7) Sex Steroid Hormones Flashcards
What is the function of GnRH?
Stimulates synthesis and secretion of LH and FSH
What is the function of FSH?
Follicle growth and oocyte maturation
What is the function of LH?
Ovulation and causes ruptured follicle to become corpus luteum
What is the function of oestrogen in the menstrual cycle?
Repair and growth of endometrium
What is the function of progesterone in the menstrual cycle?
Preparation of endometrium for implantation and promotes growth of mammary glands
How are the sex steroids transported?
Bound to sex hormone binding globulins (except progesterone) and albumin
What regulates sex hormone binding globulins?
Production upregulated by oestrogen
How can the sex steroids be stored?
In fatty tissue (adipocytes and brain), complex into plasma membrane
How are the sex steroids excreted?
Metabolites excreted in faeces and urine as glucuronides and sulphates
Describe the enterohepatic recirculation of oestrogen:
Oestrogen conjugated with glucuronide and into bile. Intestinal bacteria unconjugate oestrogen so it gets recycled into blood
How is sex steroid hormone binding to nuclear receptors regulated?
Co-factors stabilise the hormone-receptor complex
Integrators have the opposite effect
Describe the isoforms of steroid hormone receptors:
Oestrogen: ER alpha, ER beta
Progesterone: PR-A and PR-B
Androgen: AR1 and AR2
What are the 3 sex steroid hormones and their effects?
Oestradiol - stimulates growth of endometrium, breast and production of PR
Progesterone - maintains pregnancy, growth of endometrium and breast, inhibits production of ER
Testosterone - simulates male characteristics, anabolism, aggression
How are the sex steroids synthesised?
Synthesised from cholesterol
Oestradiol formation occurs in adrenal, adipose and gonads
Progesterone and testosterone in gonads
What molecule can be used as a pregnancy marker?
Estriol
What are the side effects of too much oestrogen?
Breast tenderness
Water retention (bloating)
Thromboembolism
Breast, ovary and endometrial hyperplasia + cancer
What are the side effects of too much progesterone?
Weight gain Acne Irritability Depression PMS
What are the side effects of too much testosterone?
Adverse effects on lipid profile to increased risk of atherosclerosis
What are the types of COCP?
Monophasic - fixed oestrogen and progestin
Biphasic - oestrogen constant, progestin increases second half
Triphasic - oestrogen for first 14, progestin 1-7 and 14-21
Describe the COCP:
Synthetic oestrogens and 1st to 4th generation progesterone
How can the COCP be administered?
Oral, transdermal patch, implants
What is the mechanism of action of the COCP?
Inhibits FSH and LH to prevent ovulation, also thickens cervical mucus and keeps endometrium atrophic
What are the adverse effects of the COCP?
Venous thromboembolism
MI and HTN
Gallstones (increased cholesterol to liver)
What potential drug interactions can occur with the COCP?
Inducers: rifampicin, carbamazepine, phenytoin, St John’s Wort
What should be monitored when on the COCP?
BP, BMI, side effects
Describe the POP:
28 days of progestin
What can be used as emergency contraception up to 72 hours post coitus?
Levonorgestrel
What can be used as emergency contraception up to 120 hours post coitus?
Ullipristal acetate - selective progesterone receptor modulator
Copper IUD
When is hormone replacement therapy prescribed?
For hot flushes and vaginal dryness (symptoms of menopause)
When is HRT contraindicated?
Heart disease
What is the difference between ERT and HRT?
ERT - oestrogen replacement therapy
HRT - hormone (progesterone and oestrogen) replacement therapy
What are the risks of ERT?
Increased risk or endometrial and ovarian cancer
What are the risks of HRT?
Increased risk of breast cancer
Risk of stroke, risk of VTE
What are the routes of administration for HRT?
Oral, transdermal, implant, transvaginal, nasal
What is the mechanism of action of clomiphene and what is it used for?
Inhibits oestrogen by binding to ER in anterior pituitary causing decreased negative feedback and increased FSH and LH
Used for ovulation induction in IVF
What is the mechanism of action of tamoxifen and what is it used for?
Binds to ER in breast and blocks oestrogen stimulated myoepithelial cell division
Decreases risk of breast cancer
What is the mechanism of action of mifepristone and what is it used for?
Partial agonist at PR and sensitises uterus to prostaglandins
Used for medical termination of pregnancy or induction of labour
Describe an androgen replacement therapy and its use:
Finasteride blocks 5-alpha reductase from catalysing testosterone -> 5DHT
Prevents hair loss and BPH
