Sex Steroid Hormones

Question 1

State the actions of oestradiol

Answer 1

• Stimulates growth of the endometrium and breast
• Stimulates production of progesterone receptor
• Sodium and water retention
• Raises HDL, lowers LDL

Question 2

State the actions of progesterone

Answer 2

• Stimulates growth of the endometrium and breast
• Maintains pregnancy
• Inhibits production of oestradiol receptor

Question 3

State the actions of testosterone

Answer 3

• Stimulates male characteristics
• Hairy body
• Deep voice
• Aggression
• Metabolic - adverse effects on lipid profiles particularly the HDL/LDL ratio - increase atherosclerotic disease risk in males

Question 4

Describe the PK of sex hormones including transport, metabolism, storage and excretion

Answer 4

• Transport bound to sex hormone binding globule (SHBG) (except progesterone) and albumin
• Liver metabolism
• Storage increases half life - easily stored in fatty tissues as lipophilic
  
  • Complex into the plasma membrane (similar to cholesterol)
• Metabolites excreted in faeces and urine

Question 5

Describe how sex hormones bind to its target site

Answer 5

• Sex hormones cross the cell membrane and bind to nuclear receptors
• Bind to receptors specific for the hormone (ER, PR, AR)

Question 6

Describe the regime and mechanism of COCP

Answer 6

• Can be given 21 days and then stopped, or given 21 days + 7 days placebo
• Mode of action
  
  • Suppression of ovulation - inhibits FSH and LH
  • Thickens cervical mucus
    
    • Prevents secretory phase of endometrium - prevents implantation

Question 7

Describe the regime and mechanism of POP

Answer 7

• Taken everyday
• Work by thickening the cervical mucous and endometrium
• Works best when started in the follicular phase of the menstrual cycle

Question 8

List potential side effects of COCP and POP

Answer 8

• Venous thromboembolism leading to PE
• Myocardial infarction
• Hypertension
• Decrease glucose tolerance
• Increase risk of stroke in women with focal migraine
• Headaches
• Mood swings
• Cholestatic jaundice
• Increase incidence of gallstones
• Precipitate porphyria

Question 9

Describe potential adverse drug interactions with COCP and POP

Answer 9

• Metabolised by cytochrome P450
• COCP’s efficacy will be reduced by P450 enzyme inducing drugs
  
  • Anti-epileptics - carbamazepine, phenytoin
  • Some antibiotics - rifampicin, rifabutin
  • Some natural products - St John’s Wort
    
    • Increase production of hepatic P450
• Soya protein products enhance oestrogen absorption and reduce its storage in adipose and muscle
  - Reduces its half life

Question 10

Give missed pill advice

Answer 10

• One missed pill - take the last pill immediately, even if this means taking two pills in one day
  
  • Continue taking the rest of the pack as normal
  • Take seven-day pill-free break as normal
• Two missed pills - take the last pill immediately, even if this means taking two pills in one day
  
  • Continue taking the rest of the pack as normal
  • Use extra contraception for the following seven days
• If there are 7 or more pills left in the pack after the last missed pill - finish the pack and take 7-day pill-free break as normal
• If there are less than 7 pills left in the pack, finish the pack and start a new pack the next day
  - Miss out on the pill-free break

Question 11

Understand the purpose of giving sex hormone derivatives for menopausal women

Answer 11

• Hormone replacement therapy given to relieve symptoms of menopause
• Reduces hot flushes/sweats, vaginal dryness, dyspareunia
• Prevent osteoporosis
• Not useful in reducing CVD risk

Question 12

Describe the different sex hormone derivatives given for menopause and its routes of administration

Answer 12

• HRT contains both oestrogen and progestin
  
  • Given to women who have not had hysterectomy, to reduce chance of getting endometrial cancer
• ERT contains only oestrogen
  Routes of administration - oral, transdermal (skin patches, gels, creams), implant, transvaginal, nasal

Question 13

Describe the major side effects of HRT/ERT

Answer 13

• Unopposed oestrogen (ERT) - increases risk of developing endometrial and ovarian cancers
• Opposed oestrogen (HRT) - increases risk of developing breast cancer
• Increased risk of stroke and ischaemic heart disease
  
  • However, beneficial effect on lipid profile - increased HDL, decreased triglyceride
• Increase risk of venous thromboembolism
  
  • Increased activated protein C resistance, increased thrombin activation, decreased protein S levels

Question 14

Outline the action of anti-oestrogens

Answer 14

• Weak oestrogens that block receptors
• Clomiphene - ovulation induction
  
  • Inhibits oestrogen binding to its oestrogen receptor in the anterior pituitary
  • Inhibits negative feedback
  • Results in increased FSH, LH expression
  • Used to treat infertility
• Tamoxifen - reduces risk of breast cancer
  
  • Binds to oestrogen receptor in breast tissue and blocks oestrogen-stimulated myoepithelial cell division
    
    • Also causes ovulation induction

Question 15

Outline the action of anti-progestogens

Answer 15

• Mifepristone
• Partial agonist to progesterone receptor, inhibits progesterone action
• Sensitizes the uterus to prostaglandins
• Used for medical termination of pregnancy and induction of labour

Question 16

Outline the action of SERMS

Answer 16

• Selective Estrogen Receptor Modulators
• Raloxifene - has oestrogenic and anti-oestrogenic effects depending on tissue
  
  • Protects against osteoporosis
  • Oestrogenic effects on bone, lipid metabolism and blood coagulation
  • No proliferative effects on endometrium and breast
• Reduced risk of invasive breast cancer in post menopausal women with osteoporosis
• Increases hot flushes

Question 17

Outline the action of anti-androgens

Answer 17

• Cyproterone - progesterone derivative
• Weak progestogenic effect - partial agonist at the progesterone receptor, that competes with dihydrotestosterone
• Used in combined contraceptive pill
• Can be used to treat advanced prostate cancer