Sex Steroid

Question 1

Where is oestrogen absorbed?

Answer 1

• GI tract

- Skin and mucous membranes

Question 2

Where is oestrogen metabolised?

Answer 2

• Liver

Question 3

How is oestrogen excreted?

Answer 3

• In the urine as glucuronides and sulfates

Question 4

What is the main mode of transport of progesterone in the body and where is it stored?

Answer 4

• Albumin bound

- Stored in adipose tissue

Question 5

Where is progesterone metabolised?

Answer 5

• In the liver

Question 6

How is progesterone excreted?

Answer 6

• Excreted in the urine conjugated to glucuronic acid.

Question 7

How are COCP and POP metabolised?

Answer 7

• Metabolised in the liver by CYP450 enzymes

Question 8

How would the efficacy of oral contraceptives be reduced?

Answer 8

• By enzyme inducing drugs which increase the amount of CYP450 so increased metabolism of COCP occurs. This means less COCP is available in the plasma to cause a response at the receptor = decreased efficacy of COCP.
• Presence of phytoestrogens in soya enhance oestrogen absorption and reduce its storage in adipose and muscle, causing T1/2 to become reduced.

Question 9

Name some CYP450 inducing drugs

Answer 9

• Anti-epileptic = carbamazepine
• Antiobitic = rifmapicin
• Natural products such as St John’s Wort

Question 10

Risk of ERT (unoppposed oestrogen)

Answer 10

• Increased risk of endometrial and ovarian cancers

Question 11

Risk of HRT (opposed oestrogen)

Answer 11

• Increased risk of developing breast cancer
• Increased risk of venous thromboembolism (usually for oral HRT).
• Beneficial on lipid profile as it increases HDL-C and decreased oxidised LDL-C and TAG; decreased CVD.
• Increased risk of stroke (oral usage).

Question 12

Why are HRTs prescribed?

Answer 12

• To alleviate symptoms - hot flushes, dyspareunia and osteoporosis.
• NOT to reduce risk of heart disease

Question 13

What is mifepristone (RU486) and describe its mechanism of action?

Answer 13

• Progesterone and glucocorticoid receptor antagonist
• Progesterone cannot act on the myometrium so lack of blockage of prostaglandin effect on myometrium
• Prostaglandin-induced myometrial contractions occur

Question 14

What is the usage of mifepristone?

Answer 14

• Termination of pregnancy

Question 15

Name some selective oestrogen receptor modulator

Answer 15

• Clomiphene
• Tamoxifen
• Raloxifene

Question 16

What is the mechanism of action of clomiphene?

Answer 16

• Competes with oestrogen for ER binding making the pituitary gland think there is a lack of oestrogen so increased production of AP hormones is stimulated - eventually leading to ovulation.

Question 17

What is clomiphene used for?

Answer 17

• Treatment of anovulation.

Question 18

Describe the metabolism of tamoxifen.

Answer 18

• A pro-drug that is metabolised in the liver to its active derivatives.
• Has little affinity for the oestrogen receptors

Question 19

What is the mechanism of action of tamoxifen?

Answer 19

• Comoetes with oestrogen for binding to ER.

Question 20

What are the agonist and antagonist effects of tamoxifen?

Answer 20

• In endometrium = ER agonist

- In breast = ER antagonist as it causes oestrogen responsive cells to become arrested in cell cycle.

Question 21

Name a selective progesterone receptor modulator.

Answer 21

• Ulipristal acetate

Question 22

What is the mechanism of action of ulipristal acetate?

Answer 22

• Delays or inhibits ovulation as LH surge is prevented.

Question 23

Why is SPRM used as emergency contraception?

Answer 23

• It has a higher efficacy than COCP.

Question 24

What is ulipristal acetate also used as treatment for?

Answer 24

• Treatment of uterine fibroids