Transcript The menopause and HRT

The Menopause and HRT
Aims
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Gain an understanding of what is meant by
“menopause”, and how it is diagnosed
Gain an understanding of the treatment options
Think about the risks and benefits of HRT
Objectives
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The menopause
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What is it?
What are the symptoms?
How should it be investigated?
 HRT
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Indications
Choice
Risks
Side effects
 Alternatives to HRT
The Menopause
The menopause – what is it?
From the British Menopause Society:
 Permanent cessation of menstruation
 Only diagnosed after 12 months
spontaneous amenorrhoea – a retrospective
diagnosis
 Climacteric/perimenopause – period of
change leading up to the menopause
The menopause – why does it
happen?
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Women are born with around 1.5m oocytes
1/3 are lost by the time of menarche.
Most women menstruate about 400 times, and 2030 follicles start to develop each time.
Eventually the supply of responsive oocytes in the
ovaries runs out
The menopause – hormonal
changes
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Ovarian follicular activity begins to fail as
responsive oocytes run out
Leads to reduction in oestrogen and progesterone
levels
Low level of oestrogen causes disruption of cycle
and menopausal symptoms
-ve feedback loop causes rise in levels of
luteinising hormone and follicle stimulating
hormone
Epidemiology – UK
 Final menstrual period usually occurs between
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the ages of 40 and 58, with an average age of 511
Final menstrual period below the age of 40 is
considered to be premature menopause1
Evidence suggests that in the average woman
symptoms start to increase from 2 years before
the last menstrual period, reach a peak at 1 year
following it, and have resolved by 8 years2
1) Nelson H; Lancet, 2008 Mar
2) Politi MC, Grimm C, Bentz EK et al; J Gen Intern Med. 2008 Sep
How common are symptoms?
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80% of women experience menopausal
symptoms1
45% of these find the symptoms
distressing1
Most women manage the symptoms
themselves – 10% seek medical advice for
their symptoms2
1) RCPE, 2003
2) Roberts; BMJ, 2007
Symptoms
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Menstrual irregularity
Hot flushes/sweats
Urinary/vaginal symptoms
Sleep disturbance
Mood changes
Loss of libido
Others
Menstrual irregularity
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Cycle may lengthen to months, or shorten
to weeks1
Increase in blood loss is common1
Majority of women experience
irregularities, but 10% have a sudden
cessation of menstruation2
1) Nelson H; Lancet, 2008 Mar
2) “Menopause”; Clinical Knowledge Summaries
Hot flushes/sweats
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Common 70-80% of peri-menopausal women1
Tend to affect head, neck, face and chest.
Usually last for a few minutes but can happen
multiple times during the day and night.
Most common in the first year after the last
menstrual period2
1) RCPE 2003
2) “Menopause” Clinical Knowledge Summaries
Urinary/vaginal symptoms
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Dyspareunia
Vaginal discomfort/dryness
Recurrent UTI
Urinary incontinence
Occur in 30% in early post-menopausal
period, rising to 47% later in life1
1) Grady; NEJM, 2006
Sleep disturbance and mood
change
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Sleep disturbance – commonly reported
symptom, probably related to mood changes –
anxiety, depression, memory loss, poor
concentration1
Development of psychological symptoms has
been linked to high BMI, and low amounts of
physical activity2
1)Young T et al;. Sleep, 2003, Sep
2) Di Donato P et al;. Maturitis, 2005, Nov
Loss of libido/other changes
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Loss of libido may be related to hormonal
changes, but also psychological factors,
vaginal dryness, partner
Others (probably due to low oestrogen):
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Brittle nails
Thinning of skin
Hair loss
Generalised aches and pains
Investigations
Generally not required, but blood tests
include:
 TFT
 FBC
 ?FSH
 LH, oestrogen and progesterone levels not
normally helpful
FSH1
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Only needed if doubt about diagnosis – eg. in
premature menopause
Can be very variable during peri-menopause –
single measures are unreliable, and levels should
be checked when women are not using any
oestrogen containing medications (including
COCP)
FSH > 30 is generally taken as post-menopausal
range.
1) “Menopause” Clinical Knowledge Summaries
Associated problems1
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Increased risk of cardiovascular disease +
stroke
Increased risk of osteoporosis
Redistribution of body fat
?Alzheimer’s Disease – more common in
women so may be hormonal link, but no
evidence HRT reduces risk
1) British Menopause Society
Treatment - HRT
HRT
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Effective treatment for menopausal
symptoms
Previously used widely and for prolonged
periods
However:
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Women’s health initiative (2002) – increased risk of
coronary heart disease, stroke, breast cancer, PE
Million women study (2003) – increased risk breast and
ovarian cancer
Indications for HRT1
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Treatment of menopausal symptoms where the
risk benefit ratio is favourable, in fully informed
women, in the lowest possible dose needed to
control symptoms and for the shortest possible
time
In women with premature menopause until the age
of natural menopause (50)
For prevention of osteoporosis in women unable
to use other medications
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1) “Menopause” Clinical Knowledge Summaries
Choice
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Oestrogen + progestogen
Oestrogen alone
Tibolone
Routes of delivery
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Oral tablets
Patches
Creams/gels
Nasal sprays
IUS
Oestrogen releasing vaginal ring
S/C implants
Which preparation?
Questions:
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Does the women have an intact uterus?
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Are symptoms primarily vaso-motor or
urogenital?
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Systemic or local treatment?
4.
Combined or oestrogen only?
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Cyclical (oestrogen with progestogen from day
12-14) or continuous?
She has a uterus
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Symptoms mainly vasomotor:
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Perimenopausal – Systemic cyclical combined HRT
Postmenopausal – Systemic continuous combined HRT
 Symptoms mainly urogenital:
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Perimenopausal – local oestrogen OR systemic cyclical
combined HRT
Post menopausal – local oestrogen OR systemic continuous
combined HRT
She has no uterus
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Symptoms mainly vasomotor – systemic
oestrogen only HRT
Symptoms mainly urogenital – local
oestrogen OR systemic oestrogen only HRT
Tibolone
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Selective oestrogen receptor modulator
Oestrogenic, progestogenic and androgenic properties
Can be used if intact uterus and no bleeding for >1yr
Evidence for improvement in sexual function and
vasomotor symptoms1
Increased risk of stroke and breast cancer, especially in
over 60s2
Less risk with DVT and IHD
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1) Al-Azzawi et al; Obstet Gynecol 1999 Feb
2) Kenemans P et al; Lancet Oncol 2009 Feb
HRT Snap!
Contraindications to HRT1
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Pregnancy and breast-feeding
Undiagnosed vaginal bleeding
VTE
Active/recent angina or MI
Suspected, current, or past breast Ca
Endometrial Ca
Active liver disease with abnormal LFTs
1) “Menopause”; Clinical Knowledge Summaries
What are the risks?
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Venous thromboembolism
Coronary heart disease
Stroke
Breast cancer
Endometrial cancer
Ovarian cancer
What are the risks?
Venous thrombo-embolism
 Increased risk of DVT and PE; highest risk in the
first year of use.
 Number of women having VTE/1000 over 5 years
(figures from BNF):
No HRT
Oestrogen
only HRT
Combined
HRT
50-59
5
7
12
60-69
8
10
18
What are the risks?
Coronary heart disease
 Evidence for protection from CHD is
lacking
 Increased risk of heart disease for women
starting combined HRT more than 10 years
after the menopause (extra 15 cases/1000
women over 5 years)1
Rossouw JE et al; JAMA 2007, Apr
What are the risks?
Stroke
 Small increased risk of stroke for younger women on
HRT, rising in older women
 Number of women having stroke/1000 over 5 years
(figures from BNF):
No HRT
Oestrogen Combined
only HRT
HRT
50-59
4
5
5
60-69
9
12
12
What are the risks?
Breast cancer
 Increased risk is
proportional to the
duration of treatment
 Risk returns to untreated
levels after 5 years
 Number of women having
breast cancer/1000 over 5
and 10 years (figures from
BNF):
Over 5
years
No HRT
Oestrogen
only HRT
Combined
HRT
50-59
10
12
16
60-69
15
18
24
Over 10
years
No HRT
Oestrogen
only HRT
Combined
HRT
50-59
20
26
44
60-69
30
39
66
What are the risks?
Endometrial cancer
 Substantial increased risk with oestrogen only HRT
 Use of progestogen eliminates risk, but needs to be weighed
against increased risk of breast cancer
 Number of women having endometrial cancer/1000 over 5 and
10 years (figures from BNF):
No HRT – 5
years
Oestrogen
only HRT – 5
years
No HRT – 10
years
Oestrogen
only HRT –
10 years
50-59
2
6
4
36
60-69
3
9
6
54
What are the risks?
Ovarian cancer
 Small increased risk of
ovarian cancer, rises
with duration of use
 Number of women
having ovarian
cancer/1000 over 5
and 10 years (figures
from BNF)
Over 5
years
No HRT
Oestrogen
only HRT
Combined
HRT
50-59
2
2
2
60-69
3
3
3
Over 10
years
No HRT
Oestrogen
only HRT
Combined
HRT
50-59
4
5
5
60-69
6
8
8
Follow-up1
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Initial follow up after 3 months
Thereafter, a minimum of annual checks
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Check effectiveness
Side-effects
BP + weight
Breast examination – if appropriate
Pelvic examination – if appropriate
Review of risks/benefits
1) “Menopause”, Clinical Knowledge Summaries
Follow-up
Effectiveness – if symptom control not good consider:
 Poor absorption – eg. Bowel problem
 Drug interaction – eg. Carbemazepine, phenytoin
 Incorrect diagnosis – eg. Hypothyroidism, diabetes
 Patient expectations
Consider – increasing oestrogen dose, altering brand,
changing delivery method
What are the side-effects?
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Oestrogen:
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Breast tenderness
Leg cramps
Bloating
Nausea
Headaches
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Progestogen:
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Breast tenderness
Backache
Depression
Pelvic pain
 Bleeding – cyclical preparations produce regular and
predictable bleeds, usually towards the end of the progestogen
phase
Oestrogen related side-effects
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More likely to occur and be problematic when
there has been a longer duration of ovarian failure
Often resolve with continued use
Consider –
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Breast tenderness – low fat, high carbohydrate diet
Leg cramps – exercise and calf stretches
Nausea, bloating – adjust timing of dose, take with
food
Headaches – try patches (may produce more stable
oestrogen levels)
Progestogen related side-effects
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May be more problematic; may be connected to
type, dose and duration of progestogen
Consider –
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Changing progestogen type
Reducing dose
Altering route to something other than oral
“Long-cycle” HRT – (progestogen for 14 days every 3
months – only suitable if periods have stopped).
Continuous combined therapy or tibolone (if postmenopausal)
Managing bleeding
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Heavy/prolonged bleeding – increase dose or
duration of progestogen ?IUS
Bleeding early in progestogen phase – increase
dose, change type of progestogen
Painful bleeding – change type of progestogen
Irregular bleeding – increase progestogen
No bleeding – may occur in 5% due to atropic
endometrium; confirm compliance and remember
to exclude pregnancy!
Bleeding – when to refer?
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Perimenopausal woman with intact uterus
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Change in pattern of withdrawal bleeds
Breakthrough bleeding persisting for more than 6
months, or does not reduce on “long-cycle” HRT
Persistent or unexplained bleeding after cessation of
hormone therapy for 6 weeks
Bleeding – when to refer?
 Postmenopausal women with an intact
uterus
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Breakthrough bleeding persists for more than 6 months
after starting HRT
Bleeding occurs after amenorrhoea
Persistent or unexplained bleeding after cessation of
hormone therapy for 6 weeks
But before changing treatment!
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Pelvic examination – including visualising
cervix
Confirm smears up to date
TV USS
And don’t forget contraception!
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HRT does not suppress ovulation –
contraception is still needed
If an intact uterus:
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>50 – for one year after LMP
<50 – for two years after LMP
HRT Snap!
Treatment - Alternatives
Lifestyle measures1
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Regular aerobic exercise
Avoid triggers – caffeine, alcohol, smoking,
spicy food
Wear light clothing
Good sleep hygiene
Weight loss
1) Alternatives to HRT for management of symptoms of menopause; ROCG (2006)
Medications1
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SSRIs/SNRIs – fluoxetine, paroxetine, citalopram
and venlafaxine have been shown to reduce
symptoms; unlicensed for this use
Clonidine – evidence of efficacy in treating hot
flushes, but high frequency of side-effects
Gabapentin – evidence of efficacy for treating hot
flushes; for specialist use
1) Nelson HD et al; JAMA, 2006 May
Complementary therapies
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Many OTC preparations available
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Black cohosh
Evening primrose oil
Dong quai
Ginkgo biloba
Ginseng
St John’s Wort
 Limited evidence of efficacy and long term safety
 Some preparations contain oestrogens
 Some preparations can interact with other
medications and may have other adverse side
effects
Summary
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The menopause is a natural and inevitable part of
life
Menopausal symptoms are very common but most
women never seek advice regarding management
Although HRT carries risks, it is a good and
effective treatment for symptoms
Patients should be fully informed and allowed to
make the decision themselves about whether to
commence HRT
References
As detailed on slides +
 www.gpnotebook.co.uk
 www.patient.co.uk
 www.bnf.org
 NHS CKS
 RCOG
 British Menopause Society