L6 - Sex Steroids Flashcards
What are sex steroids derived from
Cholesterol
Sex steroids
Progesterone
Oestradiol
Testosterone
Oestrogen post menopause
Estrone - less potent
Sex steroid mechanism of action
- Hydrophobic therefore can pass through the cell membrane
- Bind to a nucleur receptor
- Activate gene transcription therefore gene expression
- lag between exposure of the agonist and interactions downstream effect
Effects of oestradiol
- endometrium proliferation
- thin cervical mucus
- proliferation of breast tissue
- myometrium contractions
- stimulates the expression of progesterone receptors
Effects of progesterone
- inhibits myometrium contractions
- production of thick acidic cervical mucus
- stimulates growth of secretory glands in endometrium
- maintains pregnancy
- inhibits expression of oestrogen receptors
Testosterone
Stimulates male characteristics:
- facial and body hair
- deep voice
- anabolism
- aggression
Oestrogen secondary actions
- mildly anabolic
- sodium and water retention
- raises HDL
- lowers LDL
- inhibits osteoclasts activity’s therefore maintains bone density
- impairs glucose tolerance
- increases blood glucose coagulability
Oestrogen side effects
- tender breasts
- nausea and vomiting
- water and retention
- increased risk of DVT and thromboembolism
- impaired glucose tolerance - diabetes
- endometrial hyperplasia - cancer
- ovarian metaplasia - cancer
- breast hyperplasia - cancer
Progesterone secondary actions
- stimulates secretory gland formation in endometrium
- anabolic
- increases bone mineral density
- fluid retention
- mood changes
- inhibits myometrium contractions to maintain pregnancy
Side effects of progesterone
- weight gain - anabolic
- fluid retention - oedema
- acne
- nausea and vomiting
- irritability, depression and PMS
- lack of concentration
Testosterone actions and side effects
- male secondary sex characteristics
- anabolic
- acne
- voice changes
- increased aggression
- lower HDL: LDL ratio - increased risk of atherosclerotic disease
Mechanisms of oestrogen entry
- well absorbed in the GI tract - oral intake
- hydrophobic - readily absorbed from skin and mucous membranes - can be given in patches
Metabolism and excretion of oestrogen
Metabolism:
- occurs in the liver - drug is conjugated for excretion (phase 2 metabolism)
Excretion:
- in the urine via glucuronides and sulfates
Pharmacokinetics of progesterone
Injected progesterone is bound to albumin
Some stored in adipose tissue
Metabolised in liver
Excretes in the urine when conjugated to glucuronic acid
COCP side effects
Small risk of thromboembolism Increased risk: - smoking - prolonged use in over 35 year olds - obese - hypertension
Metabolism of oestrogen and progesterone
CYP 450 enzymes in the liver
Reduction in contraceptive efficacy
CYP 450 enzyme inducing drugs such as:
- carbamazepine or phenytoin ( anti- epileptic)
- rifampin and rifabutin
- St John’s Wort (anti depressant)
More oestrogen and progesterone is metabolised as there is increased production in CYP 450
Soya protein
Enhances oestrogen absorption
Reduces storage in adipose tissue and muscles - decreased Vd
Decreases half life from 15 to 7 hours
Why is hormone replacement therapy given?
Unmanageable symptoms of:
- hot flushes
- sweats
- dyspareunia
- insomnia
- protective against osteoporosis - oestrogen inhibits osteoclasts activity
- not protective against heart disease
Steroids used in hormone replacement therapy
Oestradiol:
- valerate
- enanthate
- Premarin
Progesterone:
- medroxyprogesterone acetate
- norethisterone
- levonorgestrel
HRT routes of administration
Oral - tablet Transdermal - patches Implant Transvaginal - pesaries Nasal
Risk factors of HRT
Unopposed oestrogen - increased risk of ovarian and endometrial cancer
Opposed oestrogen - increased risk of breast cancer
Increased risk of DVT - primary oral route
Increased risk of stroke in patients under 60- oral use (tibolone)
Active Protein C
Inhibits the activation of factor VIII
Inhibits the activation of factor V
