Menopause Flashcards

1
Q

What are the definitions of:
1. Menopause
2. Premenopause (2)
3. Perimenopause
4. Climacteric
5. Early menopause
6. Premature ovarian failure

A
  1. Cessation of menstruation for >12 months. Average age 51
  2. -Early transition to menopause - persistent difference of > 7 days in length of cycle
    -Late menopause - amenorrhoea for >60mdays - onset of perimenopausal sx
  3. Time of onset of irregular cycles till 12 months after LMP
  4. Time interval between reproductive life and non reproductive life
  5. Early menopause <45
  6. Premature ovarian failure <40 (1%)
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2
Q

How is menopause diagnosed (4 points)

A
  1. Clinical diagnosis - retrospective
  2. No need to test hormone levels in suspected menopause if women has amenorrhoea from -hysterectomy/ablation/Mirena
  3. Consider testing hormone levels if younger than 45 and suspect early menopause = 2 x FSH >30 4-6 weeks apart
  4. Test hormone levels if suspecting POF = 2 x FSH > 30 4-6 weeks apart
  5. If testing someone over 50 the FSH >30 on one occasion is sufficient.
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3
Q

What are the symptoms commonly experienced with menopause and incidence (5)

A
  1. Vasomotor symptoms - night sweats, hot flushes
    -40% of women aged 60-65 have VMS
    -80% of women experience these symptoms
    -20% are severely affected
    -10% have VMS lasting >10 yrs
  2. MSK symptoms - joint and muscle aches (80%)
    -Next common after VMS
  3. Genital symptoms
    -Vaginal dryness, dyspareunia, vulval itching, prolapse
  4. Urinary symptoms
    -Urinary frequency, incontinence
    -UTI, dysuria
  5. Psychological symptoms
    -Insomnia, fatigue
    -Depression and anxiety, mood instability, decreased libido
    -Short term memory loss
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4
Q

What is the proposed mechanism of hot flushes

A

Disruption in thermoregulatory centre in the hypothalamus resulting in a reduced thermoneutral zone
Due to the drop in estrogen levels which causes reduction in the thermoneutral zone by variety of possible mechanisms
Results in frequent misinterpretation that body temperature is too high
Body takes action to cool down by sweating and radiation of heat

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5
Q

What are the health consequences of menopause (4)

A
  1. Rapid bone loss and increased fracture risk
  2. Metabolic changes
    -Central fat deposition
    -Increased insulin resistance
  3. Cardiovascular
    -Impaired endothelial function and inflammation
    -Dyslipidemia
    -Increased BP
    -Decreased NO synthase, increased ACEII
  4. Cognition
    -Contraversial whether loss of estrogen impacts cognition
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6
Q

Discuss management of menopausal symptoms
1. Behavioural measures (5)
2. Non pharmacological measures (5)

A
  1. Behavioural
    -Light clothing in layers
    -Small fans
    -Sleep in cool room
    -Exercise - may improve sleep and wellbeing. Unclear for VMS
    -Diet - avoid excess etOH and caffeine
  2. Non-pharmacological
    -CBT / mindfulness/ paced respiration
    -Accupuncture - no effect
    -Hypnotherapy - effect
    -Vaginal moisturisers, gels, lubricants
    -Phytoestrogens (No better than placebo)
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7
Q

Discuss pharmacological management of menopausal symptoms (4)

A
  1. Herbal remedies
    -Phytogenes, red clover, black cohosh
    -Not shown to be effective in large RCT
  2. Gabapentin
    -Equally effective as low dose oestrogen for VMS
    -Reduces VMS 31%
  3. SNRI’s
    -Effective for VMS but not as good as HRT
    -Venlafaxin reduces VMS by 34%
    -OK with tamoxifen
  4. SSRI’s
    -Effective for VMS but less cf HRT
    -Paroxetine first line - reduces VMS by 30%, fluoxetine 24%
    -Should not be used if on tamoxifen
  5. Clonidine
    -Reduces VMS by 27%. Some studies show no benefit over placebo
  6. Hormonal
    -SERMS
    -Tibolone
    -HRT
    -Topical estrogen
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8
Q

Discuss tibolone in management of menopausal symptoms
-Class of medication
-Efficacy for VMS, fracture
-Impact on cancers and VTE
-When to use
-Contra-indications

A
  1. Synthetic steroid with oestrogenic, progestogenic and weak androgenic effects
  2. Efficacy for VMS - 35-50%
  3. Reduced vertebral fracture risk RR 0.55, reduction in non-vetebral fracture RR 0.74
  4. Risk for breast cancer unclear. May increase so avoid in women with Hx Breast cancer
    Increased risk stroke 2.2 if >60
    No impact VTE and CHD
    Concern over breast cancer recurrence
  5. Use when >12 months post menopausal as can cause irregular bleeding
    Can use with or without uterus
    Less PVB cf MHT
  6. Contra-indicated in breast cancer survivors
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9
Q

How should menopausal symptoms be managed in those with breast cancer (4 points)

A
  1. HRT contraindicated generally
    -HABITS trial shows increased recurrence
  2. Treatment options
    -Lifestyle, non-pharmacological, SSRI,SNRI, Clonadine, Gabapentin
  3. Avoid tibolone
  4. Treatment should be individualised
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10
Q

How does estrogen protect against osteoporosis
-4 mechanisms

A

E2 receptors are in bone
-Estrogen inhibits osteoclast action and increases osteoclast apoptosis
-Estrogen extends osteoblast lifespan and increase osteoblast proliferation
-Increases intestinal calcium reabsorption
-Protects bone from PTH which drives bone reabsorption

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11
Q

Describe the demographics of osteoporosis
-Incidence in over 50yrs
-Age of maximum bone density
-Time of maximum bone loss
-Risk factors

A
  1. 50%
  2. 30-35
  3. Rapid decline in bone density directly after menopause
    -1-2% loss per annum
  4. Risk factors
    -Age, gender (f), late menarche, early menopause, post menopause, diet low in vit D and calcium, ethnicity, low BMI, heavy EtOH use, smoking, medications, inactive lifestyle
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12
Q

Describe how bone density should be monitored

A
  1. Use FRAX score to determine high risk of fracture. If score high risk then opt for DEXA scan
  2. DEXA scan gives two values
    T score compares BMD with women in 30’s
    -Osteoporisis =< -2.5
    Z score compares BMD with women same age
    -Osteoporosis = < -2.5
    -No evidence to use ongoing scanning to monitor treatment
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13
Q

What is the management for osteoporosis
-Non pharmacological - 7
-Pharmacological - 4

A
  1. Management non-pharmacological
    -Maintain wt >60kg, Exercise
    -Avoid steroids
    -Avoid smoking and reduce etOH use (<2 standard drinks / day), reduce caffeine intake
    -Calcium 1000mcg /day; Vit D >10mcg / day from diet/sups
  2. Pharmacological
    -Bisphosphonates - first line
    -PO alendronate + calcium +/- Vit D
    -Zoledronate IV infusion annually
    -Tibolone
    -Increases BMD but unclear if decreases fracture risk
    -SERMS
    -Tamoxifen - reduces risk of fracture by 32%
    -Raloxifen - reduces risk of fracture by 55%
    -HRT - not recommended first line but may be considered if <10 yrs PM and other options contra-indicated (Effect same as bisphosophnates)
    -reduces hip fractures by 40%
    -Reduces fractures at all sites
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14
Q

Discuss tamoxifen
-Class of medication
-Effect of specific tissue (6)
-Management for
-Screening
-If symptomatic
-Pregnancy

A
  1. Selective estrogen receptor modulator - SERM
  2. Effect on tissue
    -Anti estrogenic effects on breast
    -Acts on uterus, vagina, ovaries, blood and bone
    -Increased risk of VTE
    -Increased risk of cystic hyperplasia and adenocarcinoma (RR = 4 in post menopausal women. Risk increases with duration of use, 1.6% at 5yrs, 3.1 at 5-14yrs)
    -Increased risk benign cystic hyperplasia and polyps
    -Increased risk ovulation induction in premenopausal women
  3. Management
    -Screening for endometrial changes in aSx women not recommended
    -Incidental finding of thickened ET management = controversial. Consider other risk factors for hyperplasia / cancer
    -Unclear if LNG-IUS for prevention
    -If Sx screen with USS + endometrial Bx
    -If atypical hyperplasia on Bx consult with oncologist about management (switch or stop)
    -Use contraception to avoid pregnancy.
    -Use in pregnancy can increase risk of congenital abnormalities
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15
Q

Discuss Post menopausal bleeding
-Definition
-Incidence
-Causes - 6 with frequency (%)

A
  1. New PVB after 1 yr amenorrhoea
  2. Incidence 4-11%. 90% of time benign cause
  3. Causes:
    -Atrophy 60-80%
    -HRT - 15-25%
    -Polyps 2-12%
    -Endometrial hyperplasia - 10%
    -Cervical cancer <1%
    -Infection - rare
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16
Q

How should post menopausal bleeding be investigated?
-Firstline and sensitivity of tests. Advantages and disadvantages
-Second line and when indicated

A
  1. Endometrial bx with pipelle
    -99.6% sensitive for endometrial cancer
    -81% sensitive for atypical hyperplasia
    Advantages: cheap, easy, fast, office based
    Disadvantages: Samples <50% of endometrium, misses focal pathology, false negative rate 11%
  2. TVUSS
    ->ET >=4mm has 96% sensitivity, 99% NPV
    -Probability of Endometrial cancer if ET <3-4mm = <1%
    -ET of 5mm or more has a 50% false positive rate
  3. Hysteroscopy D&C
    -If patient can’t tolerate pipelle
    -If cx stenosis and can’t achieve sample
    -If sample insufficient and high suspicion of cancer
    -TVUSS suggests polyp or mass
    -After benign histology on pipelle but ongoing abnormal uterine bleeding
17
Q

How should the following circumstances in post menopausal bleeding be managed:
-Insufficient sample on pipelle
-Previous investigated and benign
-Asymptomatic thickened endometrium
-On HRT
-On tamoxifen

A
  1. Insufficient sample
    -If no ongoing PVB repeat TVUSS
    -If ongoing PVB hysteroscopy
  2. Previous investigation and benign histo
    -TVUSS if low suspicion for cancer
    -Hysteroscopy if high suspicion for cancer
  3. aSx with thickened ET
    -ET >11mm (risk of endometrial cancer - 6.7%
    -If other features on USS suspicious for cancer
    -If risk factors for endometrial cancer
  4. On HRT
    -Any bleeding after 6 months HRT if on continuous HRT
    -Any unscheduled bleeding on cyclical HRT
  5. On Tamoxifen
    -If incidental thickened ET consider other RF for cancer
    -If symptomatic
18
Q

Discuss primary ovarian insufficiency
-Definition
-Incidence
-Causes (5 groups)

A
  1. Loss of ovarian function before 40yrs of age
  2. 1:250 by 35, 1:100 by 40
  3. Causes - hypergonadotrophic hypogonadism
    -Idiopathic -25% can resume mensturation 1-5% pregnant
    -Genetic - turners, Premutations of fragile X
    -Infection - mumps, TB
    -Autoimmune - Autoimmune oophoritis
    -Iatrogenic - surg/rad/chemo/ Uterine after embolisation
    -Toxins - Galactosaemia
19
Q

Discuss primary ovarian insufficiency:
-Presentation (3)
-Diagnosis
-Sequalae of POI (6)

A
  1. Presentation
    Oligo/Amenorrhoea test if 4 months
    -50-75% can have intermittent ovulation
    -1-5% can become pregnant
    Hypoestrogen symptoms - hot flushes, vaginal dryness, night sweats
    -Infertility
  2. Diagnosis
    -2 x FSH >30 4-6 weeks apart
    -Exclude other causes of oligo/amenorrhoea
    -Hypothalamic driven
    -Pregnancy
    -Hyperpolactimenia
    -Investigate for cause
    -Karyotype, FMR1 mutation, thyroid, adrenal and 17-hydroxylase antibodies
  3. Sequalae:
    -Decreased life expectancy
    -decreased fertility
    -decreased sexual function
    -decreased bone health
    -decreased CV health
    -Decreased neurological health
20
Q

Discuss the management of primary ovarian insufficiency
-5 topics)

A
  1. Fertility counselling
    -Likelihood of conception low but not impossible
    -Ovulation induction success rates low
    -IVF and donor egg or embryo in most cases
    -If not desiring pregnancy HRT is not a contraceptive
  2. Hormone replacement
    -HRT recommended until at least age of natural menopause (51)
    -Higher doses usually required
    -Benefits: reduced CVD risk, reduced osteoporosis, reduced vasomotor sx, no increase in breast cancer <50yrs
    -Use Mirena + patches if not desiring pregnancy or COC (No first line, avoid hormone free interval)
  3. Cardiovascular health
    -Modify modifiable risk factors
    -manage HTN and hyperlipidemia
    -Annual CVD review - BP, lipids, HBA1c
  4. Bone health
    -DEXA scan 2-5 yearly
    -Weight bearing exercises
    -Vit D and calcium intake
  5. Psychological wellbeing
    -increased anxiety and depression
    -Counselling and FU
21
Q

Discuss use of HRT
1. What are the indications (3)
2. What are the contra-indications of HRT
-Absolute (6)
-Relative (4)

A
  1. Indications
    -Treatment of VSM
    -Prevention of osteoporosis - if within 10yrs of menopause and other treatments are inappropriate
    -POI
  2. Contraindications
    -Absolute:
    Breast or endometrial cancer - ever (past, current)
    Undiagnosed PVB
    Current VTE / MI
    Untreated HTN
    Untreated liver disease or renal disease
    Porphyria cutanea
    Unmanaged endometrial hyperplasia. OK if treated
    -Relative:
    CVD or high risk CVD. OK if HTN and treated
    Previous VTE
    Active liver disease
    Active SLE
22
Q

What are the basic regimens for MRT (HRT) (4)

A
  1. Oestrogen only - no uterus
  2. Oestrogen + progesterone - uterus
  3. Continuous - 1yr post menopausal
  4. Sequential progesterone (10-14 days a month) - <1 yr post menopausal / perimenopausal - stops irregular bleeding
23
Q

Discuss the benefits of MHT (9)

A
  1. Improves VMS by 87% - most effective treatment
  2. Prevents osteoporosis - not first line treatment. Benefit stops after treatment stops
  3. Vuvlovaginal atrophy - topical estrogen suitable
  4. Coronary heart disease - decreases risk of CHD
    -Estrogen only regimen has this effect
    -Only if <60yrs of age or within 10yrs of menopause
    -Early start decreases risk, late start increases risk
    -No difference in CHD if don’t include VTE in analysis
  5. Endometrial cancer - continuous HRT reduces risk
  6. Reduces all cause mortality if initiated before 60yrs or within 10yrs of menopause (RR 0.7)
  7. Reduces colorectal cancer in combined (E+P) regimen
  8. Memory - no evidence it prevents cognition decline if >65yrs (Cochrane review)
  9. Reduces T2DM incidence in E+P and E only
24
Q

Discuss the concerns associated with HRT use (7)

A
  1. Breast cancer
    -Increased risk with E+P >5yrs use = 0.1%
    -No increase in risk of E only HRT
    -Increased risk of breast cancer with increased duration of use for both E & E+P
    -Higher risks with breast cancer if continuous use cf cyclical
    -Risk remains elevated for >10yrs post discontinuation
    -PV estrogen not ass with increased Breast cancer risk
  2. CVD
    -If started within 10yrs of menopause then decreased risk of CVD
    -No increased risk if started after 10yr of CV events / mortality
  3. VTE risk
    -RR 2.0 if E+P
    -E only = borderline significance
    -Higher risk if initiating >10yrs from menopause
    -Risk is increased in first yr of use
    -Transdermal estrodiol unlikely to increase VTE risk above non-users
  4. Stroke
    -Increased risk of stroke
    -Absolute risk of stroke rare if HRT initiated <60yrs or within 10yrs of menopause
    -No increase in risk with low dose transdermal estrogen
  5. Endometrial cancer
    -Increased risk if unopposed estrogen in women with uterus.
  6. Ovarian cancer
    -Increase in serous and endometriod
    -Reduced in clear cell and mucinous
  7. Gall bladder disease
    -Increase of cholecystitis 12 extra case per 1000 in 5 yrs
    -Reduced risk in transdermal estrogen
25
Q

Discus the WHI study regarding E+P regimen
-impact per 10,000 women for specific outcomes (7)

A
  1. 18 more VTE per 10,000 women (RR 2.13)
  2. 8 more breast cancers per 10,000 women (RR 1.26)
  3. 8 more strokes per 10,000 women (RR 1.41)
  4. 7 more heart attacks per 10,000 women (RR 1.29)
  5. 1.5 more ovarian cancers per 10,000 women
  6. 5 fewer hip fractures per 10,000 women (RR 0.66)
  7. 6 fewer will develop colorectal cancer per 10,000 women (RR 0.63)
26
Q

Discuss the WHI study regarding E regimen
-5 main outcomes

A
  1. Increased risk of stroke HR 1.39
  2. Increased risk of VTE HR 1.33
  3. Decreased risk of hip fracture HR 0.7
  4. No effect on CHD, all cause mortality, breast cancer colorectal cancer
  5. In 12 yr FU reduction in breast cancer, all cause mortality and CHD
27
Q

What are the major criticisms of the WHI study (5)

A

WHI primary outcome was prevention of CHD
1. Did not assess risks and benefits of HRT in the short term for menopausal sx
2. Was terminated early as increased risk breast cancer (E+P) and VTE (E only)
3. Average age was 63
4. Participants were not appropriately screened for baseline risks - HTN, obesity, smoking
5. Only one type and dose of HRT used

28
Q

Discuss the findings from the Million women Study
-primary aim
-Study type (2)
-Findings regarding breast cancer (3)
-Findings regarding endometrial cancer (2)
-Criticism (4)

A
  1. Primary aim
    - effect of HRT on breast cancer incidence and mortality
  2. Study type
    -Cohort of 1 000 000 women 50-64
  3. Findings regarding breast cancer
    -RR 1.6 for E current use vs never use for breast cancer (SS)
    -RR 2.0 P+E use vs never use for breast cancer (SS)
    -RR for breast cancer with Tibolone 1.45 (SS)
    -+ 5 cases per 1000 on E only if used >10yrs
    -+ 19 cases per 1000 on E+P if used for >10yrs
    -Type of E+P used or regimen had no impact
  4. Findings regarding endometrial cancer
    - +4 cases in E only group in 5yrs use
    - -2 cases in E+P group in 5yrs use
  5. Criticisms
    -Assumptions made about menopausal status
    -Poor study design with selection bias towards use of HRT and higher SES
    -Previous use of estradiol included in never used group - impacts endometrial cancer outcomes
    -Average age 55.9
29
Q

Discuss the prescribing principles for MRT
-Indication
-Timing of initiation
-Route
-Type of hormone
-Dose
-Follow-up
-Duration
-Stopping
-Contraception

A
  1. Indicated for management of VSM
  2. Safest when initiated within 10yrs of menopause or <60yrs
  3. Transdermal estrogen more favourable for reducing VTE and stroke risk
  4. Best to use biological E + neutral P
  5. Lowest dose used to achieve control of symptoms
  6. Follow-up
    Review after 6 months.
    Review annually after 60 or >10yrs use
    Review if unexpected bleeding after 6 months of use
  7. Duration
    -Shortest time possible (<5yrs)
    -Use beyond 60-65yrs not contraindicated
    -For POI use at least until natural menopause would be expected
  8. Stopping
    -Gradually reducing HRT may limit recurrence of symptoms
    -50% have recurrence of VMS
  9. Contraception
    -Use COC or mirena + patch if perimenopausal or POI
    -Need contraception for 1 yr post LMP if >50 and for 2yrs post LMP if <50
30
Q

Describe the types of HRT
1. Low dose estrogen
2. Low dose progesterone
3. Medium dose estrogen
4. Medium dose progesterone
5. High dose estrogen
6. High dose progesterone

A
  1. Low dose estrogen
    -Tablet 1mg
    -Patch 25mcg
  2. Low dose progesterone
    -Mirena - 20mcg/day
    -Provera 2.5mg
    -Norethisterone - 1.25mg
    -Micronised progesterone 100mcg - 25 days of 28day cycle
  3. Medium dose estrogen
    -Tablet - 2mg
    -Patch - 50mcg
  4. Medium dose progesterone
    -Same as low dose
    -Can increase provera to 5mg
  5. High dose Estrogen
    -Patch 75mcg
  6. High dose progesterone
    -Provera 10mg
    -Norethisterone - 2.5mg
    -Micronised progesterone 200mcg - 12 days of 28 day cycle
31
Q

Discuss HRT following cancer
-Which gynae cancers is it OK to have HRT after (5)
-Which gynae cancers should HRT be avoided (2)
-Use with BRCA positive women

A
  1. Gynae cancers HRT can be used
    -Epithelial ovarian cancer
    -Endometrial cancer - if surgically treated and early stage
    -Carcino/adenosarcomas
    -Cervical cancer
    -Vulval vaginal caner
  2. Gynae cancers where HRT should be avoided
    -Endometrial stromal sarcoma
    -Leiomyosarcomas
    -Low grade or endometriod ovarian cancers
  3. BRCA + women
    -If still have breasts and no Hx breast cancer can have till natural age of menopause
    -If prophylactic mastectomy should have till age of natural menopause
32
Q

What are the 23 recommendations of RANZCOG for HRT

A
  1. Women approaching menopause should be informed about sx and options for Rx
  2. Routine health assessment at this time is important (Breast, Cx, bone if RF, CVD)
  3. If women have a h of affective disorder or POI can experience increased anxiety and depression and should have MH ref considered
  4. Lifestyle advice should be part of menopausal treatment
  5. VMS is the most common use of MHT
  6. Women with PIO should be offered MHT until 50
  7. Commencement of MHT after 60yrs is generally not recommended as risks outweigh benefits
  8. MHT should be considered for Sx women with reduced bone density but without fracture
  9. Oral MHT is contraindicated in women with personal Hx of VTE
  10. MHT should not be used as primary prevention of CVD
  11. In women within 10yrs of menopause MHT doesn’t increase the risk of CHD
  12. MHT should be avoided in women with a person Hx of breast cancer
  13. MHT should be reviewed annually and continuation >5-7 yrs should be individualised based on risk/benefit profile
  14. Oestrogen only Rx is appropriate for women who have undergone hysterectomy
  15. E+P should be used if woman has intact uterus
  16. Dose and duration of Rx should be consistent with Rx goals
  17. For women with vaginal sx only, local vaginal Oestrogen is the most suitable Rx
  18. Sht term (1-2 yr) Ovestin is safe. Long term data is lacking. Consider withdrawal and review
  19. Ovestin doesn’t require concomintant progesterone in women with a uterus
  20. Review MHT 6/12 after commencing and have regular reviews to assess risk / benefits
  21. Tibolone should only be used in women >12 months since menopause - may cause irregular bleeding in younger women
  22. Bioidentical hormonal Rx are not recommended
  23. Paroxetine and fluoxetine should not be used in women taking tamoxifen as can impact tamoxifen metabolism
33
Q

Discuss testosterone use
-Indication (1)
-How to use (3)

A
  1. Indication
    -Reduced libido
  2. How to use
    -Use with E or E+P
    -Topical cream
    -Need to monitor testosterone levels so they are within normal female range
34
Q

Discuss prescribing MHT in women with pre-existing CVD
-Very high risk women
-High risk women
-Low risk women
-Use to prevent CVD

A
  1. Very high risk women
    -Use local vaginal estrogens only
    -Encourage secondary prevention of RF
  2. High risk
    -Can use local vaginal estrogens
    -Transdermal MHT on personalised basis
    -Encourage primary and secondary prevention of RF
  3. Low risk
    -Can have any MHT
    -Encourage primary prevention for RF
  4. Use to prevent CVD
    -Not recommended for CVD prevention