lecture 9: menopause Flashcards
1
Q
What is the menopause?
A
- The menopause is the final menstrual period
- the average age of menopause is around 51-52 years (age range 48 - 55 years)
- defined retrospectively after 12 months of absent periods
2
Q
What is perimenopause?
A
- climacteric, menopause transition
- the period when ovarian function declines, cycles are irregular and menopausal symptoms appear
- begins mid to late forties, ends one year after menopause
- lasts for years
3
Q
What is post menopause?
A
- is the whole of women’s life after menopause
- no periods, no ovulation, hormones low, cannot conceive
4
Q
What is early menopause?
A
- 40 - 45 years
- 5%
5
Q
What is premature ovarian insufficiency?
A
- premature menopause
- menopause prior to 40 years
- 1%
6
Q
In what ‘state’ does a woman spend a lot of her life?
A
- postmenopause
7
Q
How many women can expect to reach the menopause?
A
- 95% of women
- female life expectancy has increased while age of menopause has remained constant
- around a third of our life is spent beyond the menopause
8
Q
What is the aetiology of menopause?
A
- loss of ovarian follicular activity at menopause
- decline in quantity and quality in the years preceding
9
Q
How many eggs are in the ovary?
A
- atresia (degeneration) of ovarian follicles (eggs) during the lifespan
- foetus at 20 weeks’ gestation
- each ovary contains about 5 million follicles
- term
- 1-2 million follicles
- puberty
- 300 000 - 400 000
- 37 years
- 100 000, then rapid loss
- perimenopausal threshold
- <1000 follicles?
- also a decline in quality of the follicles
- the follicles are not lost just through ovulation
- the vast majority of follicles are lost through atresia and apoptosis
10
Q
What is the age related decline in follicle numbers?
A
11
Q
What are factors regulating the age at natural menopause?
A
- poorly understood
- not influenced by race, age of menarche, parity, OCP
- genetic factors – are important
- cigarette smoking
- menopause is 1 - 2 years earlier
- surgical history
- hysterectomy may reduce the age at menopause by around 3 - 4 years
- may be due to impairment of the ovarian blood supply
12
Q
What is the aetiology of premature menopause (POI)?
A
- idiopathic
- karyotypically normal
- spontaneous POI (1%)
- iatrogenic
- surgery/chemo/radiotherapy (8 - 19% of women under 40)
- rare causes:
- galactosaemia (excess milk products, galactose is stored in the ovaries and is toxic to oocytes)
- auto-immune
- auto-immune
- genetic
- turner’s syndrome
- fragile x syndrome
13
Q
What chromosomal abnormalities can affect ovarian function?
A
- deletion in X chromosome between positions 13 and 26 can affect ovarian function
14
Q
What are physiologic changes associated with reproduction?
A
- hypothalamus becomes activated around puberty with pulsatile release of GnRH
- causes release of LH and FSH in a pulsatile manner from the anterior pituitary
- FSH affects the ovaries
- binds to granulosa cells and grows follicles
- follicles produce oestrogen
- results in secondary sexual development (eventually menstruation)
- LH binds to theca cells (stroma around the follicles)
- results in androgen production
15
Q
What is the ovarian follicle?
A
- secondary oocyte
- corona radiata
- cumulus oophorus
- antrum
- granulosa cells
- theca interna
- theca externa
produce oestrogen, activin, inhibin, follistatin, AMH
16
Q
What are varying stages of follicular development?
A
- in the cortex
- primary follicles as they are stimulated by FSH get larger, secondary
- produce oestrogen which thickens the lining of the uterus, and increasing oestrogen causes a surge of LH → stimulates ovulation
17
Q
What are the phases of menstruation?
A
- proliferative/follicular and secretory
- follicular phase
- FSH grows follicles
- follicles grow the lining of the uterus
- the glands are being developed
- increased growth and height
- as the follicles get larger and larger more oestrogen is produced
- this results in an LH surge
- produces a dominant follicle
- this dominant follicle produces progesterone
- important event because it stabilises this lining
- secretory phase
- further development of the glands
- they become secretory
- progesterone maintains the lining
- women who are anovulatory and don’t produce progesterone
- lining keeps growing and growing
- very long and irregular cycles
- at risk of endometrial hyperplasia and cancer
18
Q
Why is the dominant follicle able to continue growing for a while?
A
- follicles as well as producing oestrogen produce inhibin
- inhibin inhibits FSH
- FSH peak but then starts to come down
- yet one of the follicles continues to grow (dominant follicle) while the rest start to undergo atresia
- the dominant follicle essentially self-selects
- has more FSH receptors so can mop up more
19
Q
What is seen at the menopause?
A
- ovarian primoridal follicle stores are exhausted by atresia and ovulation
- ovulation will not occur after menopause, by this is retrospective
- therefore use contraception until no periods for one year, as ovulation may occur right up until last period, though less frequently
20
Q
What is the aetiology of perimenopause?
A
- ovarian primordial follicles decrease with age with an accelerated rate of loss from 37 years
- follicles become progressively more resistant to stimulation by gonadotrophins
- follicles that do develop may not secrete sufficient oestradiol (E2) and progesterone (P4) to produce regular menstruation
- during perimenopause, irregular anovulatory cycles lead to prolonged unopposed E2
- may lead to endometrial hyperplasia and cancer risk
21
Q
What are perimenopausal hormonal changes?
A
- decreased ovarian inhibin B, AMH from the ovarian granulosa cells
- gradual rise in FSH
- fluctuations in oestradiol and progesterone
- no substantial changes in androgen levels
- sex steroid levels fluctuate markedly on a daily basis
- measuring sex steroids is not useful when a woman of normal menopausal age develops symptoms
22
Q
What are hormone changes after the menopause?
A
- oestradiol declines following menopause
- FSH > 40 u/l
- LH > 30-40 u/l
- FSH starts to change before LH does
- androstenedione is still produced by the ovary and adrenal gland and is converted in peripheral tissues to oestrone (E1)
- androgens gradually decline during reproductive life but no dramatic change after menopause
23
Q
What are hormonal transitions?
A
- FSH less than 10 is normal for younger
24
Q
What are the investigations and treatment in POI?
A
- no periods for 4 months before age 40
- FSH levels greater than 40mlU/nl on 2 occasions at least 1 month apart (never rely on one of level); day 2- 6 if cycling
- exclusion of all other causes of absent periods, chromosome test
- acutally still need contraception: lifetime chance of ever conceiving 5 - 10%
- HRT/Contraception until around 50 years
- important to test for fertility reasons, depression, the effect on bones and even cardiovascular risk
- mortality increases by about 2% per year for the years of ‘periods lost’
25
What are the consequences of menopause?
* 20 - 40% of women have menopausal symptoms requiring treatment
* short-term:
* vasomotor symptoms (hot flushes, night sweats, formication)
* urogenital symptoms: vaginal dryness, atrophic vaginitis, dyspareunia, dysuria, frequency of urine
* sleep disturbance
* reduced libido
* depression, anxiety, labile mood
* memory loss, fatigue (may be due to other not sleeping etc)
* medium to long-term:
* bone loss and osteoporosis
26
What are hot flushes?
* occur in ~80% of women
* mechanisms not known
* maybe due to abnormal hyperthalamic regulation, thermoregulation
* last 4 min on average
* can last up to hours
* up to 30-50% resolve in 3/12 months
* up to 40% may continue to have significant symptoms up to 10 years after menopause
* increased with smoking, ETOH, surgical menopause, caffeine
* main reason why women request treatment
* oestrogen: most effective, 80% reduction
* meditation, relaxation, CBT to reduce anxiety
* think it is because of abnormal hype
27
What are urogenital symptoms?
* affects ~40% of postmenopausal women
* persist or worsen over time
* vaginal dryness
* discomfort
* dyspareunia
* UTI
* urgency
* pallor dryness
* redness
* decreased rugosity
* endometrial atrophy
* first line is intravaginal oestrogen (not systemic)
28
What affects emotional health during menopause?
* empty nest
* changing roles
* frail or ill parents
* loss of parents
* loss of fertility, identity as a woman
* sensual difficulties → marital difficulties
* loss of partner
* change in physical image/attractiveness
* retirement of self or husband
* adolescent children
29
What are bone symptoms and osteoporosis?
* oestrogen deficiency increases bone reabsorption
* directly impairs gut calcium absorption
* directly increases renal calcium excretion
* sharp acceleration of bone loss during the initial 5 years following menopause (3 - 5%/year)
* rate of loss then falls back to the age related loss of 1%/year
* low bone mass increases fracture risk
* prevalence 4% around 50 - 59 yo, greater than 50% by 80 yo
* mortality is increased by 25% in the first year after a fracture
* 25% of women, if they survive, need long term care
* can be treated/prevented/managed by increasing weight bearing exercise, vitamin D, calcium intake (1200mg/day)
30
What is the cardiovascular risk?
* after menopause, increasing central adiposity, decreased resting energy expenditure, worsening CVS, lipid and metabolic profiles
* hypertension (HT)
* potentially mediated by low oestrogens and loss of inhibition of metabolic neuropeptides
* HRT does not prevent Cardiovascular Disease (CVD)
31
What is the risk of HRT?
* combined oestrogen and progestogen, 50-79 years
* increased risk of stroke (0.8/1000/year)
* increased risk of clots (0.8/1000/year)
* increased risk of breast cancer with greater than 5 years use (0.8/1000/year)
* increased incidence of coronary heart disease
* WHI JAMA 2002, 2004
32
What are the benefits of HRT?
* most effective treatment for menopausal symptoms
* reduces frequency and severity of vasomotor symptoms by 75 - 85%
* improves vaginal dryness
* maintains or improves bone density and reduces fracture risk (1/1000 women/year)
* may improve quality of life, sleep, muscle aches and pains
* reduced colorectal cancer risk 0.8/1000/year (combined long term)
* however because of the risks of HRT it is not the firstline treatment for osteoporosis
33
What is HRT?
* hormone replacement therapy
* HRT contains oestrogen to treat symptoms and progestogen (if needed) to protect the endometrium
* would generally never prescribe to someone over 60 years of age
* usually prescribed for short-term gain
* lowest dose possible
* less than 5 years
* individualised risk
* contraindications
* history of breast cancer
* individualised
* endometrial cancer
* known clots and CVD
* do use it in the short term to treat menopausal symptoms
* mainly flushes, if required
* if someone has a uterus and is given oestrogen alone they are at risk of endometrial cancer, so also give progestagen
* can be administered in various ways:
* pills
* implant under the skin (under anterior abdominal skin)
* patches (replaced every three days)
* vaginal oestrogen
* oestrogen gels
* can be administered cyclically or continuously
* cyclically:
* oestrogen every day
* progestagen two weeks on two weeks off
* whenever you give a hormone and withdraw it, that will induce a period
34
What are clinical practice guidelines for HRT?
* ACEC, FDA
* limited efficacy/safety data on complementary medicines
* HRT indicated only for moderate to severe menopausal symptoms (flushes, urogenital), women should consider the risks and benefits
* use HRT at the lowest dose and for the shortest duration possible, in perimenopausal or early postmenopausal women not older than 60 years
* healthy women with no contraindications
* do not use HRT for the prevention of CVD or dementia
* HRT is not a first line treatment for osteoporosis
35
What are conclusions about menopause?
* menopause may be associated with significant physiological, physical emotional changes in mid-life
* important to understand these changes so we may best address the needs of women
* lifestyle evaluation and advice remain the cornerstone of advice for the mid-life woman
