Endocrine HRT Flashcards
What is menopause?
The permanent cecassion of menstruations because of loss of ovarian follicular activity
What is the normal age in which menopause occurs?
It normally occurs between the age of 45-55 (average 51) but can be later
What is Climactenic?
The transition period before menopause when periods start to become irregular
What are the symptoms of menopause?
- Hot Flushes
- Urogenital atrophy, dyspareunia (painful sex)
- Sleep disturbance
- Depression
- Decreased libido
- Joint pain
What happens to the symptoms of menopause?
They normally diminish/ disappear within time
What are the hormonal changes in menopause?
Loss of negative feedback of oestrogen/inhibin on hypothalamus lading to an increase in LH and FSH
What are the major complications during and after menopause?
- Osteoporosis
- due to oestrogen deficiency
- resutling in a 10fold increase of fractures
- CVS riks
- before menopause: oestrogen has protective effect on CVS diesease
- This effect is lost after menopause (because loss of oestrogen)
When would you consider a HRT?
When someone has extreme burden of the symptoms of menopause (e.g. hot flushes)
–> HRT helps with vasomotor symptoms
Which Hormone(S) are replaced in HRT?
Why?
- Oestrogen
- promotes endometrial proliferation
- risk of endometrial carcinoma
- Progestarone
- to prevent endometrial hyperplasia
- not necessary in hysterectomy
What two forms of formulations are there to administer HRT?
- Cyclical (Estrogen every day + 12-14 days Progesterone)
- Continous combined
Via which routes can oestrogen be administered?
- Orally
- estradiol
- oral conjugated equine oestrogen
- Transdermal
- Intravaginal
In which chemical forms can oestrogen be administered?
What are each characteristic
Estradiol: high absorbance but also high fist pass metabolism –> low bioavailibility
Estrone sulphate (conjugated oestrogen)
Ethinyl estradiol :a semi-synthetic oestrogen. The ethinyl group protects the molecule from first pass metabolism
What are the side effects of HRT?
How likely are they to occur?
- Breast cancer
- Coronary heart disease
- Deep Vein Thrombosis
- Stroke
- Gallstones
–> very low risk if a healthy, postmenopausal symptomatic woman in her 50s taking HRT for 5 years
What are the effects of oestrogen and progesterone in HRT on Coronary heart disease?
For young women:
- Oestrogen:
- beneficial effects on lipid profile &
- endothelial function
- Synthetic progestins:
- Negate these effects of estrogen
Older women (>60):
- • Atherosclerosis
- Susceptible to prothrombotic & proinflammatory effects of oestrogen
–> Oestrogen replacement is good in younger women, bad in older women
What is Tibolone?
When is it used?
Prohomone with oestrogenic+ progesterongnic + slightly androgenic effects
reduces fracture risk
Increases Risk of Stroke
Might increase risk of Breast cancer
What is Raloxifene?
When is it used?
What are the risk and side effects?
•Selective oestrogen receptor modulator
- Oestrogenic in bone:
- Reduces risk of vertebral fractures
- Anti-oestrogenic in breast & uterus
- reduces breast cancer risk
- Does not reduced vasomotor symptoms
- increases risk of VTE (venout thromboemolism) & fatal stroke
What is Tamoxifen?
When is it used?
- Anti-oestrogenic on breast tissue
- Used to treat oestrogen-dependent breast tumours & metastatic breast cancers
What is premature ovarian insuficciency?
How often does this occur?
•Menopause occurring before the age of 40
(in about 1% of women)
What are the causes of premature ovarian insufficiency?
- Autoimmune
- Surgery
- Chemotherapy
- Radiation
Explain the mechanism and use of combined oral contraceptives
Oestrogen (ethinyl oestradiol) + Progestogen (e.g. levonorgestrel or norethisterone)
- Suppress ovulation:
- E&P: negative feedback actions at hypothalamus/pituitary
- P thickens cervical mucus
•Take for 21 days (or 12 weeks), stop for 7 days (normally stop after 5 years to let body recover)
What is the clinical use and indication of progesterone only oral contraceptive?
It is taken when:
- When oestrogens contra-indicated
- –-> smoker, > 35 yrs old, migraine with aura
- Must be taken at the same time each day
- Short half-life
- Short duration of action
•Long acting preparations may be given via an intra-uterine system
Which methods are the for emergency (post coital) contraception?
-
Copper IUD (intrauterine contraceptive device)
- exclude pregnancy first
- affects sperm viability and function
- Effectiveness not reduced in overweight/obese women
- 5 (up to 7) days after unprotected intercourse
- Levonorgestrel (within 72 hours)
-
Ulipristal (up to 120 hours after intercourse)
- Anti-progestin activity
- delay ovulation by as much as 5 days
- Impairs implantation
