Menopause, Contraceptives, HRT and SERMs Flashcards
What is menopause?
Permanent cessation of menstruation
- loss of ovarian follicular activity
What is the average age of a patient experiencing menopause?
51 (45-55)
What is the climacteric period?
The climacteric period is a period leading up to the menopause where the patient experiences irregular periods
What are symptoms of menopause?
- Hot flushes (head, neck, upper chest)
- Urogenital atrophy and dyspareunia (painful sex, as a result of urogenital atrophy, very dry)
- Sleep disturbance
- Depression
- Decreased libido
- Joint pain
What happens to the symptoms of menopause, are they alleviated over time or with treatment?
Symptoms usually diminish/disappear over time
Describe and draw on paper the hypothalamo-pituitary-gonadal axis (HPG axis) in women.
- Hypothalamus releases GnRH
- GnRH stimulates pituitary to produce LH/FSH
- LH/FSH stimulates ovaries to produce oestradiol and inhibin B
- Oestradiol and inhibin B exert negative feedback on pituitary and hypothalamus release of LH/FSH and GnRH
How does the HPG axis differ during menopause?
Oestradiol and inhibin B production is stopped thus LH/FSH levels rise (GnRH rises as well)
No negative feedback now so production is no longer inhibited
What are the 2 main complications of menopause and what are their main features?
Osteoporosis
- Oestrogen deficiency
- Loss of bone matrix
- 10-fold increased risk of fracture
Cardiovascular disease
- Protected against CVD before the menopause due to oestrogen effects
- Have the same risk as men by the age of 70 (risk rises with age)
What is the main reason HRT can be prescribed?
If the patient has disabling symptoms e.g. severe hot flushes
Why are oestrogen and progestogens given together in HRT?
Oestrogen causes:
- endometrial proliferation
- increases risk of endometrial carcinoma
Progestogens act to prevent endometrial hyperplasia
- thus preventing the potentially negative effects of the oestrogen alone from manifesting
What is the patient history that allows you to just give oestrogen replacement without progestogens?
If they have had a hysterectomy
- not worried about the possibility of endometrial cancer
What are the two types of HRT you can give?
Cyclical
Continuous combined
What is the rotation of hormone dose in cyclical HRT?
Oestrogen every day
Progestogens for 12-14 days
What are the 4 types of oestrogen replacement preparations?
- Oral oestradiol
- Oral conjugated equine oestrogen
- Transdermal (patch) oestradiol
- Intravaginal
How well is oestradiol is absorbed, what is its bioavailability and why?
- Oestradiol is very well absorbed
- Low bioavailability because undergoes extensive first pass metabolism in the liver
What is an example of a ‘conjugated’ oestrogen replacement form?
Estrone sulphate
What is ethinyl estradiol?
Ethinyl estradiol is a semi-synthetic oestrogen
- the ethinyl group protects the molecule from first pass metabolism, increases the bioavailability
What administration method can most oestrogens by administered by?
Transdermal skin patch
What negative effects does oestrogen have
Pro-thrombotic effects
Pro-inflammatory effects
Seen in older women because they have greater atherosclerosis whereas in younger women there is nowhere near the same degree of atheroma
What are the side effects of HRT?
- Breast cancer
- Coronary heart disease
- Deep vein thrombosis
- Stroke
- Gallstones
BCD are the main ones to remember
How high is the absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years?
Very low absolute risk
Who published a trial indicating HRT increases risk of of coronary heart diseae, what was the mean age, what is important in interpreting these results and what is the actual risk in younger menopausal women?
Women’s Health Initiative trials (WHI)
- 19 additional events a year per 10000 women
- mean age 63
- Timing of exposure is important
- No excess risk in women <10 years since menopause or 50-59 years
What is the general trend of increase in risk in breast cancer, CHD, DVT, stroke after taking HRT for 5 years?
Additional cases per 1000 women
- Breast cancer - 3
- CHD - 2.5
- DVT - 5
- Stroke - 2.5
What are the positive and negative effects in younger and older women (>60 yrs)?
Beneficial effects on lipid profile and endothelial function
- Synthetic progestins administered with the oestrogen negates the beneficial effects of the oestrogen
Older women (>60)
- Atherosclerosis (or degree of)
- susceptible to pro-thrombotic and pro-inflammatory effects of oestrogen
