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
