Sex Steroids Flashcards
How are sex steroids transported around the body?
Bound to SHBG (not progesterone) and albumin
What happens when a steroid binds to its receptor?
The steroid binds at the ligand binding site and causes removal of the heat shock protein to reveal the DNA binding site to regulate DNA synthesis in the nucleus
What effect does oestrogen have on progesterone receptors?
Stimulates production
What effect does progesterone have on oestrogen receptors?
Inhibits production
How are metabolites of sex steroids excreted?
In urine as glucuronides and sulphates
What are the main actions of oestrogen?
Mildly anabolic
Na+ and K+ retention
Raises HDLs and lowers LDLs
Reduces glucose tolerance
Increases coagulability
Decreases bone resorption
What are the ADRs of oestrogen?
Breast tenderness
Nausea, vomiting
Water retention
Increased coagulability
Endometrial hyperplasia and cancer
Ovarian metaplasia and cancer
Breast hyperplasia and cancer
What are the actions of progesterone?
Stimulates a secretory endometrium
Anabolic
Increased bone mineral density
Fluid retention
Mood changes
Maintains pregnancy
What are the ADRs of progesterone?
Weight gain
Fluid retention
Acne
Nausea, vomiting
Irritability
Depression
Lack of concentration
What are the actions/ADRs of testosterone?
Make secondary sexual characteristics
Anabolic
Acne
Voice changes
Increases aggression
Affects HDL:LDL increasing the risk of atherosclerosis
What is the difference between monophasic, biphasic and triphasic COCPs?
Monophasic - each tablet contains the same
Biphasic - fixed oestrogen, progestin increases in the second half
Triphasic - fixed/variable oestrogen, progestin increases in 3 phases
What are the contraindications for prescribing COCP?
Hypertension, high BMI, VTE history, prolonged immobility, breast cancer, smoking over 35
Describe the mechanism of action of COCP
Oestrogen and progesterone feed back negatively on the hypothalamus/anterior pituitary preventing follicle growth and the LH surge (thus ovulation). Progesterone causes thickening of the cervical mucus and thins the lining of the endometrium.
What are the ADRs of COCP?
VTE, hypertension, headache, mood swings, increased risk of stroke
What are the indications for POP?
Women unsuitable for COCP e.g. Hypertension
Emergency contraception
What are the ADRs of the POP?
Irregular menstruation, headaches, breast tenderness, skin tenderness, breast cancer
What are the indications for HRT?
Hot flushes/sweats, vaginal dryness/dyspareunia, osteoporosis
What should you not prescribe HRT for?
IHD
What are the ADRs for ERT and HRT?
ERT (unopposed oestrogen) - increased risk of endometrial and ovarian cancer
HRT (opposed oestrogen) - increased risk of breast cancer
Increased risk of stroke (but beneficial for IHD)
VTE - protein C resistance, increased thrombin
What are the two selective estrogen receptor modulators, what are they used for?
They are oestrogen receptor agonists and antagonists in different tissues.
Raloxifene - to prevent breast cancer in postmenopausal women with increased risk of breast cancer/osteoporosis
Tamoxifen - to prevent breast cancer and in the treatment of estrogen receptor positive breast cancer
What are the differences in action between raloxifene and tamoxifen?
Raloxifene - antioestrogenic actions at breast and endometrium, oestrogenic effects on bones, lipids and coagulation
Tamoxifen - OESTROGENIC EFFECT AT ENDOMETRIUM (risk of endometrial cancer), lipids and bone, antioestrogenic effects at breast
Name an antioestrogen, it’s effect and what it is used for
Clomiphene inhibits oestrogen binding in the anterior pituitary (competes with oestrogen) increasing gonadotrophin release and thus oestrogen, stimulating the ovaries and inducing ovulation.
Used to treat infertility caused by lack of ovulation.
Name an antiprogestogen, it’s action and what it is used for
Mifepristone is a PR antagonist in the presence of progesterone and sensitises the uterus to prostaglandin (involved in ischaemic necrosis of the endometrium).
This is used in combination with prostaglandin for medical termination of pregnancy.
Name a steroidal anti androgen, how it works and what it is used for.
Cyproterone has week progesterone effects and competes with dihydrotestosterone in androgen tissues. It acts at the hypothalamus to decrease the amount of gonadotrophin.
Used to treat prostatic cancer, precocious puberty in males and masculinisation in women.
Name a non steroidal anti androgen, how it works and it’s uses.
Flutamide competes with androgens for ARs in the prostrate, preventing hyperplasia.
Used to treat prostate cancer
Name an anti androgen enzyme inhibitor, how it works and when it is used
Finasteride inhibits 5a reductase which converts testosterone to dihydrotestosterone which has higher affinity for AR in the prostate.
Used to treat benign prostatic hyperplasia
