Androgens Flashcards
(32 cards)
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.
What are the PK’s of SERMS?
Readily absorbed after oral administration. Tam. CYP450. Raloxifene is highly bound to plasma protein. Primary route of excretion is bile - faeces.
What are some of the ADR’s of SERMs?
Tamoxifen - commonly hot flushes and nausea. Menstrual disturbances, vaginal bleeding. Endometrial malignancy.
Affected by CYP inducers/inhibitors.
Raloxifene - also commonly hot flushes and leg crampls. Increased risk of DVT, PE, retinal vein thrombosis. Hx DVT contraindicated and is pregnancy.
Clomiphene - Dose dependent - nausea, headache, vasomotor flushes, visual disturbances, ovarian enlargement. Increased risk of multiple births.
What are some of the actions of progesterone?
Development of secretory endothelium in luteal phase.
Maintenance of endometrium in pregnancy.
Reduction in uterine contractions.
Makes cervical mucous thick and acidic.
Increases hepatic glycogen
Decreased Na+ reabsorption in kidney (in competition with aldosterone)
Increase in temperature
Decrease in smooth muscle contraction.
Decrease in plasma AA’s
Increase in excretion of urinary nitrogen.
What are the indications for progesterone?
Treat hormonal deficiency
Contraception (mainly with oestrogen)
Progestin (synthetic) - DUB, dysmenorrhea, endometriosis and infertility.
What are the PK’s of Progesterone?
Micronized progesterone is rapidly absorbed after oral administration. Short half life in plasma and is mostly metabolised by the liver. Excreted by the kidney.
Synthetic Progestins are less rapidly metabolised. When injected IM half life 40-50days Oral medroxyprogesterone has a half life of 30 days.
Other progestins 1-3 days so allow daily dosing.
Give some examples of progesterones:
Synthetic - norethindrone, norgestrel, levonorgestrel.
Injectable - Medroxyprogeterone. (also the oral component of HRT)
What are some of the adverse effects of progesterones?
Headache
Depression
Weight gain
Changes in libido
Some progestins have androgenic activity and increase HDL:LDL ration and cause acne and hirsutism.
Medroxyprogesterone has an increased risk of osteoporosis and therefore its use is limited to two years.
Give and example of and an indication of antiprogestin:
Mifepristone
Causes abortion of the foetus in early pregnancy.
Given with prostaglandin analogue to induce uterine contraction which increase the chances of successful termination.
What hormones do the testes secrete?
Testosterone
5-alpha-dihydrotesterone DHT
Androstendione
DHEA
