Sex Steroid Flashcards
Where is oestrogen absorbed?
- GI tract
- Skin and mucous membranes
Where is oestrogen metabolised?
- Liver
How is oestrogen excreted?
- In the urine as glucuronides and sulfates
What is the main mode of transport of progesterone in the body and where is it stored?
- Albumin bound
- Stored in adipose tissue
Where is progesterone metabolised?
- In the liver
How is progesterone excreted?
- Excreted in the urine conjugated to glucuronic acid.
How are COCP and POP metabolised?
- Metabolised in the liver by CYP450 enzymes
How would the efficacy of oral contraceptives be reduced?
- 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.
Name some CYP450 inducing drugs
- Anti-epileptic = carbamazepine
- Antiobitic = rifmapicin
- Natural products such as St John’s Wort
Risk of ERT (unoppposed oestrogen)
- Increased risk of endometrial and ovarian cancers
Risk of HRT (opposed oestrogen)
- 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).
Why are HRTs prescribed?
- To alleviate symptoms - hot flushes, dyspareunia and osteoporosis.
- NOT to reduce risk of heart disease
What is mifepristone (RU486) and describe its mechanism of action?
- 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
What is the usage of mifepristone?
- Termination of pregnancy
Name some selective oestrogen receptor modulator
- Clomiphene
- Tamoxifen
- Raloxifene
What is the mechanism of action of clomiphene?
- 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.
What is clomiphene used for?
- Treatment of anovulation.
Describe the metabolism of tamoxifen.
- A pro-drug that is metabolised in the liver to its active derivatives.
- Has little affinity for the oestrogen receptors
What is the mechanism of action of tamoxifen?
- Comoetes with oestrogen for binding to ER.
What are the agonist and antagonist effects of tamoxifen?
- In endometrium = ER agonist
- In breast = ER antagonist as it causes oestrogen responsive cells to become arrested in cell cycle.
Name a selective progesterone receptor modulator.
- Ulipristal acetate
What is the mechanism of action of ulipristal acetate?
- Delays or inhibits ovulation as LH surge is prevented.
Why is SPRM used as emergency contraception?
- It has a higher efficacy than COCP.
What is ulipristal acetate also used as treatment for?
- Treatment of uterine fibroids
