Sex Hormones and HRT Flashcards
What are the sex hormones?
- Progesterone
- Oestrogen
- Testosterone
What are the sex hormones derived from?
Cholesterol
What do many of the sex hormones share?
Anabolic pathways
What can synthetic sex hormones be produced to do?
Act on the receptors with good effect
How can useful drugs be produced from sex hormones?
By minor modifications of parent groups
What drugs are used in contraception and HRT?
Oestrogen and progesterone
Are progesterone and oestrogen receptor intra- or extracellular?
Intra
What is affected when oestrogen and progesterone bind to their receptors?
Gene transcription
Where are oestrogen and progesterone receptors found at particularly high levels of expression?
In the female tract
What are the actions of progesterone around the body?
- Secretory function of endometrium
- Anabolic effects
- Increased bone density
- Fluid retention
- Mood changes
What are the side effects of progesterone?
- Weight gain
- Fluid retention
- Acne
- Nausea and vomiting
- Irritability
- Lack of concentration
What are the actions of oestrogen around the body?
- Mild anabolic effects
- Sodium and water retention
- Raise HDL, lower LDL
- Decrease bone reabsorption
- Improve blood coagulability
What are the side effects of oestrogen?
- Nausea and vomiting
- Water retention
- Risk of thromboembolism
- Impaired glucose tolerance
- Endometrial hyperplasia and cancer risk
What does the COCP contain?
A variety of synthetic oestrogens in combination with 1st-4th generation progesterone
How does the COCP work?
By acting with the endocrine system to prevent ovulation, and the reproductive tract to cause cervical mucus thickening and endometrial thickening
What are the adverse effects of the COCP?
Quite minor
- Increased risk of DVP
- Raising of blood pressure
- Increased risk of gallstones
- Decreased glucose tolerance
- Increased risk of stroke
How are COCPs metabolised?
They undergo metabolism in both phase I and II hepatic pathways
What is the result of COCPs undergoing metabolism in phase I and II hepatic pathways?
They are affected by CYP inducers
What are the CYP inducers?
- Phenytoin
- Carbamazapine
- Barbituates
- Rifampicin
- Alcohol
- Sulphonylureas
What effect can broad-spectrum antibiotics have on the COCP?
It can reduce the efficacy of the COCP
Why does the use of broad-spectum antibiotics reduce the efficacy of COCP?
The effect they have on intestinal flora will reduce their re-uptake into the circulation by lowering enterohepatic recycling
What risk factors need to be evaulated before commencing on COCP?
- BMI
- Blood pressure
- Migraines
- Smoking history
What advice is given to a patient taking COCP?
- Taking it every day
- Any missed days will require use of other contraceptives for 7 days
- Any vomiting or diarrhoea may make COCP ineffective
- Blood pressure checks needed every 3-6 months
What is the main action of the progesterone only pill (POP)?
Thickening of cervical mucus
What are the secondary actions of the POP?
- Endometrial thickening
- Endocrinological effects
What are the disadvantages of the COCP compared with the POP?
- Much narrower window of use
- Much less reliable
- More side effects than COCP
What side effect may occur with POP?
Spotting
In whom is the POP indicated?
- Risk factors for venous thromboemboli
- Smokers
- Hypertensive
These women are not suitable for COCP
What progestorone implants provide long term contraception?
- Intramuscular implant
- Subcutaneous deposition
- Intra-uterine device
How long to progesterone implants provide contraception for?
Between 3 months and 5 years
What is hormone replacement therapy used for?
- To prevent the symptoms of the menopause
- Limit the early effects of osteoporosis
Give a symptom of the menopause that can be prevented using HRT
Hot flushes/sweats
Should HRT be used to prevent IHD?
No
How can HRT be administered?
- Orally
- Transdermally
- Implant
- Transvaginaly
What risks does HRT carry?
- Increased risk of endometrial cancer and ovarian cancer
- Increased risk of breast cancer
- Increased risk of stroke
- Increased risk of DVT
What should be done before starting any woman on HRT?
All the side effects should be discussed, and baseline investigations should be undertaken
What properties do the selective oestrogen receptor modulators (SERMs) exhibit?
Mixed agonist/antagonist properties
What is the specific outcome of SERMs dependant on?
- Tissue specific expression of oestrogen receptors
- Genes associated with receptors
- Presence of transcription factors
Give three examples of SERMs
- Clomiphene
- Tamoxifen
- Raloxifene
What is clomiphene?
An oestrogen antagonist acting on the pituitary
What does clomiphene do?
Induces ovulation
How does clomiphene induce ovulation?
By inhibiting negative feedback
What properties do tamoxifen and raloxifene have?
Differing agonist/antagonist tissue profiles
How do tamoxifen and raloxifene have differing agonist/antagonist tissue profiles?
By acting as anti-oestrogenic in breast tissue, but oestrogenic in endometrium
What effect does tamoxifen and raloxifene have on breast cancer risk?
Reduces it by 50%
What effect does tamoxifen and raloxifene have on endometrial cancer risk?
It increases it
What effect does tamoxifen and raloxifene have on oestroporosis risk?
Decreases it
