7. WOMEN'S HEALTH Flashcards
This module covers: • Sex hormones. • Endocrine disruptors. • Phytoestrogens. • Hormone balancing approach. • Premenstrual syndrome (PMS). • PCOS. • Endometriosis. • Fibrocystic breasts. • Uterine fibroids. • Menopause.
What does the hypothalamic-pituitary-ovarian (HPO) axis do?
Maintains hormonal balance within the female reproductive system
What does GnRH stimulate to produce and release what hormones?
GnRH stimulates the anterior pituitary to produce and release LH and FSH
What do LH and FSH do?
support follicle development, ovulation, corpus luteum maintenance and production of progesterone, oestrogen and inhibin
What is pregnenolone?
And what is it a precursor of?
- A hormone synthesised from cholesterol in steroidgenic tissues such as adrenal gland, gonads and the brain
- synthesised by mitochondrial enzyme CYP11A1.
- Anti-inflammatory and neuroprotective.
- precursor of DHEA, testosterone, DHT, oestradiol, progesterone and cortisol
What are the causes low levels of pregnenolone and what are the symptoms?
Advanced age (>30) and statin use.
- Poor memory
- Declining concentration and attention
- Fatigue
- Dry skin, joint and muscle pain
- Decreased libido
How to support pregnenolone levels
- Improve sleep
- Manage stress
- Healthy fats: Avocado, flax and chia seeds, olive oil, walnuts, B vits, Vit K and D3.
- DHEA balance: maca, rhodiola, magnolia, perilla oil, tribulus.
What is the pregnenolone steal theory?
High stress increases the use of pregnenolone for cortisol production, reducing amount of pregnenolone for sex hormone production
What affect does cortisol have on LH and FSH?
downregulation, reduces ovulation
Where is progesterone produced?
- In the corpus luteum after ovulation
- In the adrenal cortex and by the placenta during pregnancy
(Lack of ovulation=lack of progesterone!)
Functions of progesterone
- Maintains endometrium for implantation and pregnancy
- Increases cervical mucus
- Progesterone metabolites potentiate inhibitory actions of GABA by modulating receptors; helps relax smooth muscle
- Support bone health and mammary development
Low progesterone leads to____ ______.
What are the causes of low progesterone?
Oestrogen dominance.
chronic stress, synthetic progesterones, xenoestrogens
Signs and symptoms of low progesterone
irritability, mood swings and insomnia.
Also higher risk of breast cancer in premenopausal women
How to balance progesterone
Support oestrogen detoxification, increase fibre; 3 balanced meals/day, no snacking, avoid alcohol until balanced, Mg, vit C and B6, Zn. Agnus castus, Aus bush flower essence (she oak), exercise and box breathing (where accompanied by anxiety).
Name the three groups of oestrogen
Oestrone (E1), oestrodiol (E2) and oestriol (E3)
How is oestrogen produced and where?
By conversion of androgens via aromatase (aromatisation) in ovaries, bone, breast and adipose tissue
How does oestrogens exert their actions?
Binds to specific oestrogen receptors: ERa, ERb, and GPER.
Excess oestrogen induces an overexpression of ERa and ERb.
Functions of oestrogen
- reproductive tract development
- menstrual cycle
- promotes cell proliferation esp breasts
- glucose homeostasis
- immune robustness
- bone and CV health
What is oestrogen dominance associated with?
Fibroids, endometriosis, PMS, fibrocystic breasts, dysmenorrhoea, infertility, miscarriages, perimenopuase, breast/ovarian/endometrial cancers, IR, thyroid dysfunction, brain fog, anxiety, depression
Causes
Oestrogen dominance aetiology
- HRT and OCP
- xenoestrogens
- heavy metals
- obesity
- poor liver detoxification and methylation
- constipation
- genetic mutations (COMT SNP)
- intestinal dysbiosis
- chronic stress
How does obesity contribute to oestrogen dominance?
increased aromatisation of testosterone to oestrogen
CYP450 enzymes convert E1 into one of three metabolites. Describe 4-OH-E (CYP1B1) metabolite in phase I oestrogen ‘biotransformation’
a pro-carcinogenic oestrogen metabolite neautrilsed by COMT into protective 4-MeOE1 metabolites. Oveuse in this pathway=problematic
CYP450 enzymes convert E1 into one of three metabolites. Describe 2-OH-E (CYP1A1) metabolite in phase I oestrogen ‘biotransformation’
Weakest, protective form. COMT deactivates 2-OHE1 to protective 2-MeOE1 metabolite
CYP450 enzymes convert E1 into one of three metabolites. Describe 16a-OH-E (CYP3A4) metabolite in phase I oestrogen ‘biotransformation’
Highest binding affinity for oestrogen receptors with high proliferative effects.
High levels is associated with higher risk of oestrogen dependent conditions
2-OH-E and 4-OH-E undergo methylation via what gene to become less active?
COMT
In phase 2 oestrogen metabolism what may cause 4-OH-E and 16-OH-E levels to elevate?
Compromised methylation
(e.g., due to lack of key nutrients or COMT SNP)
Poor methylation increases the conversion of 4-OH-E to _____ which can cause oxidative damage to DNA
quinones
In Phase 2 oestrogen metabolism 16a-OH-E metabolises to _____ and undergoes ______
E3, sulphation
In phase 2 oestrogen metabolism 2-OH-E and 4-OH-E undergo methylation via COMT and also undergoes _____ and _____
sulphation and glucoronidation
Supporting phase I oestrogen metabolism
- Support CYP3A4, CYP1A1, CYP1B1: I3C, cruciferous veg, antioixdants, glutathione (also neutralises reactive quinone species), turmeric, resveratrol, berries, rooibos tea and celery.
- Support gut microbiome.
- Avoid CYP450 inducers: paracetamol, PCBs, smoking, grapefruit
Support phase II oestrogen metabolism
Include conjugation pathway support - cruciferous veg, allium veg, Mg, antioxidants, glutathione.
Methylation support - folate, B12, B6, SAMe, choline
Avoid - OCP, high alcohol, high cortisol, mould exposure
What is the oestrobolome and what do they produce?
A collection of microbes capable of metabolising oestrogens.
They produce beta-glucuronidase.
What does beta-glucuronidase do?
It is an enzyme which deconjugates (reactivates) oestrogen that has already been conjugated for elimination. These deconjugated oestrogens can be reabsorbed via the enterohepatic circulation - increasing oestrogen load in the body.
Imbalance of beta-glucuronidase can promote conditions such as…
- endometriosis
- breast cancer
- ovarian cancer
- PCOS
- endometrial cancer
- endometrial hyperplasia
advice for high and low levels
How to maintain healthy beta-glucuronidase levels
Optimise the microbiome (probiotics, prebiotics)
if high, increase:
- fibre
- calcium D-glucarate (inhibitor)
- glucaric acid-rich foods e.g., mung bean sprouts, apples, cruciferous veg, milk thistle, lactobacilli and bifidum bacteria
Consider 5R protocol.
if low:
focus on commensal support e.g., probiotics
Testosterone:
- Produced
- Converted to
- Functions
- in the ovaries and adrenal cortex
- E2 via aromatase (most testosterone) and DHT
- ovarian density, libido, bone strength, mood, cognition
5a-Reductase:
- Function
- Upregulated by
- Downregulated by
- Function: converts testosterone into more potent form (DHT)
- Upregulated by: Insulin, inflammation, obesity.
- Downregulated by: Nettle, saw palmetto, lycopene, turmeric, green tea, zinc, GLA and EPA
Sex hormone binding globulin (SHBG):
- Produced by
- Function
- A glycoprotein synthesised by the liver
- Binds to oestradiol, testosterone, DHT (only unbound hormones are biologically active)
SHBG imbalance:
- Lower levels
- High levels
- Lower levels = higher ciculating free/active levels of oestradiol, testosterone, DHT. Associated with hyperinsulinemia, obesity, metabolic syndrome, T2DM, hypothyroidism, PCOS.
- High levels: Seen in anorexia, pregnancy, androgen deficiency, hyperthyroidism, liver disease
Prolactin:
- controlled by
- Functions
- Increased by
- Oestrogen and dopamine
- Lactation, breast maturation, inhibits menstruation
- High cortisol (stress), pituitary tumours, circadian distruption, renal failure, vit D deficiency, drugs e.g., domperidone