Sex Hormones

Question 1

Hypothalamic-pituitary-ovarian (HPO) axis

Answer 1

Maintains hormonal balance within the female reproductive system.

Question 2

GnRh

Answer 2

GnRH stimulates the anterior pituitary
to produce and release LH and FSH.

Question 3

LH and FSH

Answer 3

• LH and FSH support follicle development, ovulation, corpus luteum maintenance and the production of progesterone, oestrogen and inhibin.
• Raised oestrogen and testosterone exert
  negative feedback over FSH and LH secretion.
• Progesterone and oestrogen regulate the function of target organs, e.g., uterus, mammary glands.

Question 4

Pregnenolone

Answer 4

A hormone synthesised from cholesterol in steroidogenic tissues such as the adrenal gland, gonads, and brain by the mitochondrial enzyme CYP11A1.
* A precursor of DHEA, testosterone, DHT, oestradiol, progesterone and cortisol.
* Anti-inflammatory and neuroprotective.

Question 5

Low levels of Pregnenolone

Answer 5

• Advancing age (>30)
• Statin use.

Question 6

Symptoms of low pregnenolone

Answer 6

Poor memory; declining concentration and attention; fatigue; dry skin; joint and muscle pain; decreased libido.

Question 7

Supporting healthy pregnenolone levels:

Answer 7

• Improves sleep, manages stress. Healthy fats.

Question 8

Pregnenolone steal theory’

Answer 8

States that high stress increases the use of pregnenolone for cortisol production, reducing the total amount of pregnenolone available for production of sex
hormones.

Question 9

Progesterone

Answer 9

• Produced: In the corpus luteum after ovulation, in the adrenal cortex and by the placenta during pregnancy. So, a lack of ovulation = a lack of progesterone.

Question 10

Progesterone: Functions

Answer 10

‒ Maintains the endometrium for implantation and pregnancy. Increases cervical mucus (producing a barrier)
‒ Progesterone metabolites potentiate the inhibitory actions of GABA by modulating receptors; help relax smooth muscle.
‒ Supports bone health and mammary development.

Question 11

Progesterone Imbalances

Answer 11

Perimenopause, PCOS, infertility

Question 12

Low progesterone:

Answer 12

Leads to oestrogen dominance / tipping the ratio of oestrogen:progesterone (O:P).

Question 13

Low Progesterone: Causes

Answer 13

Chronic stress, synthetic progesterones, xenoestrogens.

Question 14

Low Progesterone: Signs and Symptoms

Answer 14

Irritability, mood swings and insomnia.
Also = a h igher risk of breast cancer in premenopausal women.

Question 15

To balance progesterone

Answer 15

Support oestrogen detoxification , increase fibre , 3 balanced (not processed) meals / day, no snacking, avoid alcohol until balanced, magnesium, vitamin C and B6, zinc. Vitex Agnus castus , Australian bush flower essence ( she oak ), exercise and box breathing with anxiety

Question 16

Oestrogens

Answer 16

A group of steroid hormones, including
oestrone (E1), oestradiol (E2) and oestriol (E3).

Produced: By conversion of androgens via aromatase (aromatisation), e.g., in the ovaries, bone, breast, adipose
* Activity: Oestrogens exert their actions by binding to specific oestrogen receptors : ER α, ER β, and GPER . Oestradiol (E2) ―
most physiologically active during reproductive years.

Question 17

Oestrogen Functions

Answer 17

Reproductive tract development, menstrual cycle, promotes cell proliferation (esp. breasts), glucose homeostasis, immune robustness; bone and cardiovascular health.

Question 18

Oestrogen dominance

Answer 18

A state of excess
oestrogenic activity encompassing some or all of:
 Elevated oestrogen relative to progesterone.
High O:P ratio despite normal oestrogen.
 Elevated specific types of oestrogen or metabolites due to poor detoxification and elimination.
 Excess oestrogen induces an overexpression of ER α and ER β.
* Associated with: Fibroids, endometriosis, PMS, fibrocystic breasts, dysmenorrhea, infertility, miscarriages, perimenopause, breast / ovarian / endometrial cancers, insulin resistance, thyroid dysfunction (e.g., Hashimoto’s), brain fog, anxiety and depression.

Question 19

Oestrogen dominance ― aetiology

Answer 19

• Synthetic HRT and oral contraceptive pills
• Xenoestrogens
• Heavy metals
• Obesity
• Poor liver detoxification and methylation
• Constipation
• Genetic mutations
• Intestinal dysbiosis
• Chronic stress

Question 20

2 OH E (CYP1A1)

Answer 20

Weakest, protective form. COMT de-activates 2 OHE1 to the protective 2 MeOE1 metabolite.

Question 21

4 OH E (CYP1B1)

Answer 21

A pro-carcinogenic oestrogen metabolite
n eutralised by COMT into protective 4 MeOE1 metabolites. Overuse of this pathway is, therefore, problematic.

Question 22

16 α OH E (CYP3A4)

Answer 22

Highest binding affinity for
oestrogen receptors with high proliferative effects.
High 16 α OH E is associated with a higher risk of oestrogen dependent conditions, e.g., breast cancer, fibroids, endometriosis.

Question 23

Oestrobolome

Answer 23

A collection of microbes
capable of metabolising oestrogens .
* These bacteria produce beta-glucuronidase
Bacteroides fragilis, Bacteroides vulgatus ,
Escherichia coli, Clostridium perfringens.
* Beta-glucuronidase is an enzyme which deconjugates (reactivates)
oestrogens that were already conjugated for elimination.
* These deconjugated oestrogens can be reabsorbed via the
enterohepatic circulation increasing oestrogen load in the body.
* A healthy gut produces the right amount of beta glucuronidase to maintain oestrogen homeostasis.
* A dysbiotic microbiome, especially when coupled with low fibre intake and poor bile flow , increases
the chances of the entero
toxigenic circulation. Hence why improving GIT function and microbial patterns can help with overall oestrogenic load.

Question 24

Beta-Glucuronidase conditions

Answer 24

Endometriosis
Ovarian Cancer
PCOS
Breast Cancer
Endometrial Hyperplasia

Question 25

Maintaining healthy beta
glucuronidase levels

Answer 25

• Optimise the microbiome ( probiotics, prebiotics
• If high: ↑ dietary fibre ; calcium D glucarate (a beta glucuronidase inhibitor) and glucaric acid rich foods such as mung bean sprouts, apples, cruciferous vegs. Milk thistle, Lactobacilli and Bi fidum bacteria. Consider the 5R protocol.
• If low: Focus on
  commensal support (e.g. probiotics ).

Question 26

Testosterone

Answer 26

• Produced: In the ovaries and adrenal cortex.
• Converted to: E2 via aromatase (most testosterone), and DHT.
• Functions: Ovarian density, libido, bone strength, mood, cognition.
• Testosterone imbalances:
  ‒ Androgen dominance is seen in PCOS. Associated with anovulation, hirsutism and acne vulgaris. This is driven by insulin resistance so create your client’s plan accordingly.
  ‒ Low testosterone may be associated with low mood, low libido and cognitive dysfunction. This is noted during perimenopause.
  L-tyrosine may help but also address the cause.

Question 27

Testosterone
DHT:

Answer 27

• 5α-reductase converts
  testosterone into a more potent form (DHT). This pathway is:
• Upregulated by:
  Insulin, inflammation, obesity.
• Downregulated by:
  Nettle (esp. nettle root),
  saw palmetto, lycopene,
  turmeric, green tea, zinc,
  GLA and EPA.

Question 28

Sex hormone binding globulin (SHBG)

Answer 28

Sex hormones are not water soluble so need to be transported in blood bound to SHBG.
* Produced: A glycoprotein synthesised by the liver.
* Functions: Binds to oestradiol , testosterone, DHT. Only unbound hormones are biologically active.
* SHBG imbalances:
‒ Lower levels = higher circulating free / active levels of these hormones. Associated with hyperinsulinemia, obesity, metabolic syndrome, 2DM, hypothyroidism, PCOS.
‒ High levels: Seen in anorexia, pregnancy, androgen deficiency, hyperthyroidism, liver disease.

Question 29

Prolactin

Answer 29

A key hormone controlled by oestrogen and dopamine.
* Functions: Lactation, breast maturation, inhibits menstruation.
* Hyperprolactinaemia: Occurs naturally in pregnancy and lactation but can also occur in non pregnant women.
- Associated with: Infertility, menstrual
irregularities, low libido, osteopenia, breast pain and vaginal dryness.
* Increased by: High cortisol (stress), pituitary tumours, circadian disruption, renal failure, vitamin D deficiency, drugs
e.g., domperidone (dopamine antagonists).