Reporoductive And Post Reproductive Health Flashcards
What are 3 drug groups
• Sex steroid hormones
• Oestrogens, progestagens, androgens
• Inhibitors & antagonists • RU486, finasteride
• Mixed agonists/antagonists
• Selective estrogen receptor modulators (SERMs) and selective
progesterone receptor modulators (SPRMs)
What are 3 sex steroids synthesised from cholesterol
Progesterone, oestradiol, testosterone
Describe sex steroid synthesis
Ss
Describe steroid hormone receptors
• Classic nuclear receptors
• Exert effects through gene
transcription - need time for effects to happen
• But also a membrane receptor for oestrogen
What a re the major effects of oestradiol
Stimulates growth of the endometrium and breast; stimulates production of PR.
What are the major effects o progesterone
Stimulates growth of the endometrium and breast; maintains pregnancy; inhibits production of ER.
What are the major effects of testosterone
Stimulates male characteristics; hairy body; deep voice; anabolism; aggression.
What are the actions o oestrogen
Actions • Mild anabolic • Sodium and water retention • Raises HDL, lowers LDL • Decrease bone resorption • Impair glucose tolerance • Increase blood coagulability
What are the side effects of oestrogen
- Side effects
- Breasttenderness
- Nausea, vomiting
- Waterretention
- Increased blood coagulability • Thromboembolism
- Impaired glucose tolerance
- Endometrial hyperplasia & cancer • Ovarian metaplasia & cancer
- Breast hyperplasia & cancer
What are the actions of. Progesterone
Actions • Secretory endometrium • Anabolic • Increases bone mineral density • Fluid retention • Mood changes • Maintains pregnancy
What are the side effects of progesterone
Side effects • Weight gain • Fluid retention • Anabolic • Acne • Nausea/vomiting • Irritability Depression, PMS • Lack of concentration
What re the actions and side effects of testosterone
- 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
What are some pharmacokinetic points about oestrogen
Natural and synthetic oestrogens well absorbed in the GI tract
Also readily absorbed from skin and mucous membranes
Metabolism – liver
Excretion – in the urine as glucuronides and sulfates
What are some pharmacokinetic points about progesterone
pharmacokinetics points
Injected progesterone is bound to albumin with some stored in adipose tissue
Metabolised in the liver
Metabolites excreted in the urine conjugated to glucuronic acid
What are adverse effects of the cocp
Risk of thromboembolism is small
• 15 / 100 000 users / year compared to 5 / 100 000 non-users / year
• Smoking increases this risk substantially
• Also for long-term use in women over 35
• Also consider other risk factors such as obesity and hypertension
What are harmacokinetic points of oral contraceptives
• COCP and POP contraceptives are metabolised in the liver by CYP 450 enzymes
• Therefore oral contraceptive efficacy is reduced by enzyme inducing drugs – anti-epileptics such as carbamazepine or phenytoin;
– some antibiotics such as rifampicin and rifabutin and – some natural products such St John’s Wort
• because they all increase the production of hepatic CYP450
• Soya protein products enhance oestrogen absorption and reduce its storage in adipose and muscle and so cause the T1/2 to be reduced from ~15 to 7 hours
What happens in menopause
Ovarian follicle supply depleted
• Consequently ovarian sex steroid production stops • End of female reproductive capacity
• ALSO
Loss of oestrogen and progesterone leads to a range of systemic effects as symptoms of menopause
Why prescribe hrt
✓ Symptoms: e.g. hot flushes /sweats and vaginal dryness /
dyspareunia
✓Osteoporosis
X Heart disease
What are steroids used in hrt
Oestradiol: e.g. valerate, enanthate, micronised oestradiol, ethinyl estradiol, etc.
(1-2 mg/day)
Premarin® (0.625-1.25 mg/day)
Medroxyprogesterone acetate (Provera®) (2.5 mg/day) Norethisterone (1 mg/day)
Levonorgestrel (1.5 mg/day)
What are the routes of administration of hrt
ORAL TRANSDERMAL
IMPLANT TRANSVAGINAL NASAL
NICE Guidelines: HRT is NOT effective for the prevention of Heart Disease and should NOT be prescribed for that indication
What re the risks of hrt
▪ Unopposed oestrogen (ERT): increases risk of developing endometrial and ovarian cancers
▪ Opposed oestrogen (HRT): increases risk of developing breast cancer
▪ Increase risk of venous thromboembolism
▪ Adverse effect on thromboembolism profile – increased activated protein C resistance, increased thrombin activation, decreased anti-thrombin III activity, decreased protein S levels, decreased Factor VII levels and decreased tissue factor pathway inhibitor (but only for oral delivery systems)
▪ Cardiovascular disease
▪ Beneficial effect on lipid profile – increased HDL-C, decreased oxoLDL-C, decreased triglyceride, decreased lipoprotein(a) (not an effect if patient is already overweight, dose related and tibolone precipitates stroke > 60 years of age)
▪ Increased risk of stroke
▪ Use of oral but not transdermal oestrogen is associated with a small increase in the risk of stroke (against a baseline low population risk of stroke in women under 60 years)
What is mifepristone
Sensitising the myometrium to prostaglandin-induced contractions
Used for termination of pregnancy
What is a serum
Selective Estrogen Receptor Modulator
• cf pure agonists and pure antagonists
• SERMs are distinct in having varying effects in differing tissues
• Drugs in this class have important clinical usage • Tamoxifen
• Raloxifene
What is clomiphene
Clomiphene used in the treatment of anovulation Competes with oestrogen for ER binding
Leads to ovulation induction through increased production of anterior pituitary hormones
promotif pituitary to produce fsh - follicular development
What is tamoxifen
• A pro-drug
• Little affinity for the ER
• Metabolised in the liver to a active derivatives
• Tamoxifen active metabolites compete with oestrogen for binding to the ER
Some women dont benefit from it based on the isoform in the liver that is metabolising it. If the right one doesnt then it wont work
Describe tamoxifen acting as a serm
- Tamoxifen has converse effects in breast tissue and endometrial tissue
- In endometrium, acts as ER agonist
- In breast, acts as ER antagonist
- In breast, binding of the ER following tamoxifen treatment causes cells to arrest the cell cycle
What is ulipristal acetate
- 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
