4.2 Sex Steroid Pharmacology Flashcards
What are sex steroids synthesised from?
Cholesterol
How do steroid hormones exert their effects?
Classic nuclear receptors
Exerts effects through gene transcription
But also a membrane receptors
What are the major effects of oestrodiol?
Stimulates growth of the endometrium and breast
Stimulates production of progesterone
Actions
- mild anabolic
- sodium and water retention
- raised HDL, lower LDL
- decreased bone resorption
- impaired glucose tolerance
- increase blood coagulability
What are the major effects of progesterone?
Stimulates growth of the endometrium and breast
Maintains pregnancy
Inhibits production of ER
actions
- secretory endometrium
- anabolic
- increase bone mineral density
- fluid retention
- mood changes
- maintain pregnancy
What are the major roles of testosterone?
Stimulates male characteristics
Hairy body
Deep voice
Anabolism
Aggression
acne
what are the side effects of oestrogen?
breast tenderness nausea, vomiting water retention increased blood coagulability thromboembolism impaired glucose tolerance endometrial hyperplasia and cancer ovarian metaplasia and cancer breast hyperplasia and cancer
what are the side effects of progesterone?
weight gain fluid retention anabolic acne nausea/vomiting irritability depression, PMS lack of concentration
what are the side effects of testosterone?
metabolic - adverse effects on lipid profiles, particularly the HDL-C/LDL-C ratio, hence increased risk of atherosclerotic disease in males
what are the main pharmacokinetic points of oestrogen?
- natural and synthetic oestrogen well absorbed in the GI tract
- also readily absorbed from skin and mucous membranes
- metabolism = liver
- excretion = in the urine as glucuronides and sulphates
what are the main pharmacokinetic points of progesterone?
injected progesterone is bound to albumin with some stored in adipose tissue
metabolised by the liver
metabolites excreted in the urine conjugated to glucuronic acid
what are the adverse effects of the combined pill?
- risk of thromboembolism is small
- smoking increases this risk substantially
- also for long term use in women over 35
- consider other risk factors e.g obesity and hypertension
what are the COCP and POP contraceptives metabolised by? what can effect their efficacy as a result?
COCP and POP are metabolised in the liver by CYP 450
Therefore, efficacy is reduced by enzyme inducing drugs
e. g anti-epileptics such as carbamazepine or phenytoin
e. g antibiotcs such as rifampicin and rifabutin
e. g some natural products such as St johns wort
because they all INCREASE the production of hepatic CYP450
how do soya protein products effect oestrogen absorption?
enhance oestrogen absorption and reduce its storage in adipose tissue and muscle
as a result, cause the half life to be reduced from 15 to 7 hours
why would you prescribe hormone replacement therapy to a menopausal woman?
symptom management e.g hot flushes/sweats and dyspareunia
osteoporosis prevention
HOWEVER: not good for the prevention of heart disease and shouldn’t be prescribed for that
what steroid can be used in hormone replacement therapy and how is it administered?
oestrodial
administered
- orally
- transdermally
- implant
- transvaginally
- nasally
what are the risks of hormone replacement therapy?
- (ERT) unopposed oestrogen = increased risk of developing endometrial and ovarian cancers
- (HRT) opposed oestrogen = increased risk of developing breast cancer
- increased risk of venous thromboembolism
- cardiovascular disease
- increased risk of stroke
how does hormone replacement therapy have adverse effects on the thromboembolism profile?
increased activated protein c resistance
increased thrombin activation
decreased anti thrombin III activity
decreased protein S levels
Decreased factor VII levels
decreased tissue factor pathway inhibitor
how does hormone replacement therapy have a beneficial effect on the lipid profile?
increased HDL-c
decreased oxoLDL-c
decreased triglyceride
decreased lipoprotein (a)
what is Mifepristone (RU486)?
progesterone (and glucocorticoid) receptor antagonist
acts as a anti-progesterone
sensitising the myometrium to prostaglandin-induced contractions
used for termination of pregnancy
what is a SERM?
a selective oestrogen receptor modulator
consists of pure agonists and pure antagnoists that act on oestrogen receptors
are distinct in having varying effects in differing tissues
drugs in this class have important clinical usage e.g tamoxifen, raloxifene
give an example of three Selective oestrogen receptor modulators
clomiphene
Tamoxifen
Raloxifene
what is clomiphene?
a selective oestrogen receptor modulator (SERM)
used in the treatment of anovulation
competes with oestrogen for ER binding
leads to ovulation induction through increased production of anterior pituitary hormones
what is tamoxifen and how does it act?
It is a selective oestrogen receptor modulator (SERM)
has little affinity for oestrogen receptor
metabolised in liver to active derivatives which then compete with oestrogen for binding to the ER
in endometrium, acts as an ER agonist
in breast, acts as ER antagonist (causes cells to arrest in the cell cycle)
what is ulipristal acetate?
a selective progesterone receptor modulator
when used for emergency contraception, the primary mode of action is thought most likely to be delay or inhibition of ovulation
also effective for the treatment of uterine fibroids
