contraceptives, HRT and SERMs Flashcards
what is menopause?
Permanent cessation of menstruation
Loss of ovarian follicular activity
what is the average age for menopause?
Average age 51 (range 45-55)
what is climacteric?
Climacteric: period of transition period
what are some symptoms of menopause?
Hot flushes (head, neck, upper chest) Urogenital atrophy and dyspareunia (difficult or painful sexual intercourse)
Sleep disturbance
Depression
Decreased libido
Joint pain
Symptoms usually diminish/disappear with time.
how does hypothalamo-pituitary-gonadal axis work?
GnRH from the hypothalamus stimulates the anterior pituitary to produce LH and FSH.
This makes ovaries make oestradiol and inhibin B.
Oestradiol and inhibin inhibit LH and FSH.
what hormonal changes occur during menopause?
low levels of oestradiol and inhibin B because of the follicular atresia.
This means that there is a less negative feedback so gonadotrophin levels go up.
So in a 55 year old woman you’d expect the LH and FSH to be high.
What complications occur in menopause?
Osteoporosis
- Oestrogen deficiency
- Loss of bone matrix
- 10-fold increased risk of fracture
Cardiovascular disease
- protected against CVD before the menopause
- have the same risk as men by the age of 70
what does hormone replacement therapy (HRT) control?
controls vasomotor symptoms
what are the hormones used in HRT and what are the pros and cons?
Oestrogen (E):
- endometrial proliferation
- risk of endometrial carcinoma (hence you can’t just give oestrogen, you need to combine it with progesterone as it inhibits endometrial proliferation)
Progestogens (P)
HRT: E + P to prevent endometrial hyperplasia
(If hysterectomy: E only since there is no uterus so don’t need to worry about the endometrial proliferation)
what are the HRT formulations used?
2 types:
Cyclical: Take oestradiol every day and for the last 12-14 days you take some progesterone.
Continuous combined- take a bit of oestrogen and progesterone every day.
what are some HRT/oestrogen preparations that can be taken?
Oestrogen preparations
Oral estradiol (1mg)
Oral conjugated equine oestrogen (0.625 mg)
Transdermal (patch) oestradiol (50 microgram/day)
Intravaginal
**note that patch has a much lower dose than the others
what are the different oestrogens that can be used?
Estradiol is well absorbed Low bioavailability (first pass metabolism)
Estrone sulphate (‘conjugated’ oestrogen)
Ethinyl estradiol :a semi-synthetic oestrogen
The ethinyl group protects the molecule from first pass metabolism
Most oestrogens can also be administered via transdermal skin patches
what are some side effects of taking oestrogen/HRT?
Breast cancer Coronary heart disease Deep Vein thrombosis Stroke Gallstones
The absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years is very low.
what is the link between HRT and coronary heart disease?
Timing of exposure is important
No excess risk in younger menopausal women.
Those who were in their 60s and started HRT have a greater risk. You can reassure the younger women that the absolute risk is very small but have some consideration for the people who have risk factors for breast cancer, heart disease and stroke.
how do oestrogen and progesterone contrast in the way they affect the body?
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
what is tibolone and what does it do?
Synthetic prohormone
Oestrogenic, progestogenic & weak androgenic actions
Reduces fracture risk
Increased risk of stroke (RR: 2.2)
possibly increased risk of Breast Ca
what is raloxifene and what does it do?
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
risk of VTE & fatal stroke
SERMs have tissue selective effects
what is tamoxifen and what does it do?
Anti-oestrogenic on breast tissue
Used to treat oestrogen-dependent breast tumours & metastatic breast cancers
what is premature ovarian insufficiency
Menopause occurring before the age of 40
1% of women
***treatment for these women would be HRT as you want to protect their bones.
what might be the possible causes for premature ovarian insufficiency?
Autoimmune
Surgery
Chemotherapy
Radiation
what are combined oral contraceptives?
Oestrogen (ethinyl oestradiol) + Progestogen (e.g. levonorgestrel or norethisterone)
Mechanism is to suppress ovulation:
E&P: negative feedback actions at hypothalamus/pituitary
P thickens cervical mucus making it more difficult for the sperm to pass through
Take for 21 days (or 12 weeks), stop for 7 days
what is progesterone only contraceptive?
When oestrogens contra-indicated (eg this is if there is a risk of thrombosis, since oestrogens have pro-coagulant effects)
smoker, > 35 yrs old, migraine with aura
this is less effective than the combined contraceptive but if there are contra-indications then the progesterone only contraceptive is the best option.
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
what are some examples of 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
