in fat - human fat cells or meat/fish and dairy
Exposure - mainly food. Small amounts inhaled, absorbed through skin or mucus membranes.
Considerations/concerns with dairy milk?
From pregnant cows
E1, E2 and E3 found in milk - higher in whole milk.
Plus other hormones - IGF, PCBs, dioxins, insecticides, bovine growth hormone (growth hormones banned in EU/UK)
Add to overall oestrogen load and should be avoided in hormonal imbalances.
What are phytoestrogens and their key benefits?
Plant compounds structurally similar to 17b-oestradiol (E2) - oestrogen-modulators.
High oestrogen - weak anti-oestrogenic effect by reducing circulating bioavailable E2
Low oestrogen- weakly oestrogenic effect.
Disrupt aromatase
Benefits: lower menopause symptoms, CVD, obesity, metabolic syndrome, T2DM, breast cancer.
3 key types of phytoestrogens and plant foods they are found in
Flavonoids (isoflavones, genisten, daidzein) - soybeans, legumes, lentils, chickpeas
