Reproductive Flashcards
Describe the HPO axis and relevant hormones
Hypothalamic-Pituitary-Ovarian axis. GnRH stimulated LH & FSH which in turn support folicle development, ovulation, corpus luteum maintenance and production of Oest, Prog, Inhibin.
What impact does raised oest & test have of HPO hormones?
exert negative feedback over LH, FSH
Describe pregnenolone
Pregnenolone is a cholesterol synthesized hormone which is precursor to steroid hormones, DHEA, DHT, oestrodial, progesterone and cortisol. Its produced in steroegeneic tissues such as adrenals, gonads & brain. AI and neuroprotective.
What causes low prehnenolone and what are the s/s?
Advancing age (>30) and statin use. S/S Poor memory, concentration and attention, fatigue, dry skin, decreased libido
How do you support healthy pregnenolone levels?
Healthy fats - avocado, flax, chia, O3, walnut, D3&K2, B vits. Sleep, manage stress
Describe the pregnenolone steal theory
In states of prolonged stress cortisol uses some of the sex hormone pregnenolone - however no shared pool. Stress does suppresss LH & FSH however
Describe progesterone and conditions of progesterone imbalance
“Progesterone is produced by the corpus luteum after ovulation, by the adrenals and by the placenta in pregnancy. Potentiates calming effects of GABA - helping to relax smooth muscle. Supports bone health and mammary development.
Imbalance: Peri, PCOS, infertility”
What can low progesterone lead to, what are the causes, s/s and how can it be rebalanced?
“Lead to: Oest dom - imbalance of oest/prog
Causes: Chronic stress, synthetic progesterones xenoestrogens
S/S: irritability, mood swings, insomnia, higher risk breast cancer in perimenopause
Rebalance: Support oest detox (fibre, cruciferous, 3 balanced meals/ day, avoid alcohol, Mg, Vit C, B6, Zn, Agnus Castus, She Oak flower escence, box breathing”
What are oestrogens? How are the produced and exert their action? What is their functions?
“A group of steroid hormones including: oestrone E1, oestrodial, E2 and oestriol, E3
Produced via conversion of androgens via aromatase in ovaries, bone, breast and adipose tissue
Exert their effect by binding to specific oestrogen receptors: ERa, ERb & DPER. Oestrodial is most active during reproductive years
Functions: Repro tract development, menstrual cycle, promots cell proliferation (esp. breasts), glucose homeostasis, bone & CV health, immune robustness”
What is oest dominance? What conditions is it associated with?
“A state of excess oest which includes:
High oest v’s prog (including when oest is not excess)
Excesses of types of oest - incl due to poor detox/ elim
Excess oest induces overexpression of ERa & ERb receptors causing more pronounced effect
Associated with: PMS, breast/ ovarian/ endo cancer, birbocystic breasts, fibroids, endo, dysmenorrhea, infertility, miscarriages, perimenopause, insulin resistance, brain fog, thyroid dysfunction, anxiety & depression”
What is the aetiology of oest dom?
”* Poor detox and methylation
* Synthetic OCP/ HRT
* Xenoestrogens/ Endocrine disruptors
* Heavy metals
* Obesity
* Constipation
* Genetic mutations - COMT SNP
* Dysbiosis
* Chronic stress (LH/ FSH)”
Describe Phase 1 oestrogen biotransformation process
“CYP450 enzymes covert E1 into 3 metabolites:
2-OH-E - (CYP1A1) weakest most protective form. Metabolised via COMT - try to promote
4-OH-E (CYP1B1) procarcinogenic pathway - neutrallised via COMT - try to avoid overuse
16-OH-E (CYP34A) most proliferative and highest binding affinity for oestrogen receptors. Can be linked to oest dominant conditions - try to modulate”
Describe Phase 2 oestrogen detoxification pathway
“2-OH- E & 4-OH-E are methylated via COMT to be excreted in urine or bile
Poor methylation due to SNP or nutrient deficiency can increase 4-OH-E and 16-OH-E. Poor methylation increases conversion of 4-OH-E to quinones = increased ox stress and DNA damage - cancer risk
16-OH-E metabolised E3 which then undergoes sulphation. 2-OH-E and 4OH-E undergo sulphation and glucuronidation “
How do you support Phase 1 oest metabolism?
“I3C, cruciferous veg, AO’s, glutathione, turmeric, reservatrol, berries, rooibos tea, celery, healthy microbiome
AVOID: CYP450 inducers, paracetamol, smoking, grapefruit”
How do you support Phase 2 oest metabolism?
“Conjugation pathway support - cruciferous, alliums, AO’s - glutathione, Mg, methylation support, B6, B9, B12
AVOID: OCP, high alcohol use, high cortisol”
What is the oestrobolome and what action does it have?
A collection of microbes which can metabolise oestrogen. Beta-glucoronidase is produced by E-coli, Clostridium perfringes, bacteriodes fragilis and vulgatas. Beta-glucorindase can deconjugate oestrogen which allows it to re-enter circulation via enterohepatic circulation contributing to oest overload. A healthy gut produces the right amount whereas dysbiosis with low fibre and poor bile flow can increase chances of entero-toxigenic circulation.
What diseases can imbalances in beta-glucuronidase cause?
“Endometriosis (higher beta-g producing bacteria increases circulating oest causing oest dom)Ovarian, Breast, Endo cancer
PCOS - lower beta-g may promote androgen biosynthesis and reduce oest levels”
How do you maintain healthy beta-glucoronidase levels
“Maintain a healthy microbiome (pre/probiotics), fibre
If high - increase fibre, calcium D-glucarate, focus on glucaric acid rich foods such as mung bean sprouts, apple, cruciferous veg. Focus on lactobacilli and bifidobacterium, milk thistle. Consider 5 R protocol
If low - focus on commensal bacteria support (probiotics)”
Describe testosterone - where is it produced? What is converted to? What are its functions and imbalances?
“Testosterone is an essential hormone for women. It is produced in the ovaries and the adrenals. It is converted mainly to E1 and some DHT.
Functions: ovarian density, libido, bone strength, mood, cognition
Imbalances: Low testosterone - perimenopause (L-tyrosine can help), low libido, low mood and cognition.
High - seen in PCOS - can cause hirsuitism, acne, male patterned baldness. PCOS driven by insulin resistance”
Describe the DHT pathway
Testosterone is converted to DHT via 5a-reductase. The pathway is upreg by obesity, insulin and inflammation and is downreg by nettle tea, saw palmetto, green tea and Zn
Describe SHBC including impact of high and low levels
“Sex hormones are hydrophobic so require glycoproteins to travel around the blood. Synthesised by the liver they bind to oestrodial, testosterone and DHT. Only unbound hormones are active.
Low levels: increased active hormomes assc with hyperinsulinemia, metabolic syndrome, T2D, hypothyroidism, obesity
HIgh levels: assc with preg, hyperthyroidism, anorexia, liver disease”
Describe Prolactin, when prolactinaemaia occurs and the impact of high levels
“Prolactin is a hormone regulated by oestrogen and dopamine. Function: lactation, breast maturation, inhibits menstruation. Prolactinaemia seen in breast feeding and pregnancy but can happen in non-pregnant women
High levels can cause infertility, low libido and menstrual irregularities
Increased by high cortisol, circadian disruption and Vit D def”
What are endocrine di+A29srupting chemicals? (EDCs)
Exogenous chemicals that exert an effect on the production, release, transport, binding, function and metabolism of hormones. They include PCB’s BPA’s, phalates, pesticides, heavy metals, tap water and drugs.
What is EDC’s mechanism and what effects can they have?
EDC affect the production, secretion, binding and function of hormones producing a greater risk for hormonal cancers, hormonal disorders, cognitive impairement and obesity
What is the critical window of susceptibility for EDC’s
In utero, neonatally, childhood and puberty
Describe xenoestrogens
Xenoestrogens are a subcategory of EDC’s that have a similar structure to oest and can bind to oest receptor. They are pesticides, herbicides, phthlaltes,BPA’s, tap water. They bioaccumulate in fat cells of fish, animals and humans as we age. Main exposure if from food or drink although some may be inhaled or absorbed via skin
