Session 4 Sex Steroid Pharmacology Flashcards
What are the three types of sex steroids?
What are they synthesised from?
- oestrogens, progestagens, androgens
Synthesised from cholesterol
What does the enzyme aromatase do in terms of sex steroid synthesis?
Converts androstenedione to oestrone
Converts testosterone to oestradiol
NB: progesterone is converted to hydroxyprogesterone then testosterone then oestradiol
What type of receptors are steroid hormone receptors?
How do they exert their effects?
- classic nuclear receptors
- exert effects through gene transcription
(Are also a membrane receptor for oestrogen)
What are the major effects of oestradiol?
- stimulates growth of the endometrium and breast
* stimulates production of progesterone receptor
Major effects of progesterone?
Stimulates growth of the endometrium and breast
Maintains pregnancy
Inhibits production of oestrogen receptor
Major effects of testosterone?
Stimulates male characteristics Hairy body Deep voice Anabolism Aggression
Oestrogen action (6) and side effects
Action:
- mild anabolic
- sodium and water retention
- raises HDL and lowers LDL
- decrease bone resorption
- impair glucose tolerance
- increase blood coagulability
Side effects:
- 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
Progesterone / Progestin action and side effects
Actions
- secretory endometrium
- anabolic
- increases bone mineral density
- fluid retention
- mood changes
- maintains pregnancy
Side effects
- weight gain
- fluid retention
- anabolic
- acne
- nausea, vomiting
- irritability, depression and PMS
- lack of concentration
testosterone action and side effects
Both:
- male secondary sex characteristics
- anabolic
- acne
- voice changes
- increases aggression
- metabolic = adverse effects on lipid profiles particularly the HDL-C/LDL-C ratio HENCE increased risk of atherosclerotic disease in males
Pharmacokinetics of Oestrogen
4 points
Natural and synthetic oestrogens are well absorbed in the GI tract
Also readily absorbed from skin and mucous membranes
Metabolism = liver
Excretion = in the urine as glucuronides and sulfates
Pharmacokinetics of progesterone
3 points
Injected progesterone is bound to albumin with some stored in adipose tissue
Metabolism = liver
Excretion = in the urine conjugated to glucuronic acid
What are some adverse effects of the combined pill?
Risk of thromboembolism is small
BUT Smoking increases the risk
Also increased risk for long-term use in women over 35
Also consider other risk factors such as obesity and hypertension
Metabolism of COCP and POP contraceptives?
What is the significance of this?
Metabolised in the liver by CYP 450 enzymes
THEREFORE, Oral contraceptive efficacy is reduced by enzyme inducing drugs such as:
* anti-epileptics (carbamazepine or phenytoin)
* antibiotics (rifampicin ad rifabutin)
* natural products (St John’s Wort)
All of these drugs INCREASE the production fo hepatic CYP450
Soya protein products enhance oestrogen absorption and reduce its storage in adipose and muscle and so cause the half life to be reduced from 15 hours to 7 hours
Enzyme inducing drugs increase the production of hepatic CYP450 enzymes which decrease the efficacy of oral contraceptives
why would hormone replacement therapy be prescribed in menopause?
- to help improve symptoms e.g. hot flushes, sweats and dyspareunia
- osteoporosis
NOT an indication for prevention or treatment of heart disease
What are the 5 routes of administration of HRT?
- Oral
- Transdermal
- Implant
- Transvaginal
- Nasal
