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HRT
Joanna Swallow
Mary Valentine
Learning objectives
► Which
preparation in which women at which
stage
► Hazards to avoid
► Risk/Benefit ratios
► Big Studies/Evidence
► Switching/Swapping/Stopping
Menopause
► Average
age 51
► 80% post menopausal by 54
► Climacteric precedes menopause
► Decreased no. of follicles, ovaries fail and
don’t respond to pituitary hormones
What symptoms do women suffer?
Symptoms
► Physical
► Psychological
► Vasomotor
► Insomnia
flushing
► Less skin collagen
► Vaginal dryness
► Urinary tract prolapse
► Reduced Bone mineral
density
► Increased CVS risk
► Reduced
concentration
► Anxiety
► Lethargy
► Reduced
libido
‘’I think I may be menopausal’’
► Women
often come to check/for reassurance
(similar to ‘I’m pregnant consultation)
► 80% do not want HRT
► They want advice and info
► Less than 50% of women prescribed hrt are using
it at 1 year
► Websites of use
http://www.cks.library.nhs.uk/menopause
► http://hcd2.bupa.co.uk/fact_sheets/html/menopau
se.html
► Consultation
ideas?
Consultation ideas
Promote health
Diet, exercise, breast awareness, mammograms, stop smoking, BP
?lipids, ?depression screening, ?urinary symptoms screening
Assess osteoporotic risk
FSH/LH,
No point if >45 (levels fluctuate massively)
If <45 +no periods can indicate premature menopause
?Another reason for symptoms
FSH/LH>15 + oestradiol <70pmol/l
2 FSH >30iu/l 6 wks apart
If taking FSH in menstruating women day 2-3 of menses
HRT
► BNF
states, HRt is suitable for relieving vaginal
atrophy or vasomotor symptoms, not 1st line for
osteoporosis
► Topical vaginal oestrogen rptd prn
local oestrogen pessarys 1 nocte 2/52, then 2-3
per week
British menopause society states that it is safe to
continue indefinitely (not premarin cream as
systemic absorption)
Alternatives to HRT for flushes
Some Evidence
Red Clover (isoflavones)
6/52<
► Sage
► Clonidine
► Phytooestrogens (soya
beans, chickpeas, cereals)
► SSRI paroxetine
► Venlafaxine+Gabapentin
► Black cohosh
► Exercise
► (healthspan-guernsey)
►
►
►
►
►
►
No Evidence
Vitamin E
St Johns Wort
Evening primrose
Risks
► Increased
risk of VTE and CVA
► Increased risk of endometrial cancer (if oestrogen
alone)
► Increased risk of breast cancer (related to duration
of use, prep, dissipates within 5yrs of stopping
► Doesn’t prevent CHD/reduce cognitive decline
► CSM advise minimum effective dose for shortest
duration
Monitoring
► Review
after 3 months and then annually
► Discuss bleeding pattern
► Weight and BP (6/12-annually)
Breast cancer
►
►
►
►
►
►
14/1000 women aged 50-64 are diagnosed with breast
cancer each year
15.5/1000 women aged 50-64 on oestrogen only HRT dx
breast cancer/year
20/1000 women aged 50-64 on combined HRT are
diagnosed with breast cancer/year
31/1000 women aged 50-79 are diagnosed with breast
cancer each year
31/1000 women aged 50-79 on oestrogen only HRT are dx
with breast cancer each year
35/1000 women aged 50-79 on combined HRT are
diagnosed with breast cancer/year
HRT and breast cancer
► Hrt
increases the risk of breast cancer
starting from the end of the 3rd year, risk
reverts to normal 1 yr after stopping
► Risk increases with duration of use
► Breast cancers in women on HRT are larger
and more advanced than those in women
on placebo
► Data from Women’s Health Initiative
Benefits
► Symptom
relief
► Osteoporosis- combined hrt reduces risk of
hip fractures 0.66 (0.45-0.98)
► NNT 200 for 1 year
► Colonic cancer, relative risk 0.80 (0.74-0.86)
risk reduced 20%
Case 1
► 44
yr woman
► Had menopause 7 years ago, her HRT was
stopped after 5 years
► Flushing is now ‘ruining her life’
► Thoughts?
Votes for action?
Early menopause
► In
women with a natural or surgical
menopause before age 45yrs HRT may be
used until the approx age of natural
menopause with no theoretical risk above
and beyond baseline
► The increase in bone density outweighs the
risk of CVD and breast cancer
Harms
► Cardiovascular
disease – combined hrt RR1.29
coronary heart disease, RR1.41 stroke
► Breast cancer as described
► Endometrial cancer combined hrt increases risk by
2 cases per 1000 women over 10yrs (unopposed
oestrogen 5)
► Venous thromboembolism, hazard ratio 2.1 (extra
4 cases per 1000 women on hrt for 5yrs)
Tibolone
► Tibolone
increases risk of breast cancer
(less than combined HRT)
► ??Duration
► Tibolone- combines oestrogenic and
progestogenic activity with androgenic
activity taken continuously and alone
(?libido/post endometriosis surgery)
Contraindications
► Pregnancy/Breastfeeding
► Oestrogen
depdt cancer
► Angina/MI
► VTE
► Liver
disease
► Untreated endometrial hyperplasia
► Undiagnosed vaginal bleeding
Caution
► Migraine
► FHx
Breast cancer
► Endometriosis (may worsen)
► VTE risk factors
► Hypertension
When would you stop HRT?
► Immediate
stop?
► Other reasons to stop?
Stop if
► Sudden
onset severe chest pain
► Sudden SOB
► Leg pain and ?DVT
► Severe headache
► Hepatitis/Jaundice
► BP > 160/100
► Prolonged immobility
► Stop HRT 4-6 wks before major surgery
Which Type?
►
►
►
►
No Uterus
►
Oestrogen only HRT
Intact Uterus
Oestrogen + Cyclical
progestogen for the last
12-14 days
If no period for >12
months then Continuous
combined
Oestrogen/Progestogen
or tibolone
(may still wish to combine
if hx of endometriosis)
Starting HRT
Begin HRT at the lowest possible dose and
increase at 3/12 intervals if reqd
► Record that the risks of HRT have been
explained and that an informed decision has
been taken by the patient
► HRT patches last ¾ days or 7 days and are
placed below waist and sites rotated
What to expect
► Cyclical
HRT causes a regular withdrawal
bleed near the end of the progestogen
phase (Note the pt on cyclical HRT has to
pay 2 prescription charges)
► The aim of continuous combined HRt is to
avoid bleeding but irreg bleeding may occur
during early treatment-if this continues an
endometrial assessment is required
Example preparations
► Continuous
combined
► E.g premique
► Ellest duet conti
► Oestrogen
only
► Eg Elleste Solo
► Cyclical
HRT
► Eg. Premique calender
pack 14 white (oest)
and then 14 green
(oest+prog)
► Prempak-C
► Elleste-Duet
Side effects
► Most
side effects disappear if the woman
persists beyond 12 weeks with the
preparation
Side Effects
►
►
►
►
►
►
►
►
Oestrogenic
Fluid retention
Bloating
Breast tenderness
Nausea
Headache
Dyspepsia (take with food)
Consider changing dose,
changing oestrogen or changing
delivery
Progestogenic
(In a cyclical pattern)
► Fluid retention
► Breast tenderness
► Mood swings
► Depression
► Acne
► Backache
► Reduce progestogen
duration to 10 days per
cycle, change progestogen
c19/21 derivatives,
delivery
►
►
Progestogens
► C19
► E.g
derivatives
Norethisterone
 Levonorgestorel
 More androgenic
 More likely to cause
side effects
► C21
derivatives
► E.g
Medroxyprogestogen
acetate
► Dydrogesterone
► Less
androgenic
Case 2
► Clara
is 52, she has been on HRT for 5
months
► She cant bear the bleeding and comes in
teary as doesn’t want flushes to return
► What
do you want to know?
► What could you do or consider?
Bleeding on HRT
► If
on a cyclical combined HRt check when the
bleeding is (should be regular and predictable at
end of prog phase)
► Check – compliance
► ?Interactions
► Try a stop in HRT
► ?Other reasons
► If bleeding stops try changing progestogen
► Refer 2 week rule if bleeding continues after HRT
has been stopped for 4 wks
Bleeding on HRT
► Refer
non urgently if change in pattern of
withdrawal bleeds and breakthrough bleeding
persisting more than 3/12
► On continuous combined there is a 40% risk of
bleeding in the 1st 4/12
► Check that they were 1 yr post bleed before
commencing
► ~If continues >6/12 then investigate
► If bleeding commences after ammenorrhea on the
prep then investigate
Stopping HRT
►
►
►
►
►
►
►
►
Stop gradually wean off over 6/12
Half dose for 2-3 months
¼ dose for 3/12 then stop
Patches may be cut to achieve this
Don’t reduce the progestogen if on a cyclical regime
If continuous reduce both simultaneously
Review after 1 month if symptoms have recurred consider
restarting at lowest dose
If only vaginal symptoms then topical oestrogen's
Consider contraception?
► HRT
is not contraception
► When
is it safe to assume contraception no
longer needed?
Pat
► Pat
is 43, she’s been on depo for 6 years
and loves it,
► What
should you consider/advise?
June
► June
is 48, She has a mirena in, shes
amenorrhoeic and having lots of hot flushes.
She wants to know about HRT and whether
she is ‘going through the change’
Contraception
► HRT
is not contraception
► If LMP >2yrs ago and <50 yrs is prob ok
► If LMP >1yr ago and >50 is prob ok
► FSH raise does not guarantee
Jan
► Jan
is 50, She has a mirena (for 2 years)
► She hasn’t had any periods since the first 3
months, she wants to know if she still needs
it.
Mirena
► Mirena
+oestrogen
► Mirena is now licensed for endometrial
protection as the progestogenic part of HRT
combined with a small amount of oestrogen
may control hot flushes
► (4yrs)
Other Questions?