Women's health Flashcards

1
Q

Describe the HPO axis

A

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.

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2
Q

Describe phase 1 oestrogen ‘biotransformation’

A

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

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3
Q

Describe phase 2 oestrogen metabolism

A

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

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4
Q

How can poor methylation occur and how does it impact oestrogen metabolism?

A
  • 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.
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5
Q

How can you support phase 1 oestrogen metabolism?

A

-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

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6
Q

How can you support phase 2 oestrogen metabolism?

A

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

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7
Q

What is beta- glucuronidase and which bacteria produce it?

A

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’

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8
Q

Why can an improvement of GIT function help with oestrogenic load?

A
  • 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
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9
Q

What is SHBG and what is its function?

A

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.

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10
Q

When would you see SHBG inbalances?

A

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

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11
Q

Describe the pathophysiology of Endometriosis and discuss signs and symptoms

A

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

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12
Q

Discuss causes, risk factors and 4 theories behind endometriosis?

A

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

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12
Q

Discuss causes, risk factors and 4 theories behind endometriosis?

A

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

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13
Q

What is the two way process of endometriosis, histamine and oestrogen?

A
  • 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.
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14
Q

Describe the vasomotor (VMS) symptoms of menopause and why they occur

A

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

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15
Q

Name 5 signs/ symptoms of menopause other that VMS

A

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

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16
Q

What are the 3 stages of menopause?

A

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

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17
Q

Name 4 herbs that can help with menopausal symptoms

A

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

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18
Q

Name 4 strategies to help alleviate VMS symptoms of menopause

A

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)

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19
Q

5 natural approaches to relieve the symptoms of menopause?

A

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

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20
Q

What is an endocrine disruptor and how does it work? Give examples

A

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)
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21
Q

What is a xenoestrogen? Give examples

A

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.

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22
Q

How and why does dairy disrupt hormones?

A

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

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23
Q

Endocrine disruptors can contribute to which adverse health effects?

A

Increased risk of cancer
hormonal disorders: PCOS, early puberty
Infertility
Cognitive deficits
obesity

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24
Q

What is a phytoestrogen and how do they function?

A

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

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25
Q

Which plant foods do phytoestrogens naturally occur in ?

A

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

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26
Q

What can account for large differences in the effects of phytoestrogens among individuals? What might you use instead?

A

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

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27
Q

Describe a hormone balancing protocol

A

1) Improve blood glucose and weight management
- avoid processed foods refined sugars and snacking
- Consider time restricted feeding
2) Reduce inflammation
- Reduce proinflammatory foods such as dairy, alcohol, sugar, processed and fried foods, arachidonic acid rich foods
- Increase colourful antioxidant rich foods, oily fish, nuts and seeds
3) Support digestion and elimination
- fat digestion for cholesterol synthesis and absorption of fat soluble nutrients (bitter foods, lecithin)
- Increase dietary fibre and ensure hydration
4) build the microbiome
- consider a 5R approach if applicable
- Prebiotic rich foods- onion, garlic, artichoke
- probiotic foods (kefir, kimchi, sauerkraut)
5) Support thyroid hormone synthesis and metabolism:
- if indicated selenium, iodine, zinc, tyrosine etc
6) Support detoxification- reduce toxic load
- environmental cleanse: No smoking, alcohol, caffeine, dairy, cleaning products, plastics, tap water etc
- support phase 1 and 2 pathways (antioxidant- rich foods, cruciferous veg) methylation support- B6, B12, folate
7) Manage stress levels, sleep wake cycle
- keep to a routine with a regular sleeping pattern
- limit evening exposure to electronics
- minimise stimulants
- use relaxation techniques (deep breathing, journaling etc)

28
Q

Describe 5 mechanisms of action to balance hormones naturally, and which nutrients would you use to do this?

A

1) Promote hydroxylation to 2-OH over 4-OH and 16-alpha-OH=
cruciferous veg, indole 3 carbinol, rosemary, isoflavones, omega-3 fats
2) Increase circulating levels of SHBG=
fibre, flaxseeds, isoflavones, nettle root
3) Inhibit the activity of aromatase=
Flaxseed/ phytoestrogens, flavonoids, green tea, kettle root, calcium, magnesium, zinc, vitamin D
4) Promote the methylation of 2-OH and 4-OH:
Folate, B2, B6, B12, TMG, magnesium
5) Inhibit the activity of beta- glucuronidase=
Fibre, probiotics, calcium d-glucarate
6) Inhibit the action of 5-alpha reductase enzyme, reducing conversion to DHT=
Nettle, Saw palmetto, lycopene, curcum,in, green tea, zinc, GLA, EPA

29
Q

Describe the pathophysiology of PCOS

A

PCOS is an endocrine and metabolic pathology , characterised by two main things:
1) increased amplitude and pulses of LH= high androgens
This reduced FSH: LH ratio reduces aromatisation of androgens to oestrogens which results in anovulation , and more androgen’s are produced from the ovarian theca cell.
2) insulin resistance - most prominent mediator
- this decreases hepatic SHBG synthesis, resulting in more active circulating testosterone and DHT.
- also increases ovarian theca cell androgen production and adrenal androgen secretion .
IR leads to leptin resistance and weight gain, making symptoms worse

30
Q

What are some signs and symptoms of PCOS?

A

Characterised by :
Ovarian dysfunction, poly cystic ovaries and hyperandrogenism
Amennorrhea, weight gain , thin hair, acne, hirsutism

31
Q

How could you decrease insulin resistance and glucose intolerance to lower androgens in PCOS ?

A

1) chromium picolinate 200-400mg to increase tyrosine kinase activity
2) quality protein with each meal
3) cinnamon - 500mg x 3 daily. Increases insulin sensitivity, lowers testosterone and lowers IGF-1 levels
4) Berberine - insulin sensitiser - 500mg x3 daily
5) Alpha lipoic Acid 600-1200 mg/ day
Antioxidant , decreases insulin resistance and increases glucose metabolism
6) limit snacking and trans / saturated fats

32
Q

How could you promote optimal liver detoxification and intestinal oestrone clearance in PCOS?

A

1) alpha lipoic acid 600-1200mg antioxidant
2) seed cycling 1-14 pumpkin and flaxseed 1tbsp each. 15-28 sunflower and sesame 1 tsp each for hormone balance
3) cruciferous veg 1 cup a day
4) fibre 30-45g day elimination support
5) prebiotics, fermented foods and probiotics, polyphenols
6) N-aceytl cysteine
7) B complex
8) magnesium glycinate 200-500mg day
9) limit alcohol/ caffeine

33
Q

In PCOS , how could you support the HPA axis , to reduce stress and cortisol levels ?

A

1) calming nervine teas - chamomile, passionflower and lemon balm
2) limit caffeine
3) promote exercise - can increase SHBG
4) adrenal adaptogens eg ashwaganda
5) improve sleep hygiene
6) magnesium glycinate 200-500mg

34
Q

What are the 5 core approaches to treating PCOS?

A

1) decrease insulin resistance and glucose intolerance to lower androgens
2) decrease central obesity
3) promote optimal liver detoxification and intestinal oestrone clearance
4) decrease oxidative stress and inflammation
5) support HPA axis to reduce stress and cortisol levels

35
Q

Name 3 nutrients that may to directly lower androgens in PCOS

A

1) Myoinositol (MI) : improves insulin sensitivity to support healthy body weight , lowers LH and androgens . Increases SHBG to reduce bioavailable testosterone. 4g / day while grains beans, nuts, fruits
2) liquorice may inhibit conversion of androstenedione to testosterone
3) Saw Palmetto- inhibits 5alpha reductase and conversion of androstenedione to testosterone

36
Q

6 causes/ risk factors of PCOS ?

A

1) chronic low grade inflammation
- diet- high refined carbs, processed trans fats, low 3:6 ratio
- metabolic endotoxaemia (permeability / mucosal degradation)
- obesity and lack of exercise
2) smoking -linked to hyperandrogens
3) gut dysbiosis- altered microbiota and diversity in PCOS
- alters hormone secretions , gut brain mediators, inflammatory pathways
4) obesity - increases insulin resistance and inflammatory adipokines
5) HPA axis dysfunction
Adrenaline and cortisol elevated = insulin resistance which stimulates DHEA and androstenedione which can convert to testosterone
6) genetics - polymorphisms in CYP11 and CYP17
7) vitamin d deficiency
Needed to convert cholesterol to pregnalone, supplementation can increase insulin sensitivity

37
Q

What is PMS- A, and how can you support naturally?

A

Pre menstrual syndrome, subtype anxiety
1) B6- cofactor for GABA , serotonin and dopamine
2) green tea- L Theanine, calming
3)Magnesium glycinate - 200-400mg for GABA and serotonin synthesis
4) address stress and optimise sleep
5) remove alcohol and caffeine
6) St Johns Wort -MAO monoamine oxidase inhibitor, GABA antagonist
7) support oestrogen detox and elimination to balance O:P ratio:
Increase fibre, cruciferous veg, broccoli sprouts, b complex and magnesium .
8) remove endocrine disrupters

38
Q

What Is PMS- C and how can you support naturally?

A

Pre menstrual syndrome subtype : craving
(Blood glucose imbalance)
1) low GI/ GL diet
2) plant based
3) complex carbs
4) good quality protein with each meal
5) ALA 600-1200mg
6) magnesium 200-400mg
7) cinnamon 500mg x3 a day
8) chromium picolinate
9) B complex

39
Q

What is PMS- D and how can you support naturally?

A

Premenstrual syndrome subtype depression :
Low oestrogen : progesterone ratio, neurotransmitter imbalances with low serotonin
1) B6 cofactor for GABA, serotonin and dopamine , O:P imbalances lead to a deficiency
2) increase phytoestrogens inc red clover tea
3) St. John’s wort- MAO inhibitor , gaba antagonist
4) vitex Agnus castus binds to dopamine receptors to reduce prolactin - helps with mood changes and irritability
5) zinc - controls prolactin
6) l- tryptophan or 5-htp

40
Q

What is PMS- H and how can you support naturally ?

A

Pre- menstrual syndrome: hyper hydration
Increased aldosterone leads to water retention , weight gain breast tenderness and abdominal bloating .
Caused by excessive salt intake , excess oestrogen, stress and magnesium deficiency.
Support by:
1) rosemary - antioxidant, reduces 16-OH-E and encourages more beneficial pathway 2-OH-E
2) Ginger root- improves circulation, cramping / congestion and reduces bloating
3) B6 - regulates aldosterone helps with O:P balances
4) Gingko biloba - decreases breast pain and vascular congestion
5) diuretics: celery, parsley, dandelion and nettle
6) Magnesium (deficiency with high aldosterone)

41
Q

4 reasons to use B6 with PMS?

A

1) cofactor for GABA , serotonin and dopamine
2) needed for corpus luteum and oestrogen metabolism in the liver - supporting healthy progesterone levels which helps to modulate oestrogen
3) low levels are associated with OCP use
4) O:P imbalances lead to a deficiency
Decreased dopamine = increased prolactin (water retention)

42
Q

Name 5 herbs you could use for PMS?

A

1) Vitex Agnus Castus: binds ro dopamine receptors ro reduce prolactin = decreased hyperprolactinemia - helps with mood changes, irritability and headaches
2) St Johns Wort- MOA inhibitor and GABA antagonist
3) Rosemary: antioxidant, neutralises quinones and reduces 16-OH-E . Encourages more beneficial 2-OH-E pathway
4) ginger root: improves circulation , cramping , congestion and reduces bloating
5) green tea: L-theanine , calming
6) gingko biloba : decreases breast pain / vascular congestion

43
Q

What are the 7 core approaches in treating PMS?

A

1) avoid/ minimise high GI, caffeine, alcohol, cigarettes, dairy, red and processed meats
2) balance O:P ratio- support oestrogen detox and elimination, increase fibre and cruciferous veg, phytoestrogens , decrease EDCs, address stress, vitex Agnus castus
3) balance blood glucose
Low GI, plantbased, complex carbs, ALA, Magnesium, Bs, cinnamon , chromium
4) reduce inflammation
Increase omega 3s, GLA (evening primrose oil, borage oil, eliminate dairy and sugar , hydrogenated oils, increase antioxidants - A, C and E
5) optimise key nutrients - Bs- B6 mg, zinc, D, calcium, EFAs
6) Balance neurotransmitters: L- trytophan, 5HTP, tyrosine, B6, B12, folate, zinc, magnesium, St. John’s wort, L- theanine,st johns wort, optimise sleep and exercise
7) reduce fluid retention - B6 regulates aldosterone . Diuretics - celery, parsley, dandelion and nettle

44
Q

What are 5 causes / risk factors of PMS?

A

1) interaction between oestrogen, progesterone and neurotransmitters:
- Progesterone metabolites bind to GABA receptors (can’t activate ) (metabolites low in PMS= fluctuations in neurotransmitters) . Progesterone and oestrogen can modify serotonin availability
2) obesity : BMI > 30 greater risk
3) smoking - affects neurocircuitry , increases stress susceptibility, HPA axis declines
4) alcohol : negative association with anxiety , mood changes and headaches in PMS
5) high omega 6:3 ratio: increases in inflammatory prostaglandins and can induce aromatisation
6) reduced cortisol awakening response (CAR) : high adrenal function / chronic stress

45
Q

Where is pregnalone produced and what is it’s function ?

A

Pregnalone is produced by cholesterol in steroidogenic tissues - adrenal , gonads and brain .
- it is the precursor of DHEA, DHT, testosterone , oestradiol, progesterone and cortisol .
- it is anti inflammatory and neuro protective

46
Q

What can cause low levels of pregnalone?
Natural support ?
Symptoms?

A
  • low levels caused by advancing age > 30 and statin use.
  • poor memory, concentration , low libido, joint and muscle pain

Natural support:
1) manage stress- pregnalone steal theory = in times of stress, pregnalone is used for cortisol production rather than other hormones
2) DHEA balance : Mac’s, rhodiola, magnolia
3) avocado, fax, chia seeds, olive oil, walnuts, Bs , k and D3

47
Q

Why does hyperprolactinaemia occur and what are the symptoms?

A

Naturally occurs in pregnancy and lactation but can also occur in non pregnancy women with:
High cortisol
Circadian disruption
Renal failure
D- deficiency
Dopamine antagonists
Symptoms are: low fertility, menstrual irregularities , low libido , breast pain, vaginal dryness , osteopenia

48
Q

What is prolactin controlled by and what are its functions ?

A

Controlled by oestrogen and dopamine
-lactation
- breast maturation
- inhibits menstruation

49
Q

Discuss the implications of low progesterone with symptoms and natural support

A

Low levels of progesterone leads to oestrogen dominance, the O:P ratio is tipped .
- can be caused by stress , synthetic progesterones and xenoestrogens
Symptoms include:
Irritability, mood swings, insomnia and a higher risk of breast cancer in pre menapausal women .
Support by:
- optimising oestrogen detoxification
- increasing fibre
- 3 balanced meals, no snacking
- magnesium, C, B6, zinc
- vitex agnus castus, she oak
- exercise

50
Q

What is progesterone responsible for?

A
  • maintaining the endometrium for implantation and pregnancy
  • increasing cervical mucous ( producing a barrier)
  • potentiates the inhibitory actions of GABA - relaxes smooth muscle, calming and sleep enhancing
51
Q

How is progesterone produced?

A

In the corpus luteum, after ovulation , in the adrenal cortex and placenta

52
Q

what are the conversion pathways of testosterone and what are these regulated by?

A

Either:
1) most of testosterone is converted to oestradiol (E2) by aromatase.
Upregulated by: insulin, obesity, cortisol and alcohol
Downregulated by : zinc, nettle , I3C, vit D , grape seed, green tea, calcium, magnesium, phytoestrogens
Or
2) Converted to DHT, the more potent form of testosterone by 5 alpha reductase.
Upregulated by:
Insulin
Downregulated by:
Nettle, saw palmetto, lycopene , curcumin, green tea, zinc, GLA, EPA

53
Q

Where is testosterone produced and what are its functions ?

A

Produced in the ovaries and adrenal cortex.
Ovarian density, libido, bone strength , mood, cognition

54
Q

How are high and low testosterone levels characterised?

A

High:
Androgen dominance as seen in PCOS - anovulation, hirsutism and acne vulgaris
Low:
Associated with low mood, low libido and cognitive dysfunction ( noted in perimenapause)

55
Q

How do you support phase 1 and phase 2 oestrogen metabolism?

A

Phase 1:
Support CYP3A4 , CYP1A1 and CYP1B1:
Indole 3-carbinol , cruciferous veg, antioxidants - glutathione - neutralises quinones, turmeric , resveratrol , berries
Phase 2: cruciferous veg, allium veg, magnesium,antioxidants, glutathione, folate, B12, B6. Avoid OCP, alcohol, high cortisol and mould exposure

56
Q

What is oestrogen dominance, why does it occur?

A

Excess oestrogenic activity due to:
1) High O:P ratio despite normal oestrogen
2) elevated oestrogens or metabolites due to poor detoxification and elimination
3 ) over expression of ERa and ERb
Causes:
-Chronic stress (Downregulates LH and FSH)
-constipation (oestrogen recirculates)
- xenoestrogens- plastics, water, non organic
- heavy metals lead, cadmium and mercury
- OCP and HRT
- obesity ( increased aromatisation )

57
Q

What are the symptoms of oestrogen dominance?

A

Fibroids , endometriosis, pms, fibrocystic breast, dysmenorrhea, infertility , miscarriages, breast / ovarian cancer, insulin resistance , thyroid dysfunction , perimenapause, anxiety and depression

58
Q

What are the oestrogens, how are they produced and what are their functions?

A

E1= oestrone
E2- Oestrodiol- most active during reproductive years
E3- Oestriol
Produced by conversion of androgens via aromatase eg in ovaries, bone, breast, adipose tissue.
They bind to specific oestrogen receptors : ERa, ERb and GPER

1) reproductive tract development
2) menstrual cycle
3) promotes cell proliferation (breasts)
4) glucose homeostasis
5) immune robustness

59
Q

What are 5 causes/ risk factors of fibrocystic breasts ?

A

1) oestrogen dominance / elevated O:P ratio with low progesterone
2) reproductive history - nulliparity and late menopause
3) obesity and T2DM associated with breast changes
4) low fibre -needed to clear out excess oestrogen
5) HRT- increased incidence with oestrogen replacement therapy
6) methylxanthines - substances found in coffee, tea, cola, chocolate and some drugs
7) iodine deficiency

60
Q

What are fibrocystic breasts?

A

A common, benign condition characterised by swollen and tender breasts common among 20-50 year old women . Minority provides to malignant phenotype due to genetics and micro biome

61
Q

What are the symptoms of fibrocystic breasts ?

A
  • cyclical breast cysts , lumpiness
  • Dull/ heavy bilateral breast pain during luteal phase
  • some experience nipple discharge
62
Q

What are the causes and risk factors for uterine fibroids ?

A

1) genetics - SNPs CYP1A1, MED12
2) hypertension- may cause smooth muscle cell injury and or cytokine release
3) vitamin d deficiency- shown to inhibit fibroid cell proliferation
4) diet/ lifestyle- increased risk with low fibre , high sat fat, refined carbs , caffeine and alcohol
5) heavy metals - cadmium and lead activate oestrogen receptors
6) poor oestrogen metabolism/ clearance : EDCs, the OCP, obesity

63
Q

What are uterine fibroids?

A

Benign tumours that originate from the myometrium and connective tissue, most common between 35-49 years

64
Q

What are the signs and symptoms of uterine fibroids?

A

50-80% are asymptomatic
Heavy/ prolonged menstrual bleeds
Pelvic discomfort / pain
Abdominal bloating
Frequent urination and constipation , depending on location

65
Q

What are 5 things you could do to naturally treat fibrocystic breasts ?

A

1) hormone balancing naturopathic diet , including xenoestrogen avoidance and support oestrogen elimination
2) Evening primrose oil (1000mg 3x daily) GLA inhibits arachidonic acid synthesis
3) vitex Agnus castus - indirectly progesterogenic
4) remove methylxanthines and caffeine , stop smoking
5) seed cycling - balances oestrogen and progesterone through phytoestrogens, zinc, selenium and vitamin E
6) vitamin e and omega 3 FAs have been shown to relieve FB pain

66
Q

5 causes and risk factors for uterine fibroids?

A

1) genetics - polymorphisms CYP1A1, MED12
2) poor oestrogen metabolism / clearance - EDCs, OCP, obesity
3) hypertension- may cause smooth muscle cell injury and/or cytokine release
4)vitamin D deficiency- shown to inhibit fibroid cell proliferation
5) diet/ lifestyle- low fibre, high sat fat, refined carbs , caffeine and alcohol, sedentary lifestyle increase risk
6) heavy metals - cadmium and lead activate oestrogen receptors

67
Q

How do oestrogen and progesterone drive uterine fibroids ?

A

-Uterine fibroids are oestrogen dependent, oestrogen receptors are over expressed in fibroid tissue.
-When oestradiol increases, so does progesterone receptor availability, which completes fibroid development
- Excess aromatisation is also seen

68
Q

Discuss the three main approaches to treating uterine fibroids

A

1) Support oestrogen balance and detoxification
- support liver detox with cruciferous veg (I3C) , B complex, magnesium, NAC.
- choleretics and cholagogues to support oestrogen clearance- globe artichoke, turmeric
- Avoid xenoestrogens. endocrine disruptors
- Increase phytoestrogen foods/ herbs- chickpeas, sage, flaxseed, red clover
- fibre rich foods to improve oestrogen excretion
- vitex agnus castus- prolactin inhibitor as prolactin has been linked
- address stress, reduce cortisol
- Green tea extract- epicatechins shown to inhibit fibroid cell growth

2) Regulate excess bleeding
- Check iron/ ferritin levels- a symptom of iron deficiency is an increased risk of heavy bleeding. focus on iron rich foods- spirulina, apricots, nettle leaf tea. vitamin C to enhance absorption
- astringent herbs can help to constrict blood vessels and control blood flow (yarrow, cranesbill, shepherds purse)

3) Reduce inflammation:
- eliminate all sources of arachidonic acid and other inflammatory foods eg refined sugars
- Add natural anti inflammatories- omega 3, curcumin, ginger, green leafy vegetables, vitamin D
- Optimise weight and address any insulin resistance to reduce inflammation and aromatisation