7a. Women's Health - Intro Flashcards

1
Q

What is the axis that maintains hormonal balance within the female reproductive system?

A

Hypothalamic-pituitary-ovarian (HPO) axis

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2
Q

Which hormones are released by the stimulation of the anterior pituitary by GnRH?

A

LH
FSH

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3
Q

What do LH and FSH do?

A

Support follicle development
Ovulation
Corpus luteum maintenance
Production of progesterone and oestrogen

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4
Q

Raised levels of which hormones exert negative feedback over LH and FSH?

A

Oestrogen
Testosterone

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5
Q

What is pregnenolone?

A

Hormone synthesised by cholesterol
Precursor of DHEA, testosterone, DHT, oestradiol, progesterone and cortisol
Anti-inflammatory

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6
Q

What are low levels of pregnenolone caused by?

A

Advancing age (30+)
Statins

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7
Q

What are the symptoms of low level pregnenolone?

A

Poor memory
Declining concentration/attention
Fatigue
Dry skin
Joint/muscle pain
Decreased libido

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8
Q

How to support healthy pregnenolone levels

A

Healthy fats - avocado, flax, chia, OO
B vits
Vit K
Vit D3
Manage stress
Improve sleep

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9
Q

What is the pregnenolone steal theory?

A

High stress means more pregnenolone is used to make cortisol
Reduces the amount available for the production of sex hormones

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10
Q

How does stress influence the sex hormones?

A

Downregulates LH and FSH
(meaning decreased ovulation)

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11
Q

When is progesterone produced?

A

After ovulation

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12
Q

Where is progesterone produced?

A

Corpus luteum

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13
Q

Which hormone is lacking if ovulation doesn’t happen?

A

Progesterone

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14
Q

What are the functions of progesterone?

A

Maintains endothelium for implantation and pregnancy
Increases cervical mucus (producing a barrier)
Helps relax smooth muscle (potentiates inhibitory actions of GABA)
Supports bone health and mammary development

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15
Q

Causes of low progesterone

A

Chronic stress
Synthetic progesterones
Xenoestrogens

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16
Q

Signs and symptoms of low progesterone

A

Irritability
Mood swings
Insomnia

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17
Q

How to balance progesterone

A

Support oestrogen detoxification
Increase fibre
Balanced meals
No snacking
Avoid alcohol until balanced
Mg, Vit C, B6, Zn
Agnus castus

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18
Q

What are the different types of oestrogen?

A

Oestrone (E1)
Oestradiol (E2)
Oestriol (E3)

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19
Q

How are oestrogens made?

A

Conversion of androgens via aromatase
(in ovaries, breast, adipose tissue, bone)

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20
Q

Which is the most physiologically active oestrogen during reproductive years?

A

Oestradiol (E2)

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21
Q

What are the functions of oestrogen?

A

Reproductive tract development
Menstrual cycle
Cell proliferation
Glucose homeostasis
Bone health
CV health

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22
Q

What can cause oestrogen dominance?

A

Elevated oestrogen relative to progesterone
Poor detoxification/elimination
Overexpression of ER-a and ER-b

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23
Q

Which conditions are associated with oestrogen dominance?

A

Fibroids
Endometriosis
PMS
Infertility
Miscarriages
Perimenopause
Breast/ovarian/endometrial cancers
Insulin resistance
Thyroid dysfunction

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24
Q

What are the causes of oestrogen dominance?

A

Synthetic HRT (synthetic progestin acts like testosterone)
OCP (negative feedback, prevention of ovulation)
Xenoestrogens
Heavy metals
Obesity (increased aromatisation of testosterone to oestrogen)
Poor liver detoxification/methylation
Constipation
Intestinal dysbiosis
Chronic stress (downregulates LH and FSH)

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25
Q

What happens during phase 1 oestrogen metabolism?

A

Liver breaks oestrogen down into smaller units

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26
Q

Which metabolites does oestrone (E1) convert to during phase 1 metabolism?

A

2-OH-E1
4-OH-E1
16-OH-E1

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27
Q

Which enzyme converts oestrone (E1) to 2-OH-E1?

A

CYP1A1

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28
Q

Which enzyme converts oestrone (E1) to 4-OH-E1?

A

CYP1B1

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29
Q

Which enzyme converts oestrone (E1) to 16-OH-E1?

A

CYP3A4

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30
Q

Describe 2-OH-E1

A

Weakest, protective form
Deactivated by COMT to 2-Methoxy-E1

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31
Q

Describe 4-OH-E1

A

Neutralised by COMT to 4-Methoyx-E1
Pro-carcinogenic if goes down the 4-Quinone-E1 route

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32
Q

Describe 16-OH-E1

A

High binding affinity
Associated with higher risk of oestrogen dependent conditions - heavy periods, clots, tender breasts, endometriosis, fibroids, breast cancer

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33
Q

How to support Phase 1 oestrogen metabolism

A

I3C (broccoli sprouts), cruciferous, AOs, glutathione, turmeric, berries, rooibos tea, celery
Support healthy microbiome
Avoid paracetamol, PCBs, grapefruit, smoking

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34
Q

What happens during Phase 2 oestrogen metabolism?

A

Broken down fat-loving, oestrogen metabolites have a water molecule added to them to enable elimination
Metabolites change from OH to Methoxy

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35
Q

How are 2-OH-E1 and 4-OH-E1 metabolised during Phase 2?

A

Methylation via COMT
Converts to 2-Methoxy-E1 and 4-Methoxy-E1

36
Q

Why might 4-OH-E1 and 16-OH-E1 levels elevate?

A

If methylation is compromised

37
Q

What does poor methylation of 4-OH-E1 mean?

A

Increased conversion to 4-Quinones-E1
(increased oxidative damage and cancer risk)

38
Q

Which detoxification pathways are used to metabolise oestrogen?

A

Methylation
Sulphation
Glucuronidation

39
Q

How can Phase 2 oestrogen metabolism be supported?

A

Cruciferous, alliums
Mg, AO, B6, B9, B12
SAMe, choline
Avoid OCP, high alcohol, high cortisol, mould exposure

40
Q

What is the oestrobolome?

A

Collection of microbes capable of metabolising oestrogens

41
Q

Examples of microbes that metabolise oestrogens

A

Beta-glucuronidase
E. coli
Clostridium perfringens
Bacteroides fragilis/vulgatus

42
Q

What is the role of beta-glucuronidase?

A

Reactivates oestrogens already conjugated for elimination

43
Q

What effect can beta-glucuronidase have one conjugated oestrogens?

A

Deconjugate them and allow them to be reabsorbed into the bloodstream via enterohepatic circulation

44
Q

What factors can contribute to an increased amount of beta-glucuronidase?

A

Dysbiosis
Low fibre intake
Poor bile flow

45
Q

What conditions can higher levels of beta-glucuronidase lead to?

A

Endometriosis
Breast/ovarian cancers
(increased circulating oestrogen = oestrogen dominance)

46
Q

What conditions can low levels of beta-glucuronidase lead to?

A

PCOS
(increased androgen synthesis and reduced oestrogen levels)

47
Q

Ways to maintain healthy beta-glucuronidase

A

Optimise the microbiome (pro/prebiotics)
If high levels - increase fibre, Ca D-glucarate (BG inhibitor), apples, cruciferous veg, milk thistle, Lactobacilli
If low levels - probiotics

48
Q

Where is testosterone produced?

A

Ovaries
Adrenal cortex

49
Q

Which form of oestrogen does testosterone get converted to?

A

Estradiol (E2)

50
Q

What converts testosterone to estradiol (E2)?

A

Aromatase

51
Q

What are the functions of testosterone in women’s health?

A

Ovarian density
Libido
Bone strength
Mood
Cognition

52
Q

What can high levels of testosterone lead to?

A

PCOS
Anovulation
Hirsutism
Acne vulgaris

53
Q

What can low levels of testosterone lead to?

A

Low mood
Low libido
Cognitive dysfunction

54
Q

What can testosterone convert to in addition to estradiol (E2)?

A

DHT

55
Q

Which enzyme converts testosterone to DHT?

A

5a-reductase

56
Q

What things can increase DHT levels?

A

Insulin
Inflammation
Obesity

57
Q

What things can decrease DHT levels?

A

Nettle root
Saw palmetto
Lycopene
Turmeric
Green tea
Zinc

58
Q

What is SHBG?

A

Glycoprotein produced to transport fat-soluble sex hormones in the bloodstream to the correct places

59
Q

Why do we need SHBG?

A

Unbound sex hormones are biologically active and could create problems if in high levels

60
Q

What does low levels of SHBG lead to?

A

Higher levels of circulating, biologically active sex hormones
Hyperinsulinemia
Obesity
Metabolic syndrome
T2D
Hypothyroidism
PCOS

61
Q

What does high levels of SHBG lead to?

A

Anorexia
Pregnancy
Androgen deficiency
Hyperthyroidism
Liver disease

62
Q

What are the functions of prolactin?

A

Lactation
Breast maturation
Inhibits menstruation

63
Q

Examples of endocrine disrupters

A

BPA (plastic bottles)
Heavy metals
Pesticides
NSAIDs
Tap water

64
Q

What do endocrine disrupters do?

A

Alter hormone receptor signalling
Alter hormone production, secretion and metabolism
Induce oxidative stress, mitochondrial damager

65
Q

What can endocrine disrupters increase the risk of?

A

Cancer
PCOS
Early puberty
Infertility
Obesity

66
Q

What are xenoestrogens?

A

Endocrine disruptors that are structurally similar to oestrogen
Bind to oestrogen receptor sites

67
Q

Examples of xenoestrogens

A

Pesticides
Parabens
BPA
Tap water

68
Q

Why is dairy a endocrine disruptor?

A

Commercial milk derived from pregnant cows who have increased hormone production during third trimester
E1, E2, E3 all found in milk
IGF, PCBs, insecticides also found in milk

69
Q

What are phytoestrogens?

A

Naturally occurring plant compounds similar to estradiol (E2)

70
Q

How do phytoestrogens work?

A

Produce a weak anti-oestrogenic effect in the presence of high endogenous oestrogen
Reduces circulating bioavailable E2
Produces a weak oestrogenic effect in the presence of low endogenous oestrogen
Disrupts aromatase - favouring 2-OH-E1 pathway

71
Q

What are the health benefits of phytoestrogens?

A

Lower risk of menopausal symptoms, CVD, metabolic syndrome, T2D, breast cancer

72
Q

What types of foods do phytoestrogens occur naturally in?

A

Flavonoids - soybeans, legumes, lentils, chickpeas
Lignans - linseed, fruit, veg
Flavones - parsley, thyme, celery, chamomile tea

73
Q

What are the better sources of soy to eat for their phytoestrogenic effect?

A

Fermented soy such as tempeh, miso
(avoid soy isolates and other processed soy)

74
Q

How can phytoestrogens ferment in the gut?

A

Microbiome

75
Q

What things can contribute to a sex hormone imbalance?

A

Blood glucose dysregulation
Excessively high or low body weight
Chronic low grade inflammation
Poor digestion
Dysbiosis
Poor detoxification/elimination
Chronic stress
Disrupted sleep
Mg, B vits, Zn deficiencies

76
Q

First step to balancing hormones

A

Avoid processed foods, refined sugar, table salt, cow’s dairy
Focus on fruit/veg, wholegrains, nuts, seeds, water, small amount of oily fish
Encourage effective digestion

77
Q

Second step to balancing hormones

A

Improve blood glucose
Weight management
Reduce inflammation - reduce inflammatory foods (dairy, alcohol, sugar, processed
Increase AO rich foods, oily fish, nuts, seeds
Support digestion and elimination - bitters, fibre, hydration
Build microbiome - 5R, pre/probiotics
Support thyroid hormone synthesis - Fe, I, Zn, Se etc
Support detoxification
Manage stress levels
Improve sleep

78
Q

Nutrients to promote 2-OH-E1 route over 4/16-OH-E1 routes

A

Cruciferous veg
I3C
O3

79
Q

Nutrients to reduce oxidation of 2-OH and 4-OH

A

A, C, E
ALA
NAC
Turmeric
Green tea

80
Q

Nutrients to promote methylation of 2-OH and 4-OH

A

B2, 6, 9, 12
Mg

81
Q

Nutrients to increase circulating levels of SHBG

A

Fibre
Flax
Nettle root

82
Q

Nutrients to inhibit aromatase

A

Flax
Phytoestrogens
Green tea
Mg
Zn

83
Q

Nutrients to promote the detoxification of oestrogens by upregulating P1 and 2 enzyme activity

A

B2, 6, 12
Mg
Protein

84
Q

Nutrients to inhibit the activity of beta-glucuronidase

A

Fibre
Probiotics
Ca D-glucarate

85
Q

Nutrients to inhibit 5a-reductase, reducing conversion to DHT

A

Lycopene
Turmeric
Green tea
Saw palmetto

86
Q

Nutrients to modify oestrogen receptor activity

A

Flax
I3C
Resveratrol