Menopause Flashcards
Metabolic pathway of oral estrogen
First pass liver metabolism
Therefore prothrombotic on coagulation cascade and adverse effect on proinflammatory markers
Percentage of women with premature menopause
1%
Age cut-off and premature menopause
<40yrs
Biochemical changes of menopause
Increased LH and FSH
Decrease inhibin
Decrease oestradiol
Symptoms of menopause
Hot flushes night sweats dry skin and hair arthralgia headaches Urinary frequency dysuria Vaginal atrophy Decreased libido Dyspareunia Mood disturbance Memory loss Insomnia
What factors reduce the age of menopause
Smoking Hysterectomy with ovarian conservation Uterine artery embolization Intrauterine growth restriction low birht weight poor weight gain in infancy childhood starvation early puberty childlessness living at high altitude Downs syndrome Congenital differences e.g, Turners or fragile X social deprivation
What factors may contribute to a later age of menopause
being breastfed
higher childhood cognitive ability
increased parity
later onset of puberty
what proportion of women in western cultures experience vasomotor symptoms
70%
Factors associated with menopausal psychological symtoms
aging parents parental dependence death of parent or close relative death of spouse divorce or separation lack of social support difficulties affecting children poor personal health work stress / redundancy financial difficulties sleep problems
what percentage of women continue to experience vasomotor symptoms at age 60-65
42%
what psychological symptoms may be associated with the menopause
depressed mood anxiety irritability mood swings lethargy lack of energy reduced concentration and memory
Vaginal symptoms of the menopause
dryness burning pruritus dysparunia prolapse
urinary tract symptoms of the menopause
urgency frequency dysuria UTIs incontinence voiding difficulties
sexual problems associated with the menopause
decreased libido
vaginal dryness
dysparunia
what is believed to be the cause of the increase in cardiovascular disease in women after the menopause
Related to decline in estrogen levels
Estrogen is known to be beneficial to cardiovascular health
When is starting HRT considered to be cardio-protective
If started in the peri-menopause or in the early menopausal years
When is starting HRT considered to increase cardiovascular risk?
If started 10+ years after menopause onset or if stopped for a prolonged period then re-started
risk factors for cardiovascular disease
Smoking hypertension abnormal lipid profile abdominal obesity diabetes psychosocial factors low intake of fruit + veg Alcohol >14 units per wk lack of activity BMI >25
What do the 2014 guidelines state as cut off for initiating pharmacological treatment of hypertension?
Men and Women under 60yrs treat if BP >140/90
Men and Women 60+yrs treat if BP >150/90
A 1mmol/L reduction in LDL cholesterol shows what % decrease in CHD mortality
20% reduction per 1mmol/L reduction in LDL cholesterol
raised LDL cholesterol increases risk of what?
increased risk of CHD incl MI and Stroke
what impact does estrogen containing HRT have on lipid profiles
estrogen replacement lowers LDL cholesterol
(but not as much as statins)
and lowers lipoprotein (a)
HRT also increases HDL cholesterol
what percentage of women have osteoporosis at age 50 and age 80
osteoporosis 2% at 50
25% at 80
what proportion of women will suffer with an osteoporotic fracture in their lifetime?
1 in 3
what factors affect bone mass
age - peaks at ~30 and declines from ~40
gender
ethnicity - higher in white europeans
genetic factors
HRT effect on fibrinogen and fibrinolysis
HRT increases fibrinolysis
And decreases fibrinogen
risk factors for osteoporosis
age - >50
Family hx of # - esp 1st degree hip #
prev hx fagility #
Premature ovarian insufficiency
early menopause
hypogonadism
BMI <18.5
alcohol >2 units / day
smoking - any amount
low calcium or vitamin D intake
lack of physical activity
Medication - corticosteroids, chemotherapy, some AEDs, some ARVs, heparin
Pmhx - RA, neuromuscular disease, chronic liver disease, malabsorption, hyperparathyroidism, hyperthyroidism, cushings
management options for preventing / treating osteoporosis
estrogen replacement - HRT 1st line for <60yo F esp if syx bisphosphonates selective estrogen receptor modulators parathyroid hormone calcitonin
factors to consider in menopausal F reporting memory problems
imapired memory common during menopause transition - related to estrogen deficiency consider stress Sleep disturbance depression alcohol or substance abuse SE of prescription medication
Is HRT beneficial for treating menopausal women with clinical depression
no - no evidence
but may help if low mood and memory affected by menopause transition - but not clinical depression.
What is the evidence re HRT and memory / dementia
HRT is not advised to improve memory or prevent dementia
But HRT does appear to decrease risk of Alzheumers in F with early menopause or POI
what impact may the menopause have on migraines
Peri-menopause may aggravate menopause due to hormonal fluctuations and associated neuro-endocrine responses
Other menopausal symptoms - VM, insomnia etc may exacerbate or provoke migraines
Some F report improvement in migraine
What impact may HRT have on migraines?
Cyclical progestogen used in HRT may induce migraine in some women
Micronised progestogens may reduce this
consider IUS or continuous combined as alternative
what proportion of women suffer with urinary incontinence at the time of the menopause
(either stress, urge or mixed)
1/3
What is the role of vaginal estrogens for women with urinary incontinence
vaginal estrogens should be used for menopausal women with vaginal atrophy and reduce the risk of recurrent UTIs
May decrease symptoms of urinary urgency
risk factors for urogenital prolpase
age parity obesity smoking chronic raised intra-abdominal pressure (constipation, chronic cough) connective tissue disorder estrogen deficiency previous hysterectomy
what proportion of women experience joint pain and stiffness around the menopause
50%
more frequent and severe if - obese, unemployed, low mood
symptoms of the menopause
daytime sweats and flushes night time sweats and flushes insomnia headaches tiredness reduced energy arthralgia and myalgia generalised itching tearfulness low mood irritability anger panic attacks palpitations day time urinary frequency / urgency nocturia urge incontinence stress incontinence vaginal dryness / soreness / itching dysparunia PCB decreased libido / difficulty achieving orgasm decreased memory / concentration menstrual irregularity / HMB / lighter bleeding
Components of a menopause consultation
symptoms menstrual hx pmhx, surgical, gynae, obs, medications family hx social hx - stress, alcohol, drugs, OTC discuss attitude to menopause / address misconceptions / concerns Contraceptive and sexual health needs HRT benefits and risks non HRT management options Baseline BP, height, weight, BMI, examination and investigation as indicated
areas to ask about regarding personal or family history with regard to a menopause consultation
Breast / bowel / ovarian cancer - 1st degree relative, what age, BRCA testing?
VTE - 1st degree relatative, when, was it provoked, what treatment
risk for heart disease / stroke - exercise, past hx, 1st degree relative + what age, smoking, HTN, DM, lipid profile, obesity
Risk for osteorporosis - menopause <45yo, corticosteroids for 6m+, anorexia, family hx, calcium / vit D deficiency, prev # + details
other - migraine, current medication, OTC / supplements / alternative remedies, risk of pregnancy, sexual health needs, discomfort with sex, bladder symptoms, diet, alcohol.
when should an FSH level be taken to diagnose menopause
< 40 and suspicion of POI
Consider if 40-45 and change in cycle
Needs to be repeated on at least 2 occasions.
Day 1-5 of cycle
At what point of the cycle should an FSH level be taken
day 1-5 of cycle
random if amenorrhoic
what contraceptives will make FSH levels unreliable
CHCs
HRT
(not depo provera - inhibits LH surge only)
when may serum estradiol levels be useful in management of a menopause patient?
for F using transdermal HRT to check absorption of estradiol
What is the major circiulating estrogen when HRT is given transdermally
estradiol
What is the major circiulating estrogen when HRT is given orally
estrone
are serum levels of LH / estradiol / progesterone / testosterone useful in assessing a suspected menopausal F
no value in making the diagnosis
estadiol used to assess absorption of transdermal HRT
Testosterone not helpful - check free androgen index when considering testosterone prescription for low libido
why are testosterone levels not helpful in assessing menopausal women?
2/3 of testosterone is bound to SHBG
1/3 is bound to albumin
~2% is free
free androgen index may be more useful = 100 x (total testosterone / SHBG)
what are the issues around measuring free androgen index for menopausal women with libido symptoms?
And why do we do it?
no universally accepted normal range
Free androgen index is not accurate
levels dont necessarily correlate with symptoms
Sometimes used for monitoring when prescribing testosterone therapy.
what secondary health investigations may be considered when assessing menopausal patients?
Consider investigation to exclude other causes of symptoms
FBC
TFT
fasting glucose
autoautibody screen
catecholamines (for phaeochromocytoma)
24 hour urinary 5-hydroxyindoleacetic acid (carcinoid syndrome)
when is a thrombophilia screen advised in managing menopausal patients?
NOT routinely <40yo with prev unprovoked VTE recurrent unprovoked VTE VTE at unusual sites family hx of unexplained VTE in 2x 1st degree relatives family hx of specific thrombophilia warfarin induced skin necrosis
what are the limitations of thrombophila screening
cannot completely exclude an underlying increased risk of thrombosis
can only test for currently known thrombophilias
investigation for bleeding outside of expected patterns whilst on HRT
speculum, bimanual + visualise cervix cervical cytology up to date TV USS - cut off 4mm for continuous combined HRT, no cut off for cyclical HRT but do USS at end of withdrawal bleed Endometrial biopsy hysteroscopy
what 9 factors account for 94% of all population attributable risk of MI in women
smoking dyslipidaemia hypertension diabetes abdominal obesity dietary daily fruit and veg regular exercise alcohol consumption psychosocial factors
What diet is recommended for post-menopausal women
High protein
include fish and lean meat, eggs, beans, peas, soy.
Avoid excessive red / processed meat - breast ca risk and increased mortality
increased fibre - decreases CVD, colon cancer and mortality
5 servings fruit / veg per day
wholegrain carbs
limit salt
calcium and vitamin D
what proportion of our vitamin D comes from food
10%
what foods contain vitamin D
egg yolks
oily fish
risk factors for bowel cancer
age family history inflammatory bowel disease obesity diet high in red meat
factors associated with a reduced risk of bowel cancer
exercise
high fibre diet
regular use of aspirin / NSAIDs
HRT
what is the NHS bowel cancer screening programme
60 to 75 yr olds
Home kit for faecal occult blood testing
2 yearly
any positive test is called for colonoscopy
Advice re IUD in peri-menopausal women
IUD fitted at age 40+ can be retained until menopause (2yr after LMP if <50, 12m after LMP if 50+)
No hormones - can diagnose menopause
Can add in HRT
Advice re IUS in peri-menopausal women
If fitted age 45+ can retain until menopause confirmed or age 55
Licensed as progestogen component of HRT FOR 4 yr (FSRH support 5 yr)
Advice re SDI in peri-menopausal women
No upper age limit
Not licensed for endometrial protection
Can be used alongside combined HRT
Advice re POIC in peri-menopausal women
Consider BMD - risk assess for osteoporosis
Re-assess suitability every 2 years
switch to alternative age 50
Advice re CHC in peri-menopausal women
Can be used up to age 50 if not CI
levonorgestrel or norethisterone should be considered 1st line CHC for >40yo - potentially lower VTE risk
And COC ≤30 μg ethinylestradiol considered first-line preparation for >40yo
Consider extended or continuous use for symptom control
May help maintain BMD
Advice re POP in peri-menopausal women
No upper age limit
No increase in VTE risk
Do not mask menopause symptoms
Can be used alongside combined HRT
Advice re condoms in peri-menopausal women
Condoms advised for STI protection
Avoid spermicide - increases HIV transmission
Avoid oil based lubricants / products
Estrogen creams can damage condoms
Risk of condom rupture is increased with vaginal atrophic changes
Advice re diaphragms in peri-menopausal women
Use with spermicide
Mucosal atrophy and / or prolapse can cause problems with fitting or retention
Estrogen creams may damage them
Advice re natural family planning in peri-menopausal women
Not recommended - too unreliable
Unpredictable cycles
Inconsistent temperature changes
Atypical mucus changes
Advice re coitus interruptus as a contraceptive method in peri-menopausal women
Unreliable
But still used by many people
Failure rate similar to that of condoms
Duration of use of local estrogen for vulvo -vaginal atrophy
As long as needed
Indefinite
Symptoms often recur once topical estrogen stopped
Difference between vaginal moisturisers and lubricants
Lubricants applied before SI - to relieve vaginal dryness
Moisturisers are water based - line vagi always walls and deliver continuous moisture - longer symptom relief - applied every few days - not just for SI
What is Ospemifene?
Selective estrogen receptor modulator
What is Ospemifene used for
Oral treatment for treating vulvo-vaginal atrophy
60mg OD
What is tibolone
Synthetic steroid
Estrogen is, progestogenic and androgenic properties
What are the 2 broad categories of estrogen available
synthetic - e.g. ethinylestradiol
natural - estradiol, estrone, estriol
Why are synthetic estrogens such as ethinylestradiol usually unsuitable for HRT
greater metabolic impact - lipoprotein changes, insulin response to glucose and coagulation factors
what is the risk of unopposed estrogen HRT and who does this apply to
Endometrial cancer
in women who still have a uterus
what is the rationale for switching from cyclical HRT to continuous combined after 5 years max
The protective effect on the endometrium of cyclical progesterone decreases after 5 years of use.
Continuous combined HRT lowers the endometrial cancer risk to below that of a post menopausal woman not on HRT
in what time frame is irregular bleeding permitted when starting continuous combined HRT
irregular bleeding / spotting may occur for 4-6m after starting continuous combined HRT
Investigate if beyond 6m or becoming heavier not better
transdermal estrogen for HRT is associated with a lower risk of what consequnces
VTE
stroke
gallbladder disease
is breast cancer risk related to HRT greater with combined or estrogen only HRT?
combined
Do women who have had endometrial ablation require combined or estrogen only HRT?
Combined - cannot guarantee endometrium fully ablated
Estrogen related SE from HRT
fluid retention bloating breast tenderness headaches leg cramps dyspepsia
progestogen related SE from HRT
fluid retention breast tenderness headaches migraine mood swings low mood acne low abdominal pain backache
What are progestogenic SE related to
dose
type
duration
can try changing type, changing route or changing dose
Why do different routes of HRT administration have different risks?
They follow different metabolic pathways
Oral estrogen follows first pass metabolism and has a pro-thrombotic effect on the coagulation cascade and adversely affects pro-inflammatory markers
What is the risk of stroke / VTE with transdermal combined HRT
Not increased with transdermal therapy - therefore consider transdermal 1st line
What is the risk of stroke / VTE with transdermal estrogen only HRT
Not increased with transdermal therapy - therefore consider transdermal 1st line
What form of HRT increases the risk of Stroke / VTE
Oral combined or oral estrogen only HRT
But not significant if started <60yo / within 10 yrs of menopause
How is micronised progesterone different to synthetic progestogens
micronised progesterone selectively binds to the progesterone receptors.
Fewer adverse effects via the androgenic, mineral corticoid and glucocorticoid receptiors than synthetic progestogens.
May have a better safety profile - less risk of VTE, CVD and breast cancer
With HRT what is the ‘cardiovascular timing hypothesis’?
Concept of a window of opportunity for reducing CVD risk when HRT started before age 60.
Starting HRT within 10 years of menopause decreases CVD by 50%, reduced atherosclerosis progression + decreased mortality.
most common indication for HRT
Treatment of vasomotor symptoms
median duration of vasomotor symptoms at menopause
7.4 years
Most effective treatment for menopasual vasomotor symtoms
Estrogen replacement
Treatments for urogenital symptoms of the menopause
estrogen replacement - vaginal or systemic
Follow up recommended for women on systemic HRT
Annual review
No arbitrary limit of used based on age or duration of use
Follow up recommended for women using vaginal estrogens
None required
can continue long term for as long as symptoms are an issue.
Very low systemic absorption,
No need for endometrial monitoring
Treatments for sexual dysfunction symptoms of the menopause
Estrogen replacement - sytemic or vaginal
+/- systemic testosterone if HRT alone not effective
Systemic treatment can act additionally on the arousal centres of the brain.
Estrogen has a proliferative effect on the vulva and vaginal epithelium and improve atrophy and dysparunia
Tibolone may also have an effect - has weak androgenic effect
when should testosterone treatment be considered as part of menopause management
For sexual dysfunction and reduced sexual desire or anorgasmia related to the menopause which has not been resolved by HRT alone.
Tibolone may also have an effect - has weak androgenic effect
Impact of HRT on mood
HRT improves mood, anxiety and dressive symptoms during the menopause transition / early menopause
Not beneficial for clinical depression.
NOT an alternative to anti-depressant treatment
Impact of HRT on cognition
HRT imroves cognition.
Possible reduction in Alzheimers if used for women with POI or in early menopause
May increase risk of dementia if started >10 yrs after menopause
impact of HRT on the musculo-skeletal system
may have a protective effect on connective tissue.
May reduce myalgia and arthralgia symptoms
impact of HRT on colorectal cancer risk
possible reduced risk with oral combined HRT - mechanism unknown
more evidence needed re PO estrogen only or transdermal methods
Impact of HRT on breast cancer risk
combined HRT increases the risk by 4 in 1000 over 5 years
oestrogen only HRT reduces the risk by 4 in 1000 over 5 years
Risk returns to baseline 5 years after stopping HRT
Number of increased cases of breast cancer per 1000 women using combined HRT for 5 years
3 in 1000 more
Baseline breast cancer incidence per 1,000 women aged 50-59
23 in 1000
Is it the estrogen or progestogen component of comined HRT that carries the breast cancer risk?
Progestogen
Are there any progestogens with a lower breast cancer risk?
Insufficient evidence
Possibly micronised progestogen or dydrogesterone
Impact of drinking 2+ units of alcohol on breast cancer risk per 1000 in F aged 50-59 over 5 years
Increases risk by additional 5 per 1000
compared to 4 per 1000 increase risk from combined HRT
Impact of being a current smoker on breast cancer risk per 1000 in F aged 50-59 over 5 years
Increases risk by additional 3 per 1000
compared to 4 per 1000 increase risk from combined HRT
Impact of having a BMI >30 on breast cancer risk per 1000 in F aged 50-59 over 5 years
Increases risk by additional 24 per 1000 (double)
compared to 4 per 1000 increase risk from combined HRT
Impact of doing 2.5 hours of moderate exercise per week on breast cancer risk per 1000 in F aged 50-59 over 5 years
Reduces risk by 7 per 1000 (double)
compared to 4 per 1000 increase risk from combined HRT
management options for low mood related to the menopause
Exclude +/- treat clinical depression
For menopause related low mood consider
- CBT
- HRT
Advice for women stopping HRT re best way to stop
Choice of reducing dose and stopping gradually
or stopping immediately
No evidence to support either way
No arbitrary time limit on duration of use
does the peri-menopausal or menopausal levels of FSH correlate with symptom severity of menopause?
No
diet and lifestyle advice for menopause
Smoking cessation Alcohol reduction weight loss increasing exercise stress management / reduction techniques
BMS guidance for GPs on follow up for women commencing HRT
review at 3 months after starting HRT
Once settled on treatment review annually
