Menopause Flashcards
What is the literal definition of menopause?
Last menstrual period
What is a woman described has having gone through the menopause clinically?
12 months of absent menses in a woman with a uterus who is not pregnant or taking hormones that might induce amenorrhoea
What is the definition of perimenopause?
The years leading up to the menopause, associated with fluctuating levels of oestrogen due to declining ovarian function
How can the short-term symptoms of menopause be classified into 4 groups?
- Vasomotor symptoms
- Psychological
- Sexual problems
- Musculoskeletal
What are 4 vasomotor short-term problems associated with the menopause?
- Hot flushes
- Night sweats
- Headaches
- Palpitations
What are 7 short-term psychological symptoms of the menopause?
- Insomnia
- Irritability
- Poor concentration
- Poor short-term memory
- Depression/ low mood
- Lethargy
- Decreased self-confidence
What are 2 short-term sexual problems associated with the menopause?
- Decreased libido
- Dyspareunia
What is a short term musculoskeletal symptom associated with the menopause?
Joint aches
What intermediate term type of problem is commonly associated with the menopause?
Urogenital
What are 4 intermediate-term urogenital symptoms of the menopause?
- Atrophic vaginitis
- Vaginal dryness
- Urethral symptoms
- Urge incontinence/ frequency
What are 2 groups of long-term problems associated with the menopause?
- Circulation
- Skeletal
What are 2 long-term circulation problems associated with the menopause?
- Cardiovascular disease
- Cerebrovascular disease
What are 3 long-term skeletal problems which may be associated with the menopause?
- Osteoporosis
- Hip fracture
- Vertebral fracture
What is another term used to describe ‘peri-menopause’?
Climacteric
On average, when does the perimenopause (or climacteric) begin?
4 years before last menstrual period (may be months or year)
For how long can perimenopause symptoms last?
may last for years after last menstrual period
What is the median age at menopause in the UK?
50.8 years
What physiologically causes menopausal symptoms to occur?
when supply of oocytes becomes exhausted
How many oocytes is a newborn girl born with?
Over half a million
What happens to the 500 000+ oocytes between birth and the menopause in a woman?
over third disappear before puberty
most of the remainder lost during reproductive life
How many primordial follicles are involved in each menstrual cycle?
20-30 follicles begin to develop in each menstrual cycle and most become atretic
What is the average number of menstrual cycles which occur during a woman’s lifetime?
400 cycles
How are most oocytes lost during reproductive life (i.e. after puberty has occurred before the menopause)?
most lost spontaneously through ageing rather than through ovulation
What happens physiologically in the ovary as a woman becomes peri-menopausal?
- premenopause, oestradiol produced by granulosa cells of developing follicle
- production of oestradiol becomes variable as menopause approaches
- proportion of anovulatory menstrual cycles increases, progesteone production declines
What happens to FSH and LH levels during the menopause and why?
Levels rise due to diminishing negative feedback from oestrogen and other ovarian hormones such as inhibin
What blood test can be used to clinically clarify a diagnosis of menopause?
serum FSH > 30IU/L (when associted with irregular or absent periods)
Why is it important to use FSH levels along with the clinical picture when suspecting menopause?
levels of FSH begin to rise significantly around age of 38 in normally cycling women
What is a better marker of follicular reserve than FSH and what can it be used for in particular?
Müllerian hormone: used particularly to assess response to ovarian stimulation during assisted conception
What is the predominant circulating oestrogen form after the menopause?
Oestrone: formed from androstenedione, mainly of adrenal origin which is converted to oestrone
This is a less potent form of oestrogen compared to ovarian oestrogens (oestradiol)
What causes irregular periods before the menopause?
usually result of anovulatory menstrual cycles
What should be done if irregular bleeding at the menopause persists?
Endometrial assessment to exclude endometrial carcinoma
What proportion of postmenopausal bleeding is due to gynaecological malignancy?
10%
What is a hot flush?
Uncomfortable subjective feeling of warmth in the upper part of the body
How long do hot flushes typically last for?
around 3 minutes
What proportion of menopausal women experience vasomotor symptoms (e.g. hot flushes) and what proportion seek medical advice?
- 50-85% experience vasomotor symptoms
- 10-20% seek medical advice
What are 4 features that may accompany hot flushes?
- Nausea
- Palpitations
- Sweating
- Particularly troublesome at night ► insomnia
What is thought to be the cause of hot flushes?
Thought to be of hypothalamic origin, may be in some way related to LH release. Thought a fall in oestrogen levels affect central neurotransmitters such as alpha-adrenergic or serotonergic systems which affect central thermoregulatory centres and LH-releasing neurons
What proportion of women begin experiencing flushes while still menstruating regularly?
20%
What is the prognosis of hot flushes associated with the menopause?
usually improve as body adjusts to new low oestrogen concentrations but in 25% of women, continue for >5 years - can impair quality of life, distressing
In what proportion of women is HRT (exogenous oestrogen) effective in relieving symptoms of hot flushes?
90%
What happens to the genitourinary tract in the menopause and why?
genital system, urethra and bladder trigone are oestrogen dependent, undergo gradual atrophy after the menopause
What can occur as a result of vaginal atrophy due to the menopause?
can cause dyspareunia and bleeding
Why can peri- or postmenopausal women experience more vaginal infections?
Loss of vaginal glycogen causes rise in pH
What urinary symptom is common following the menopause and why?
urgency of micturition due to atrophic change in the trigone
What is the prognosis of atrophic genitourinary symptoms following the menopause?
may appear years after menopause and do not improve spontaneously
What is an effective treatment for genitourinary atrophy?
short course of local or systemic oestrogen
What is thought to be an effective treatment for irritability and lethargy in the menopause?
hormone therapy thought to improve more effectively than placebo
What is thought to be effective treatment for low mood and depression associated with the menopause?
thought that HRT may relieve low mode but clinical depression might not be relieved, as not usually caused directly by oestrogen withdrawal
What are 3 key diseases whih the menopause increases a woman’s susceptibility to?
- Breast cancer
- Cardiovascular disease
- Osteoporosis
How is the relationship with breast cancer related to the menopause?
Risk reduced if premature menopause, increased if it occurs late (double risk if menopause in late 50s compared with early 40s)
What is thought to be the effect of postmenopausal HRT on cardiovascular disease?
Unclear - HRT at start of natural menopause not associated with increased incidence of CVD events, may be associated with decrease
Impact in women over 60-65 when initiated is unclear
How does the menopause affect bones physiologically?
- Bone resorption by osteoclasts is accelerated by the menopause
- Oestrogen receptors shown to be present on bone cells, and oestrogens stimulate osteoblasts directly
- Calcitonin and prostaglandins may also be involved as intermediate factors in link between oestrogen and bone metabolism
What is the rate of decline in bone mass following the menopause?
in first 4 years after menopause, annual loss of 1-3% of bone mass, falling to 0.6% per year thereafter
What are 3 common areas for fractures following the menopause due to osteoporosis?
- Distal radius
- Vertebral body
- Upper femur
What proportion of women over 65 years will be affected by one of the 3 commonest fractures secondary to osteoporosis (distal radius, vertebral body, upper femur)?
40%
What is meant by ‘dowager’s hump’ and what proportion of women are affected?
- wedge compression fractures of spine cause this
- affects 25% of white women over 60 years of age
How common are hip fractures following the menopause?
occur in 20% of women by age of 90
What are 2 further risk factors for osteoporosis following the menopause?
- Underweight women
- White or Asian women have higher risk than Afro-Caribbean women who have greater in initial bone mass
What proportion of women who suffer femoral fractures die in hospital?
17%
What is the first line treatment for osteoporosis in women over 60? What are 3 further aspects of management?
- a bisphosphonate = first line
- oestrogen used only where bisphosphonate inappropriate
- elderly women: supplementation with calcium, calcitonin and vitamin D - reduces risk of hip fractures
- moderate exercise may slow rate of bone loss (but poor compliance with exercise programmes)
What are 7 differentials for the menopause?
- Pre-menstrual syndrome
- Depression
- Thyroid dysfunction
- Pregnancy
- Phaeochromocytoma
- Carcinoid syndrome
- Vasomotor symptoms: calcium antagonists and tricyclic antidepressants
How is the diagnosis of post-menopause made?
Clinical - can only be made in retrospect after 12 months of amenorrhoea (sometimes 6 in women under 40 years of age)
What investigations can be performed to diagnose the menopause if there is confusion e.g. in younger woman?
serum FSH measured - >30IU/L postmenopausally
What tests should be performed in women younger than 40 years with suspected menopause?
2 serum FSH levels, measured 6 weeks apart
often fluctuate considerably during perimenopause
Why is FSH measured twice 6 weeks apart in women under 40 years?
FSH levels fluctuate so perimenopausally, level may be in premenopausal range - FSH leels peak physiologically mid cycle, so worth re-checking apparently high levels again
When might you consider a therapeutic trial of HRT in cases of diagnostic doubt about the menopause? What does the result indicate?
women over 45 years
absence of satisfactory response suggests symptoms unrelated to low levels of oestrogen
What hormonal therapy may be given to treat menopausal symptoms?
- Oestrogen supplementation is the basis
- Progestogen - small role in relieving vasomotor symptoms, but mainly added to protect endometrium from hyperplasia + malignancy
What are 4 types of oestrogen replacement forms available?
- Daily oral tablets
- Twice-weekly or weekly transdermal patches
- Subcutaneous implants every 6-8 months
- Daily nasal sprays, skin creams, 3 monthly vaginal rings - some countries
When must progestegen therapy be given with oestrogen and why?
women who have not undergone hysterectomy
to minimise risk of endometrial cancer associated with unopposed oestrogen therapy
also applies if have undergone endometrial resection
What is a benefit of giving oestrogen replacement as oral tablets?
Beneficial effect on lipid profiles leading to higher HDL level (non-atherogenic) and lower LDL levels (atherogenic)
What is a disadvantage of oral preparations of oestrogen replacement?
potentially more thrombotic than parenteral therapy
In what 2 forms is oral oestrogen replacement available?
- Oestrogen only if have had hysterectomy
- Oestrogen-progestogen if have not undergone hysterectomy
What are 2 ways that oral combined oestrogen and progestogen tablets can be taken?
- Cyclically
- Continuously
When are cyclical and continuous preparations of combined oral oestrogen and progestogen used?
- Cyclical - cause monthly withdrawal bleeds - used perimenopausally
- Continuous - no period - option from more than 2 years after LMP
Why is continuous combined oral HRT useful for many patients?
more convenient for the majority who do not suffer unscheduled bleeding
(erratic bleeding beyond first 6 months of treatment warrants further investigation)
What are 2 alternatives to oestrogen-progesterone preparations as oral HRT?
- Tibolone
- Raloxifene
What is tibolone?
synthetic steroid with weak oestrogenic, progestogenic and androgenic effects
How many tibolone be used to treat menopausal symptoms?
oral drug, may be started 2 years after periods have ceased (similar to continuous combined preparations)
What is raloxifene?
synthetic selective oestrogen receptor modulator (SERM) used to treat menopausal symptoms: has oestrogenic effects on bone and lipid metabolism, but minimal effect on uterine and breast tissue
What is and isn’t raloxifene used for treating in terms of menopausal symptoms?
- Bone and lipid metabolism - good effects, useful in protecting against osteoporosis, doesn’t cause vaginal bleeding
- Uterine and breast tissue -minimal effect, ineffective for controlling perimenopausal symptoms
What types of new preparations for oral treatments of menopausal symptoms are being developed?
combination of oestrogens and SERM bazedoxifene - recently reached market
What 2 types of transcutaneous administration of HRT can be used?
- transdermal patches available as unopposed oestrogen form, or as cyclical or continuoous oestrogen-progestogen combinations
- percutaneous oestrogen gels
How are transdermal patches containing replacement hormone usually used?
applied to buttock, each patch lasts for between 3 and 7 days, depending on formulation
What is a type of adverse reaction that sometimes occurs in transcutaneous administration of HRT?
skin reactions, from hyperaemia to blisters, affect small percentage of users
What are 3 potential advantages of transcutaneous administration of HRT?
- No increase in risk of thrombosis - minimised effect on hepatic production of coagulation factors
- May avoid GI side effects
- May also avoid change sin lipoprotein levels
What different types of transdermal HRT patches are available?
available as unopposed oestrogen form, or as cyclical or continuoous oestrogen-progestogen
How are percutaneous oestrogen gels used for HRT? What is an advantage of the gels?
measured dose rubbed into skin, avoids prolonged skin contact of patches
What is present in subcutaneous implants for HRT symptoms? 2 types
- oestradiol
- testosterone implants if low libido
Where are subcutaneous implants for HRT inserted?
lower abdomen
For how long can subcutaneous HRT implants be inserted?
no less than 5 or 6 months
What are 2 disadvantages of subcutaneous oestrogen implants?
- Oestradiol level doesn’t always fall away to baseline before symptoms recur
- Risk of tachyphylaxis (persistent symptoms despite ever-increasing oestradiol levels) unless strict dose control observed
How can the risk of tachyphylaxis from subcutaneous oestrogen implants be minimised?
pre-implant oestradiol levels should be monitored
What are 4 types of vaginal preparations that can be used to treat vaginal symptoms of menopause?
- Oestradiol tablets
- Low-dose oestradiol-releasing silastic ring pessaries
- Oestriol vaginal pessaries
- Vaginal cream
In what form are vaginal preparations useful for menopausal symptoms and what are they good for?
Low-dose preparations - useful to treat atrophic vaginitis, since systemic absorption very small after first few weeks of administration
What are 4 side-effects associated with HRT?
- Nausea
- Breast-tenderness
- Uterine bleeding (investigate irregular bleeding)
- Cholelithiasis
What proportion of patients taking HRT do nausea and breast tenderness occur in?
5-10%
With what regimens of HRT does uterine bleeding commonly occur in?
low dose regimens
With what HRT preparations is there a slight risk of cholelithiasis?
oral
What endocrine disease may improve/ the risk of be reduced with HRT?
Diabetes - control improved, incidence lowered
What are 4 major things that the risk of is increased with HRT?
- Breast cancer
- Endometrial carcinoma
- Venous thromboembolic disease
- Stroke
By what factor is the risk of endometrial carcinoma increased with 1) unopposed oestrogen therapy and 2) opposed therapy with progesterone for at least 10 days per cycle?
- 4x
- RR <1.0
What is an effective way of protecting the endometrium effectively when using oestrogen-only HRT in postmenopausal women?
Levonorgestrel-releasing intra-uterine system (Mirena)
What is believed to cause the increase in the incidence of breast cancer in menopausal women using HRT?
progesterone - no increase in incidence observed when using oestrogen-only therapy in women who have had hysterectomy
When is the increased risk of breast cancer from HRT eliminated?
no increased risk in those who stopped taking HRT more than 5 years previously
What type of cancer has reduced incidence in women taking HRT?
colorectal cancer
When is the risk of venous thromboembolic disease with HRT present?
largely confined to first year of use, only oral HRT (no increased risk for transdermal)
When should pre-screening for thrombophilia be carried out in someone who may start taking HRT?
if personal or family history of venous thromboembolic disease
What is the relative risk of VTE with HRT?
4.0 in first 6 months, 3 in second 6 months
What effect is there on stroke with HRT?
significant increase in likelihood of stroke in all age groups with oral HRT, but impact small in younger menopausal women as baseline risk low
What are 5 contraindications to hormone treatment?
- Pregnancy
- Venous thromboembolic disease
- History of recurrent thromboembolism
- Liver disease
- Undiagnosed vaginal bleeding
- History of breast carcinoma and advanced endometrial carcinoma
Are hypertension/ cardiovascular risk factors contraindications for HRT?
not if effectively managed
How long are oestrogens given for vasomotor symptoms usually continued?
2 or 3 years then stopped
How should you decide whether to continue oestrogen therapy for vasomotor symptoms beyond 2-3 years?
whether symptoms recur, weighing up risks of osteoporosis against potential side-effects, including breast cancer, for particular individual
What are 2 types of non-hormonal treatment for menopausal symptoms?
- Drugs
- Psychological support
What are 8 drug treatments for symptoms of the menopause?
- Clonidine - vasomotor symptoms
- SSRIs - vasomotor symptoms
- Beta-blockers - palpitations, tachycardia
- Sedatives - non-vasomotor
- Hypnotic - non-vasomotor
- Antidepressants - non-vasomotor
- Bisphosphante - osteoporosis
- Calcium, calcitonin, vitamin D - hip fractures
How does clonidine act to treat vasomotor symptoms of menopause?
acts directly on hypothalamus (no more effective than placebo in RCTs)
is an alpha-agonist hypotensive
What suggests that psychological support is very important to treat menopausal symptoms?
marked placebo benefits in various studies - shows psychological support and sympathetic ear needed
What type of psychological support may be needed in menopausal women?
as many symptoms resolve with time, reassurance important
others may have particular stresses e.g. children leaving home - may accentuate symptoms
