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Flashcards in Sex hormones and disease Deck (29):
1

Briefly describe the release and regulation of sex hormones?

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2

Describe the synthesis of the sex hormones?

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3

Which enzymes are potential targets in the synthesis of sex hormones?

Aromatase (testosterone > oestradiol and androstenedione > oestrone)

5a reductase (testosterone > dihydrotestosterone)

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4

Describe the clinical uses of oestrogens?

Children: hypogonadism

Adults: primary amenorrhoea, contraception, menopause

5

Describe the benefits and risks associated with postmenopausal hormone therapy?

BENEFITS

Improved bone density
Relief from flushes, fatigue and vaginal dryness
Reverses atrophy of vulva, vagina and urethra
Improved sleep
Reduced incidence of colorectal cancers 
Reduced CHD incidence
Possible reduced incidence of Alzheimer's

RISKS

Breast tenderness, nausea, fluid retention
Increased risk breast and uterine cancer
Increased risk of thromboembolism/stroke

6

How do the benefits and risks of postmenopausal hormone therapy weigh up?

Benefits believed to outweigh risks

7

Describe the mechanism of action of oestrogen?

Cross membrane > activates cytoplamic receptors > homodimers formed > homodimers interact with EREs in nucleus > gene activation/repression

Potential to form heterodimers with different transcription factors > activate signalling in different ways

Receptor may be located on the membrane > fast actions 

 

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8

Why are some of the actions of oestrogen rapid, whilst others are slower?

Fast actions as a result of binding membrane receptors 

Slower actions associated with intracellular receptors

9

Describe different ways in which the signalling of oestrogen may be altered?

Different receptor location

Interaction with different transcription factors 

Different receptor subtypes

10

Describe how oestrogen is thought to be involved with breast cancer?

Binding to ER stimulates growth

Binding to ER also switches on progesteron receptor > growth and differentiation 

 

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11

Describe the ER and PR receptor levels in breast cancer?

Pre-menopausal: 60-65% ER/PR +ve

Post-menopausal: 70-75% ER/PR +ve

12

What are SERMs?

What are they used for?

Selective oestrogen receptor modulators

Oestrogen blockade > application in breast cancer

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13

What is tamoxifen and what is it used for?

Partial agonist at oestrogen receptors 

Palliative treatment of metastatic breast cancer
Adjuvant after lumpectomy

14

Describe the adverse effects of tamoxifen?

Endometrial hyperplasia, polyps and cancer
Thromboembolic events
Thrombocytopenia
Ocular toxicity
Menopausal symtpoms

Resistance > tumours may recur

15

What is exemestane?

What is it used for?

Aromatase inhibitor

Decrease oestrogen production > inhbit receptor activation > applications in breast cancer to improve disease free survival after tamoxifen

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16

Describe the adverse effects of aromatase inhibitors?

Increased bone loss and fracture risk
Increased arthralgia
Potential poorer lipid profile, hepatic steatosis and metabolic syndrome
Menopausal signs

17

Describe the effect of androgens?

Anabolic and masculinising effects in males and females

18

Which androgens are synthesised in males and females?

Testosterone and dihydrotestosterone

19

Where are androgen receptors located?

Nucleus

20

Describe the process of androgen receptor activation?

Testosterone released from SHBG > enters cell > converted to DHT by 5a reductase > binds nuclear and cytoplasmic androgen receptors > gene transcription

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21

Describe the actions of testosterone and dihydrotestosterone?

TESTOSTERONE
Gonadotrophin release
Spermatogenesis
Sexual differentiation
Anabolic effects

DHT
Prostate development
External virilisation
Sexual maturation

22

Describe the therapeutic uses of androgens?

Androgenic: hypogonadism

Anabolic: senile osteoporosis, recovery from surgery and chronic diseases

Growth: pituitary dwarfism

Endometriosis

23

Describe the non-therapeutic uses of androgens?

Increase lean body mass

Muscle strength

Aggressiveness

24

Describe the adverse effects of androgens?

Increase LDL, decrease HDL

Females: acne, facial hair, deep voice, male pattern baldness, excessive muscle development and menstrual irregularities

Males: priapism (penis stays erect), impotence, decreased spermatogenesis, gynaecomastia

Children: premature closure of epiphyseal plates, abnormal sexual maturation

 

25

Which antiandrogens are available?

Receptor antagonists: cyproterone, flutamide

5a reductase inhibitors: finasteride

26

What is cyproterone?

What is it used for?

Androgen receptor antagonist

Used in prostate cancer in males and androgenisation in females

27

What is flutamide?

What is it used for?

Androgen receptor antagonist

Used for metasatic prostate cancer 

28

What is finasteride?

What is it used for?

5a reductase inhibitor

Used for benign prostatic hypertrophy and hair loss

29

Give a brief summary of the drugs that can be used to block sex hormones, including their targets?

Aromatase inhibitor: exemestane

5a reductase inhibitor: finasteride

Oestrogen receptor blockers: tamoxifen, raloxifene, fulvestrant

Androgen receptor blockers: cyproterone, flutamide

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