Androgens Flashcards
Name the three oestrogens and explain their differences:
Oestradiol - most potent and secreted by the ovary. Principal oestrogen in pre-menopausal women.
Oestrone - a metabolite of oestradiol that has approximately one third the oestrogenic potency of oestradiol. Primary circulating oestrogen after the menopause. Synthesised in peripheral tissues.
Oestriol - another metabolite of oestradiol that is present mainly in pregnancy. The principal oestrogen produced by the placenta.
What are the functions of the oestrogens?
Mild anabolic Sodium and water retention Raise HDL and lower LDL Decrease bone resorption Impair glucose tolerance Increase blood coagulability
What is the indication for hormone replacement therapy?
Relief of post-menopausal symptoms such as vasomotor instability (hot flushes), vaginal atrophy.
What drugs make up hormone replacement therapy?
Oestrogen
Progesterone (needed for women who have a uterus otherwise disorder growth by oestrogen would lead to neoplasia.
What methods can be used to deliver HRT?
Transdermal patch, regional delivery if only vaginal symptoms present.
What are the benefits or HRT?
Decreased resorption of bone
Control of adrenaline secretion to reduce adrenaline secretion
Reversal of atrophy of vulva, vagina, urethra and trigone of bladder.
What are the indications for oestrogen therapy?
Primary hypogonadism - development of secondary sexual characteristics.
Secondary hypogonadism - experience premature menopause or premature ovarian failure.
Describe the PK of naturally occurring oestrogens:
Readily absorbed through GI, skin and mucous membranes. Oestradiol is rapidly metabolised by the liver, the micronized has better bioavailability. To bypass the effects of first pass metabolism oestrogen can be given via topical gel, emulsion or spray and can be given intra-vaginally or by injection.
Describe the PK of synthetic oestrogen analogues:
Well absorbed after oral administration - metabolised more slowly by liver and peripheral tissues. Fat soluble and sorted in adipose tissue which allows for slow release giving it a higher potency and prolonged action compared to natural oestrogens.
Describe the metabolism of oestrogens:
Liver
Phase 1 and 2
Secreted into the bile and recycled via the enterohepatic circulation. Active metabolites continue to circulate whereas inactive are excreted by the kidney.
ADRs of oestrogens?
Breast Tenderness Nausea Vomiting Postmenopausal uterine bleeding Increased risk of thromboembolic events MI Breast and endometrial cancer (endometrial offset if combined with progesterone) Hypertension Headache Peripheral oedema
Give some examples of oestrogen receptor modulators:
Tamoxifen
Raloxifene
Clomiphene
Give the mechanism of action of SERMs:
Competes with oestrogen for binding to oestrogen receptors in breast tissue (and other types of tissue) Preventing oestrogen from producing an effect.
Actions of SERMs?
Tamoxifen - prevent growth of breast tissue
Raloxifene - as above and decreases bone resorption, total cholesterol and LDL.
Clomiphene - Partial oestrogen agonist - causes ovulation
What are the indications for SERM’s?
Tamoxifen - Palliative treatment of metastatic breast cancer, adjuvant therapy to mastectomy/radiation. Also can be used prophylactically if breast cancer risk is high.
Raloxifene - prophylactically to reduce risk of breast cancer in those high risk. Can be used to reduce risk of osteoporosis in postmenopausal women.
Clomiphene - used to treat infertility in women with anovultary cycles not due to pituitary failure.
