Women's health Flashcards
Describe the HPO axis
The hypothalamic- pituitary-ovarian axis maintains hormonal balance in the female reproductive system.
-GnRH stimulates anterior pituitary to produce and release LH and FSH
= both support follicular development, ovulation, corpus luteum maintenance and production of progesterone, oestrogen and inhibin.
- Raises oestrogen and progesterone exerts negative feedback over FSH and LH secretion.
Describe phase 1 oestrogen ‘biotransformation’
CYP450 enzymes convert E1 into 1 of 3 metabolites:
1) 2-OH-E1. weakest, protective form. COMT deactivates 2-OHE1 to protective 2-MeOE1 metabolite
2) 4-OH-E1. Pro-carcinogenic metabolite neutralised by COMT into 4-MeOE1 metabolites. Excessive use of pathway is problematic
3) 16-alpha-OH-E1. Very active, highest binding affinity for oestrogen receptors with high proliferative effects. High levels associated with oestrogen dependent conditions
Describe phase 2 oestrogen metabolism
Happens through sulphation, methylation or glucuronidation pathways.
-2-OH-E and 4-OH-E undergo methylation via COMT to become less reactive and excreted. Can also undergo sulphation and glucuronidation
- 16-alpha-OH-E metabolises to E3, then undergoes sulphation
How can poor methylation occur and how does it impact oestrogen metabolism?
- Poor methylation can happen with a lack of key nutrients or a COMT SNP
- Can elevate levels of 4-OH-E and 16alpha-OH-E
- can increase conversion of 4-OH-E to quinones which can cause oxidative damage to DNA, increasing the risk of cancer.
How can you support phase 1 oestrogen metabolism?
-Support CYP3A4, CYP1A1 and CYP1B1 by including I3C, cruciferous veg, antioxidants like glutathione can neutralise quinones, turmeric, resveratrol, berries, roobios tea and celery.
- Avoid CYP450 inducers: paracetamol, PCBs, smoking, grapefruit
How can you support phase 2 oestrogen metabolism?
Include conjugation pathway support- cruciferous vegetables , allium vegetables, magnesium, antioxidants inc. glutathione
Methylation support (eg folate, B12, B6, SAMe, choline
Avoid OCP, high alcohol, high cortisol, mould exposure
What is beta- glucuronidase and which bacteria produce it?
An enzyme which deconjugates (reactivates) oestrogens that were already conjugated for elimination, these can be reabsorbed back into circulation creating an increased oestrogen load in the body.
- produced by: bacteroides fragilis, bacteroides vulgatus, escherichia coli , clostridium perfringens- ‘Oestrobolome’
Why can an improvement of GIT function help with oestrogenic load?
- A dysbiotic microbiome coupled with low fibre intake and poor bile flow can increase the chances of the enterotoxigenic circulation
- A healthy gut produces the right amount of beta-glucuronidase to maintain oestrogen homeostasis
What is SHBG and what is its function?
Sex hormones are not water soluble so they need to be transported in blood bound to sex hormone binding globulin, a glycoprotein synthesised by the liver
- binds to oestradiol, testosterone and DHT, only unbound hormones are biologically active.
When would you see SHBG inbalances?
Low levels: higher circulating active levels of these hormones found in:
- hyperinsulinemia, obesity, metabolic syndrome, T2DM, PCOS, hypothyroidism
- High levels : Anorexia, pregnancy, androgen deficiency, hyperthyroidism, liver disease
Describe the pathophysiology of Endometriosis and discuss signs and symptoms
Endometriosis happens when endometrial tissue is found outside of the uterine cavity eg fallopian tubes, ovaries , rectum and pouch of douglas and sometimes outside of the pelvic area eg lungs. The tissue responds to the normal hormonal cycle of the body, causing it to grow, break down and bleed but the blood has no exit point, leading to pain, inflammation, scarring and adhesions. Sometimes scarring can happen to ligaments that suspend organs and this causes pain on movement.
- Dysmenorrhoea, dyspareunia, heavy menstrual bleeding, chronic pelvic and lower back pain, cyclical GI problems such as painful bowel movements, anxiety and depression.
- Complications can include infertility, ovarian cancer and bowel obstruction
Discuss causes, risk factors and 4 theories behind endometriosis?
Theories include:
- Immune dysfunction. An altered immune surveillance in the pelvic area can lead to endometrial cells not being recognised and destroyed outside of the uterus. Inflammatory mediators are elevated
- Retrograde menstruation- endometrial cells flow back from uterine cavity- generally disregarded
- Surgical scar implantation- endometrial cells may attach to a surgical incision after surgery
- Metaplasia- cells found in pelvic or abdominal area change into endometrial like-cells
- Endometrial cell transport- transported via lymphatics
Causes and risk factors:
- prolonged oestrogen exposure including nulliparity, early menarche and OCP
- Poor oestrogen detoxification and clearance
- Obesity- increased inflammation and aromatase activity
- Hereditary
- Low vegetable and fibre intake
- Environmental toxin exposure including PCBs and dioxins from plastics
- Compromised mucosal barrier leading to high circulating LPS driving inflammation and immune overactivity
- Microbial infections can be a trigger- EBV, HSV and bacterial infections eg E-Coli
- High histamine drives inflammation and angiogenesis
Discuss causes, risk factors and 4 theories behind endometriosis?
Theories include:
- Immune dysfunction. An altered immune surveillance in the pelvic area can lead to endometrial cells not being recognised and destroyed outside of the uterus. Inflammatory mediators are elevated
- Retrograde menstruation- endometrial cells flow back from uterine cavity- generally disregarded
- Surgical scar implantation- endometrial cells may attach to a surgical incision after surgery
- Metaplasia- cells found in pelvic or abdominal area change into endometrial like-cells
- Endometrial cell transport- transported via lymphatics
Causes and risk factors:
- prolonged oestrogen exposure including nulliparity, early menarche and OCP
- Poor oestrogen detoxification and clearance
- Obesity- increased inflammation and aromatase activity
- Hereditary
- Low vegetable and fibre intake
- Environmental toxin exposure including PCBs and dioxins from plastics
- Compromised mucosal barrier leading to high circulating LPS driving inflammation and immune overactivity
- Microbial infections can be a trigger- EBV, HSV and bacterial infections eg E-Coli
- High histamine drives inflammation and angiogenesis
What is the two way process of endometriosis, histamine and oestrogen?
- Endometriosis is associated with a high O:P ratio, mast cells contain oestrogen and progesterone receptors, oestrogen can trigger histamine degranulation, and overrides progesterone
- Histamine itself is also able to induce ovarian E2 synthesis.
High histamine drives inflammation and angiogenesis, hence endometriosis proliferation.
Describe the vasomotor (VMS) symptoms of menopause and why they occur
Hot flushes/ flashes characterised by sudden intense sensation of warmth (Face, neck, chest) often followed by a chill .
Oestrogen is a neuromodulator - changes in levels can impact areas involved in temperature homeostasis
- can be negatively affected by obesity, smoking, alcohol, spicy foods, caffeine, stress
Name 5 signs/ symptoms of menopause other that VMS
1) Weight gain and obesity- genetic and hormonal factors, poor nutrition, low activity
2) Sleep disturbance- night sweats and mood changes contribute
3) Genitourinary symptoms- dysuria, dyspareunia, dry/sore vagina
4) Mood disturbances- irritability, aggressiveness, mood swings, anxiety and depression
5) Hair loss
6) Low libido
7) joint and muscle pains
What are the 3 stages of menopause?
1) Perimenopause- 45-50, Irregular menstrual cycles, fluctuating O:P ratio, ovarian follicular activity fails. Transition phase of declining reproductive hormones
2) Menopause- 50-55 After 12 months of amenorrhoea. Low oestrogen, persistently high FSH >30iu/L
3) Post menopause >55 worst hormonal symptoms subsided
Name 4 herbs that can help with menopausal symptoms
1) Black Cohosh - oestrogen modulating activity, helps with hot flushes
2) Shatavari: Reproductive tonic, testosterone like effects, improves vaginal dryness
3) Valerian, passionflower, chamomile (nervines)
4) Liquorice root: Mildly oestrogenic
5) Maca: Improves libido, sleep, mood and hot flushes
6) Sage can help with hot flushes
Name 4 strategies to help alleviate VMS symptoms of menopause
1) Avoid smoking, alcohol and caffeine
2) reduce weight and balance blood sugar
3) Increase phytoestrogen foods and herbs eg flaxseed, fermented soy, sage
4) Evening primrose oil (GLA content)
5 natural approaches to relieve the symptoms of menopause?
1) Manage stress- yoga, L-theanine, B vitamins, magnesium, ashwagandha
2) Support bone density- calcium, C, D, K2, magnesium, black cohosh
3) Choose more plant than animal based proteins, eat organic to reduce endocrine disruption
4) Include a phytoestrogen source daily
5) increase antioxidants and fibre through fruit and veg
6) Improve sleep- remove stimulants, use passionflower valerian and magnesium
What is an endocrine disruptor and how does it work? Give examples
Endocrine disrupting chemicals (EDCs) are exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of bodily hormones.
They can alter hormone receptor signalling and sex hormone production, secretion and metabolism. Induce oxidative stress and mitochondrial damage
- BPAs- plastic bottles/ packaging
- PCBs/ phthylates eg beauty products
- Heavy metals- lead/arsenic, mercury
- pesticides , herbicides
- dioxins
- drugs eg NSAIDS
- Tap water (contain many of above)
What is a xenoestrogen? Give examples
A subcategory of endocrine disrupting chemicals that are structurally similar to oestrogen and can bind to oestrogen receptor sites with potentially hazardous outcomes.
- pesticides, herbicides, dioxins, parabens, BPAs, phthalates, preservatives, tap water (chlorine/ pharmaceuticals)
- Can build up in the fat of meat/fish, dairy products. Exposure by food and drink and absorbing through skin.
How and why does dairy disrupt hormones?
Commercial dairy is mostly derived from pregnant cows with increased hormone concentrations
-E1, E2, and E3 steroid hormones are found in all milks , adding to the overall oestrogen load and should be avoided in imbalances
- Dairy products contain other hormones such as IGF, PCBs, dioxins and insecticides
Endocrine disruptors can contribute to which adverse health effects?
Increased risk of cancer
hormonal disorders: PCOS, early puberty
Infertility
Cognitive deficits
obesity
What is a phytoestrogen and how do they function?
Naturally occuring plant compounds structurally similar 17beta- oestradiol (E2)
- considered oestrogen modulators
- produce a weak anti- oestrogenic effect in the presence of high endogenous oestrogen, reduces circulating bioavailable E2
- produces a weakly oestrogenic effect in the presence of low endogenous oestrogen
Which plant foods do phytoestrogens naturally occur in ?
1) Flavonoids found in soybeans, legumes, lentils and chickpeas
2) Lignans found in most cereals, linseed, fruit and vegetables
3) Flavones found in parsley, thyme, celery and chamomile tea
What can account for large differences in the effects of phytoestrogens among individuals? What might you use instead?
Differences in microbiome. A healthy microbiome is needed for the fermentation of phytoestrogens by intestinal bacteria. Any variation from a healthy microbiome will reduce the benefits from these foods and so tinctures/ teas may be more appropriate eg
- Black cohosh
- Agnus Castus
- Red Clover
- Dong quai